#Addenbrooke’s hospital

[sp00kysk3lly]

Date: 25th January 2023

Time: 03:24 AM

Feeling: Exhausted, Depressed, Given Up On, Lost. Angry.

Explanation: I’ve had 2 hospital appointments. One last week (Thursday 19th) and another one on Monday 23rd.

Both appointments were stupid and useless and I wish I had never gone to them.

The first one (Thursday) was my first diabetes appointment since 2021, (which they messed up a few times, I’m suppose to be seen every few months, not once a year!)

Before I even sat down in the doctors office the doctor, mentions my weight gain, knowing full well that I have issues with my looks and especially my weight. Then she just assumes I am eating large portions! Which I am not, I barely eat anymore. Not due to weight issues, more due to my very severe bowel condition that affects me with everything I eat.

Also she said “more activity” meaning get more exercise. Which I have done and I also have the proof off on my Apple Watch which I got for the purpose of tracking my activity. (I am disabled, my bones don’t really work how they’re suppose too so I have been walking a lot lately. (Proof in pictures below, some of them anyway. I’m not going to sit here and take pictures of all of them. I’ve been walking every day since 6 July 2022 when I got this watch)).

As you can see by my evidence, I have been doing a lot of “activity” every single day. So, yeah, clearly something is wrong with my body that they don’t want to admit.

Which is understandable because, they are the reason for my abundance of illnesses. They also know this, but like many doctors, do not like to admit that fact.

Early on when I was diagnosed in 2016 as a 18 nearly 19 year old with Type One Diabetes, I constantly and continuously asked for support. I begged them to help me get control of my sugars. I even wrote them a detailed letter asking for this support, saying that I don’t feel supported with my diabetes care. And they did take that on board, but it only lasted a couple of months and then they were right back onto not supporting me with anything.

They won’t let me and still don’t let me do the DAFNE course (Dose Adjustment For Normal Eating) which is a carb counting course for diabetics to go on to manage their sugars and so on.

Their reasoning for not doing this is “you have to talk in the meetings and you won’t.” Ummm… how do you know I won’t talk? Also, I have spoke to many diabetics who have gone on this course and they have told me, that they don’t have to speak if they don’t want too. If you don’t want to talk then you just explain or you can take someone with you who will speak on your behalf.

So, they are the reason why I have all these illnesses and conditions that I now have to live with for the rest of my life. And they know this. They know that I blame them for EVERYTHING to do with those conditions and illnesses.

But I will post more on that maybe in the future. My point is, she was totally wrong to say anything about my weight, or my exercise which she knows NOTHING about. She knew this would hurt me, she also knew that I would go home and constantly think about it. Because I care a lot about my looks, she knows this. I have lost my teeth, all of them because of their no support. Which makes me even more self-conscious in my day to day life.

I will now go on to the Monday appointment with my Gastro clinic.

I hate this clinic even more than diabetes. You’ll see why in a minute.

First off, my gastro doctor never actually sees me, he always has his lackeys do it for him. I don’t know why this is, the man acts like I’m going to beat him up every chance I get. (Which obviously I wouldn’t, but that’s what they think of me, mainly because I have anger issues. But it’s not my fault that they (The NHS) treat me like crap most of the time!)

So I went and got my weight checked (I hate that part) and my height. Then I waited for the doctor to come get me.

Once in the doctors room he asked me the usual questions. (i.e how many times do you go to the toilet? Do you have any nausea or vomiting? Etc.)

Once that is done then he goes on about the colorectal appointment that I couldn’t go to, because my mum had a virus. I’m not going to make my mum go to an appointment with me (she’s my carer) when she’s ill. Am I?

So he starts acting like it’s our fault and that we wasted his time in making the referral, which apparently took 6 months. (DISCLAIMER! The colorectal clinic is the place where they discuss stoma bags and all sorts of stuff like that, which I had asked about). It wasn’t my fault I couldn’t go, I can’t just assume my mums going to be sick or well on certain days can I? Just like I can’t assume I’ll be well enough on certain days.

He tells me that there’s a tablet that I could try, which honestly, considering all the other enzymes and medications these people have given me have not done anything to help I don’t really have much hope for it. But I agreed that I would try them for a month and see how I get on.

Then he began telling me that “badly controlled diabetes” causes gastrointestinal problems. Which I already knew about (I do a lot of research on my illnesses so I know what to expect later on in life). And apparently there’s another medication I could try (remember this for later down the post). So that’s it, appointment over. He said he’ll make another referral to the colorectal clinic and we leave.

Yesterday morning (24th January) I get a letter which I normally do after my appointments explaining what was said, and so on.

So I read it, and it’s fine. Until I get to the last part of the letter. Which says this. (Photo down below)

So, that’s it! Gastro have given up on me! Without any actual help. They diagnosed me with EPI (Exocrine Pancreatic Insufficiency) which I still don’t think I have, because everything and I mean EVERYTHING I eat doesn’t stay inside my body and the fact that it even happens when I am eating absolutely NOTHING!! Which if you know what EPI is, then you’d know shouldn’t actually happen.

So, they’ve pretty much left me with nothing. No help, started me on these stupid pathetic tablets that won’t work, and now if they don’t work, I won’t be able to tell them or even explain to them why they’re not working! So yeah, that’s why I feel given up on and lost.

They’ve also made me angry. Because not only do I feel even more self conscious of my looks and weight now, I also have no help from the gastro clinic. And I basically have to deal with this terrible rare illness on my own. Which is going to result in me probably starving myself! Something I shouldn’t obviously be doing but I have absolutely no choice anymore.

When is the NHS going to understand that people with chronic lifelong conditions, need complete 100% help and support.

This makes me feel like it’s personal. Because I have seen them behave completely different with other patients. And then they get to me and it seems like they hate me and don’t want me there at all.

Like my DSN (Diabetes Specialist Nurse, for those that barely go to hospital), she speaks to every single person and when she gets to me acts funny with me.

I feel like just giving up on all my illnesses. The diabetes, by not taking my insulin even if I do have a pump now I’ll just take it off and ignore it. The bowel condition by just starving myself.

Will they care then? Will they care when I’m dead? Will they see that I need support when I’m laying on a hospital bed in hospital because I’m giving up on everything because they gave up on me? Why should I care when they don’t?

I understand that the NHS is “under funded” I get that. But you go into the job to HELP people. That’s what makes good doctors and nurses because they are passionate with their jobs. They actually care about their patients and want the best for them. But mine don’t care about me. I know they don’t. I can see it every time they speak to me, every time they have a appointment with me. And honestly I feel like sending them a link to this post so they can see what they have done to someone like me.

Who knows who else they are doing it to. Probably no one because they only seem to act this way with me. My friends have noticed it, my family have noticed it. So I am not the only one who has seen this.

Also the reason I am exhausted, is because for the past few days since Saturday, I haven’t slept properly and I have no idea why. I’ve tried everything. Lights off, TV off, Reading, Walking around. Taking tablets to aid sleep. And guess what?

If you guessed that the NHS didn’t care, you’ve got it in one. I’m still trying to get into the doctors to be put on sleeping medication. I’ll try again in the morning, but looks like sleep won’t be coming for me tonight. Getting more headaches, more eye problems (I’m losing my sight) because I’m up all night for no reason. I am even surprised that I am still functioning normally, but it’s whatever. Maybe I should stay up all night and then maybe I’ll get a decent nights sleep.

Vent Over!

[warningsine]

A British toddler has had her hearing restored after becoming the first person in the world to take part in a pioneering gene therapy trial, in a development that doctors say marks a new era in treating deafness.

Opal Sandy was born unable to hear anything due to auditory neuropathy, a condition that disrupts nerve impulses travelling from the inner ear to the brain and can be caused by a faulty gene.

But after receiving an infusion containing a working copy of the gene during groundbreaking surgery that took just 16 minutes, the 18-month-old can hear almost perfectly and enjoys playing with toy drums.

Her parents were left “gobsmacked” when they realised she could hear for the first time after the treatment. “I couldn’t really believe it,” Opal’s mother, Jo Sandy, said. “It was … bonkers.”

The girl, from Oxfordshire, was treated at Addenbrooke’s hospital, part of Cambridge university hospitals NHS foundation trust, which is running the Chord trial. More deaf children from the UK, Spain and the US are being recruited to the trial and will all be followed up for five years.

Prof Manohar Bance, an ear surgeon at the trust and chief investigator for the trial, said the initial results were “better than I hoped or expected” and could cure patients with this type of deafness.

“We have results from [Opal] which are very spectacular – so close to normal hearing restoration. So we do hope it could be a potential cure.”

He added: “There’s been so much work, decades of work … to finally see something that actually worked in humans …. It was quite spectacular and a bit awe-inspiring really. It felt very special.”

Auditory neuropathy can be caused by a fault in the OTOF gene, which makes a protein called otoferlin. This enables cells in the ear to communicate with the hearing nerve. To overcome the fault, the new therapy from biotech firm Regeneron sends a working copy of the gene to the ear.

A second child has also recently received the gene therapy treatment at Cambridge university hospitals, with positive results.

The overall Chord trial consists of three parts, with three deaf children including Opal receiving a low dose of gene therapy in one ear only.

A different set of three children will get a high dose on one side. Then, if that is shown to be safe, more children will receive a dose in both ears at the same time. In total, 18 children worldwide will be recruited to the trial.

Opal is the first patient globally to receive the therapy and is “the youngest globally that’s been done to date as far as we know”, Bance said.

The gene therapy – DB-OTO – is specifically for children with OTOF mutations. A harmless virus is used to carry the working gene into the patient.

The trial is “just the beginning of gene therapies”, Bance said. “It marks a new era in the treatment for deafness.”

Martin McLean, a senior policy adviser at the National Deaf Children’s Society, said deafness should never be a barrier to happiness or fulfilment. “Many families will welcome these developments, and we look forward to learning about the long-term outcomes for the children treated.”

With Opal’s hearing restored, her parents now have a fresh problem to contend with: their daughter’s new favourite hobby is slamming cutlery on the table to make as much noise as possible.

[thatsonemorbidcorvid]

https://www.telegraph.co.uk/health-fitness/conditions/cancer/the-little-known-cancer-thats-linked-to-the-gut/

“The surge in cases of cancer in the under-50s has made many of us worry, with bowel, breast and lung cancers among those increasing most rapidly. But what is more surprising is that rates of aggressive gallbladder cancer have risen even more sharply, affecting many more women than men, particularly those who have had children. It’s also more likely in those who have suffered from the common problem of gallstones.

The figures are alarming, with cases having doubled in British people aged between 24 and 49 in the past three decades, according to Cancer Research UK. But the good news is that there are measures you can take to limit the risk of the disease, through changes to your diet and lifestyle.

Here, our experts explain what exactly the cancer is, the reasons it is spiking in younger people and what we can do to increase our chances of avoiding it.

What is gallbladder cancer?

The gallbladder is an apple-sized organ near the liver and is primarily responsible for storing bile, a substance produced by the liver and used by the body to break down the fats we eat.

Thousands of years ago, humans might have eaten one big meal every few days and “we might have needed that extra boost of bile to help us digest it, if the liver couldn’t produce it fast enough,” says Dr Anita Balakrishnan, a consultant hepatopancreatobiliary (HPB) surgeon at Addenbrooke’s Hospital and an associate lecturer at the University of Cambridge..

“The gallbladder is a vestigial organ, like the appendix – now we don’t really need it for normal digestion, and sometimes it causes trouble.’”

Cancer occurs when healthy cells in the gallbladder develop genetic mutations that cause them to grow and multiply out of control. Just over 1,000 cases have been diagnosed in the UK each year, equivalent to about three per day and, “sadly, it’s an aggressive cancer,” says Dr Balakrishnan.

What are the risk factors?

According to Cancer Research UK, women account for 71 per cent of cases. In women who have given birth, particularly those who have had five or more children, the risk is increased.

The reason for this is not fully known, but women are two to three times more likely to suffer from gallstones, which are a major risk factor for gallbladder cancer. Oestrogen can increase cholesterol levels in bile and decrease gallbladder contractions, which can lead crystals to form in the bile and create stones. During pregnancy, the gallbladder also grows in volume.

