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How Hair-Loss Treatments Have Evolved Over Time – NewBeauty Magazine

Since the dawn of time, men and women have been combating sparse strands with a myriad of odd treatments and protocols. In the 21st century, we may have cracked the code and stopped the speed of shedding using breakthrough science and innovation.

In Ancient Egypt, castor oil and almond oil were often used to promote hair growth. They would also use concoctions made of dates, dog paws and donkey feet, says New York facial plastic surgeon Yael Halaas, MD. In India, they also had a tradition of standing on your head to increase blood flow to the scalp to improve hair loss, adds New York dermatologist Julie Russak, MD.

Spices, beetroot, myrrh, and some eyeopening ingredients like urine were used during the Greco-Roman era, when hair was an indicator of youth, wealth and status. The famous Greek physician Hippocrates believed that a mixture of spices, pigeon droppings, horseradish, beetroot, and opium could cure hair loss, which he suffered from himself, says Dr. Halaas.

In 8th century China, safflower oil, rosemary, Fo-Ti root, and various Chinese herbs were ground together with animal parts and used as a hair growth potion. Across Scandinavia, follicularly challenged Vikings would rub goose droppings on their heads in hopes of growing new strands. Saint Hildegard of Bingen, who lived in 12th century Germany, wrote of a baldness cure that called for leaving bear fat and ashes on the scalp for a long while.

Like the Ancient Egyptians, Victorians used castor oil, almond oil and gentle tonics, but also relied on rigorous scalp massages to promote blood flow. Silk nightcaps were also introduced to fight friction and minimize hair loss.

Modern-day restoration stems back to work done in Japan in the 30s, but it wasnt until the 50s that hair transplant surgery was born. A dermatologist named Dr. Norman Orentreich discovered that hair follicles could survive when moved from one site to another, says New York dermatologist Doris Day, MD. At first, the outcomes appeared unnatural in that clumps of follicles, called plugs, were placed with little regard to the natural hairline or final look.

Hair transplant surgery evolved in the 90s with Follicular Unit Transplants, where donor follicles are removed as a full strip from an area of healthy growth, explains Wayne, NJ facial plastic surgeon Jeffrey B. Wise, MD. Follicular Unit Extraction, a technique whereby grafts are harvested individually using a small punch, emerged in the 2000s.

Thankfully, today we dont rely on antiquated animal-based mixtures, but we are using follicle-stimulating growth factors. A treatment plan might include platelet-rich plasma injections, topicals, supplements like Nutrafol, nutritional changes, and lasers, notes Dr. Day. Doctors may prescribe medications like finasteride and topical minoxidil says Dr. Russak. Recently, low-dose oral minoxidil has also emerged as an effective hair growth solution.

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Dermatologist Jessie Cheung on How to Make Your Penis Bigger – Men’s Health

NO SURPRISE TO anyone whos been living on planet Earth, but a lot of men want to have a bigger penis. The thing is, we cant go to the gym, do three sets of dumbbell penis reps, and get a larger schlong. If it were that easy, nearly every guy would be walking around with a snake in his pants.

Still, there actually are some things you can do to get a bigger penis, but many of these procedures are not cheap and come with some serious health risks. Nevertheless, we know you're probably curious about the wild world of penis enlargement, which is why we reached out to Jessie Cheung, M.D., a board-certified dermatologist who specializes in some of these techniques. Cheung has been a dermatologist for nearly 20 years, and six years ago, she moved from doing medical dermatology to focusing exclusively on cosmetic and sexual dermatology.

In addition to standard facial cosmetic procedures, Cheungwho's based in Manhattan and Chicagoperforms a slew of penis procedures, including fillers, fat injections, Bocox (that's Botox for your cock, FYI), and Emsella (a form of electromagnetic therapy that helps with premature ejaculation and erection strength.)

We interviewed Cheung about her dermatological methods for making patients' penises bigger, longer, and even capable of lasting longer during sex.

This interview has been lightly edited and condensed for clarity.

I dont want to brag, but a lot, hundreds. As a dermatologist, I'm used to looking at skin everywhere, including the penis, anus, scrotum, and perineum, and dealing with warts, hemorrhoids, and fissures. I stopped doing medical dermatology years ago and now focus on cosmetics, hormones, and sexual health. So that brings in men who need help with their erectile function, libido, premature ejaculation, and men who have purely cosmetic issues. The big one, of course, is increasing their penis size.

Actually, I see more men who complain about erectile dysfunction instead of size, but they always say that even if they are happy with their size, they wouldn't mind more length or girth.

I give them statistics: Numbers are facts. Interestingly, many of my men who want bigger penises have above-average length and girth. I think porn makes them lose touch with reality, just like we're seeing social media distort our perception of beauty.

Penis length must be 2.5 standard deviations below the average for that age to be considered a micropenis. For adults, that is 9.3 cm when stretched or 3.6 inches. In my office, I consider it a micropenis if they are too short to penetrate their partner.

Not that often. I would say my whole career, probably two that were so small they couldn't penetrateand that's really short. When its that small, they may want surgical intervention, and I dont do penis surgeries. So because of that, I don't see many men with a proper micropenis.

Yeah, so I perform filler injections. I also perform P-shots, which are designed to treat ED but have the additional benefit of increasing size, specifically girth. P-shots involve injecting biological substances such as Platelet-rich plasma (PRP). PRP is a source of growth factors for blood vessels and tissue, so activating the hibernating stem cells in the arteries and nerves stimulates repair and the production of healthy tissue.

P-shots start at $1800 and increase depending on the protocol used.

Ill try not to be too technical, but we draw your blood in these special tubes. We spin it down on the centrifuge, and on the top coat, there's a layer that's kinda yellowy, that's very rich with platelets, which contains eight to ten growth factors that are good for your blood vessels, collagen, and stem cell activation. So we inject that into places where you want to turn on stem cells, whether into your scalp to grow hair, your skin to help with wound healing, or the penis to activate stem cells to make blood vessels and nerves again. That said, PRP is about 10 to 15 years old. I prefer to use exomes.

So, I perform a topical infusion of exosomes, which really is the cutting edge of regenerative medicine. Exosomes are basically little email packets of information that your stem cells secrete to turn each other on and talk to each other. And they're filled with RNA, proteins, and peptides. Exomes have hundreds of more growth factors than PRP. They're also anti-inflammatory. So I use exosomes the exact same way I use P-shots, to help with ED, functionality, and size.

