COVID-19 has been all-consuming. For nearly two years, the world has been focused on the race for vaccines, the pressures on providers, the best testing protocols, and simply staying safe.

COVID-19 also slowed some research efforts, but scientists still managed to seek solutions for many other pressing concerns Alzheimers disease, maternal mortality, and prostate cancer among them that have bedeviled patients for decades.

Below are eight medical advances that may not have grabbed your attention but could ultimately improve the lives of millions.

Assessing a stroke demands a rapid, life-or-death assessment: Is the culprit a clot, which requires a blood thinner, or bleeding in the brain, which requires surgery? Now, a portable MRI device can help make that assessment right at a patients bedside and in much less time than required by a trip to a standard machine.

The Swoop MRI which was created with input from Yale Medicine in New Haven, Connecticut received Food and Drug Administration (FDA) approval in August 2020 and is already at work in several U.S. hospitals.

The new portable machine offers many advantages over its massive cousin, says Yale neurologist Kevin Sheth, MD.

The very strong magnets in regular MRIs bring a lot of challenges, he explains. You need intensive power and cooling, precautions like a shielded room, and a lot of training. If you use a weaker magnet, all those problems go away.

The weaker magnet is effective, according to an August 2021 study, which asked clinicians to identify various cerebral pathologies using Swoop images. The goal is not to be as good as a high-magnet MRI, but to be good enough for clinical decisions, says Sheth, who co-authored the study but has no financial interest in Hyperfine, the Connecticut-based company that produces the machine.

Swoops size its smaller than some refrigerators eliminates the need to move frail patients down hospital hallways. Whats more, its cost around $100,000 compared to $1 million for the bigger machine puts it within reach of hospitals and regions with fewer resources. This could essentially democratize brain imaging, argues Sheth.

Prostate cancer strikes 1 out of 8 U.S. men, and it is expected to take more than 34,000 lives this year alone. When it metastasizes, the disease is almost always incurable, leaving physicians focused only on postponing death and improving patients lives.

A promising new approach has succeeded at both goals and did so among men with an advanced form of the disease whose condition had deteriorated despite receiving standard treatments.

In fact, it more than doubled how long patients lived without their cancer worsening, according to a paper published in September. The study, which followed 831 men in 10 countries for a median of 20 months, compared patients who continued to receive standard care with ones who got the new treatment.

The treatments name is complex: lutetium-177-PSMA-617. But its approach is straightforward: Drive radiation directly into a cancer cell while sparing healthy tissue around it.

The method uses a compound called PSMA-617 to hone in on a protein found almost exclusively in prostate cancer cells, explains Oliver Sartor, MD, study co-lead investigator and medical director of Tulane Cancer Center in New Orleans. Then, a radioactive particle carried by the compound blasts the cancer cells, wherever they are.

Its like a little smart bomb, says Sartor.

In September, the FDA granted the treatment priority review status, according to drug manufacturer Novartis, which funded the study. An answer is expected in the first half of 2022.

Sartor feels hopeful. Ive been working in prostate cancer for more than 30 years, and this is the largest advance Ive ever been associated with.

For more than 5,000 years, sickle cell disease (SCD) has caused untold suffering in people of African descent. In patients with the genetic illness, red blood cells are not round but crescent-shaped like a sickle and can clog blood vessels, depriving the body of oxygen and causing tremendous pain. For a long time, the only cure has been a bone marrow transplant, but new gene-editing techniques now may offer a safe and effective alternative.

In research conducted at Boston Childrens Hospital, scientists used a virus to switch off the gene that triggers cells sickling, according to a January 2021 study. The patients subsequently produced healthy red blood cells and nearly all were able to discontinue the blood transfusions SCD often requires.

One participant used to have transfusions every month but has not needed any in three years, says David Williams, MD, chief of the Division of Hematology/Oncology at Boston Childrens and head of the research team. This has completely changed his life.

The study followed six patients for a median of 18 months and found that the treatment completely halted the diseases more severe symptoms.

Im so happy for my sickle-cell patients. This is a terrible disease, notes Williams.

Next up for Williams is a trial with 25 patients. Meanwhile, SCD researchers elsewhere are studying other gene-editing techniques. All these approaches look promising, and we need a lot more research to determine if one or another is better, Williams says.

This is a very exciting time. In the past, we havent had any particularly good treatments, and now we have several possibilities," he adds.

When a womans uterus fails to contract after childbirth, tremendous blood loss can ensue, possibly leading to an emergency hysterectomy or even death. In fact, postpartum hemorrhage affects 3% to 10% of all childbirths in the United States and causes more than one-third of childbirth-related maternal deaths worldwide.

Treatment options include medications that dont always work and inserting a balloon to put pressure on the uterus much like exerting pressure on a cut that comes with risks and must remain in place for a day.

But providers now have another option.

A new vacuum device aids natural post-birth contractions, putting pressure on leaking blood vessels. The FDA approved the device the Jada vacuum uterine tamponade in September 2020 following a 12-site research study.

The vacuum approach is very logical since its like what the body is supposed to do, says Dena Goffman, MD, the primary investigator at Columbia University Irving Medical Center in Manhattan. Also, the vacuum is used for less time than the balloon roughly two or three hours. For moms, thats a big deal because it makes it easier to breastfeed, get out of bed, and bond with their child, she adds.

The vacuum controlled bleeding in a median of three minutes and successfully treated 94% of participants, according to the study, which was funded by the devices manufacturer, Alydia Health. In comparison, other research puts the balloons effectiveness at 87%.

When a patient has a postpartum hemorrhage and youre the doctor at the bedside, its scary because you know how quickly things can deteriorate, says Goffman. Using this device, when you see the bleeding slowing quickly and you can feel the uterus contracting, its just incredible.