“Having gallstones doesn’t necessarily mean you’ll get cancer, but they cause inflammation of the gallbladder, which puts people at a higher risk,” says Mr Shahid Farid, a consultant surgeon with a specialism in gallbladder surgery at Nuffield Health Leeds Hospital.

People with a family history of gallbladder cancer are five times more likely to develop the disease, and it is more common in people of Asian descent.

Smoking and obesity also increase the risk, with the rise in obesity since the mid-1990s believed to be a major factor in the increase in cancer among younger people, in particular.

What are the main symptoms, treatment and survival rate?

Unfortunately, gallbladder cancer is often a silent disease which becomes symptomatic only in its later stages.

“Any symptoms people have are usually non-specific, such as tiredness and perhaps some abdominal discomfort,” says Mr Farid.

Eventually, symptoms can include jaundice, pain in the upper right abdomen, weight loss, nausea and vomiting. “By that stage, it has usually grown beyond the gallbladder and is at an advanced stage,” he says.

It is often detected by chance during operations, for instance to remove gallstones, and if it is contained within the gallbladder, the five-year survival rate is 60-70 per cent. If it has spread to local tissues or lymph nodes, survival rates are almost 30 per cent, while if it has spread to more distant areas, rates are under 5 per cent.

If possible, treatment involves surgery, along with chemotherapy.

What can we do to minimise our risk?

1. Maintain a healthy weight

Being overweight and obese is the second biggest cause of cancer in the UK, after smoking. Several studies have found a link between an increased risk of gallbladder cancer and a BMI of over 25, with the World Cancer Research Fund stating that the risk increases by 25 per cent per 5 kg/m2 increase in BMI.

One recent Norwegian study found a concerning 47 per cent increased risk in women per 5 kg/m2 increase in BMI, while the increased risk in men was smaller and not statistically significant. It also showed a decreased survival rate for overweight and obese women with gallbladder cancer.

“Eating a healthy diet and staying within a healthy BMI range will help avoid gallbladder cancer,” says Dr Balakrishnan. “Giving up smoking and keeping alcohol consumption under recommended limits is also vital.”

2. Look after your microbiome

In recent years, scientists have increasingly focused on the microbiome, the ecosystem of bacteria which populates the gut, when searching for causes of the increase in early-onset cancers.

“Research into the influence of the microbiome on cancers including gallbladder cancer is still in its early days, but it’s only logical that it plays a part,” says Mr Farid. “Our microbiome can contribute to inflammation, and that can predispose us to cancer.”

A Chinese study from 2023 investigated the microbiome of patients with biliary tract cancers, of which gallbladder cancer is one. It found patients with the disease had increased levels of the Enterobacteriacae bacteria, and decreased levels of others including Clostridia, suggesting an imbalance. Both are associated with inflammation.

We can boost the diversity and good bacteria in our microbiome with fermented foods such as kefir, sauerkraut and kimchi, and prebiotic foods like mushrooms, onions, garlic, asparagus, leeks and apples, which feed the bacteria in our gut.

Good bacteria such as Clostridia can naturally be found in food such as vegetables, while high-fibre foods such as fruit, wholegrains and nuts will also nurture the microbiome.

3. Avoid fried, fatty foods and sugary drinks

The link between different types of diet and higher rates of gallbladder cancer is still being researched, but some studies have highlighted certain principles by which it’s best to live.

Eating too many fatty and fried foods have been linked to an increased chance of getting the disease because they raise cholesterol which is linked to gallstones, which are in turn strongly linked to gallbladder cancer.

Red meat, and particularly processed meat containing nitrates, is also associated with a higher risk, so cutting down to 455g of cooked lean red meat per week is recommended.

Drinking sugar-sweetened and artificially sweetened beverages has been shown to double the risk of gallbladder cancer when individuals drank 400ml or more per day. This is thought to be because increased sugar consumption is linked to a higher BMI, and also to Type 2 diabetes, which increases the risk of cancer.

Ultra-processed foods (UPFs) are linked to a higher incidence of all cancers, and researchers believe they may be a major driver of the increase in cancers among under-50s. “Reducing the amount you consume and eating unprocessed food where possible is best,” says Mr Farid.

4. Eat the DASH diet

One Swedish study revealed that two types of healthy diet are associated with a lower risk. One is the Dietary Approach to Stop Hypertension, or DASH, which includes fruits, vegetables, whole grains, low-fat dairy, and lean protein from chicken, fish, beans and nuts. It avoids foods high in salt, saturated fat, and added sugar. The second is the Mediterranean diet, which follows very similar principles.

One Indian study reported that eating sweet potatoes was associated with a lower risk of gallbladder cancer, along with green chillis, radish, mango, orange and melon – all of which contain high levels of antioxidants.

5. Exercise regularly

Regular physical activity has been shown to be likely to reduce the risk of gallbladder cancer, and studies have shown it can increase the diversity of the gut microbiome.

“Exercise also promotes cell turnover in a different way to when you’re sedentary,” says Mr Farid. “It also reduces the amount of fat and also inflammatory cytokines in your blood. So it’s one of the most important things you can do to modify your risk of many cancers, including gallbladder.���”

[beardedmrbean]

Giving out free vapes in A&E helped to double the number of people that quit smoking cigarettes, a trial has found.

Around a quarter of the 24 million people that attend an NHS emergency department each year are smokers.

Researchers found that by giving smokers an e-cigarette starter pack, which included a vape and a referral to stop smoking services, they were almost twice as likely to successfully quit after six months compared to standard NHS care.

The trial involved almost 1,000 people who smoked cigarettes at six NHS hospitals in England and Scotland.

Half of the participants were given the vape starter packs and the other half were given information about local stop smoking services, which is the advice routinely provided.

Almost one in four, or 23.9 per cent, of the smokers that left A&E with a free vape had quit after six months, compared to 12.9 per cent who did not.

The study, led by the Norwich Clinical Trials Unit at the University of East Anglia (UEA), also found that the people who were given vapes but did not manage to quit smoking were more likely to cut down the number of cigarettes they smoked.

Dr Ian Pope, from UEA’s Norwich Medical School and an emergency doctor, said there was a “valuable opportunity for people to be supported to quit smoking” when they attend A&E.

He said it would “improve their chances of recovery from whatever has brought them to hospital, and also prevent future illness”.

“Swapping to e-cigarettes could save thousands of lives,” he said. “We believe that if this intervention was widely implemented it could result in more than 22,000 extra people quitting smoking each year.”

76,000 deaths each year

Smoking is the leading cause of preventable death in the UK. It is the cause of as many as 76,000 deaths each year, according to the NHS, while thousands more live with debilitating smoking-related illnesses.

The Government has pledged to ban smoking and create a “smoke-free generation”. The Tobacco and Vapes Bill, if it becomes law, will ensure that children who are turning 15 this year and younger can never legally be sold tobacco.

It will also ban disposable vapes and place new restrictions on flavours and packaging designed to appeal to children, with Rishi Sunak, the Prime Minister, vowing to “stop our kids getting hooked on nicotine”.

The Government’s proposals aim to prevent children and teenagers from smoking and vaping.

The researchers said their trial results showed that vapes were a suitable tool to help people quit cigarettes.

The trial lasted 30 months and took place at Norfolk and Norwich University Hospital, the Royal London Hospital and Homerton University Hospital in London, Leicester Royal Infirmary, Addenbrooke’s hospital in Cambridge and the Royal Infirmary of Edinburgh. The hospitals are no longer giving out vape starter packs.

An NHS spokesman said: “Smoking costs the NHS and the taxpayer billions every year in avoidable health and social care costs. Encouraging more people to stop smoking tobacco will support them to have healthier lives.”

The study was published in the Emergency Medicine Journal.

[portraituresque]

John Bellany - 1988 - Self-Portrait ( Addenbrook's Hospital ) - watercolour on paper - 77.4 x 56.8 cm 

[coochiequeens]

A birth center lost diversity points for using the term Mother.

https://archive.is/2023.11.19-103726/https://www.telegraph.co.uk/news/2023/11/18/maternity-hospital-downgraded-use-term-mother-diversity/

The Rosie Birth Centre at Addenbrooke's Hospital CREDIT: CAMimage/Alamy Stock Photo

A maternity hospital received a low grade on a diversity assessment because staff only use the term “mother” when discussing maternity leave, The Telegraph can disclose.

The Cambridge University Hospital Trust, which manages a maternity hospital called the Rosie, lost points because staff use the term “mother” when referring to the policies it had in place regarding paid leave, instead of broadening it to include gender-neutral alternatives.

The report was carried out by the NHS’ “Rainbow Badge” scheme, which assesses hospitals based on how they treat LGBT patients.

The trust also lost points for not providing staff with guidance on what trans and non-binary employees should wear, pointing out how the trust’s “trans inclusion policy” did not provide “guidance on the dress code for trans employees, including non-binary employees.”

The report also flagged a “cause for concern” about a deluge of comments from staff criticising the trust’s inclusivity efforts for “virtue signaling” instead of providing care, including one comment which said: “We cannot waste taxpayers’ money on tokenism.”

The report said: “0 points were awarded for the Maternity Leave Policy. The policy does not have an inclusion statement to make clear that it applies to all irrespective of gender/gender of partner etc. The policy also refers to “mother” without expanding to include gender-neutral/inclusive terms and only uses he/she pronouns throughout.”

‘I just want to live my life’

One member of staff who said he was gay is cited calling the Rainbow Badge “insulting.”

They wrote: “I feel it is excessive - I just want to live my life; I don’t want to be asked; I don’t want my identity reduced to a label. I am tired of it - I just want to live my life like everyone else.”

Another said: “Rainbow badges are just performative; I would prefer all staff be properly trained and supportive to all needs, not singling out one or two.”

Another wrote: “I am gravely concerned about the influence on the NHS of organisations like Mermaids and Stonewall. I am concerned about the protection of single-sex spaces like hospital wards. 

“I am concerned that men are being allowed to self-ID into women’s protected single-sex spaces, and the serious safeguarding risk this poses. I am concerned that this is all being ignored in favor of mindless virtue signaling like this latest ‘NHS Rainbow’ scheme.”

The report recommended that hospital staff “signal” to patients that they are LGBT inclusive by introducing themselves to patients with their pronouns and putting sanitary products in all toilets.

The report, however, did praise aspects of the trust’s approach to inclusion that were already in place.

It endorsed the fact that the group tasked with hiring senior staff has to include a “Diversity Inclusion Panellist” with “lived experience of a protected characteristic” whose role is to ensure that the staff carry out hiring processes “fairly.”

It also commended how the hospitals set “inclusion-based objectives” to senior managers as part of their annual appraisal.

The “Rainbow Badge” initiative began as a physical badge launched by Evelina London’s Children’s Hospital in February 2019 that staff could wear to show they are aware of the issues LGBT people face in the NHS.

Matt Hancock supported the scheme as health secretary.

Staff members celebrating the NHS Rainbow Badge scheme - developed by Evelina London Children's Hospital - during the 2019 Pride in London Parade in central London CREDIT: PA/Guy's and St Thomas' NHS Foundat

In 2021, the “Rainbow Badge” went from a physical symbol to a nationwide scheme that assesses hospitals based on how they treated LGBT staff by placing them on a scale between gold, silver, and bronze.

The report on the Cambridge University Hospital trust received the lowest possible grade, referred to as “initial stage,” meaning it failed to even qualify for the “bronze” award.

The scheme is commissioned by NHS England but run by trans rights groups, including Stonewall and the LGBT Foundation, who carry out the grading.

In August, it was revealed that 77 trusts have signed up for the scheme.

The Cambridge University Hospital Trust declined to comment.