Anti-inflammation helps prevent tissue from aging. So in the case of penises, this will help you retain your functionality and erection strength as you age.

Fat is a great filler, and since fat is full of stem cells, I recommend fat for improving size and restoring erectile function. You will see increased girth and can regain lost length, both flaccid and erect.

A fat transfer to the penis is very straightforward. The injection technique is similar to how we inject the penis with regular fillers, but we are harvesting your own fat with gentle liposuction and processing the fat with PRP or exomes. I like to take fat from the pubic mound, which helps to expose more of the base of the penis to create more visible length. I call it pulling the turtle out of the shell.

Fat is a very cost-effective filler, and since fat functions as a natural implant, it lasts much longer than other fillers. The most significant benefit of using fat is the improvement of functionality, as the wound-healing activation of stem cells will target nerves and blood vessels to improve sensitivity and circulation. I like to transfer at least 20 mL of fat, which starts at $8,000.

There are risks associated with any injection! But understanding the anatomy and potential complications will mitigate those risks. For example, you don't want any material getting into large arteries, which can cause tissue to die. You also have to respect the layers and boundaries of the penis to avoid migration of the filler (i.e., the filler all moving to one place and sitting there). Bruising, swelling, uneven appearance, and infection are potential complications that I warn my patients about.

No, I have never had a patient who asked for a smaller penis. But penises do shrink over time, as testosterone levels fall and there is a decrease in blood flow. The blood vessels and tissue scar down and get stiff, so they can't stretch and fill up with blood for a full erection. As a result, men will notice their penis looking smaller while flaccid and erect and report softer erections.

Typically men in their fifties and sixties, though Ive seen men coming and seeking help for their shrinkage in their thirties.

Staying healthy [and] keeping your hormone levels optimized. [And you do that by] having a good quality of sleep, a healthy diet, keeping stress levels low, and not smoking. So things that are generally thought of as bad for you will negatively affect your penis size as you age.

Yes, my patients love Bocox! It helps with size and erections. Botulinum toxin works by relaxing the smooth muscle in the blood vessels of the penis. This means the blood vessels are more dilated and filled with blood at rest, so the penis hangs longer and thicker when flaccid. So its great if youre a grower and not a shower. But even with an erection, the penis is even more full of blood than usual, so it is harder and may be thicker. Bocox is a relatively safe treatment. It's usually two pokes after the application of a topical numbing cream. Risks include mild bruising and swelling.

So it's electromagnetic therapy. Basically, you're sitting on a chair, and a powerful magnet is at the chair's base. That magnet makes your pelvic floor muscles activate. So essentially, you're doing kegel exercises, whether it be for the penis, the vagina, or the anus. For the penis, that can help with premature ejaculation, but also erection strength and even size because of the increased blood flow. We have men who do Emsella for the anus, specifically sphincter control. There's a statistic that you complete over 11,000 Kegel exercises in 28 minutes on the Emsella chair. So it's very legit, and I love using it on my patients.

I will refuse to treat a patient who has unrealistic expectations. Beyond that, everyone has their own desired aesthetic, so I won't judge a man if he wants to have a huge penis. To each their own!

Social media and porn have created unrealistic expectations for bodies, faces, and genitalia. It's difficult to maintain a smooth, pink anus or vagina or penis or even nipples as we age, and sexual confidence is at an all-time low. Sex is excellent for your physical and mental health and appearance, so a therapeutic procedure that encourages sexual wellness and confidence is not really up to public judgment. It's a private health issue.

I had a patient who had filler injections done elsewhere. He had 15 syringes done in one session, and all the filler clumped up at the head of his penis. It was this huge blob. It looked like a golf ball.

So he came after it was botched to get it fixed. But didnt want to get the filler removed. So what I did was add more filler at the shaft and base, essentially to blend it in better.

Aside from the usual wows, what's memorable are the stories I hear when my patients return: sex multiple times a day, getting propositioned on Snapchat, video parties, and underground fame. My patients are definitely more confident. I had one patient who was too short to penetrate his partner, and after a combination of hormones, a P-shot, and fat transfer, he was finally able to have penetrative sex!

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Dermatologist Jessie Cheung on How to Make Your Penis Bigger - Men's Health

Stem cell research can help people with hard-to-heal wounds – EurekAlert

Advances in burns treatment open up new possibilities for healing other complicated wounds. For the first time, stem cells produced in compliance with the regulations governing the manufacture of medicinal products, are now being tested as a treatment for hard-to-heal leg ulcers in Linkping, Sweden.

Using stem cells in the treatment of hard-to-heal wounds and burns is a new method under development. Its success depends on close collaboration between researchers and health care staff. The objective is clear: meeting health care needs.

I recall a man in his 40s, this was a couple of months after I came to Linkping Universityas a researcher, who was fighting for his life. Im sad to say he died. If wed had the technologies we have now, we might have been able to help him. I still think about him, says Ahmed Elserafy, who was recruited to Linkping University (LiU) as a researcher to find the right type of cells to treat wounds.

One of Swedens two national Burn Centres is located at Linkping University Hospital. Here, near-clinical and internationally recognised research is carried out next to advanced burns care. One important task is developing the burn care of the future.

Burn treatment has been the same for a very long time and is based on taking skin grafts from the patient for transplant to the wound area. Our research focuses on finding other ways to cover open wounds, says Folke Sjberg, professor at LiU and consultant at the Linkping national Burn Centre (Brnnskadecentrum).

But not only burns cause serious open wounds. A very large group of wounds identified as hard-to-heal wounds, cause extensive suffering and present a difficult health care challenge.

There are significant differences between burns and hard-to-heal wounds. Burns occur suddenly. Burn patients do not normally have underlying diseases adversely affecting the healing of wounds. A hard-to-heal wound, however, is caused by underlying conditions that impair healing, such as diabetes, or multimorbidity in the case of elderly people.

The prognosis is grim for the around 100,000 people in Sweden with hard-to heal wounds. In more than half of the cases, such wounds lead to amputation of the limb affected. Hard-to-heal wounds are most often treated with dressings and wound care products. It is also possible to transplant the patients own skin to the wound.

The team of researchers and care staff have developed a model for growing new skin cells from a tissue sample from the patient. The cells are administered to the wound area in the form of a solution. The team has shown that the wound heals from the edges to the centre, just like it would naturally. Most wounds have shrunk to only half the size after 15 days.

This model forms the basis for the researchers next step, where they investigate the viability of using cells from another person instead of the patients own.