Tearing an anterior cruciate ligament (ACL) the flexible band inside the knee that helps stabilize it can upend a sports career and sideline weekend athletes. Between 100,000 and 200,000 ACL tears occur each year in the United States.

The most effective repair option has been removing the ruptured ACL, harvesting a graft from the shin or elsewhere, sewing that tissue into the knee, and hoping both surgical sites heal well.

In December 2020, the FDA approved a simpler, more natural method: the Bridge-Enhanced ACL Restoration (BEAR).

We basically stimulate the ACL to heal itself, says Martha Murray, MD, orthopedic surgeon-in-chief at Boston Childrens Hospital and BEARs creator.

The approach involves placing a protein-based sponge, prepared with some of the patients own blood, between the torn ACL ends. Murray explains that the blood promotes the connection of the two ACL pieces to the sponge and, ultimately, to each other.

So far, the approach has been tested on more than 100 patients. In a May 2020 study, patients and physicians reported that BEAR performed as well as the standard repair and without the graft surgery that can cause ongoing pain or weakness at the donor site. Miach Orthopaedics, which has the worldwide exclusive license for the BEAR implant, has already begun making it available through orthopedic surgeons in the United States.

For Murray, the experience has highlighted the value of serving as a physician-researcher. When youre faced with a patient with a problem and the current solution is imperfect, its great to be able to say, Were working on a better solution. Its incredibly gratifying.

For the first time since 2014, a new obesity medication has hit the market, offering hope to the 78 million Americans who face the many risks of excess weight: cancer, heart disease, diabetes, and complications from COVID-19, among others.

And the new medication semaglutide, also known as Wegovy is significantly more powerful than its predecessors, according to research that helped it garner approval from the FDA in June.

Weve seen 1 to 2 times the amount of weight loss compared to other medications, says Robert Kushner, MD, a researcher at Northwestern University Feinberg School of Medicine who has led semaglutide studies. That's a leapfrog advance.

In fact, semaglutide recipients lost nearly 15% of their body weight on average compared with 2.4% among controls, according to one study of nearly 2,000 patients.

Semaglutide an injectable medication is not entirely new. A synthetic version of a natural hormone that quells appetite, its already used to treat Type 2 diabetes. But the obesity trials, paid for by pharmaceutical company Novo Nordisk, used a much higher dose.

High doses havent been studied long enough to identify long-term side effects, notes Kushner, a paid consultant to Novo Nordisk. But the recent research reported mild-to-moderate gastrointestinal issues that lessened over time.

Now Kushner hopes semaglutide will help spark interest in obesity medications.

Over 40% of U.S. adults have obesity, and the number who are getting a pharmacologic treatment is under 3%, he says. Part of the challenge is educating primary care providers that providing evidence-based obesity care includes consideration of medication."

Randall Bateman, MD, a Washington University School of Medicine in St. Louis (WUSTL) neurologist, is thrilled to have contributed to the first blood test for Alzheimer's disease a devastating condition that affects as many as 5.8 million Americans.

Back in 2017, though, as Bateman geared up to share the discovery that would enable the test, he worried about his peers reaction. After all, scientists were convinced that the blood marker he studied couldnt predict the disease.

But the WUSTL method was much more sensitive and direct than prior approaches. The resultant test called PrecivityAD effectively detects the amyloid plaques that are a hallmark of Alzheimers disease and has proven as accurate as the previously used tools of a spinal tap or positron emission tomography (PET) scan, which are far more costly and complex.

The test, developed by a company called C2N Diagnostics that Bateman co-founded, has been available to physicians since October 2020, when it received approval through a federal lab certification program. It now awaits additional approval from the FDA.

Weve been hoping for a test to diagnose Alzheimers for more than 20 years, says Bateman, WUSTLs Charles F. and Joanne Knight distinguished professor of neurology. Currently, up to half of people with Alzheimers are misdiagnosed.

The road to success in science is paved with hard work and great uncertainty, he adds. Its a real gamble. Youre investing your life in this work, and you hope it will have a positive impact. And then its like, Wow, it worked!

Anger, fear, recurring nightmares, and intense flashbacks are among the many symptoms that can batter patients with post-traumatic stress disorder (PTSD). The condition, which affects about 15 million U.S. adults in a given year, can be extremely difficult to treat.

A potentially groundbreaking PTSD treatment now lies in a seemingly unlikely source: MDMA, better known as the illegal drugs ecstasy and molly that fueled all-night dance raves and caused potentially fatal side effects.

In June, a study in Nature Medicine reported that patients with severe PTSD combat veterans, first responders, and victims of sexual assault and mass shootings, among others experienced significant relief from MDMA.

In fact, two months after treatment, 67% of subjects who received MDMA together with talk therapy no longer qualified for a diagnosis of PTSD. I saw this amazing transformation in patients, says Jennifer Mitchell, PhD, the studys lead author and a University of California, San Francisco, School of Medicine neurology professor.

The treatment involved three eight-hour sessions a month apart during which patients ingested MDMA and processed painful memories and emotions in talk therapy.

MDMA releases a powerful supply of serotonin and stimulates hormones associated with emotional bonding, Mitchell explains. The idea is that it helps patients be open in a way that enables them to connect well with therapists and work through their problems more quickly.

Before the drug can receive FDA approval for PTSD, researchers need to complete one more clinical trial. Even if it succeeds, Mitchell is aware that MDMA still bears stigma from its party drug image.

I hope people are going to be open-minded and look at the data, which included no abuse potential or other serious side effects from MDMA as used in the study. We are talking about use in a controlled, therapeutic situation, she says. Using drugs recreationally is entirely different. Otherwise, people would come back from [the art and community event] Burning Man cured of their psychological issues.