[consultatiiladomiciliu-ro]

Masurarea sistematică a acidului formic urinar ca un nou biomarker pentru boala Alzheimer

Citeste articolul pe https://consultatiiladomiciliu.ro/masurarea-sistematica-a-acidului-formic-urinar-ca-un-nou-biomarker-pentru-boala-alzheimer/

Masurarea sistematică a acidului formic urinar ca un nou biomarker pentru boala Alzheimer

1Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

2Department of Data and Analytics, WuXi Diagnostics Innovation Research Institute, Shanghai, China

3PET Center, Huashan Hospital, Fudan University, Shanghai, China

4State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

Introducere:

Acumularea de formaldehidă endogenă este considerată un factor patogen în boala Alzheimer (AD). Scopul acestui studiu a fost de a investiga relația dintre acidul formic urinar și biomarkerii plasmatici în AD.

Analiza costa 78lei

Efectuează analiza

  Materiale și metode:

Cinci sute șaptezeci și patru de participanți au fost împărțiți în cinci grupuri în funcție de diagnosticul lor: 71 cu tulburări cognitive normale (NC), 101 cu declin cognitiv subiectiv (SCD), 131 cu tulburări cognitive fără tulburări cognitive ușoare (CINM), 158 cu insuficiență cognitivă ușoară (MCI) și 113 cu AD.

Rezultate:

Odată cu progresia bolii, nivelurile de acid formic urinar au arătat o tendință generală ascendentă. Acidul formic urinar a fost corelat semnificativ cu scorurile Mini-Mental State Examination (MMSE), versiunea chineză a scorurilor Addenbrooke’s Cognitive Examination III (ACE-III) și timpul Montreal Cognitive Assessment-Basic (MoCA-B). Zonele de sub curbele caracteristice de funcționare a receptorului (ASC) ale acidului formic urinar în distingerea NC de AD au fost 0,797, ceea ce a fost similar cu cel al lanțului ușor al neurofilamentului plasmatic (NfL; AUC = 0,768) și mai bun decât alți biomarkeri plasmatici (Aβ40, Aβ42, Aβ42/Aβ40, T-tau, P-tau181 și P-tau181/T-tau). De asemenea, am descoperit că utilizarea acidului formic urinar și a nivelurilor de formaldehidă ar putea îmbunătăți acuratețea utilizării biomarkerilor plasmatici pentru a determina stadiul bolii AD.

Discuție:

Studiul nostru a dezvăluit posibilitatea acidului formic urinar ca un potențial biomarker nou pentru diagnosticul precoce al AD.

Introducere

Boala Alzheimer (AD) este cea mai comună formă de demență, caracterizată prin tulburări cognitive și comportamentale progresive. Principalele caracteristici patologice ale AD includ acumularea anormală de p-amiloid extracelular (Aβ), acumularea anormală de încurcături neurofibrilare ale proteinei Tau și deteriorarea sinaptică (Wu și colab., 2015). Patogeneza AD nu este pe deplin înțeleasă. Ceea ce poate fi determinat din cercetările actuale este că AD este o boală cronică continuă și ascunsă, ceea ce înseamnă că AD se poate dezvolta și dura mulți ani înainte de apariția unei deficiențe cognitive evidente. Întregul curs al AD este împărțit în stadii prodromale, preclinice și de demență. Progresia de la declinul cognitiv subiectiv (SCD) la afectarea cognitivă ușoară (MCI) are loc înainte de stadiul de demență ireversibilă a AD, iar aceasta este fereastra de aur pentru intervenție și tratament (Khan și colab, 2020).

Având în vedere îmbătrânirea populației globale și costurile sociale enorme cauzate de AD, este necesară screening-ul timpuriu pe scară largă a AD (Asociația Alzheimer, 2016). Măsurarea neuropsihologică sensibilă este complexă și necesită timp, astfel încât este dificil de efectuat în mod obișnuit pentru populația în vârstă. Tomografia cu emisie de pozitroni–tomografia computerizată (PET-CT) poate detecta depozitele precoce de Aβ, dar această tehnică este costisitoare și expune pacienții la radiații. Biomarkerii provin în principal din testele invazive ale lichidului cefalorahidian (LCR) și plasmei, care par a fi eficiente pentru diagnosticarea precoce a AD (Dubois și colab, 2016; Jack și colab, 2018; Graff-Radford și colab, 2021). Compoziția urinei este complexă și poate reflecta modificări sensibile ale metabolismului și leziunilor. Unele studii au demonstrat că biomarkerii urinari au potențialul de screening pentru pacienții cu AD (Tong și colab, 2017).

În ultimii ani, metabolismul anormal al formaldehidei a fost recunoscut ca una dintre caracteristicile esențiale ale deficienței cognitive legate de vârstă (Yu și colab., 2014; He, 2017). Studiul nostru anterior a raportat o corelație între nivelurile de formaldehidă urinară și funcția cognitivă, sugerând că formaldehida urinară este un potențial biomarker pentru diagnosticul precoce al AD (Wang și colab., 2022). Formaldehida joacă un rol vital în metabolismul celular și este implicată în metabolismul cu un singur carbon, furnizând carbon pentru sintetizarea și modificarea compușilor biologici, cum ar fi ADN-ul, ARN-ul și aminoacizii (Li și colab., 2021; Morellato și colab, 2021). În creier, formaldehida poate promova formarea memoriei spațiale în condiții fiziologice, iar concentrațiile mari de formaldehidă pot duce la denaturarea proteinelor și pot afecta funcția memoriei (Tulpule și Dringen, 2013; He, 2017; Kou și colab., 2022). Unele studii au raportat că concentrațiile de formaldehidă au fost mai mari în creierul pacienților cu AD (He et al, 2010). Este bine cunoscut faptul că agregarea Aβ este un mecanism patologic esențial și o caracteristică a AD (Huang și colab, 2021). S-a descoperit că formaldehida leagă monomerii Aβ netoxici pentru a forma dimeri sau oligomeri toxici (Fei și colab., 2021; Zhao și colab., 2021). Aβ poate induce, de asemenea, producția de formaldehidă (Fei și colab., 2021). Acidul formic este un produs metabolic al formaldehidei, iar o parte din acidul formic este excretat în urină sub formă de formiat (Morrow et al, 2015). Acidul formic urinar reflectă metabolismul formaldehidei și are potențialul de a fi un biomarker pentru diagnosticul progresiei clinice de menaj în AD.

Ne-am propus să explorăm relația dintre nivelurile de acid formic urinar și modificările cognitive de-a lungul progresiei AD. Am analizat în continuare relația dintre acidul formic urinar și alela apolipoproteinei E (APOE) ε4, o genă cu risc ridicat pentru AD (Serrano-Pozo et al, 2021). Alela APOE ε4 este cel mai important factor de risc genetic pentru AD după vârsta de 65 de ani și este asociată cu diverse modificări patologice și tulburări cognitive în AD. Am comparat efectele diagnostice ale mai multor biomarkeri plasmatici și acid formic urinar, precum și efectele precipitațiilor Aβ asupra acidului formic urinar. În final, am analizat nivelul de formaldehidă urinară pentru a vedea dacă au existat efecte sinergice sau diferențe între cei doi indicatori urinari în diagnostic. Evaluarea noastră sistematică a arătat că acidul formic urinar ar putea fi un biomarker nou pentru diagnosticarea precoce a AD.

Materiale și metode

Participanți Studiul a inclus 574 de participanți recrutați de la Clinica de memorie a Spitalului al șaselea popor din Shanghai, China, și prin publicitate. Toți participanții au fost supuși testelor funcției cognitive de către personal instruit într-o sală de evaluare a neuropsihologiei între noiembrie 2019 și iunie 2021. Conform diagnosticului clinic obținut în urma testelor funcției cognitive, participanții au fost împărțiți în cinci grupuri: 71 cognitive normale (NC), 101 SCD, 131 tulburări cognitive fără tulburări cognitive ușoare (CINM), 158 MCI și 113 AD. Diagnosticul de SCD a adoptat standardele lui Jessen și ale altor cercetători (Jessen și colab, 2014; Huang și colab, 2018; Miebach și colab, 2019; Jessen și colab, 2020). CINM a prezentat un singur simptom cognitiv și un declin cognitiv subtil obiectiv. Criteriile pentru MCI se refereau la metoda neuropsihologică actuarială propusă de Thomas et al. (2018) și Bondi și colab. (2014). Diagnosticul AD s-a bazat pe criteriile Asociației Institutului Național pentru Îmbătrânire–Alzheimer (NIA-AA) (McKhann și colab., 2011). Consimțământul informat scris a fost obținut de la toți participanții sau îngrijitorii acestora. Comitetul de etică al celui de-al șaselea spital popular afiliat la Universitatea Jiao Tong din Shanghai a aprobat acest studiu.

Evaluări clinice

Toți participanții au susținut teste neuropsihologice standardizate, inclusiv Mini-Mental State Examination (MMSE) (Katzman și colab., 1988), Montreal Cognitive Assessment-Basic (MoCA-B) (Huang și colab., 2018), versiunea chineză a Addenbrooke’s Cognitive Examination III (ACE-III) (Pan și colab., 2022) și Shape Trial Test (SST), Test de învățare verbală auditivă (AVLT) (Considine și colab., 2017), Test de fluență animală (AFT) și alte teste care au implicat memorie, limbaj, atenție, funcție executivă și capacitate vizuală spațială. Evaluatorii bine pregătiți au efectuat teste neuropsihologice pe toți participanții la mandarină și au înregistrat date clinice detaliate.

Analiza formaldehidei urinare prin cromatografie lichidă la presiune înaltă

Am colectat urina de dimineață de la participanții care nu au abuzat de alcool sau droguri în aceeași săptămână după testul neuropsihologic. Proba de urină a fost centrifugată la 4°C și 12.000 rpm timp de 10 minute. Supernatantul de urină 0,4 ml a fost amestecat cu 2,4-dinitrofenilhidrazină (DNPH, concentraţie finală 0,1 g/L acetonitril) şi 0,1 ml acid tricloracetic. Proba a fost rotită violent timp de 30 s, apoi centrifugată la 4°C și 12.000 rpm timp de 10 min. Supernatantul a fost transferat într-o sticlă de sticlă de 2 ml și încălzit într-o baie de apă la 60°C timp de 30 de minute. Un sistem de cromatografie lichidă de înaltă performanță a analizat supernatantul cu un detector de ultraviolete (LC-20 A, Shimadzu, Japonia). Faza mobilă a fost 65% acetonitril-apă, debitul a fost de 0,8 ml/min, temperatura coloanei a fost de 35°C, timpul de retenție a fost de 6–7 min și lungimea de undă de detecție a fost de 355 nm. Urmele de cromatografie lichidă de înaltă presiune (HPLC) de detectare a formaldehidei au fost prezentate în Figura suplimentară 1.

Măsurarea acidului formic din urină

Nivelurile de acid formic din probele de urină colectate au fost determinate de Formate Assay Kit (ab111748, Abcam, Cambridge, Marea Britanie), urmând protocolul de la producător. S-au folosit zece microlitri de urină per godeu, iar absorbanța la 450 nm a fost măsurată pe un cititor de microplăci cu 96 de godeuri (SpectraMax Paradigm Multi-Mode, Molecular Devices, San Jose, CA, SUA). Concentrația de acid formic a fost calculată conform curbei standard.

Achiziția și analiza tomografiei cu emisie de pozitroni 18F-florbetapir

O sută nouăzeci și cinci de participanți au fost scanați de 18F-florbetapir PET (Biograph mCT Flow PET/CT; Siemens, Erlangen, Germania) la Centrul PET al Spitalului Huashan al Universității Fudan în termen de 1 lună de la recrutarea în studiu. Subiecții au primit o injecție intravenoasă de 18F-AV-45 la o doză de aproximativ 10 mCi (370 MBq) și s-au odihnit timp de 50 de minute. Apoi, imagistica PET a fost efectuată timp de 20 de minute folosind CT cu doză mică. După achiziție, algoritmul de retroproiecție filtrat a reconstruit imaginea PET; atenuarea, normalizarea, timpul mort, atenuarea fotonilor, împrăștierea și coincidența aleatorie au fost corectate. Rezultatele au fost determinate independent de trei clinicieni care au fost orbiți la diagnosticul clinic. Orice opinii diferite au fost rezolvate folosind criteriul conform căruia raportul global al valorii de absorbție standardizat de amiloid (SUVR, întreaga materie cenușie/valoarea de absorbție bilaterală a vițelului cerebelos) a fost <1,29.