Cells from elderly patients are not optimal for transplantation. What were doing now is that we use cells from younger individuals with much better healing potential, says Folke Sjberg.

Specialist nurse Matilda Karlsson and consultant Moustafa Elmasry are working on a clinical study at the Burn Centres wound clinic. It is the first study in the world where stem cells, produced in compliance with the regulations governing the manufacture of medicinal products, are tested on patients with hard-to-heal leg ulcers.

Its a revolutionising, active treatment compared with traditional treatment using dressings or transplantation of the patients own skin, which is a very invasive procedure, says Moustafa Elmasry.

The cells used are derived from fat harvested from plastic surgery patients. The researchers collaborate with the company Xintela in Lund, which purifies a well-defined group of stem cells. What is unique about stem cells is that they can be developed into any type of cell in the body. Studies have shown that even if the cells come from another person, the bodys immune defence system does not react to them.

The study, which will comprise eight patients, is in its start-up phase. As with all clinical studies, the first step is to find out whether the treatment is safe. The researchers hope that the stem cells will also have a positive effect on wound healing. Should this turn out to be the case, it will be interesting to develop the process to ensure a sufficiently large amount of cells at a reasonable cost, to enable broad application in health care. The larger the wound, the more cells are required.

If the treatment proves successful, the researchers hope that, in the long term, it can also be used to cover extensive burns. Matilda Karlsson does not hesitate for a second when asked what they hope their research will eventually lead to:

A product that can heal all types of hard-to-heal wounds, with no need for skin grafts from the patient. This could hopefully save people from amputation of the limbs affected and, in the case of severe burns, save lives.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Girl in the fight of her life looks for stem cell donor – BlackburnNews.com

By Paul Pedro April 12, 2023 11:28am

A little girl who desperately needs a Stem Cell Transplant to survive is asking area residents for help.

Zoe Dudzianiec, 7, of Tecumseh has a rare disease called Diamond-Blackfan Anemia, which is a very rare bone marrow disorder with no cure.

She has been getting treatment since birth and must receive 10 hours of medical treatment every day. Zoe also gets blood transfusions every 10 days at Sick Kids Hospital in Toronto because the blood she requires isnot available to her in Windsor anymore.

Her best treatment option is a stem cell transplant. She needs to rely on the generosity of a stranger to save her life by registering as a potential donor, said officials with The Katelyn Bedard Bone Marrow Association.

They are hosting a swab clinic at St. Clair College in Chatham next week to find a potential donor for Zoe. The clinic will be held at the Chatham Campus of St. Clair College on Monday, April 17, 2023 from 10 a.m. to 2 p.m. The swabbing event will be held in the lobby of the main building at 1001 Grand Avenue West.

Zoe needs someone who shares her Middle Eastern/European ethnic background to donate stem cells to save her life.

Sign up here to become a stem cell donor if you cant make it to the clinic in Chatham. Your stem cells could give her the carefree childhood she deserves. Those wishing to register must be between the ages of 17 and 35. Potential donors of all ethnic backgrounds are welcome, according to organizers.

Diversification of the Canadian Registry is vital, organizers said.

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Clinical Commentary: Tawbi Assesses Toxicities of Therapies in … – Targeted Oncology

We have randomized phase 3 data for pembrolizumab [Keytruda], nivolumab, andnivolumab plus ipilimumab [Yervoy], so I completely agree that all of these [agents are considered] category 1 treatments by the NCCN [National Comprehensive Cancer Network] because all have shown improvements over single-agent ipilimumab.1 That is kind of where the category 1 comes from when including overall survival [OS] benefit. I consider NCCN guidelines to bevery safe. They dont include options just because they exist.

However, [combination] pembrolizumab and low-dose ipilimumab has been tried in 1 large single-arm study called KEYNOTE-29 [NCT02089685] and [found to be]safer than the combination of ipilimumab and nivolumab or high-dose ipilumumab.2 Yet, most of[the] relevant data are from a second-line study that showed about a 25% response rate in the second line low dose of ipilimumab or pembrolizumab. So, personally, I dont necessarily agree with this recommendation as a first-line regimen for low-dose ipilimumab/ pembrolizumab, but obviously this is up for discussion.

Relatlimab is a novel antibody that blocks LAG3. Its one of those interesting receptors and is quite different than PD-1. Its expressed on activated T cells and exhausted T cells. Initially, people were thinking that it has an association with MHC class II, the primary ligand, but more and more data are arising to show that its directly associated with the TCR CD3, basically signaling cascade.3 It actually modulates TCR signaling, so it makes a bigger impact in a place where theres a lot more TCR signaling happening, and thats probably why it works better in the first line than in the second line.

We just published in Nature [results of a] neoadjuvant study where the response rate in our neoadjuvant patients was 57%, so the earlier you use it, the more signaling happens through TCR, and the more you can modulate anti-LAG3.4 Now, the RELATIVITY-047 study [NCT03470922] was a phase 3 trial followed by the FDA approval of nivolumab plus relatlimab [for patients 12 years and older with unresectable/metastatic melanoma].5,6

With ipilimumab/nivolumab in any setting, you get grade 3 to 4 toxicity of at least 50%, and the highest discontinuation rate because of an adverse event [AE] was 36% in the CheckMate 067 [NCT01844505] study.7 [The rate of any grade 3/4 AEs with] nivolumab and relatlimab was 21%, and this is why I do feel like its slightly more toxicbut the pattern oftoxicity is similar [Table7]. With [this combination] every toxicity Ive encountered feels the same as when you encounter a singleagent toxicity. It doesnt feel a lot more recalcitrant and its not a lot harder, and you get 1 toxicity per patient, just like you would get it with the single-agent PD-1 inhibitor. The other factor that I share with [patients] is that Ive run 2 trialswith it. Both are randomized, double-blind studies vs nivolumab as a single agent. I had a fellow in my clinic who was seeing a patient on the adjuvant trial,[and I challenged him to find out which treatment the patient was on based on toxicity presentation]. He told me he wasnt sure he could do that and thats the point. If we were treating the patient with ipilimumab/nivolumab, you would know which arm. If it was blinded and [using] ipilimumab/nivolumab, you would know which arm, but because its nivolumab/relatlimab, it was impossible to tell.

The phase 1 [portion of the] study had about 25 patients treated with [relatlimab as a] single agent in the second line, and it had no activity, but we only use it in combination because of the way it works; it has a lot more potential for working only in combination because it potentiates the TCR signaling. So once you use a PD-1 [inhibitor], you increase the TCR signaling, and then the LAG3 amplifies that signal and makes it better.