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8 medical advances you may have missed during COVID-19 - AAMC

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StemCells21s laboratory is a full-scale culture & analysis laboratory specialising in the production & treatment of Mesenchymal Stem Cells (StemCells21), and Natural Killer Cells (ImmuneCells21). It has also launched a new generation of regenerative medicine called Pluripotent Stem Cells (iPSC21), which hold great potential for impacting chronic diseases in the quest for anti-ageing.

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Before StemCells21 was created, Managing Director Paul Collier and co-founder Sergei Dmitrievs experienced the power of stem cells either first hand or through the treatment of someone close to them. They knew that stem cells could deliver positive health results, and also knew stem cell treatmentsand the clinics that administered themhad room for improvement.

After deep laboratory investigation, they came to see that most clinics utilised relatively low-quality stem cells and incomplete treatments. While these clinics could deliver a certain level of positive results, they were only scratching the surface of the promise that stem cell treatments could deliver.

Furthermore, the clinics themselves frequently provided a less-than-ideal patient experience. Clinics were generally hectic, unprofessional, and unwelcoming. Patients were often administered a single treatment and sent on their way, unsure if they had experienced an efficacious treatment or if they had travelled and paid for nothing.

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Outpatient services for anti-ageing, immunotherapy and regenerative medicine are available at the centre. The anti-ageing clinic has a cutting-edge approach to skin rejuvenation, dermatology, detoxification, and wellbeing. A youthful appearance, more energy, improved mental capacity and mobility, reduced aches and pains, and a stronger immune system are among the benefits.

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The high level of traditional medicine and the unique protocols designed by the IH+ teams give patients real therapeutic benefits and longevity.

According to Paul Collier, a client typically receives two sessions of stem cell injections during a treatment intravenous for systemic and local to the target and is required to stay in Bangkok for two days following their procedure to monitor any complications that may arise. Then theyre given a two-month take-home kit that comprises self-administered injections (similar to insulin) that target specific growth factors in organs or tissues that need to be repaired. These can also be taken orally, but they are less effective.

He goes on to say that stem cells are the foundation of the human body. They split over and over to produce humans from an embryo at the start of our lives. They restore cells in your blood, bone, skin, and organs throughout your life to keep you alive and functioning. Stem cells have two distinct properties that distinguish them from other types of cells in our bodies.

First, they can self-renew (mitosis), which is a stage of the cell cycle in which replicated chromosomes are divided into two new nuclei. As a result, identical duplicated cells are produced.

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SC21- 21st century cellular medicines specialists - The Thaiger

UNC-Chapel Hill and UC San Francisco scientists have published work in Nature, laying the groundwork for better anti-itching medications with fewer side effects. The work was led by UNC School of Medicine scientists Bryan L. Roth, MD, PhD, Jonathan Fay, PhD, and Can Cao, PhD.

CHAPEL HILL, NC Ever wonder whats going on when you get itchy skin, whether from a rash or medication or some other bodily reaction? And why do some strong anti-itching medications make us nauseous, dry-mouthed zombies? Scientists at the UNC School of Medicine and the University of California at San Francisco conducted research showing in precise detail how chemicals bind to mast cells to cause itch, and the scientists figured out the detailed structure of receptor proteins on the surface of these cells when a compound is bound to those proteins.

This work, published in Nature, was led by the labs of Bryan L. Roth, MD, PhD and Jonathan Fay, PhD at UNC-Chapel Hill, and Brian Shoichet, PhD, at UC San Francisco, co-senior authors who have collaborated on previous studies of important cell receptors protein complexes that chemicals (including drugs) bind to cause or stop a reaction inside cells.

Our work provides a template for the design of new anti-itch medications, said Roth, the Michael Hooker Distinguished Professor of Pharmacology. Also, our research team did a truly remarkable job showing precisely how chemically distinct compounds induce itching through one of two distinct receptors known to be involved in itching.

First author Can Cao, PhD, a postdoctoral research in the Roth lab, and co-senior author Jonathan Fry, PhD, now an assistant professor in the UNC Department of Biochemistry and Biophysics, led the experiments during the COVID pandemic.

On the surface of cells sit receptor proteins you can think of as complex locks. When a chemical key enters the lock, not only does the cell open, but the chemical causes a chain reaction of signals inside cells. Many chemicals do this, from naturally occurring dopamine in the brain to caffeine and cocaine.

When it comes to itch, Roths lab identified two receptors called MRGPRX2 on the surface of mast cells and MRGPRX4 on itch-sensing neurons that live in connective tissue and play roles in allergies, immune tolerance, wound healing and other factors in health and disease.

Several drugs unintentionally flood these receptors to trigger the release of histamines, causing the side effect of itching. Drugs such as

nateglinide for diabetes, as well as morphine, codeine, and the cough suppressant dextromethorphan are known to cause this reaction. Antihistamines are designed to tamp down the itch response, but they and other anti-itching medications do so clumsily, tripping other cell signaling pathways to cause side effects such as drowsiness, blurred vision, dry mouth, nausea, etc.

The researchers used the experimental technique electron microscopy to create high-resolution maps of these complex receptor proteins when bound to a compound that causes the release of histamines to cause itchiness. They also clarified how drugs bind to MRGPRX4 to cause itch related to various drugs and liver diseases. The researchers used the CryoEM Core Facility at UNC-Chapel Hill to determine the receptor structures.

Knowing precisely how all this plays out at the molecular level will help us and others create better ways to control the role of these two receptors in itchiness and other conditions, Roth said.

MRGPRX2 and MRGPRX4 have also been implicated in inflammation arising from the nervous system, eczema, ulcerative colitis, and pain.

The relatively potent agonists and antagonists described in our Nature paper provide chemical probes we can use to explore the biology of these receptors, Roth said, And the structures we revealed so far should accelerate the search for specific medications targeting MRGPRs.