Genotiparea apolipoproteinei E

Folosind un kit de separare a ADN-ului coloanei de spin (Shanghai General Biotechnology Co, Ltd, Shanghai, China), ADN-ul genomic a fost extras din probe de sânge integral conform instrucțiunilor producătorului. Cele două situsuri polimorfe ale genei APOE, rs.429358 și rs.7412, au fost identificate prin reacția de detectare a ligazei (LDR) folosind nanosfere fluorescente (New England Biolabs, Ipswich, MA, SUA). Amplificarea multi-ligazei a fost efectuată utilizând nanosfere magnetice marcate cu fluorescență combinate cu sonde LDR din amonte și sonde marcate din aval cu grupări fluorescente unice la fiecare situs de polimorfism cu o singură nucleotidă (SNP). Produsele LDR amplificate au fost separate cu nanosferele magnetice și scanate pentru spectre de fluorescență.

Măsurătorile biomarkerilor din sânge

Probele de sânge au fost centrifugate, separate în mod egal și depozitate la −80°C până la utilizare. Conform instrucțiunilor producătorului (Chong și colab., 2021), toți biomarkerii au fost măsurați pe o platformă de analiză HD-1 cu o singură moleculă (SIMOA) (Quanterix, Billerica, MA, SUA). Concentrația de tau181 fosforilat (P-tau181) în plasmă a fost determinată utilizând un imunotest SIMOA ultrasensibil cu anticorpi monoclonali de șoarece AT270 împotriva situsului de fosforilare a treoninei-181. Plasma Aβ40, Aβ42 și tau total (T-tau) au fost măsurate folosind un kit A de 3 plex. Kitul SIMOA NF-light VR Advantage a detectat lanțul ușor de neurofilament (NfL; Quanterix, Billerica, MA, SUA).

Analiza statistica

Analiza unidirecțională a varianței (ANOVA) a fost utilizată pentru a evalua diferențele de vârstă, nivel de educație, scoruri cognitive și neuropsihologice ale testelor și concentrațiile medii de acid formic urinar și formaldehidă urinară între diferitele grupuri de diagnostic. În post-test au fost utilizate mai multe teste de comparație Bonferroni. Comparațiile valorilor continue între grupurile APOE ε4+ și APOE ε4− și grupurile Aβ+ și Aβ− au fost testate folosind testul Mann–Whitney U. Dacă este cazul, s-a folosit testul exact 12 sau Fisher pentru a testa diferențele dintre diferitele rapoarte. Pentru toate datele cantitative, rezultatele sunt exprimate ca medie ± abatere standard. Coeficientul de corelație de rang al lui Spearman a fost utilizat pentru a evalua corelația dintre nivelurile de acid formic urinar și formaldehidă și scorurile cognitive sau biomarkerii plasmatici. Curbele caracteristicilor de funcționare a receptorului (ROC) au fost utilizate pentru a evalua puterea de diagnostic a biomarkerilor de acid formic urinar, formaldehidă și plasmă. Valorile p– <0,05 au fost considerate semnificative statistic. Toate analizele au fost efectuate folosind software-ul SPSS (v 22.0; IBM Corp., Armonk, NY, SUA) și software-ul R (v. 4.0.3; Fundația R, Viena, Austria).

Rezultate studiu acid formic seric si urinar in prognosticul aparitiei Bolii Alzheimer

Caracteristicile demografice și clinice ale grupurilor de diagnostic Un total de 574 de subiecți au fost împărțiți în 5 grupuri de diagnostic, inclusiv NC (n = 71), SCD (n = 101), CINM (n = 131), MCI (n = 158) și AD (n = 113). Nivelurile urinare de acid formic și formaldehidă au fost măsurate la toți pacienții. Tabelul 1 prezintă statistici descriptive detaliate ale caracteristicilor demografice și clinice esențiale ale celor cinci grupuri de diagnostic. Nu au existat diferențe semnificative în ceea ce privește vârsta, sexul sau indicele de masă corporală între cele cinci grupuri. Scorurile testelor neuropsihologice care controlează anii de educație în grupul AD au fost semnificativ diferite de cele din grupul NC (P < 0,01). În grupul AD, nivelurile de educație au fost scăzute și tulburările cognitive au fost severe (P < 0,05). Am efectuat o analiză de corelație între formaldehida urinară și nivelurile de acid formic și vârstă; nu au existat diferențe semnificative în formaldehida urinară și acidul formic la diferite vârste (Figura suplimentară 2).

Table 1. Demographics, disease characteristics, urinary formaldehyde and formic acid of five diagnostic groups.

Relația dintre formaldehida urinară, acidul formic urinar și capacitatea cognitivă Comparativ cu grupul NC, nivelurile de acid formic urinar au fost semnificativ mai mari în grupurile SCD, CINM, MCI și AD (toate P < 0,05). În general, nivelurile de acid formic urinar au fost ușor mai scăzute în grupul CINM în comparație cu grupurile SCD, MCI și AD, dar nu a existat nicio diferență statistică între ele. Nivelurile urinare de formaldehidă au fost semnificativ mai mari în AD decât în NC (P < 0,05), dar nu a fost observată nicio diferență statistică între grupurile rămase. Nivelurile urinare de formaldehidă au arătat o tendință similară “sus-jos-up” ca și nivelurile de acid formic urinar, iar nivelul de acid formic urinar a fost mai scăzut în CINM (Figura 1). Deoarece acidul formic este un produs metabolic al formaldehidei, am comparat nivelurile de acid formic plus formaldehidă în diferite etape AD, iar rezultatele au arătat, de asemenea, că nivelurile de acid formic plus formaldehidă au fost semnificativ mai mari în SCD, CINM, MCI și AD comparativ cu NC. Mai mult, am descoperit că nivelurile de acid formic plus formaldehidă au fost semnificativ mai mari în AD decât în CINM și MCI (Figura 1 D).

Figure 1. Urinary formaldehyde and formic acid level are associated with cognitive abilities of Alzheimer’s disease (AD). (A) With the progress of the disease, urinary formic acid showed an overall upward trend but decreased slightly in the mild cognitive impairment (MCI). (B) The level of urinary formaldehyde decreased in cognitive impairment without mild cognitive impairment (CINM) and reached its peak in MCI. (C) The trend of two urinary biomarkers shows a “double turning” points. (D) Normalized sum of formic acid and formaldehyde levels across various AD stages. Normalization formula: zi = [xi – min(x)]/[max(x) – min(x)]. zi, the ith normalized value in the dataset; xi, the ith value in the dataset. min(x), the minimum value in the dataset; max(x), the maximum value in the dataset. *p < 0.05; **p < 0.01; ***p < 0.001, and ****p < 0.0001.

Am estimat relația dintre ace��ti doi biomarkeri urinari și nivelurile de abilități cognitive. Nivelurile urinare de formaldehidă au fost corelate negativ cu scorurile MMSE (r = −0,091, P < 0,05), scorurile ACE-III (r = −0,099, P < 0,05) și scorurile MoCA-B (r = −0,084, P < 0,05), și au fost corelate pozitiv cu timpul MoCA-B (r = 0,095, P < 0,05). Corelații similare, ușor mai mari, au fost observate între acidul formic urinar și scorurile MMSE (r = −0,114, P < 0,01), scorurile ACE-III (r = −0,101, P < 0,05), scorurile MoCA-B (r = −0,111), P < 0,01) și timpul MoCA (r = 0,105, P < 0,05)

Nivelurile a două tipuri de markeri de urină sunt legate de scorul testului neuropsihologic. (A) Corelația dintre acidul formic și MMSE. (B) Corelația dintre formaldehidă și MMSE. (C) Corelația dintre acidul formic și ACE-III. (D) Corelația dintre formaldehidă și ACE-III. (E) Corelația dintre acidul formic și MoCA-B. (F) Corelația dintre formaldehidă și MoCA-B. (G) Corelația dintre acidul formic și timpul MoCA-B. (H) Corelația dintre formaldehidă și timpul MoCA-B.

Table 2. Correlation of urinary formic acid and urinary formaldehyde for each cognitive domain score in the Chinese version of Addenbrooke’s cognitive examination III (ACE-III).

Efectul acumulării creierului Aβ asupra acidului formic urinar și formaldehidei în diferite grupuri de diagnostic Două sute patruzeci și cinci de participanți au fost supuși imagisticii PET cu 18F-florbetapir pentru a identifica depozitele Aβ. Am analizat în continuare diferența dintre acidul formic urinar și formaldehidă în diferite stări de amiloid. Pe baza prezenței plăcii, am împărțit cele cinci grupuri de diagnostic în subgrupuri Aβ− și Aβ+. Grupul Aβ− a inclus 13 cazuri în grupul NC, 30 cazuri SCD, 33 cazuri CINM, 45 cazuri MCI și 11 cazuri AD. Grupul Aβ+ a avut 12 cazuri NC, 13 cazuri SCD, 24 cazuri CINM, 24 cazuri MCI și 40 cazuri AD. Nivelurile de acid formic urinar nu au fost semnificativ diferite între subgrupurile din grupurile de diagnostic NC, SCD, CINM, MCI și AD (Figura 3 A). Nivelurile urinare de formaldehidă în subgrupul Aβ− au fost mai mari decât cele din subgrupul Aβ+ la pacienții din grupul NC (P = 0,0012), în timp ce nu au existat diferențe semnificative în celelalte grupuri de diagnostic

Boxplot of urinary indicator levels separated by PET status and apolipoprotein E (APOE) ε4 status. (A) Formic acid levers of PET negative and positive across normal cognitive (NC), subjective cognitive decline (SCD), cognitive impairment without mild cognitive impairment (CINM), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) subgroup. (B) Formaldehyde levers of PET negative and positive across NC, SCD, CINM, MCI, and AD subgroup. (C) Formic acid levels of APOE ε4 negative and positive across NC, SCD, CINM, MCI, and AD subgroup. (D) Formaldehyde levels of APOE ε4 negative and positive across NC, SCD, CINM, MCI, and AD subgroup. The P-values were obtained by Mann–Whitney U test.

Efectul genotipului apolipoproteinei E asupra acidului formic urinar și formaldehidei în diferite grupuri de diagnostic Am evaluat relația dintre alelele APOE ε4 privind concentrațiile urinare de acid formic și formaldehidă în fiecare grup de diagnostic. Genotiparea APOE a fost efectuată la toți participanții. În funcție de prezența sau absența alelei APOE ε4, subiecții din fiecare grup de diagnostic au fost împărțiți în APOE ε4+ (ε2/ε4, ε3/ε4, ε4/ε4) și APOE ε4− (ε2/ε2, ε2/ε3, ε3/) grupuri). Afișat pe baza grupului de diagnostic, aceasta a dus la: NC, 52 APOE ε4− și 19 APOE ε4+; CINM, 73 APOE ε4− și 26 APOE ε4+ în CINM; MCI, 115 APOE ε4− și 43 APOE ε4+; și AD, 62 APOE ε4− și 50 APOE ε4+. Nivelurile de acid formic urinar nu au fost semnificativ diferite în NC, SCD, CINM, MCI și AD între subgrupuri (Figura 3C). Nivelurile de formaldehidă urinară au fost mai mari în subgrupul APOE ε4+ decât în subgrupul APOE ε4− în NC (P = 0,027), în timp ce nu au existat diferențe semnificative în celelalte grupuri de diagnostic (Figura 3D). Deoarece acidul formic este un produs metabolic al formaldehidei, am analizat acidul formic plus formaldehida pentru a diferenția genotipurile APOE ε4 și stările plăcii Aβ în diferite stadii AD și nu au fost găsite diferențe semnificative (Figura suplimentară 3).