If you have an immune-suppressed individual who is already [being treated in the] second line and [is] resistant to immunotherapy, the TCR signaling is going to be so much more limited, and youll not [be] able to reverse the exhaustion with either single agent, whereas with a combination, you get about a 13% response in the second line [From the Data5]. Now, 13% [is a smaller response] and 1 out of 7 patients responded, so Im not surprised that some patients feel like it never works. Every time Ive used it in the metastatic [setting] in the second or third line, Im just candid with patients [and I discuss how much of a response] I expect. I dont do 3 months in that situation. I just repeat their scans in 2 months because if they are going to progress I may want to do something different.

The data that we have [show] that if the patient is requiring steroids at the time of initiation, when youre starting ipilimumab and nivolumab, their chances of a response are only 18%, so its limited. If you have already treated them with ipilimumab and nivolumab, and now youre treating the toxicity with steroidsI would focus on finishing the steroids completely tapering them off if you canand thenconsider rechallenging.

In CheckMate 067, the study that I ran in that population, if you had a grade 3 to 4 toxicity, they basically never rechallenged you with immunotherapy. They just took you off. We allowed [rechallenging] on the study after they taper off steroidsand we got away with it about half the time. The other halfwould get hepatitis back or other things back, but you can get away with a rechallenge about half the time.

KEYNOTE-006 [NCT01866319], which compared 2 doses of pembrolizumab with single agent ipilimumab,is interesting because we used to dose [patients] so high, [at about] 10 mg/kg every 2 weeks.8 The 200 mg that you currently use every 3 weeks is equivalent to 3 mg/kg every 3 weeks, so imagine how much more of a dose that was. And it didnt matter, so theres not a lot of dose-response relationship with pembrolizumab. By even decreasing the dose by almost twothirds, you still get the same outcome.

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Clinical Commentary: Tawbi Assesses Toxicities of Therapies in ... - Targeted Oncology

American Association for Cancer Research Recognizes 2022-2023 … – American Association for Cancer Research (AACR)

PHILADELPHIA TheAmerican Association for Cancer Research(AACR) is proud to announce its newest class of grant recipients.

Since 1993, the AACR has allocated $133 million and awarded 880 research grants to support hundreds of scientists devoted to advancing the understanding, prevention, diagnosis, and treatment of cancer. Our grants support researchers domestically and abroad at every stage of their careers, representing a global commitment to cancer prevention, early detection, interception, and cure.

Fellowships

2021 AACR-Bristol Myers Squibb Immuno-oncology Research Fellowship

2022 AACR-Amgen Fellowship in Clinical/Translational Cancer Research

2022 AACR-Day One Biopharmaceuticals Pediatric Cancer Research Fellowship

2022 AACR-Exelixis Renal Cell Carcinoma Research Fellowship

2022 AACR-Genmab Non-Hodgkin B-Cell Lymphoma Research Fellowship

2022 AACR-Merck Cancer Disparities Research Fellowship

2022 AACR-Merck Immuno-oncology Research Fellowship

2022 AACR-Mirati Cancer Chemical Biology Research Fellowship

2022 AACR-QuadW Foundation Sarcoma Research Fellowship, in Memory of Willie Tichenor

2023 AACR Fellowship to Further Diversity, Equity, and Inclusion in Cancer Research

2023 AACR-Bristol Myers Squibb Immuno-Oncology Research Fellowship

2023 AACR-D-Team Sarcoma Research Fellowship

2023 AACR-D-Team Sarcoma Research Fellowship

2023 AACR-Incyte Immuno-oncology Research Fellowship

2023 AACR-John and Elizabeth Leonard Family Foundation Basic Cancer Research Fellowship

2023 AACR-QuadW Foundation Sarcoma Research Fellowship, in Memory of Willie Tichenor

Career Development Awards

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Cancer Research

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Cancer Research

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Cancer Research

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Cancer Research

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Cancer Research

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Clinical Cancer Research

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Clinical Cancer Research

2022 AACR Career Development Award to Further Diversity, Equity, and Inclusion in Clinical Cancer Research

2022 AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grant

2022 AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grant

2022 AACR-Novocure Career Development Award for Tumor Treating Fields Research

2022 Victorias Secret Global Fund for Womens Cancers Career Development Award, in Partnership with Pelotonia & AACR

2022 Victorias Secret Global Fund for Womens Cancers Career Development Award, in Partnership with Pelotonia & AACR

2022 Victorias Secret Global Fund for Womens Cancers Career Development Award, in Partnership with Pelotonia & AACR

2022 Victorias Secret Global Fund for Womens Cancers Career Development Award, in Partnership with Pelotonia & AACR

2022 Victorias Secret Global Fund for Womens Cancers Career Development Award, in Partnership with Pelotonia & AACR

2023 Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, in Honor of John Robert Lewis

2023 Lustgarten Foundation-AACR Pancreatic Cancer Career Development Award, in Honor of Ruth Bader Ginsburg

Independent Investigator Awards

2021 AACR-Bayer Innovation and Discovery Grant

2021 AACR-Bristol Myers Squibb Midcareer Female Investigator Grant

2021 AACR-Novocure Tumor Treating Fields Research Grant

2022 Friends of the AACR Foundation Early Career Investigator Award

2023 Lustgarten Foundation-Swim Across America-AACR Pancreatic Cancer Early Detection Research Grant

2023 Victorias Secret Global Fund for Womens Cancers Rising Innovator Research Grant, in Partnership with Pelotonia & AACR

2023 Victorias Secret Global Fund for Womens Cancers Rising Innovator Research Grant, in Partnership with Pelotonia & AACR

2023 Victorias Secret Global Fund for Womens Cancers Rising Innovator Research Grant, in Partnership with Pelotonia & AACR

2023 Victorias Secret Global Fund for Womens Cancers Rising Innovator Research Grant, in Partnership with Pelotonia & AACR

2023 Victorias Secret Global Fund for Womens Cancers Rising Innovator Research Grant, in Partnership with Pelotonia & AACR

Grants Supporting Researchers in Africa

2022 Beginning Investigator Grant for Catalytic Research (BIG Cat)

2022 Beginning Investigator Grant for Catalytic Research (BIG Cat)

2022 Beginning Investigator Grant for Catalytic Research (BIG Cat)

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American Association for Cancer Research Recognizes 2022-2023 ... - American Association for Cancer Research (AACR)

2023 drug discovery forecast: emerging trends and disruptors … – Drug Target Review

With advancements in artificial intelligence, precision medicine and gene editing, the field of drug discovery is undergoing a rapid transformation. In this article, Drug Target Reviews Izzy Wood gets the insider knowledge from industry leaders at SLAS 2023, who are experiencing these changes first hand.