The National Institutes of Health funded this research.

Media contact: Mark Derewicz, 919-923-0959

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Researchers Reveal Structure of Itch Receptors on Cells | Newsroom - UNC Health and UNC School of Medicine

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Mercks anti-PD-1 therapy, for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. The approval is based on data from the pivotal Phase 3 KEYNOTE-564 trial, in which KEYTRUDA demonstrated a statistically significant improvement in disease-free survival (DFS), reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) compared to placebo. Median DFS has not been reached for either group.

Despite decades of research, limited adjuvant treatment options have been available for earlier-stage renal cell carcinoma patients who are often at risk for recurrence. In KEYNOTE-564, pembrolizumab reduced the risk of disease recurrence or death by 32%, providing a promising new treatment option for certain patients at intermediate-high or high risk of recurrence, said Dr. Toni K. Choueiri, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and professor of medicine, Harvard Medical School. With this FDA approval, pembrolizumab may address a critical unmet treatment need and has the potential to become a new standard of care in the adjuvant setting for appropriately selected patients.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

KEYTRUDA is foundational for the treatment of patients with certain advanced cancers, and this approval marks the fourth indication for KEYTRUDA in earlier stages of cancer, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. KEYTRUDA is now the first immunotherapy approved for the adjuvant treatment of certain patients with renal cell carcinoma. This milestone is a testament to our commitment to help more people living with cancer.

In RCC, Merck has a broad clinical development program exploring KEYTRUDA, as monotherapy or in combination, as well as other investigational products across multiple settings and stages of RCC, including adjuvant and advanced or metastatic disease.

Data Supporting the Approval

KEYTRUDA demonstrated a statistically significant improvement in DFS in patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions compared with placebo (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010). The trial will continue to assess overall survival (OS) as a secondary outcome measure.

In KEYNOTE-564, the median duration of exposure to KEYTRUDA was 11.1 months (range, 1 day to 14.3 months). Serious adverse reactions occurred in 20% of these patients receiving KEYTRUDA. Serious adverse reactions (1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2% of those treated with KEYTRUDA, including one case of pneumonia. Adverse reactions leading to discontinuation occurred in 21% of patients receiving KEYTRUDA; the most common (1%) were increased alanine aminotransferase (1.6%), colitis and adrenal insufficiency (1% each). The most common adverse reactions (all grades 20%) in the KEYTRUDA arm were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%) and hypothyroidism (21%).

About KEYNOTE-564

KEYNOTE-564 (ClinicalTrials.gov, NCT03142334) is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating KEYTRUDA as adjuvant therapy for RCC in 994 patients with intermediate-high or high risk of recurrence of RCC or M1 no evidence of disease (NED). Patients must have undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion[s] in M1 NED participants) with negative surgical margins for at least four weeks prior to the time of screening. Patients were excluded from the trial if they had received prior systemic therapy for advanced RCC. Patients with active autoimmune disease or a medical condition that required immunosuppression were also ineligible. The major efficacy outcome measure was investigator-assessed DFS, defined as time to recurrence, metastasis or death. An additional outcome measure was OS. Patients were randomized (1:1) to receive KEYTRUDA 200 mg administered intravenously every three weeks or placebo for up to one year until disease recurrence or unacceptable toxicity.

About Renal Cell Carcinoma (RCC)

Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCCs. Renal cell carcinoma is about twice as common in men than in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Worldwide, it is estimated there were more than 431,000 new cases of kidney cancer diagnosed and more than 179,000 deaths from the disease in 2020. In the U.S., it is estimated there will be more than 76,000 new cases of kidney cancer diagnosed and almost 14,000 deaths from the disease in 2021.

About Mercks Early-Stage Cancer Clinical Program

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS 1)] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

Non-muscle Invasive Bladder Cancer

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

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FDA Approves Merck's KEYTRUDA (pembrolizumab) as Adjuvant Therapy for Certain Patients With Renal Cell Carcinoma (RCC) Following Surgery - Business...

The COVID-19 pandemic is what historians refer to as an "inflection point," ora singleevent that has a dramatic and sweeping effect on the human story. In the case of this particular event, itchanged the way we work, raised awareness about public health policy, contributed to the toppling of a president and, in the field of medicine, resulted in a leap forward for vaccine technology. Indeed,one of the great unsung achievements amid the pandemicwas how scientists from around the world worked together to create multipleeffective vaccines in less than a year.

Yet what may provemost historicisthe biotechnologythat emerged from the pandemic. Specifically,the vision of an mRNA vaccine went from dream to reality. And the successful creation of a viable mRNA vaccine couldhave repercussions for the way diseases are treated for centuries.

That technology, whose development was quickened by the pandemic, is already being studied to treatother diseases.Earlier this month, scientists at Yale Universitycreated a prototype mRNA vaccinethat protected guinea pigs from tick-borne diseases by training their immune systems to recognize and fight proteins found in tick saliva. They hope that, with some further development, this could be used to help humans avoid developing Lyme disease if a tick bites them.

Yet this is merely one example of mRNA vaccines'potential, revealing howthey have far more utility than merely fighting COVID-19. Indeed, mRNA vaccines are something of a holy grail of medical innovation and researchers believe thatmRNA vaccines and their underlying biotechnology could be used tofight diseases like HIV, cancer, and influenza.

The promise of mRNA vaccines

As their name suggests, mRNA vaccines depend on the nucleic acid known asRNA.RNA isa molecule similar to DNA, but it is single-stranded (DNA is double-stranded)and plays a large number of roles in keeping your cells alive and healthy. But don't think they are unique to humans: They are found in all living things. There are alsocertain types ofviruses like SARS-CoV-2, which causes COVID-19 that could be characterized as little more than RNA strands surrounded by protein shells. Like all viruses, theytake over cells and force them to churn out other copies of themselves, the worst kind of mooch you can imagine.