Analiza corelației biomarkerilor plasmatici ai bolii Alzheimer și a nivelurilor urinare de formaldehidă și acid formic Pentru a investiga asocierea potențială dintre markerii plasmatici și acidul formic urinar și formaldehidă, am analizat corelația acestora la 326 de participanți (Tabelul 3). Formaldehida urinară a fost corelată pozitiv cu T-tau (r = 0,110, P < 0,05) și corelată negativ cu Aβ42 (r = −0,162, P < 0,01), raportul Aβ42/Aβ40 (r = −0,180, P < 0,01) și raportul P-tau181/T-tau (r = −0,128, P < 0,05). Nu a existat nicio corelație între nivelurile de acid formic urinar și acești biomarkeri plasmatici.

Având în vedere perspectiva de aplicare a biomarkerilor de urină ca screening pentru afectarea cognitivă, am folosit curbele ROC pentru a analiza nivelul de discriminare al biomarkerilor plasmatici și al acestor doi biomarkeri de urină în diagnosticarea NC și AD. NfL (ASC = 0,768, P < 0,001, standard >18,506, sensibilitate: 61,9%, specificitate: 86,6%), P-tau181 (ASC = 0,749, P < 0,001, standard ≤3,037, sensibilitate: 92,1%, specificitate: 55,6%) și P-tau181/T-tau (ASC = 0,711, P < 0,001, standard ≤0,6577, sensibilitate: 57,9%, specificitate: 81%) au prezentat cele mai bune efecte diagnostice dintre biomarkerii plasmatici, în timp ce zonele de sub curbele caracteristice de funcționare a receptorului (ASC) de acid formic urinar a fost superior acestor trei. Nivelurile de formaldehidă din urină nu au prezentat o valoare diagnostică bună

Figure 4. Receiver operating characteristic (ROC) curve of two urine biomarkers and plasma biomarkers for diagnosis of normal cognitive (NC) and Alzheimer’s disease (AD). Urinary formic acid: AUC = 0.797, P < 0.001, standard >0.2119, sensitivity: 66.7%, specificity: 78.9%; Urinary formaldehyde: AUC = 0.571, P > 0.05; Plasma neurofilament light chain (NfL): AUC = 0.768, P < 0.001, standard >18.506, sensitivity: 61.9%, specificity: 86.6%; Plasma T-tau: AUC = 0.537, P > 0.05; Plasma P-tau181: AUC = 0.749, P < 0.001, standard ≤3.037, sensitivity: 92.1%, specificity: 55.6%; Plasma P-tau181/T-tau: AUC = 0.711, P < 0.001, standard ≤0.6577, sensitivity: 57.9%, specificity: 81%; Plasma Aβ42: AUC = 0.506, P > 0.05; Plasma Aβ40: AUC = 0.544, P > 0.05; Plasma Aβ42/Aβ40: AUC = 0.575, P > 0.05.

Biomarkerii urinari au îmbunătățit acuratețea predicției biomarkerilor plasmatici pentru stadiul bolii Studiile au arătat că biomarkerii plasmatici pot prezice stadiile bolii, iar integrarea mai multor biomarkeri plasmatici ar putea îmbunătăți acuratețea predicției. Am investigat capacitatea de a prezice stadiile bolii integrând biomarkeri de plasmă și urină față de utilizarea doar a biomarkerilor de plasmă pentru prima dată (Figura 5). ASC a fost de 0,805 (IC 95%: 0,722, 0,888) folosind biomarkeri plasmatici singuri, incluzând Aβ40, Aβ42, T-tau, P-tau181 și NfL, iar ASC a fost de 0,905 (IC 95%: 0,847, 0,963) folosind biomarkeri combinați. ASC a fost de 0,813 (IÎ 95%: 0,733; 0,894) utilizând cei 5 biomarkeri plasmatici şi formaldehida urinară, iar ASC a fost de 0,894 (IÎ 95%: 0,833; 0,956) utilizând cei 5 biomarkeri plasmatici şi acidul formic urinar. Aceste rezultate au sugerat că acidul formic urinar și formaldehida ar putea îmbunătăți acuratețea predicției biomarkerilor plasmatici pentru stadiile bolii AD, iar nivelurile de acid formic urinar au arătat mai multe beneficii decât formaldehida.

Figure 5. Prediction of disease stages by plasma and urine biomarkers alone versus plasma biomarkers only. Receiver operating characteristic (ROC) plots for showing the efficiency of logistic model for distinguishing the Alzheimer’s disease (AD) patients from normal cognitive (NC) patients. (NC: n = 38; AD: n = 63).

Discuție studiu acid formic seric si urinar in prognosticul aparitiei Bolii Alzheimer

Dezvoltarea AD are loc prin procese pe termen lung și este în mare parte ascunsă. Nu este posibilă inversarea leziunilor neuronale și a tulburărilor cognitive chiar dacă factorii patogeni, cum ar fi acumularea plăcii Aβ, sunt eliminați. Prin urmare, diagnosticul precoce în stadiul preclinic este crucial în tratamentul AD. În prezent, cei mai buni biomarkeri utilizați pentru a detecta AD în stadiu incipient sunt biomarkerii patologici Aβ și Tau, detectați folosind scanarea PET-CT sau detectarea LCR (Lista și colab., 2014; Jack și colab, 2018). Cu toate acestea, PET-CT este costisitor, iar examinarea LCR este invazivă. Biomarkerii plasmatici, inclusiv Tau, NfL și Aβ, sunt din ce în ce mai folosiți pentru a diagnostica și a stadializa AD (De Wolf și colab., 2020). În comparație cu LCR invaziv și testele de sânge, testarea urinei este mai potrivită pentru screening-ul pe scară largă (Tong și colab., 2017). În studiul de față, am avut patru constatări principale. În primul rând, nivelurile de acid formic urinar au fost mai mari în grupurile de diagnostic SCD, CINM, MCI și AD decât în grupul NC, iar nivelurile de formaldehidă urinară au fost semnificativ mai mari în AD decât în NC. În al doilea rând, atât nivelurile urinare de acid formic, cât și de formaldehidă au fost corelate negativ semnificativ cu scorurile MMSE, scorurile ACE-III și scorurile MoCA-B și corelate pozitiv cu timpul MoCA-B. În al treilea rând, în grupul de diagnostic NC, nivelurile de formaldehidă urinară au fost mai mari în subgrupul APOE ε4+ decât în subgrupul APOE ε4−, iar nivelurile de formaldehidă urinară au fost mai mari în subgrupul Aβ− decât în subgrupul Aβ+. În al patrulea rând, nivelurile de acid formic urinar și formaldehidă nu numai că ar putea fi utilizate pentru a diferenția între AD și NC, dar ar putea îmbunătăți acuratețea predicției pentru stadiul bolii atunci când sunt combinate cu biomarkeri plasmatici.

Cercetările privind biomarkerii AD urinari au progresat, iar unii biomarkeri urinari pot fi utilizați pentru a diagnostica MCI sau AD. Cu toate acestea, nu există rapoarte privind acidul formic urinar pentru diagnosticul precoce al AD (Praticò și colab., 2002; Youn și colab., 2011; Ma și colab., 2015; García-Blanco și colab., 2018). Studiile au arătat că formaldehida excesivă poate provoca “formaldehidă stress” și poate deteriora neuronii (He et al, 2010; Zhao et al, 2021; Kou et al, 2022). În plus, formaldehida poate iniția, de asemenea, modificări patologice semnificative legate de AD, cum ar fi fosforilarea tau, agregarea tau și depunerea de Aβ. Formaldehida este considerată un “trigger” al AD, ceea ce înseamnă că captarea modificărilor dinamice ale formaldehidei poate ajuta foarte mult la diagnosticarea AD timpurie (Tong și colab., 2017). Studiul nostru anterior a explorat posibilitatea formaldehidei urinare ca biomarker potențial pentru diagnosticul precoce al AD și a obținut unele rezultate pozitive (Wang și colab., 2022). Acidul formic este un produs metabolic al formaldehidei și poate fi excretat sub formă de formiat (Bruckner și colab, 2008; Kageyama și colab, 2008; Burgos-Barragan și colab, 2017; Liu și colab, 2017). Acidul formic urinar poate reflecta mai sensibil modificările metabolice ale formaldehidei și este un biomarker important care a fost neglijat. În acest studiu, am raportat pentru prima dată că nivelurile de acid formic urinar s-au schimbat odată cu deteriorarea funcției cognitive. Acidul formic urinar a arătat o eficacitate unică în diagnosticul AD. În plus, a existat o creștere semnificativă a acidului formic urinar în grupul de diagnostic SCD, ceea ce înseamnă că acidul formic urinar poate fi utilizat pentru diagnosticul precoce al AD. Studiul de față a arătat încă o dată că, odată cu progresia bolii, formaldehida urinară a arătat o tendință “sus-jos-up”; nivelurile urinare de formaldehidă au fost ridicate în SCD, semnificativ mai scăzute în CINM și din nou mai mari în MCI și AD. Nivelurile urinare de acid formic au fost ușor mai scăzute în CINM, dar aceasta a fost totuși semnificativ mai mare decât în NC. Acest lucru sugerează că poate fi o problemă cu sistemele de clearance ale sistemului nervos central în stadiile incipiente ale AD.

Un mecanism esențial al AD este dezechilibrul dintre producția și clearance-ul metaboliților din creier (Querfurth și LaFerla, 2010; Gallina și colab, 2015). Fără un sistem limfatic obișnuit, creierul are în schimb un sistem glimfatic “. Sistemul glimfatic se bazează pe astrocite sănătoase, care excretă deșeuri metabolice din creier, inclusiv Aβ și tau, pentru a asigura stabilitatea mediului, care este crucială pentru sănătatea neuronilor (Guenette, 2003; Reeves et al, 2020). S-a constatat că agregarea Aβ determină depolarizarea acvaporinei-4 (AQP4) pe astrocite. Mai mult, depolarizarea AQP4 face ca astrocitele să-și piardă funcția excretoare, agravând și mai mult agregarea metaboliților precum Aβ (Lan și colab., 2016). Astrocitele joacă un rol esențial în metabolismul formaldehidei. Mai mult, formaldehida poate promova depunerea de Aβ, perturbând astfel funcția astrocitelor (Tulpule și Dringen, 2012). Astrocitele afectate vor afecta grav excreția formaldehidei, ducând la o scădere a formaldehidei urinare. În schimb, acidul formic este mai ușor metabolizat decât formaldehida, astfel încât nivelurile de acid formic urinar pot rămâne ridicate. Niciun studiu nu a raportat efectele sistemului glimfatic asupra nivelurilor de formaldehidă și acid formic, care ar trebui efectuate în viitor.

Prezentul studiu a raportat câteva constatări demne de remarcat. A existat o relație între nivelurile urinare de formaldehidă, depunerea de Aβ și alela APOE ε4. Pe scurt, nivelurile urinare de formaldehidă au fost mai mari în subgrupurile Aβ− și APOE ε4+ din grupul NC. În plus, nivelurile urinare de acid formic și formaldehidă nu au reflectat domeniile cognitive exacte.

Multe studii anterioare au arătat că biomarkerii plasmatici ar putea prezice stadiul bolii și că integrarea biomarkerilor plasmatici multipli ar putea îmbunătăți acuratețea predicției (Palmqvist și colab, 2021; West și colab, 2021; Cheng și colab, 2022). În studiul de față, am investigat capacitatea de predicție pentru stadiile bolii de integrare a biomarkerilor de plasmă și urină în comparație cu utilizarea biomarkerilor de plasmă singuri, dezvăluind că combinarea tuturor biomarkerilor ar putea îmbunătăți acuratețea predicției. Nivelurile urinare de acid formic au arătat o utilitate mai mare decât formaldehida. Prin urmare, studiul nostru a demonstrat că biomarkerii urinari neinvazivi și rentabili au îmbunătățit acuratețea predicției stadiilor bolii de către biomarkerii plasmatici. Având în vedere unele studii anterioare au raportat că expresia crescută a nivelurilor de formaldehidă la șobolanii diabetici, în țesutul canceros, boala Parkinson, bolile de inimă și bolile hepatice cronice (Tong și colab., 2011; Rana și colab., 2021; Zhang și colab, 2021). Studiul de față a arătat, de asemenea, că nivelurile de formaldehidă din urină nu au arătat un efect diagnostic bun. Prin urmare, credem că formaldehida urinară singură nu este un biomarker util pentru diagnosticul AD, dar poate fi folosită ca dovadă a deficitului cognitiv.