AI has seen quite a boom in the last couple of years, overcoming challenges such as limited and low-quality data. Researchers can avoid numerous delays by employing AI for drug discovery, often using computational approaches in combination with their own techniques, for a faster and smoother path to the clinic.1

Getting to grips with what AI can do and how best to acquire and utilise its skills.

According to Cyrill Brunner, Application Specialist at Bruker Daltonics, effective AI calls for good data because you can predict a lot of things, but if your data is not good, your results will lack quality. Its therefore vital to invest in high quality instruments that have the ability to deliver quality data in a short time.

Yet, even with the positive advances in AI, it does not come without its challenges. Brunner continued to explain that one of the biggest changes in the pharmaceutical industry is that AI has moved over from just making data predictions to also analysing data.

For instance, if we look at mass spectrometry, the data is increasingly being analysed by computational methods, so it can be faster to keep up with all of the other screening technologies. Given the increasing amounts of generated data, manual analysis becomes unfeasible from a timescale perspective.

Michael A Norman, Lab Automation GM & VP of Sales at Flow Robotics, concurred that advancements in AI and machine learning were disrupting the drug discovery landscape.

Norman reflected that AI and machine learning will usher in an era of quicker, cheaper and more effective drug discovery. But whether this remains a good or bad thing remains sceptical.2

Most experts do expect these tools to become increasingly important. This shift presents both challenges and opportunities for scientists, especially when the techniques are combined with automation.2 Yet it is this combination of tying in automation and equipment that will create the lab of the future.

As emphasised by the experts, it is a case of getting to grips with what AI can do and how best to acquire and utilise its skills.

According to the National Health Service (NHS), the basis for personalised medicine is understanding the role DNA plays in ones health, transforming healthcare by delivering the four Ps:

Analysing the genome allows patterns to be identified that can help determine individual risk of developing diseases.

Jovi Jenkins, VP of Business Development at SPT Lab Tech, explained: Scientifically, what we are seeing is a lot more interest in genomic applications within the drug discovery process. Using genomics is becoming routine, such as CRISPR screening.

Norman echoed these predictions, suggesting that there will be advancements in individualised personal medicine, like gene therapy and CRISPR, on a much larger level.

The use of automation in drug discoveryprovides more consistent data that allows labs to make better decisions, faster. It also facilitates the testing of hundreds of thousands of compounds and samples.

Automation involves a verybroad range of technologiesincluding robotics and expert systems.4

Nick Ritzo, Genie Life Sciences, suggested that a big trend in drug discovery is going to be how modular lab spaces can gain the ability to quickly pivot from the discovery of one molecule to another. In this space, that is going to be really important to bring more drugs into the market.

Following on, Steven Watters, North America Sales Manager at HighRes Biosolutions, explained how automation is all about how we get more connected data into scientists hands. He emphasised the importance of the enablement of scientists to review their work, make predictions, and then drive forwards.

References:

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2023 drug discovery forecast: emerging trends and disruptors ... - Drug Target Review

Roundtable Discussion: Kishtagari Reviews Treatment and … – Targeted Oncology

KISHTAGARI: The challenge as treating clinicians these days in the clinic is that almost 34% of the patients present with severe thrombocytopenia of less than 50 109/L platelets at the time of initial diagnosis of myelofibrosis. Most patients, 66%, presented with thrombocytopenia of over 50 109/L.1,2 This is a significant challenge when treating patients, especially with ruxolitinib [Jakafi], the medication that has had FDA approval for the longest time. The medication itself can cause [decreased] blood counts as well. A lot of patients do have anemia at baseline, and that gets worse with the disease evolution as well. So both thrombocytopenia and anemia are huge challenges for us. I think this is important in the sense that we need to monitor these patients frequently while they are on treatment. I think one [issue] is how frequently to monitor them. We should monitor them frequently initially, but once theyve stabilized, we can probably monitor them every 6 weeks to 2 months. Its been my practice to do 6 weeks to 2 months once they have

stability in their platelet counts, based on their treatment. Of course, if any drop in the platelet counts or hemoglobin happens, I tend to monitor them more frequently and include dose reduction of the treatment they are on.

ZAMAN: Recently I had a couple of patients who had hemolytic anemia, so they didnt take the prednisone. I gave rituximab [Rituxan] to a patient and she did not respond. I stopped it after 4 cycles with no response. Suddenly, 3 or 4 months later, she was not requiring as many transfusions. How often do you see hemolytic anemia?

KISHTAGARI: In my practice, I have seen 1 patient with hemolytic anemia with myelofibrosis. Its not that common, if you look at the literature as well. I keep thinking about management for this patient. Fortunately, my patient responded very well to high-dose steroids. But, like you said, its a challenge. That is something [that reminds us] when we see a drop in hemoglobin, we should always think broadly, not [only] of the disease but of the adverse effects [AEs] of the medication. We need to think broadly and keep our differentials broad. Look for hemolysis as a cause as well. But its rare, and it is reported in less than 5% [of patients], based on the literature.

BHANDARI: In my opinion, [the goals are] improvement of the symptoms and improved quality of life. The platelet count of 43 109/L is less concerning. I think the symptoms are more important.

KISHTAGARI: I think thats a good [approach]. A lot of these patients come with such a huge symptom burden, and I think thats the most important thing to address while we are thinking about the long term for this patient.

MAHAJAN: This is a 68-year-old patient. [Although] his ECOG performance status is 2, will a stem cell transplant [SCT] be a possibility for him? He is relatively young.

KISHTAGARI: Absolutely. I think a lot of times I give these patients the benefit of the doubt. I always refer for SCT, just for an evaluation. It doesnt mean that they will go for SCT. I think they need to at least be evaluated by a transplant physician to see if they can be considered for SCT. The oldest I have sent for transplant [was a 79-year-old patient], and this was a patient who was very active with an ECOG performance status of 0 to 1. This patients ECOG performance status of 2 is likely from the severe symptom burden he has been experiencing secondary to myelofibrosis. Given that, it is always good to initiate treatment and send them for transplant evaluation because we all know that the ultimate treatment or cure, especially for high-risk myelofibrosis, is SCT.