Yet RNA and mRNA are not precisely the same thing.mRNA refers to "messenger RNA," a specific type of RNA that (as indicated by its name) transmits information from genetic codes in the nucleus to the cytoplasm where proteins are manufactured.

This hints at how mRNA vaccines work, which is essentially by giving your cells a blueprint of a part of a virus, and then having them manufacture what they need on their own. Previously,vaccines contained either a dead or weakened version of a pathogen, which the immune system would then learn to recognize. But mRNA vaccines don't actually contain any of a live or dead virus; instead, they contain a set of instructions (in mRNA) that infects some of the host's cells and makes them spit out a piece of protein associated with a pathogen. One's cells never manufacture the actual virus; only a piece of its "shell," say. Those pieces are then detected by the immune system and identified and destroyed. It would be a bit like learning the presence of a criminal by identifying the look of their clothing, rather than the criminal themselves.

In the case of the mRNA vaccines manufactured by Pfizer and Moderna, the mRNA contains instructions for one's cells on how to create the spike protein. The spike proteins are the little points that emerge out of the coronavirus, like spines jutting from a sea urchin,and they are what the SARS-CoV-2 virus uses to enter your cells and get you sick with COVID-19.The mRNA vaccineshave been extraordinarily successful in protecting the vaccinated; even though they have not entirely thwartedbreakthrough cases, they significantly reduce the likelihood of getting sick, and the people who do develop infectionswith evasivemutant variants rarely become seriously ill. Most notably, mRNA vaccines were the first ones to be released on the market, with Pfizer/BioNTech and Moderna winning the vaccine race exactly one year ago this month.

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The next mRNA vaccines

In terms of their world-changing potential,mRNA vaccines have two key characteristics: They are quick to make, as demonstrated by the speed with which Pfizer/BioNTech and Moderna came out with their products, and by their very nature they are versatile.

As the Association of American Medical Colleges (AAMC) wrote in March, mRNA vaccine technology has the potential to treat diseases like malaria and cystic fibrosis, tuberculosis and hepatitis B. All scientists will have to do is modify RNA strands as needed to account for the different antigens (foreign substancesrecognized by the immune system as threats) produced by each pathogen.Instead of making do with the materials immediately available to them, mRNA vaccines make it possible for scientists to create more specialized weapons based on detailed knowledge of their enemies'specific characteristics.

Take the influenza epidemic. Oneso-called "holy grail"of immunology is a universal influenza vaccine. Right now there are four influenza viruses in circulation, all of which evolve so quickly that vaccines which were effective in one year may be obsolete by the next. This puts manufacturers in a crunch, as it takes at least six months to create the conventional vaccinationswith attenuated viruses grown inside chicken eggs. The final product, though almost always safe, has a very hit-and-miss rate ofeffectiveness. An mRNA vaccine, by contrast, could in theory be designed to effectively fight all four strains and be quickly modified as necessary when they evolve. In addition, while conventional vaccine platforms have to hit a precise target in order to destroy a givenintruder,an mRNA vaccine couldtargetmultiple parts of an influenza virus at once, overwhelming it with a full-body assault that can't be easily shaken off.

In fact, we already know that the early stages of mRNA flu vaccines were effective because scientists used that research to help develop their COVID-19 vaccines. This speaks to how malleable the platform is: While conventional vaccine platforms require patients to hope that the pathogen injected into their body is similar enough to a possible flu infection to be effective, mRNA vaccines could be precisely designed to meet the specific characteristics of each new strain as it emerges.

There will be challenges to pulling this off, of course. Anna Blakney, an RNA bioengineer at the University of British Columbia, told the journal Nature that there is no guarantee mRNA will be an effective vehicle for transportinghaemagglutinin glycoproteins, the protein that flu vaccines use to fight the different bugs. As Blakney put it,"Did we just get really incredibly lucky with COVID vaccines because of the antigen design and the immunodominancy of that protein? Or have we stumbled on something that's functional for other viral glycoproteins as well?"

In addition to aiding in the war against influenza, mRNA vaccines could also be a game-changer in the fight against cancer. In the pre-mRNA vaccine world, the mere notion of a "cancer vaccine" would have seemed ludicrous; vaccines work by protecting your body against a foreign invader, and cancers (as far as we know) are caused by your own body producing mutated cells. Yet just as an mRNA vaccine can help your immune system recognize and destroy proteins associated with dangerous pathogens, they could in theory be developed to identify and eliminate proteins associated with cancer cells and, of course, the cancer cells themselves.

"A successful therapeutic cancer vaccine should induce strong T cell responses, particularly with CD8+ T cells, which have a known capacity to kill malignant cells," Dr. Norbert Pardi, whose research led to the develop of the Pfizer and Moderna vaccines, explained to the University of Pennsylvania. "Therapeutic cancer vaccines would be given to cancer patients with the hope that those vaccine-induced cytotoxic T cells would clear tumor cells."

HIV mRNA vaccines are theorized to be possible, though there are massive hurdles to be overcome. The challenge so far has been that none of the vaccine candidates developed up to this point have produced broadly neutralizing antibodies, which are vital to blocking HIV in target cells. Scientists hope that an mRNA vaccine would create an immunogen (an antigen that induces an immune response) that resembles the HIV virus and can help the body develop those broadly neutralizing antibodies against it. Unfortunately, researchers are still very early in working through this, and it seems like a HIV vaccine using this technology is not in the near future.

"We certainly think that an HIV vaccine will be far and away the most complicated vaccine that we've ever had to put into the population," Derek Cain of Duke University's Human Vaccine Institute told The Guardian. "We don't expect it to work 100% or 90% like the Covid vaccines, but even if we can get to 50-60% that would be a success; 70% would be amazing."