Desigur, există unele limitări ale cercetării actuale. Acest studiu transversal nu poate demonstra cauzalitatea, iar concluziile trebuie verificate printr-un studiu de urmărire pe termen lung. Explicațiile bazate pe metabolismul formaldehidei și acidului formic rămân teoretice și sunt necesare experimente corespunzătoare pe animale pentru a confirma acest lucru. Dimensiunea eșantionului pentru datele PET-CT nu a fost suficientă pentru a analiza și a trage concluzii fiabile, în special în grupul de diagnostic NC. Deoarece PET-CT expune pacienții la radiații și trebuie utilizat mediu de contrast, prin urmare, majoritatea pacienților cu NC nu pot accepta utilizarea PET-CT. Vom crește dimensiunea eșantionului pentru a demonstra în continuare concluziile aferente în viitor.

Este posibil ca acidul formic urinar și formaldehida să fie noi biomarkeri, independent de criteriile de diagnostic AD existente. Credem că cercetările ulterioare pot determina cele mai bune modele de diagnostic folosind nivelurile de acid formic urinar și formaldehidă pentru a îmbunătăți semnificativ eficiența diagnostică a biomarkerilor de urină în AD. Testarea urinei are avantaje unice în screening-ul timpuriu în comunitate. Utilizarea acestor biomarkeri de urină poate promova în mod semnificativ popularitatea screening-ului precoce pentru AD, ceea ce poate îmbunătăți sfaturile privind diagnosticul, tratamentul și stilul de viață pentru persoanele cu risc de AD. Cercetările aprofundate asupra acestor biomarkeri vor ajuta, de asemenea, la explorarea mecanismelor și tratamentelor potențiale ale AD. Modificările dinamice ale formaldehidei urinare și ale acidului formic urinar sugerează o altă tulburare metabolică nouă în patogeneza AD.

În concluzie, nivelurile de acid formic urinar s-au modificat dinamic în legătură cu deteriorarea funcției cognitive. Nivelurile urinare de formaldehidă au fost legate de genotipul APOE ε4 și de prezența depunerilor de Aβ în creier. Nivelurile urinare de acid formic și formaldehidă ar putea fi utilizate nu numai pentru diferențierea dintre AD și NC, dar ar putea îmbunătăți și acuratețea predicției biomarkerilor plasmatici pentru stadiile bolii AD. Evaluarea noastră sistematică a relevat noua posibilitate a acidului formic urinar ca potențial biomarker pentru diagnosticul precoce al AD.

Declarație de disponibilitate a datelor Datele brute care susțin concluziile acestui articol vor fi puse la dispoziție de către autori, fără rezerve nejustificate.

Declarație etică Studiile care au implicat participanți umani au fost revizuite și aprobate de Comitetul de etică al Spitalului al șaselea popular afiliat Universității Jiao Tong din Shanghai. Pacienții/participanții și-au oferit consimțământul informat scris pentru a participa la acest studiu. Consimțământul informat scris a fost obținut de la persoana (persoanele) pentru publicarea oricăror imagini sau date potențial identificabile incluse în acest articol.

Contribuții ale autorului ZF și QG: conceptualizare. YG, FX, RH, XC și JD: analiză formală și vizualizare. YfW, YiW, JZ, ZF, YaW și QG: administrarea proiectului. YfW, YiW și JZ: scris. Toți autorii au citit și au aprobat manuscrisul final.

Finanțare Această lucrare a fost susținută de Fundația Națională pentru Științe Naturale din China (nr. 82171198), Proiect major de știință și tehnologie municipală din Shanghai (nr. 2018SHZDZX01), ZJLab Programul de S&T cheie provincială Guangdong (nr. 2018B030336001) și Programul Shanghai Pujiang (nr. 21PJ1423100). Această cercetare nu a primit finanțare externă.

Conflict de interese Autorii declară că cercetarea a fost efectuată în absența oricăror relații comerciale sau financiare care ar putea fi interpretate ca un potențial conflict de interese.

Nota editorului Toate afirmațiile exprimate în acest articol sunt exclusiv ale autorilor și nu reprezintă neapărat pe cele ale organizațiilor lor afiliate sau pe cele ale editorului, editorilor și recenzenților. Orice produs care poate fi evaluat în acest articol sau revendicare care poate fi făcută de producătorul său, nu este garantat sau aprobat de editor.

Material suplimentar Materialul suplimentar pentru acest articol poate fi găsit online la: https://www.frontiersin.org/articles/10.3389/fnagi.2022.1046066/full#supplementary-material

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Cuvinte cheie: boala Alzheimer, acid formic urinar, formaldehidă, biomarker, p-amiloid

Citare: Wang Y, Wang Y, Zhu J, Guan Y, Xie F, Cai X, Deng J, Wei Y, He R, Fang Z și Guo Q (2022) Evaluarea sistematică a acidului formic urinar ca un nou potențial biomarker pentru boala Alzheimer. Faţă. Îmbătrânirea Neurosci. 14:1046066. doi: 10.3389/fnagi.2022.1046066

Primit: 16 septembrie 2022; Acceptat: 02 noiembrie 2022; Publicat: 30 noiembrie 2022.

Editat de:

Jia-Da Li, Universitatea Central South, China Revizuit de:

Fang Cai, Universitatea din Columbia Britanică, Canada Jifeng Guo, Departamentul de Neurologie, Spitalul Xiangya, Universitatea Central South, China Copyright © 2022 Wang, Wang, Zhu, Guan, Xie, Cai, Deng, Wei, He, Fang și Guo. Acesta este un articol cu acces deschis distribuit în conformitate cu termenii licenței de atribuire Creative Commons (CC BY).

[murkyy]

Addenbrooke's Hospital

[innonurse]

AI tool developed in England improves skin cancer detection with higher accuracy

- By InnoNurse Staff -

Scientists in the East of England have developed an AI tool that outperforms existing methods in detecting skin cancer.

The AI model, created by researchers from Anglia Ruskin University, Check4Cancer, University of Essex, and Addenbrooke's Hospital, was trained on data from over 53,000 skin lesions. It uses key clinical features, such as lesion changes and hair color at age 15, to predict cancer risk, achieving a 69% accuracy rate. This is higher than traditional methods like 7PCL (62%) and Williams score (60%).

The new C4C Risk Score could reduce unnecessary biopsies and speed up skin cancer diagnosis and treatment. Regulatory approval is anticipated in 2025, offering a tool that could help prioritize patients at higher risk for face-to-face consultations and faster care.

Image: The proposed AI framework aims to identify a new set of risk factors for classifying skin lesions. Credit: Scientific Reports (2024). DOI: 10.1038/s41598-024-71244-2

Read more at Anglia Ruskin University/Medical Xpress

Other recent news and insights

Health IT: Latvian startup Longenesis wins Supernova Challenge 2.0 (Dubai World Trade Centre/PRNewswire)

[levinkgeever]

The Top 10 Plastic Surgeons in Kerala — Dr. Prince Takes the Lead

When searching for transformative aesthetic enhancements or reconstructive procedures, finding the best plastic surgeon is crucial. Kerala, a state renowned for its rich cultural heritage and medical advancements, offers access to some of the finest plastic surgeons in the country. In this blog, we will explore the top 10 plastic surgeons in Kerala, with a special focus on why Dr. Prince stands out as the best plastic surgeon in Kerala.

Why Dr. Prince is the Best Plastic Surgeon in Kerala

Unmatched Expertise and Credentials

Dr. Prince is widely recognized as the best plastic surgeon in Kerala, thanks to his extensive qualifications and impressive credentials. His academic and professional journey reflects his dedication and expertise: - MBBS from Armed Forces Medical College, Pune - MS General Surgery from Government Medical College, Kozhikode - DNB General Surgery from the National Board of India - DrNB Plastic Surgery from the National Board of India - MCh Plastic Surgery from Madras Medical College

Dr. Prince’s education is complemented by international training at prestigious institutions such as Addenbrooke’s Hospital Cambridge, St. Andrews Centre for Plastic Surgery in Chelmsford, and The Royal Preston, Mount Vernon. This exposure to cutting-edge techniques and global practices enhances his reputation as the best plastic surgeon in Kerala.

Comprehensive Range of Services

Dr. Prince’s versatility in offering a wide range of plastic surgery services sets him apart as the best plastic surgeon in Kerala: - Cosmetic Enhancements: He specializes in procedures like eyelid surgery, tummy tucks, mommy makeovers, rhinoplasty, and breast surgeries. His focus on achieving natural-looking, aesthetically pleasing results is a hallmark of his practice. - Reconstructive Surgery: Dr. Prince is also adept at reconstructive procedures, addressing issues from trauma or surgical corrections with precision and care.

Personalized Patient Care

One of the key reasons Dr. Prince is considered the best plastic surgeon in Kerala is his commitment to personalized patient care. He adopts a tailored approach to each patient, ensuring that treatment plans are customized to meet individual needs and goals. This focus on personalized care enhances patient satisfaction and contributes to his esteemed reputation.

Impressive Track Record

Dr. Prince’s track record speaks volumes about his expertise. He has successfully treated over 5000 patients from various countries, including the USA, Canada, UK, Australia, the Middle East, and Africa. This extensive experience underscores his capability and global recognition in the field of plastic surgery.

Commitment to Continuous Learning

Dr. Prince’s dedication to staying at the forefront of plastic surgery advancements ensures that his patients benefit from the latest and most effective techniques. His ongoing commitment to education and professional development reinforces his status as the best plastic surgeon in Kerala.

The Top 10 Plastic Surgeons in Kerala

While Dr. Prince leads the way as the best plastic surgeon in Kerala, several other distinguished professionals also contribute to the field’s excellence. Here’s a look at the top 10 plastic surgeons in Kerala, each known for their expertise and contributions.

1. Dr. Prince

Dr. Prince is renowned as the best plastic surgeon in Kerala due to his extensive qualifications, diverse range of services, and dedication to personalized patient care. His impressive track record and global experience make him a top choice for both cosmetic and reconstructive procedures.

2. Dr. J. K. Babu

Dr. J. K. Babu is another prominent name among the best plastic surgeons in Kerala. His vast experience in cosmetic and reconstructive surgery, coupled with a reputation for exceptional results and high patient satisfaction, highlights his standing in the field.

3. Dr. Ravi Pillai

Dr. Ravi Pillai is known for his expertise in various plastic surgeries, including aesthetic and reconstructive procedures. His broad skill set and commitment to achieving high-quality outcomes contribute to his reputation as one of the best plastic surgeons in Kerala.

4. Dr. Anil Kumar

Dr. Anil Kumar offers a wide array of cosmetic procedures with a focus on personalized care. His emphasis on achieving natural-looking results and his patient-centered approach make him a notable figure among the best plastic surgeons in Kerala.

5. Dr. R. K. Pillai

Dr. R. K. Pillai is well-regarded for his dual expertise in cosmetic and reconstructive plastic surgery. His extensive knowledge and skill set make him a leading plastic surgeon in Kerala, known for delivering comprehensive care.

6. Dr. C. V. K. Reddy

Dr. C. V. K. Reddy is recognized for his proficiency in both aesthetic enhancements and reconstructive surgeries. His skillful approach and commitment to high-quality outcomes underscore his position as one of the best plastic surgeons in Kerala.

7. Dr. Sandeep Kumar

Dr. Sandeep Kumar provides a variety of cosmetic procedures with a strong emphasis on patient-centered care. His approach to understanding each patient’s needs and delivering tailored solutions contributes to his esteemed reputation among the best plastic surgeons in Kerala.

8. Dr. Shyam Kumar

Dr. Shyam Kumar specializes in both cosmetic and reconstructive procedures, focusing on achieving optimal outcomes. His dedication to excellence and comprehensive approach make him a prominent name among the best plastic surgeons in Kerala.