ZAMAN: If they are symptomatic, we start them on ruxolitinib. We look for the risk assessment, and Johns Hopkins [Sidney Kimmel Comprehensive Cancer Center] is approximately 100 miles from here, so I call them for an evaluation to see what they think. I try to cover both things, unless they are frail and cannot travel, which also is sometimes an issue.

MENDOZA: I have a similar approach. I sit down with them, and tell them that they need pharmacologic intervention, and we look at the performance status. We say that if they have some comorbid conditions, and they are highly symptomatic andhigh-risk, typically by guidelines, they would be candidates for transplant. But if the performance status is 2 and we start treatment and that improves their symptoms, then thats when I say we are 50 miles away from [a transplant center in] Baltimore, Maryland. So we also do something different, and typically the response is quick. Now in this case, discussing the specific pharmacologic agent is a little bit tough because of the platelet count. I would be careful with the choice. I would probably phone the transplant [specialist], go over the case, and say this is what I want to do. I want to see if they improve on pacritinib [Vonjo] or some other type of agent, and if it is indicated, Ill start that, and 2 to 4 weeks later I will see them and they have improved. The patients can tell when the spleen gets smaller. That by itself improves their symptom burden, and if thats the case, then the next thing we do is send them to Baltimore [for transplant evaluation].

KISHTAGARI: Thats fantastic. I like that approach a lot.

KALRA: Most of us who are in the community dont have open trials for patients with myelofibrosis, but at least I am in Baltimore and have access to 2 large academic centers, and if this is a patient who would qualify for a trial, and its open at one of those centers, then [I would refer for clinical trials].

LANG: If a patient has high-risk myelofibrosis but does not have clinical symptoms and is a candidate for transplant, do they still benefit from bridging therapy with a JAK [Janus kinase] inhibitor?

KISHTAGARI: If they have splenomegaly, I would consider JAK inhibitor therapy prior to proceeding to allogeneic SCT because if you can control the spleen size as much as possible before going for transplant, [data from] multiple studies have shown that it has a good outcome post transplant.3,4 So at least for the spleen reduction, I recommend initiating a JAK inhibitor.

ISLAS-OHLMAYER: Would you continue the JAK inhibitor during SCT?

KISHTAGARI: That is something a lot of centers have been doing. We have also been doing it after SCT, not during SCT. After SCT we have been initiating JAK inhibitor therapy because the symptom burden sometimes comes back, and we continue them on ruxolitinib. [N]ot all of them, [however,] only a few patients. This is being done as a part of a clinical trial, not as a standard of care.

KISHTAGARI: Getting a donor is something we all face whenever we refer the patient for allogeneic SCT evaluation. I have a lot of patients in my clinic right now who do not have a donor, and thats a significant challenge. Access is also something we all face for transplant evaluation, and even the cost is something we dont talk about often, which we should. They need to be very close to the transplant center, at least for the 90 to 100 days when they are undergoing allogeneic SCT evaluation. Do you always refer for transplant if they have high-risk myelofibrosis?

MAITI: Yes, the high-risk patients. I am at a regional oncology center close to the Cleveland Clinic main campus [in Ohio], so if I see a patient with high-risk myelofibrosis, I would refer them to a [transplant physician] on the main campus and work on the bridging therapy.

KISHTAGARI: OK, good.

MISBAH: Usually [the transplant physician] will tell us the bridging therapy they want us to use.

KISHTAGARI: Do they have any preference for the bridging therapy that they recommend?

MISBAH: I havent referred anyone recently, so I wouldnt be able to speak to that. But usually they will guide us very well on what we should use or what their preference is.

KISHTAGARI: Do you have any experience? [For] how long do you use bridging therapy? I know that very few patients subsequently undergo transplant.

LANG: In the past couple of years, I referred 3 patients for transplant. I was thinking they continue the bridging therapy until you find a transplant donor.

KISHTAGARI: So until the transplant donor is identified, and then until they go to transplant, the bridging therapy is continued.

LANG: Right.

KALRA: I think its the patient population. Myelofibrosis is not a disease of young people. Its the comorbidities. Its obviously the availability of donors. Its a lot of those factors, and then, eventually, whether they can even tolerate a transplant.

KISHTAGARI: Good. I think those are the challenges we face as clinicians on getting these patients [to transplant] with their advanced age, as well as donor availability and their performance status. Other factors such as cost and access are at play. Lately we have been seeing debulking of the disease before going for transplant. I think thats less of a challenge compared with other diseases such as AML [acute myeloid leukemia] or MDS [myelodysplastic syndrome] where they prefer the [myeloablative conditioning] before going for SCT. I dont think we have that challenge here. We have other challenges with myelofibrosis.

BHANDARI: I think its promising. I have used it in 1 of my patients.

MAITI: I have not used pacritinib yet. I have only used ruxolitinib as first-line therapy. But with the data,5 I think especially in patients with a platelet count of less than 50 109/L, I would consider pacritinib.

KISHTAGARI: In patients with a platelet count greater than 50 109/L, also, one can consider pacritinib, especially in the second-line setting.

KNAPP: Patients had platelet counts of less than 100 109/L on the trial, but they only approved it for those with less than 50 109/L. Is there a reason for that?

KISHTAGARI: In the [PERSIST-2] clinical trial [NCT02055781], they looked at both groups, but patients with platelet counts below 50 109/L derived maximal benefit [From the Data5], and so the FDA only approved it for that.6

MENDOZA: If I have a patient who is on dose-adjusted ruxolitinib, hes borderline, he had initial counts greater than 50 109/L, but he developed a platelet count of less than 50 109/L, do you recommend switching to pacritinib at that point? Or would you rather hold the dose, wait, and then adjust ruxolitinib again?

KISHTAGARI: It all depends. If the patient is getting benefit from ruxolitinib and you only noticed significant thrombocytopenia, dose reduce first before switching to pacritinib. If with the dose reductions you do not see any improvement in blood counts, then definitely switch to pacritinib.

MAHAJAN: What about pacritinibs effect on anemia? Is it like ruxolitinib, or other than that do you have to wait for momelotinib [GS-0387] to be approved?

KISHTAGARI: What we have seen is pacritinib also inhibits a protein called ACVR1 more than momelotinib.7 We also see this in the clinic as well, where there is a significant improvement in hemoglobin. But you need to treat the patient longer, and there are some retrospective data where they are noticing an improvement in hemoglobin along with a stabilizing platelet count.8 So there might be a role for pacritinib in the future for patients with myelofibrosis and anemia.