What comes next

The future for mRNA technology is not one of unbounded promise. As the AAMC noted, each virus poses its own individual puzzle, which makes it unlikely that other ailments can be treated with the rapid success that occurred when fighting COVID-19. Similarly, although the COVID-19 vaccines have so far not caused widespread serious side effects, this may not be true for other mRNA vaccines; more research will definitely be needed. In addition, the COVID-19 pandemic was such an overwhelmingand serious crisis that the international community collaborated in fruitful ways that may not repeat themselves if a future outbreakseemsless urgent.

There are also logistical factors to take into consideration. The supply chain breakdowns prompted by the pandemic are poised to get worse due to climate change, and experts are already concerned that mRNA vaccines will get destroyed as they are transported because they must be kept in very clean and ultra-cold conditions. It is hard to imagine that the impendingsupply chain deteriorations won't exacerbate that problem, as will the ongoing disease of misinformation. Since anti-vaccine advocates can alter their baseless beliefs as easily as viruses change their genetic composition, some of this misinformation specifically targets mRNA platforms. One particularly prevalent myth right now is that mRNA vaccines change your DNA, even though (as the above explanation makes clear) this betrays a deep ignorance about how vaccines, viruses, cellular biology and the immune system actually work.

Finally, as with all biotechnology, governments and businesses will have to adequately invest.

"Despite the promise of mRNA vaccines, we caution that they are far from a silver bullet for future pandemics," Michael J. Hoganand Norbert Pardiwrite in anAnnual Review of Medicine article."Comprehensive pandemic preparedness requires significant new investments in viral surveillance, proactive clinical testing of vaccines for pandemic-potential viruses, new diagnostic technologies, broad-spectrum antiviral treatments, and stockpiling of materials."

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mRNA vaccines changed the course of the pandemic. Now, they could cure all kinds of other diseases - Salon

Titilope Fasipe, MD, PhD, Assistant Professor of Pediatric Hematology-Oncology, Baylor College of Medicine, served as the opening plenary speaker at the National Organization for Rare Disease (NORD) summit.

In her presentation, Fasipe shed some light on the history of sickle cell disease; she also shared about her personal experience being a doctor and a patient of the rare disease.

Sickle cell disease is a rare disease in the US, but, it's not a rare disease worldwide, Fasipe explained. Millions of people are affected by it around the world compared to under 200,000 people in the US.

"You end up seeing 2 different ways of experiencing the disease," Fasipe said. "I had the experience of having both, because I was born in Nigeria, and then I came to the United States and I've been raised in both places."

During her presentation, Fasipe shared her journey, what led her to medical school, and how she found her advocacy voice.

It was important to her to leave the audience with an understanding of sickle cell disease that included the social determinants of health.

For sickle cell in the US, that includes long-standing historical neglect, systemic racism injustices, poor access to healthcare for many of individuals, as well as decreased community awareness that's seen with all rare diseases, Fasipe explained.

"The good news is, coming together does make things count," she said. "And that was the theme of the session, and so I felt like it was appropriate to show how I see a light at the end of the tunnel even though there's challenges, and part of that is working together with others."

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Titilope Fasipe, MD, PhD, Shares Her Presentation from the NORD Summit - MD Magazine

The new technique, which was developed at the Washington University School of Medicine in St Louis, was shown to convert human stem cells into cells producing insulin. The natural hormone is produced in the pancreas and allows the body to use glucose (sugar) from food for energy. People who suffer from diabetes struggle to produce enough insulin, which leads to a build-up of sugar in the bloodstream.

The St Louis researchers, however, believe their new technique can be used to effectively control blood sugar levels using converted stem cells.

The technique has so far been successfully tested on mice injected with the converted cells.

According to a report that is due to be published on February 24 in the online edition of the journal Nature Biotechnology, the mice were "functionally cured" for nine months.

Dr Jeffrey R. Millman, the principal investigator and assistant professor of medicine and of biomedical engineering, said: "These mice had very severe diabetes with blood sugar readings of more than 500 milligrams per deciliter of blood levels that could be fatal for a person and when we gave the mice the insulin-secreting cells, within two weeks their blood glucose levels had returned to normal and stayed that way for many months."

The same team of researchers has previously discovered how to convert human stem cells into so-called pancreatic beta cells to make insulin.

READ MORE:Maya breakthrough as scan of ancient settlement re-writes history

When these cells are injected into the bloodstream, they secret the much-needed hormone.

However, the technique was found to have its limitations and was not proven to effectively control the disease in mice.

Their new research has now proven to be much more efficient and effective.

Embryonic stem cells are a type of cell that can be instructed to develop into all sorts of specialised cells.

These can range from simple tissue and muscle cells, to even brain cells.

Scientists worldwide believe stem cell research could unlock many new therapies for ailments such as Alzheimer's disease and HIV.

Dr Millman said: "A common problem when youre trying to transform a human stem cell into an insulin-producing beta cell or a neuron or a heart cell is that you also produce other cells that you dont want."

"In the case of beta cells, we might get other types of pancreas cells or liver cells."

Pancreas and liver cells do not cause any harm when injected into mice but they do not fight the disease either.

Dr Millman added: "The more off-target cells you get, the less therapeutically relevant cells you have.

"You need about a billion beta cells to cure a person of diabetes.

"But if a quarter of the cells you make are actually liver cells or other pancreas cells, instead of needing a billion cells, youll need 1.25 billion cells.

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"It makes curing the disease 25 percent more difficult."

With their new technique, the researchers found fewer off-target cells were produced and the beta cells that were created had improved.

The technique specifically targets the cell's so-called internal scaffolding or cytoskeleton.