9. Dr. Rajesh Ranjan

Dr. Rajesh Ranjan offers a wide range of plastic surgery services, known for his skillful approach and patient-focused care. His commitment to delivering exceptional results highlights his status as one of the best plastic surgeons in Kerala.

10. Dr. R. Prasad

Dr. R. Prasad is recognized for his expertise in both cosmetic and reconstructive surgeries, with a strong emphasis on patient care. His dedication to achieving high-quality results and personalized treatment makes him a notable figure among the best plastic surgeons in Kerala.

Conclusion

In the realm of plastic surgery in Kerala, the distinction of being the best plastic surgeon is earned through a combination of expertise, experience, and commitment to patient care. Dr. Prince stands out as the best plastic surgeon in Kerala due to his exceptional qualifications, diverse range of services, and dedication to personalized patient care. His impressive track record and continuous pursuit of excellence underscore his leadership in the field.

The top 10 plastic surgeons in Kerala, including Dr. Prince, represent a pinnacle of talent and expertise. Whether you are seeking cosmetic enhancements or reconstructive solutions, these esteemed professionals offer a range of options to help you achieve your aesthetic goals and enhance your well-being.

[sp00kysk3lly]

08/08/23

My eyes have fucked up yet again! Like I said they would. But do the eye clinic care? No. Why else would they give me a appointment in October when I was suppose to be seen in April??? That’s 6 months for fucks sake.

Every single time they do this. Addenbrooke’s Hospital doesn’t know it’s head from its arsehole. They fuck me about constantly. But when I go to complain to the patient liaison service I get told I can’t because “it hasn’t happened yet”.

I think you’ll find it has happened now. So I’ll try make the complaint again. I don’t give a fuck anymore. I’m done being fucked over.

I’m fucking DONE!!!!

[shafnapn]

Why Dr. Prince is Considered the Best Plastic Surgeon in Kerala

When it comes to plastic surgery, finding the right surgeon is paramount to achieving the desired results. Dr. Prince, widely regarded as the best plastic surgeon in Kerala, embodies excellence in his field. With a career that spans decades and an extensive list of qualifications, he has become the go-to professional for those seeking top-tier cosmetic procedures in Kerala and beyond.

A Journey of Dedication and Expertise

Dr. Prince’s journey in the field of plastic surgery is marked by an unwavering commitment to excellence. A graduate of the prestigious Armed Forces Medical College, Pune, he further honed his skills by completing an MS in General Surgery at Government Medical College, Kozhikode, and a DNB in General Surgery from the National Board of India. His passion for plastic surgery led him to pursue an MCh in Plastic Surgery from the renowned Madras Medical College, where he refined his expertise in this highly specialized field.

International Training and Global Perspective

What truly sets Dr. Prince apart is his extensive international exposure. He has trained at some of the world’s leading plastic surgery units, including Addenbrooke’s Hospital in Cambridge, the St. Andrews Centre for Plastic Surgery in Chelmsford, and The Royal Preston, Mt. Vernon, in the UK. This global perspective has enriched his practice, allowing him to offer cutting-edge techniques and treatments that are on par with international standards.

Dr. Prince’s fellowships in Hand and Microsurgery and Breast Aesthetic have further solidified his reputation as a versatile and highly skilled plastic surgeon.

A Patient-Centered Approach

At the heart of Dr. Prince’s practice is his belief in personalized care. Every patient is unique, and Dr. Prince tailors each treatment plan to meet the individual needs and goals of his patients. Whether it’s rhinoplasty, breast surgery, a tummy tuck, or eyelid surgery, Dr. Prince is dedicated to delivering natural-looking results that enhance both appearance and confidence.

Dr. Prince’s impact extends far beyond Kerala. With over 5000 patients treated from across India and around the world, including the USA, Canada, UK, Australia, the Middle East, and Africa, he is a trusted name in plastic surgery. His patients praise his meticulous attention to detail, compassionate care, and the outstanding outcomes he consistently delivers.He is a highly respected and considered one of the best plastic surgeon in Kerala.

Frequently Asked Questions

1. What makes Dr. Prince the best plastic surgeon in Kerala?

Dr. Prince’s combination of extensive training, international exposure, and commitment to personalized care make him a standout in the field of plastic surgery. His ability to deliver natural-looking, aesthetically pleasing results has earned him the trust and admiration of patients worldwide.

2. What procedures does Dr. Prince specialize in?

Dr. Prince specializes in a wide range of plastic surgery procedures, including rhinoplasty, breast surgeries, tummy tucks, mommy makeover surgery, and eyelid surgery. He is also an expert in Hand and Microsurgery and Breast Aesthetic.

3. Where does Dr. Prince practice?

Dr. Prince is currently a part of the Sushrutha Institute of Plastic Surgery at Elite Hospital in Thrissur, Kerala.

[medjournalhealthcare]

Dr. Rohan Bidaye: Leading ENT Surgeon in London

Dr. Rohan Bidaye, a renowned ENT doctor in London. If you're searching for the best ENT doctor in London, Dr. Bidaye's exceptional expertise and patient-centered approach make him the top choice for all your ear, nose, and throat needs.

About Dr. Rohan Bidaye

Dr. Rohan Bidaye is a highly accomplished Consultant ENT Surgeon with a focus on Laryngology and Head & Neck Surgery. His extensive training and experience across prestigious institutions in the UK, the US, and India have made him a leading figure among London ENT surgeons. He is currently associated with leading hospitals, ensuring that he offers state-of-the-art care for various ENT conditions.

Dr. Bidaye's credentials include multiple Fellowships from the Royal College of Surgeons, and Senior Fellowships at esteemed establishments such as Charing Cross Hospital (Imperial College Healthcare NHS Trust), University Hospitals Birmingham, and Addenbrooke's Hospital (Cambridge). His international experience spans institutions like Massachusetts Eye and Ear Infirmary (Harvard Medical School), Hahnemann University Hospital (Philadelphia), Tata Memorial Hospital (Mumbai), and Deenanath Mangeshkar Hospital (Pune). His ECFMG Board Certification from the US further attests to his commitment to excellence.

Comprehensive ENT Services

Dr. Bidaye offers a wide range of ENT services, ensuring that patients receive top-notch care for various conditions:

Ear Conditions: Comprehensive treatment for hearing loss, ear infections, tinnitus, and balance disorders. Dr. Bidaye uses advanced diagnostic tools and treatment methods to address both common and complex ear issues.

Nose and Sinus Issues: Effective management of sinusitis, nasal obstructions, and allergies. With expertise in endoscopic sinus surgery, Dr. Bidaye provides relief for chronic sinus problems and other nasal conditions.

Throat Conditions: Specialized care for throat infections, voice disorders, and swallowing difficulties. Dr. Bidaye’s expertise in Laryngology ensures precise diagnosis and effective treatment for a range of throat issues.

Head and Neck Surgery: Expert surgical interventions for head and neck tumors, thyroid issues, and other complex conditions. Dr. Bidaye’s proficiency in minimally invasive techniques ensures optimal outcomes and faster recovery times.

Why Choose Dr. Rohan Bidaye?

When looking for an ENT doctor in London, Dr. Bidaye stands out for several reasons:

Extensive Expertise: His background in top-tier institutions worldwide ensures that he brings a wealth of knowledge and experience to his practice. This extensive training allows him to handle even the most challenging ENT cases with confidence and skill.

Patient-Centered Care: Dr. Bidaye is dedicated to providing personalized treatment plans tailored to each patient's unique needs. He takes the time to understand each patient's concerns, ensuring they feel heard and respected throughout their treatment journey.

Advanced Techniques: Utilizes the latest medical technologies and surgical methods to achieve the best outcomes. Dr. Bidaye stays at the forefront of medical advancements, continuously updating his skills and knowledge to provide the highest standard of care.

Collaborative Approach: Works with other healthcare professionals to offer comprehensive care. By collaborating with specialists in related fields, Dr. Bidaye ensures a holistic approach to treatment, addressing all aspects of a patient’s health.

Easy Access and Convenience

Finding an ENT doctor specialty in London has never been easier. Dr. Bidaye’s practice is conveniently located, making it accessible for residents across the city. Whether you need a routine check-up, a specialized consultation, or surgery, Dr. Bidaye’s clinic is equipped to provide the highest standard of care.

Conditions Treated

Dr. Bidaye is experienced in treating a wide range of ENT conditions, including but not limited to:

Chronic Ear Infections: Persistent ear infections that do not respond to standard treatments.

Hearing Loss: Comprehensive evaluation and management of hearing loss, including hearing aid fitting and cochlear implants.

Tinnitus: Advanced treatment options for ringing in the ears.

Vertigo and Balance Disorders: Diagnosis and treatment of balance issues and dizziness.

Sinusitis: Management of acute and chronic sinusitis using medical and surgical treatments.

Nasal Polyps: Removal of benign growths in the nasal passages.

Deviated Septum: Correction of nasal septum deviations to improve breathing.

Thyroid and Parathyroid Disorders: Surgical and non-surgical treatment of thyroid and parathyroid conditions.

Head and Neck Cancers: Comprehensive care for cancers of the head and neck, including surgery, radiation, and chemotherapy.

Voice Disorders: Treatment for hoarseness, vocal cord nodules, and other voice-related issues.

Advanced Diagnostic Tools

Dr. Bidaye utilizes state-of-the-art diagnostic tools to accurately diagnose and effectively treat ENT conditions. These tools include:

Audiometry: Comprehensive hearing tests to diagnose hearing loss.

Endoscopy: Advanced imaging techniques to visualize the ear, nose, and throat structures.

CT and MRI Scans: High-resolution imaging to diagnose complex conditions.

Balance Testing: Specialized tests to diagnose balance disorders and dizziness.

Patient Education and Support

Dr. Bidaye believes in empowering his patients through education. He provides detailed information about conditions and treatments, helping patients make informed decisions about their health. His supportive approach ensures that patients feel comfortable and confident in their care.

Book Your Appointment

Are you searching for the top ENT doctor in London? Look no further than Dr. Rohan Bidaye. Contact us today to book an appointment and take the first step towards better ear, nose, and throat health.  

Are you looking for Healthcare Marketing Agency ? Please feel free to contact Kaushal Pandey .

[maheshnadgir]

Dr. Rohan Bidaye: Leading ENT Surgeon in London

Dr. Rohan Bidaye, a renowned ENT doctor in London. If you're searching for the best ENT doctor in London, Dr. Bidaye's exceptional expertise and patient-centered approach make him the top choice for all your ear, nose, and throat needs.

About Dr. Rohan Bidaye

Dr. Rohan Bidaye is a highly accomplished Consultant ENT Surgeon with a focus on Laryngology and Head & Neck Surgery. His extensive training and experience across prestigious institutions in the UK, the US, and India have made him a leading figure among London ENT surgeons. He is currently associated with leading hospitals, ensuring that he offers state-of-the-art care for various ENT conditions.

Dr. Bidaye's credentials include multiple Fellowships from the Royal College of Surgeons, and Senior Fellowships at esteemed establishments such as Charing Cross Hospital (Imperial College Healthcare NHS Trust), University Hospitals Birmingham, and Addenbrooke's Hospital (Cambridge). His international experience spans institutions like Massachusetts Eye and Ear Infirmary (Harvard Medical School), Hahnemann University Hospital (Philadelphia), Tata Memorial Hospital (Mumbai), and Deenanath Mangeshkar Hospital (Pune). His ECFMG Board Certification from the US further attests to his commitment to excellence.

Comprehensive ENT Services

Dr. Bidaye offers a wide range of ENT services, ensuring that patients receive top-notch care for various conditions:

Ear Conditions: Comprehensive treatment for hearing loss, ear infections, tinnitus, and balance disorders. Dr. Bidaye uses advanced diagnostic tools and treatment methods to address both common and complex ear issues.

Nose and Sinus Issues: Effective management of sinusitis, nasal obstructions, and allergies. With expertise in endoscopic sinus surgery, Dr. Bidaye provides relief for chronic sinus problems and other nasal conditions.