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Roundtable Discussion: Kishtagari Reviews Treatment and ... - Targeted Oncology

Getting Creative To Combat Foodborne Norovirus – Technology Networks

Every year, norovirus causes hundreds of millions of cases of food poisoning and the deaths of at least 50,000 children yet there exists no real way to control it. The virus has proven exceptionally difficult to study in the lab, and scientists have struggled to develop effective vaccines and drugs.

A new study at Washington University School of Medicine in St. Louis describes a creative way to make a vaccine against norovirus by piggybacking on the highly effective vaccines for rotavirus, an unrelated virus that also causes diarrhea.

The researchers created an experimental rotavirus-norovirus combo vaccine by adding a key protein from norovirus to a harmless strain of rotavirus. Mice that received the experimental vaccine produced neutralizing antibodies against both rotavirus and norovirus. The study, available online in Proceedings of the National Academy of Sciences, outlines an innovative approach to preventing one of the most common and intractable viral infections.

Pretty much everyone has had norovirus at some point, said senior author Siyuan Ding, PhD, an assistant professor of molecular microbiology. You go out to eat, and the next thing you know youre vomiting and having diarrhea. You will recover, but its going to be a rough three days or so. For kids in the developing world who dont have access to clean water, though, it can be deadly. The rotavirus vaccines work really well, and there are already global distribution systems set up for them, so based on that, we saw an opportunity to finally make some headway against norovirus.

Before the first rotavirus vaccines were rolled out in 2006, half a million children around the world died every year of diarrhea caused by rotavirus infection. Now, the number is estimated to be about 200,000 still high but a huge improvement. Four rotavirus vaccines are in use around the world. All are live-virus vaccines, meaning they are based on weakened forms of rotavirus capable of triggering an immune response but not of making people sick.

Human norovirus, on the other hand, has stymied scientific investigation for decades. It doesnt infect mice or rats or any other ordinary lab animals, so the kinds of experiments that led to the development of rotavirus vaccines have been impossible to replicate with norovirus.

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Ding and colleagues including first author Takahiro Kawagishi, PhD, a staff scientist in Dings lab, and co-corresponding author Harry B. Greenberg, MD, a professor emeritus of medicine at Stanford University came up with the idea of using rotavirus to bypass the technical difficulties of working with norovirus. They worked with a laboratory strain of rotavirus as a stand-in for one of the approved rotavirus vaccines, which are proprietary.

The researchers inserted the gene for the protein that forms the outer surface of human norovirus into the genome of the rotavirus lab strain. Then, they administered the modified rotavirus to immunocompromised infant mice by mouth, the same way rotavirus vaccines are given to children. They took blood and fecal samples four, six and eight weeks later. Nine weeks after the initial immunization, the researchers gave the mice a booster by injection and took samples again a week later.

A strong antibody response was evident in the blood of nine of 11 mice tested, and in the intestines of all 11 mice. Even better, some of the antibodies from the blood and the intestines were able to neutralize both viruses in human mini-gut cultures in a dish. Such cultures, also known as organoids, are grown from human stem cells and replicate the surface of the human gut.

Traditionally, vaccine studies have focused on the antibody response in the blood, because we understand that part of the immune response the best, Ding said. But norovirus and rotavirus are gut viruses, so antibodies in the blood are less important than the ones in the intestines in terms of fighting off these viruses. The fact that we saw a strong antibody response in the intestines is a good sign.

The next step is to show that animals immunized with the experimental vaccine are less likely to get sick or die from norovirus. Ding has such experiments underway.

The power of this study is that it outlines a novel approach that could accelerate vaccine development for a variety of troublesome organisms that cause diarrhea, especially in resource-limited countries where many of these infections occur.

There are a lot of intestinal pathogens out there for which we dont have good treatments or vaccines, Ding said. In principle, we could put a gene from any organism that infects the intestinal tract into the rotavirus vaccine to create a bivalent vaccine. Wed have to find the right targets to produce a good immune response, of course, but the principle is simple.

As basic scientists, we rarely get the chance to actually move something forward into the clinic, Ding continued. We study what the virus does and how the host responds at a basic level. This is a rare opportunity for our work to affect human health directly and make peoples lives better.

Reference:Kawagishi T, Snchez-Tacuba L, Feng N, et al. Mucosal and systemic neutralizing antibodies to norovirus induced in infant mice orally inoculated with recombinant rotaviruses. PNAS. 2023;120(9):e2214421120. doi:10.1073/pnas.2214421120

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Getting Creative To Combat Foodborne Norovirus - Technology Networks

The bared external anal sphincter (BEAS), a new technique for high … – Nature.com

Study design and population

The study was a retrospective analysis of prospectively collected data from a cohort from the tertiary referral center (Shuguang Hospital). Consecutive adult patients diagnosed with HHAF undergoing BEAS technique between June 2020 and January 2021 were included. Ethical approval was obtained from the ethics committee of Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine (Approval No. 2020-823-30-01). Written informed consent was obtained from each participant. All methods were carried out in accordance with relevant guidelines and regulations.

Magnetic resonance imaging (MRI) was performed on every patient, which helped to determine the extent of the HHAF lesion and its relationship with surrounding tissues. The diagnosis of HHAF was made and confirmed by at least two senior imaging specialists.

The inclusion criteria were the following: (1) male or female patients aged 18 to 65years; and (2) patients diagnosed with high cryptoglandular fistula-in-ano (involving more than one-third of the sphincter complex as assessed on MRI and intraoperative examination under anesthesia). Both primary and recurrent horseshoe fistulas were included. Patients with Crohn's disease, cancer, tuberculosis, diabetes, autoimmune diseases or patients receiving long-term steroids or corticosteroid therapy were excluded.

Patient demographics, clinical information, and short-term clinical outcome data were collected through outpatient follow-up, a WeChat questionnaire and telephone follow-up. Forty-one patients were followed-up by WeChat questionnaire and seven patients were followed-up by phone. There is no difference between these methods. The main outcomes included the 6-month cure rate, Visual Analog Scale pain score (VAS-PS) and Cleveland Clinic Florida incontinence score (CCF-IS). The secondary outcomes included the Quality of Life in Patients with Anal Fistula Questionnaire score (QoLAF-QS), Bristol stool chart and postoperative complications. Postoperative pain was measured using an 11-point Visual Analog Scale pain score (VAS-PS)14. The severity of fecal incontinence symptoms was evaluated using the Cleveland Clinic Florida incontinence score (CCF-IS)15. The Quality of Life in Patients with Anal Fistula Questionnaire score (QoLAF-QS) was used to assess the quality of life of patients with anal fistula16. Stool consistency was assessed using the 7-point Bristol stool scale17. Disease recurrence, as was reported by Mei et al., was defined as persistence or recurrence of symptoms or the relapse of the perianal sepsis within or more than 6months following surgical intervention18,19.