The cytoskeleton is what gives cells their shape and allows them to interact with their environment.

Dr Millman said: "Its a completely different approach, fundamentally different in the way we go about it.

"Previously, we would identify various proteins and factors and sprinkle them on the cells to see what would happen.

"As we have better understood the signals, weve been able to make that process less random."

Although the study's results are promising, the expert added there is a long way to go before the technique can be developed into a treatment for humans.

The converted cells will need to be tested over longer periods of time and in bigger animals.

According to Diabetes UK, some 5.5 million people are estimated to have diabetes in the UK by 2030.

Right now, more than 4.9 million people are affected by the disease and 13.6 million people are at increased risk of type 2 diabetes.

About 90 percent of people with the disease have type 2 diabetes, and only about eight percent have type 1 diabetes.

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Diabetes breakthrough: Revolutionary stem cell technique treated 'severe' disease in study - Daily Express

SAN DIEGO--(BUSINESS WIRE)--Third paragraph, sixth sentence of release should read: CNSide detected CSF tumor cells in all eleven measurements taken, compared to six of eleven using cytology. (instead of CNSide detected CSF tumor cells in all nine measurements taken, compared to five of nine using cytology.)

The updated release reads:

BIOCEPTS CNSIDE CEREBROSPINAL FLUID ASSAY AIDS IN MONITORING TREATMENT RESPONSE AND DETECTS ACTIONABLE BIOMARKERS IN PATIENTS WITH METASTATIC BREAST CANCER

Case series poster to be presented at the Society for Neuro-Oncology Annual Meeting

Biocept, Inc. (Nasdaq: BIOC), a leading provider of molecular diagnostic assays, products and services, today announced the presentation of a multi-institutional case series showing that its CNSide cerebrospinal fluid assay helps physicians monitor treatment response and detects actionable mutations in patients with metastatic breast cancer and leptomeningeal disease (LMD). The poster will be presented virtually at the Society for Neuro-Oncology Annual Meeting in Boston, Nov. 19, 2021, from 7:30-9:30 p.m. ET, and Biocept will be exhibiting at booth #303.

Breast cancer is one of the most common cancers associated with LMD, a devastating complication in which cancer spreads to the membrane surrounding the brain and spinal cord. The current standard of care for diagnosing LMD is through clinical evaluation, imaging and cytology, which have limited sensitivity. Median survival after a diagnosis of LMD is just two to three months.

The case series included four breast cancer patients, ages 32 to 57, with suspected LMD who were treated at four different institutions. CNSide and cytology were used in parallel to detect tumor cells in the cerebrospinal fluid at diagnosis and throughout treatment. CNSide was also used to determine tumor cell counts and the presence of HER2 amplification to help guide therapy. At diagnosis, CNSide detected cancer cells in three of three patients, compared with two of three patients for cytology. (The fourth patient was diagnosed before CNSide was available.) CNSide detected CSF tumor cells in all eleven measurements taken, compared to six of eleven using cytology. Throughout treatment, CNSide showed a decrease in CSF tumor cells in all four patients, ranging from 99.7% to 100%, corresponding with an improved clinical response.

Having a quantitative assay that provides tumor cell counts, rather than just a positive or negative result, is a major advance in the management of patients with leptomeningeal disease, said Priya Kumthekar, M.D., Neuro-Oncologist and Associate Professor of Neurology at Northwestern Medicines Feinberg School of Medicine, who will present the case series poster. A positive cytology result may suggest that the patient is not responding to treatment, which could lead to therapy being stopped or changed. As this case series shows, CNSides quantitative results may show that, in fact, the tumor cell count has dropped dramatically, indicating that the patient is responding, and therapy should be continued.

These cases illustrate the value of CNSide in treatment response monitoring and identification of targets for therapy that can produce a sustained response in leptomeningeal disease, said Michael Dugan, M.D., Chief Medical Officer and Medical Director of Biocept. CNSide has the potential to allow clinicians to have more confidence in their treatment decisions, improving the clinical management of leptomeningeal disease in a way that may help patients see improvement in symptoms and live significantly longer lives.

The case series was completed by neuro-oncologists from Smilow Cancer Hospital at Yale New Haven Health, Lou and Jean Malnati Brain Tumor Institute at Northwestern Medicine, UT Southwestern Medical Center and Barrow Neurological Institute. The abstract (#BIOM-05), titled Case Series of Multi-Institutional Utility of CNSide to Manage Leptomeningeal Disease in Patients with Metastatic Breast Cancer, can be accessed here.

About Biocept

Biocept, Inc., develops and commercializes molecular diagnostic assays that provide physicians with clinically actionable information to aid in the diagnosis, treatment and monitoring of patients with cancer. In addition to its broad portfolio of blood-based liquid biopsy tests, the company has developed the CNSide cerebrospinal fluid assay, designed to diagnose cancer that has metastasized to the central nervous system. Biocept also is leveraging its molecular diagnostic capabilities to offer nationwide RT-PCR-based COVID-19 testing and services to support public health efforts during this unprecedented pandemic. For more information, visit http://www.biocept.com. Follow Biocept on Facebook, LinkedIn and Twitter.