Throat Conditions: Specialized care for throat infections, voice disorders, and swallowing difficulties. Dr. Bidaye’s expertise in Laryngology ensures precise diagnosis and effective treatment for a range of throat issues.

Head and Neck Surgery: Expert surgical interventions for head and neck tumors, thyroid issues, and other complex conditions. Dr. Bidaye’s proficiency in minimally invasive techniques ensures optimal outcomes and faster recovery times.

Why Choose Dr. Rohan Bidaye?

When looking for an ENT doctor in London, Dr. Bidaye stands out for several reasons:

Extensive Expertise: His background in top-tier institutions worldwide ensures that he brings a wealth of knowledge and experience to his practice. This extensive training allows him to handle even the most challenging ENT cases with confidence and skill.

Patient-Centered Care: Dr. Bidaye is dedicated to providing personalized treatment plans tailored to each patient's unique needs. He takes the time to understand each patient's concerns, ensuring they feel heard and respected throughout their treatment journey.

Advanced Techniques: Utilizes the latest medical technologies and surgical methods to achieve the best outcomes. Dr. Bidaye stays at the forefront of medical advancements, continuously updating his skills and knowledge to provide the highest standard of care.

Collaborative Approach: Works with other healthcare professionals to offer comprehensive care. By collaborating with specialists in related fields, Dr. Bidaye ensures a holistic approach to treatment, addressing all aspects of a patient’s health.

Easy Access and Convenience

Finding an ENT doctor specialty in London has never been easier. Dr. Bidaye’s practice is conveniently located, making it accessible for residents across the city. Whether you need a routine check-up, a specialized consultation, or surgery, Dr. Bidaye’s clinic is equipped to provide the highest standard of care.

Conditions Treated

Dr. Bidaye is experienced in treating a wide range of ENT conditions, including but not limited to:

Chronic Ear Infections: Persistent ear infections that do not respond to standard treatments.

Hearing Loss: Comprehensive evaluation and management of hearing loss, including hearing aid fitting and cochlear implants.

Tinnitus: Advanced treatment options for ringing in the ears.

Vertigo and Balance Disorders: Diagnosis and treatment of balance issues and dizziness.

Sinusitis: Management of acute and chronic sinusitis using medical and surgical treatments.

Nasal Polyps: Removal of benign growths in the nasal passages.

Deviated Septum: Correction of nasal septum deviations to improve breathing.

Thyroid and Parathyroid Disorders: Surgical and non-surgical treatment of thyroid and parathyroid conditions.

Head and Neck Cancers: Comprehensive care for cancers of the head and neck, including surgery, radiation, and chemotherapy.

Voice Disorders: Treatment for hoarseness, vocal cord nodules, and other voice-related issues.

Advanced Diagnostic Tools

Dr. Bidaye utilizes state-of-the-art diagnostic tools to accurately diagnose and effectively treat ENT conditions. These tools include:

Audiometry: Comprehensive hearing tests to diagnose hearing loss.

Endoscopy: Advanced imaging techniques to visualize the ear, nose, and throat structures.

CT and MRI Scans: High-resolution imaging to diagnose complex conditions.

Balance Testing: Specialized tests to diagnose balance disorders and dizziness.

Patient Education and Support

Dr. Bidaye believes in empowering his patients through education. He provides detailed information about conditions and treatments, helping patients make informed decisions about their health. His supportive approach ensures that patients feel comfortable and confident in their care.

Book Your Appointment

Are you searching for the top ENT doctor in London? Look no further than Dr. Rohan Bidaye. Contact us today to book an appointment and take the first step towards better ear, nose, and throat health.  

Are you looking for Healthcare Marketing Agency ? Please feel free to contact Kaushal Pandey .

[drrohanbidayeentsurgeon]

Dr. Rohan Bidaye: Leading ENT Surgeon in London

Dr. Rohan Bidaye, a renowned ENT doctor in London. If you're searching for the best ENT doctor in London, Dr. Bidaye's exceptional expertise and patient-centered approach make him the top choice for all your ear, nose, and throat needs.

About Dr. Rohan Bidaye

Dr. Rohan Bidaye is a highly accomplished Consultant ENT Surgeon with a focus on Laryngology and Head & Neck Surgery. His extensive training and experience across prestigious institutions in the UK, the US, and India have made him a leading figure among London ENT surgeons. He is currently associated with leading hospitals, ensuring that he offers state-of-the-art care for various ENT conditions.

Dr. Bidaye's credentials include multiple Fellowships from the Royal College of Surgeons, and Senior Fellowships at esteemed establishments such as Charing Cross Hospital (Imperial College Healthcare NHS Trust), University Hospitals Birmingham, and Addenbrooke's Hospital (Cambridge). His international experience spans institutions like Massachusetts Eye and Ear Infirmary (Harvard Medical School), Hahnemann University Hospital (Philadelphia), Tata Memorial Hospital (Mumbai), and Deenanath Mangeshkar Hospital (Pune). His ECFMG Board Certification from the US further attests to his commitment to excellence.

Comprehensive ENT Services

Dr. Bidaye offers a wide range of ENT services, ensuring that patients receive top-notch care for various conditions:

Ear Conditions: Comprehensive treatment for hearing loss, ear infections, tinnitus, and balance disorders. Dr. Bidaye uses advanced diagnostic tools and treatment methods to address both common and complex ear issues.

Nose and Sinus Issues: Effective management of sinusitis, nasal obstructions, and allergies. With expertise in endoscopic sinus surgery, Dr. Bidaye provides relief for chronic sinus problems and other nasal conditions.

Throat Conditions: Specialized care for throat infections, voice disorders, and swallowing difficulties. Dr. Bidaye’s expertise in Laryngology ensures precise diagnosis and effective treatment for a range of throat issues.

Head and Neck Surgery: Expert surgical interventions for head and neck tumors, thyroid issues, and other complex conditions. Dr. Bidaye’s proficiency in minimally invasive techniques ensures optimal outcomes and faster recovery times.

Why Choose Dr. Rohan Bidaye?

When looking for an ENT doctor in London, Dr. Bidaye stands out for several reasons:

Extensive Expertise: His background in top-tier institutions worldwide ensures that he brings a wealth of knowledge and experience to his practice. This extensive training allows him to handle even the most challenging ENT cases with confidence and skill.

Patient-Centered Care: Dr. Bidaye is dedicated to providing personalized treatment plans tailored to each patient's unique needs. He takes the time to understand each patient's concerns, ensuring they feel heard and respected throughout their treatment journey.

Advanced Techniques: Utilizes the latest medical technologies and surgical methods to achieve the best outcomes. Dr. Bidaye stays at the forefront of medical advancements, continuously updating his skills and knowledge to provide the highest standard of care.

Collaborative Approach: Works with other healthcare professionals to offer comprehensive care. By collaborating with specialists in related fields, Dr. Bidaye ensures a holistic approach to treatment, addressing all aspects of a patient’s health.

Easy Access and Convenience

Finding an ENT doctor specialty in London has never been easier. Dr. Bidaye’s practice is conveniently located, making it accessible for residents across the city. Whether you need a routine check-up, a specialized consultation, or surgery, Dr. Bidaye’s clinic is equipped to provide the highest standard of care.

Conditions Treated

Dr. Bidaye is experienced in treating a wide range of ENT conditions, including but not limited to:

Chronic Ear Infections: Persistent ear infections that do not respond to standard treatments.

Hearing Loss: Comprehensive evaluation and management of hearing loss, including hearing aid fitting and cochlear implants.

Tinnitus: Advanced treatment options for ringing in the ears.

Vertigo and Balance Disorders: Diagnosis and treatment of balance issues and dizziness.

Sinusitis: Management of acute and chronic sinusitis using medical and surgical treatments.

Nasal Polyps: Removal of benign growths in the nasal passages.

Deviated Septum: Correction of nasal septum deviations to improve breathing.

Thyroid and Parathyroid Disorders: Surgical and non-surgical treatment of thyroid and parathyroid conditions.

Head and Neck Cancers: Comprehensive care for cancers of the head and neck, including surgery, radiation, and chemotherapy.

Voice Disorders: Treatment for hoarseness, vocal cord nodules, and other voice-related issues.

Advanced Diagnostic Tools

Dr. Bidaye utilizes state-of-the-art diagnostic tools to accurately diagnose and effectively treat ENT conditions. These tools include:

Audiometry: Comprehensive hearing tests to diagnose hearing loss.

Endoscopy: Advanced imaging techniques to visualize the ear, nose, and throat structures.

CT and MRI Scans: High-resolution imaging to diagnose complex conditions.

Balance Testing: Specialized tests to diagnose balance disorders and dizziness.

Patient Education and Support

Dr. Bidaye believes in empowering his patients through education. He provides detailed information about conditions and treatments, helping patients make informed decisions about their health. His supportive approach ensures that patients feel comfortable and confident in their care.

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Are you searching for the top ENT doctor in London? Look no further than Dr. Rohan Bidaye. Contact us today to book an appointment and take the first step towards better ear, nose, and throat health.  

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A blood test that draws on artificial intelligence can predict who will develop Parkinson’s disease up to seven years before symptoms arise, researchers say.

The test is designed to work on equipment already found in many NHS laboratories and, if validated in a broad population of people, could be made available to the health service within two years.

There are no drugs to protect the brain from Parkinson’s at present, but an accurate predictive test would enable clinics to identify people who stand to benefit most from clinical trials of treatments that aim to slow or halt the disease.

“At the moment, we’re shutting the stable door after the horse has bolted,” said Prof Kevin Mills, a senior author on the study at UCL Great Ormond Street Institute of Child Health. “We need to get to people before they develop symptoms. It’s always better to do prevention rather than cure.”

Parkinson’s disease is the world’s fastest growing neurodegenerative condition, a trend driven primarily by the ageing population. The disorder affects more than 150,000 people in the UK and 10 million worldwide. It is caused by the buildup of a protein called alpha-synuclein that damages or destroys nerve cells which produce an important substance called dopamine in part of the brain called the substantia nigra.

People who develop Parkinson’s can experience tremors, difficulties with movement and muscle stiffness, but also problems with balance, memory, dizziness and nerve pain. Many receive dopamine replacement therapy, but efforts are under way to find treatments that slow or stop the disease.

To develop the test, scientists at UCL and the University of Göttingen used a machine learning algorithm to spot a signature pattern of eight blood proteins in patients with Parkinson’s. The algorithm was then able to predict future Parkinson’s in other patients who provided blood samples. In one patient, the disorder was correctly predicted more than seven years before symptoms arose. “It is possible that it could go back even further,” said Dr Jenny Hällqvist, at the UCL Institute of Neurology, and first author on the study published in Nature Communications.

Prof Roger Barker, a consultant neurologist who specialises in Parkinson’s at the University of Cambridge and Addenbrooke’s hospital, said if validated by other groups, the test raised the possibility of diagnosing Parkinson’s at the very earliest stages, enabling patients to be enrolled in clinical trials when the disease process had just begun. “As such, we could treat people with Parkinson’s with disease-modifying therapies before they have lost many cells in their brain,” he said. “Obviously, we still need to find such therapies, but this study is a step in the right direction.”

Prof Ray Chaudhuri, the medical director of the Parkinson Foundation International Centre of Excellence, said there was a “massive unmet need” for blood tests that predict and diagnose Parkinson’s, but cautioned that such tests come with “major challenges”.

“Parkinson’s is not a single disease but a syndrome and can present in various different ways,” he said. “As such, management differs and one size does not fit all. The prediction is unlikely to signpost these subgroups at this stage.” Without effective treatments an early diagnosis raises considerable ethical issues, he added, as well as potentially affecting patients’ insurance policies.

“The process does help us have a group of people with Parkinson’s who may be ready or suitable for future trials of neuroprotective molecules,” Chaudhuri said. “Furthermore, there is some preliminary evidence that in such “at risk” people with Parkinson’s, physical activity and programmed exercise may be beneficial in terms of potentially slowing the course of the illness.”