SPSS Statistics 25.0 (IBM Inc., IL, USA) software was used for ststistical analysis. Continuous variables are presented as the meanstandard deviation (SD) or median with interquartile range (IQR) based on distribution. The independent t test was used to compare normally distributed continuous variables, and the MannWhitney U test was used to compare nonnormally distributed continuous variables. Categorical data are expressed as the number of cases and percentages. P<0.05 was considered to indicate a ststistically significant difference.

Preparation for surgery begins with a careful evaluation of preoperative MRI to assess the location of the internal opening and the extent of inflammation as well as the relationship between the fistula and the muscles. The imaging also informs about the anatomical structure of anal canal, aiding in operative planning (Fig.1).

The diagrams of preoperative MRI. (a) The cross section of the perianal structure showing the relationship between IAS, EAS and HHAF. (b) The coronal section of the pelvis showing layers of anal sphincter, especially the levator ani muscle, and HHAF. IAS=internal anal sphincter; EAS=external anal sphincter; HHAF=high horseshoe anal fistula.

The patient is given spinal anesthesia and then placed in prone jackknife position. After preparing and draping, the operating table is placed in a 10 to 15 head-side-down position. This allows the muscles and spaces exposed more clearly in posterior aspect of anal canal during the operation. The internal opening, the external opening and the fistula of HHAF is then identified again to begin dissection (Fig.2).

Anatomic Structure of HHAF. (a) View of the outside appearance. The dotted line represents the scope HHAF. (b) Sagittal section of the pelvis. (c) Schematic diagram of posture for surgical exposure. (d) Preoperative visual field. The green shaded part represents HHAF. HHAF=high horseshoe anal fistula.

The dissection is initiated with a curvilinear incision (IS approach) along the intersphincteric groove to identify the internal anal sphincter (IAS) and external anal sphincter (EAS). This incision is directly behind the anal canal, which is approximately 1/41/3 of a quadrant of the anus. Then, the dissection is performed along the plane of the intersphincteric groove to separate the IAS from EAS with an electrical scalpel. The internal opening should be concerned during the dissections. Through both the anal canal and intersphincteric plane, the internal opening can be identified easily. There is barely no blood supply in the intersphincteric plane, therefore it is a safe dissection plane. However, care should be taken to observe the muscle contraction of EAS during this dissection. Because dissection is close to the IAS and EAS, the surgeon should take care during the dissection to avoid inadvertent injury. To avoid complications of incontinence or bleeding, the surgeon should dissect the IAS and EAS strictly along the plane (Fig.3).

The operation diagram of IS approach and LES approach. (a) View of the outside appearance. (b) Sagittal section of the pelvis. The dissection of IS approach is along the intersphincteric plane to separate the IAS from EAS. (c) IS approach. (d) LES approach. The dissection of LES approach is along the outer edge of the EAS to bare the EAS. IS=Intersphincteric; IAS=internal anal sphincter; EAS=external anal sphincter; LES=Lateral-external-sphincteric.

The next step involves the dissection of the EAS, which is initiated with a curvilinear incision (LES approach) along the outer edge of the EAS on one side behind the anal canal. The dissection is performed along the outer edge of the EAS until above the level of the deep EAS so as to bare the EAS. The lateral part of the EAS in the corresponding quadrant is exposed with the traction of a self-retaining retractor (Lone Star, Cooper Surgical, Trumbull, CT). The highest risk for incontinence, which is the most common postoperative complication, may be due to the injury of EAS. The bareness of EAS can completely expose the infection focus of HHAF. In this process, the surgeon should also be mindful of avoiding the anterior displacement of anal canal caused by the injury of anococcygeal ligament (Fig.3).

Once the IAS and EAS are separated, medial to lateral dissection of the muscles are continued along the intersphincteric plane to both sides. Then, the IAS is separated from EAS by a combination of sharp and blunt dissection. Through the IS approach, the suprasphincter anal fistula can be detected above the level of the deep EAS easily. Cephalad dissection is continued above or beneath the levator ani muscle so that the DPIS and the inner part of the EAS could be completely exposed (Fig.4).

The operation diagram of exposure of DPIS and DPAS. (a) View of the outside appearance. (b) Sagittal section of the pelvis. (c) Exposure of DPIS. (d) Exposure of DPAS. Expose DPIS and DPAS to reach the fistula through IS approach and LES approach, respectively. DPIS=deep intersphincteric space; DPAS=deep postanal space.

Continuing the dissection cephalad with the assist of self-retaining retractor along the LES approach reveals the DPAS, which can then be handled at the top of the infection. Both two approaches communicate at the top of the EAS (or at the top point of the pus cavity of the HHAF). Typically, the visualization of these approaches reveals the pus cavity under direct vision. The aim of these dissections is to utilize both the IS approach and the LES approach as a landmark to ensure a complete preservation of the EAS (Fig.4).

After the DPIS, the DPAS, and the pus cavity are irrigated repeatedly with povidone and hydrogen peroxide, the bare EAS is pushed proximally to confirm that the internal opening on the musculomucosal flap could reach the inferior edge of the EAS without tension. After the musculomucosal flap and the EAS advancement are performed, they are sutured and fixed with 20 Polyglactin suture (Coated VICRYL, 20, ETHICON Inc, China) to close the intersphincteric incision in an interrupted manner. At last, the LES approach is kept open and indwelled with povidone gauze to facilitate postoperative drainage (Fig.5).

The operation diagram of musculomucosal flap and EAS advancement. (a) View of the outside appearance. (b) Sagittal section of the pelvis. (c) Musculomucosal Flap and EAS Advancement. (d) Visual field after suture. Perform advancement of the musculomucosal flap and the EAS to confirm the internal opening could reach the inferior edge of the EAS without tension. Then close the intersphincteric incision (IS approach) in an interrupted manner and keep LES approach. EAS=external anal sphincter; IS=Intersphincteric; LES=Lateral-external-sphincteric.

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The bared external anal sphincter (BEAS), a new technique for high ... - Nature.com