Forward-Looking Statements Disclaimer

This release contains forward-looking statements that are based upon current expectations or beliefs, as well as a number of assumptions about future events. Although Biocept believes that the expectations reflected in the forward-looking statements and the assumptions upon which they are based are reasonable, Biocept can give no assurance that such expectations and assumptions will prove to have been correct. Forward-looking statements are generally identifiable by the use of words like "may," "will," "could," "expect," or "believe" or the negative of these words or other variations on these words or comparable terminology. To the extent that statements in this release are not strictly historical, including without limitation statements regarding the capabilities and potential benefits of Biocepts CNSide assay and the ability of Biocepts assays to provide physicians with clinically actional information, such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to put undue reliance on these forward-looking statements, as these statements are subject to numerous risks and uncertainties, including the risk that Biocepts products and services may not perform as expected. These and other risks are described in greater detail under the "Risk Factors" heading of Biocepts Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, filed with the Securities and Exchange Commission (SEC) on November 15, 2021. The effects of such risks and uncertainties could cause Biocepts actual results to differ materially from the forward-looking statements contained in this release. Biocept does not plan to update any such forward-looking statements and expressly disclaims any duty to update the information contained in this press release except as required by law. Readers are advised to review Biocepts filings with the SEC, which can be accessed over the Internet at the SEC's website located at http://www.sec.gov.

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CORRECTING and REPLACING Biocept's CNSide Cerebrospinal Fluid Assay Aids in Monitoring Treatment Response and Detects Actionable Biomarkers in...

COVID-19 vaccine booster doses may be needed to strengthen immunity among cancer patients, a new study finds. File photo by Debbie Hill/UPI | License Photo

Nov. 17 (UPI) -- Booster doses of the COVID-19 vaccine provide vital additional immunity to cancer survivors and those receiving treatment for the disease, according to a study published Wednesday by the journal Cancer Cell.

One group of cancer patients with detectable antibodies, which are proteins produced by the immune system to fight off infections, saw their levels decline four to six months after receiving their second dose of either the Moderna or Pfizer-BioNTech vaccine, the data showed.

In a second group, 64% had detectable antibodies, while the remainder did not, the researchers said.

However, after all patients in the study received a booster dose of a COVID-19 vaccine, 80% had antibody levels that were higher than before they received their booster shot.

In addition, 56% of those who previously had no detectable antibodies after standard vaccination had them after receiving their booster shot, they said.

"We've been learning how devastating COVID-19 can be not just for the general population, but in particular for our cancer patients," study co-author Dr. Lauren Shapiro told UPI in a phone interview.

"These patients responded incredibly well to the booster vaccination, even those who had no detectable antibodies after their initial round of vaccination," said Shapiro, a third-year hematology/oncology fellow at Montefiore Medical Center and Albert Einstein College of Medicine in New York City.

This means that these patients have "some protection" against COVID-19, she said.

The Food and Drug Administration in October announced that booster doses of the COVID-19 vaccines are recommended for people in certain at-risk groups, including people with cancer and those under treatment for the disease.

Cancer can weaken the body's immune system as can some forms of chemotherapy, which is among drugs used to treat the disease.

As a result, many cancer survivors and cancer patients in treatment are considered "immunocompromised," so they may be more susceptible to COVID-19 and need additional doses of the vaccines to fight off the virus, Shapiro said.

Earlier studies have shown that the vaccines are safe for people with cancer.

For this study, Shapiro and her colleagues assessed the antibody response in 187 cancer patients at Montefiore who were fully vaccinated against COVID-19.

Participants underwent blood testing for antibodies against the virus immediately after becoming fully vaccinated and again four to six months later, the researchers said.

More than three-fourths of the participants were undergoing cancer treatment at the time of the study.

Of the participants, 88 received a booster dose of the vaccine at least 28 days after their second dose of either the Moderna or Pfizer-BioNTech vaccines, both of which require two shots, or one dose of the Johnson & Johnson vaccine.

Among participants, 70% were vaccinated with the Pfizer-BioNTech vaccine, 25% with Moderna and 5% with Johnson & Johnson, the researchers said.

Participants who received the booster were an average age of 69 and almost evenly split between men and women. In addition, 65% had blood cancer and 35% had a solid tumor.

Cancer survivors and those undergoing treatment may want to check in with the oncologists before getting vaccinated against COVID-19 or receiving a booster dose, but previous studies suggest there is no reason for them to avoid the shots, Shapiro said.

An oncologist may "recommend specific timing for their booster vaccination depending on each patient's specific situation," Shapiro said.

"Our study does show, however, that booster vaccination is both safe and efficacious even in the majority of patients on active cancer directed therapy and therefore we would advocate for timely booster vaccination in coordination with their providers," she said.

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COVID-19 vaccine booster effective in people with cancer, study finds - UPI.com

Broadcast Date:December 16, 2021Time:9:00 am PT, 12:00 am ET, 18:00 CET

The retina is a multilayered, highly heterogeneous neuronal tissue with intricate cellular interactions. Single-cell multiomics allows us to take steps toward understanding the biology of this complex tissue through the ability to identify and characterize all cell subtypes. Thus, a single cell transcriptomic and epigenomic atlas of the retina can be a valuable resource in opening new opportunities for future mechanistic studies.

In this GEN webinar, our distinguished presenter, Dr. Rui Chen, will discuss how his team at Baylor College of Medicine took on the complexity of gene expression and regulation in the human retina by generating a multiomic cell atlas at single-cell resolution. snRNA-seq data from over 250,000 nuclei and snATAC-seq data from over 150,000 nuclei were combined to form a highly comprehensive atlas, resulting in the identification of over 60 different cell types at a sensitivity of 0.01%. In addition, integrative analysis of this data showed 70,000 distal cis-element gene pairs, a majority of which were cell type-specific and had been overlooked in the previous investigation via bulk profiling. eQTLs from the bulk analysis were combined with the multiomic single-cell atlas to yield candidate causal variants for targeted genes within the context of cell-type data. Taken together, this comprehensive single-cell atlas enables systematic, in-depth molecular characterization of cell subtypes in the human retina.

A live Q&A session will follow the presentations, offering you a chance to pose questions to our expert panelists.

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Single Cell Multiomic Atlas of the Human Retina: An Integrative Analysis - Genetic Engineering & Biotechnology News