Summary

[Posted 25/May/2023]

AUDIENCE: Neurology, Internal Medicine

KEY FINDINGS: The results show that combining scRNA-seq and WGS data can successfully detect putative somatic mutations. The putative somatic mutations detected from ROSMAP data set have provided new insights into the association of AD and aging with brain somatic mutagenesis.

BACKGROUND: With age, somatic mutations accumulated in human brain cells can lead to various neurologic disorders and brain tumors. Because the incidence rate of Alzheimer disease (AD) increases exponentially with age, investigating the association between AD and the accumulation of somatic mutation can help understand the etiology of AD.

DETAILS: Authors designed a somatic mutation detection workflow by contrasting genotypes derived from whole-genome sequencing (WGS) data with genotypes derived from scRNA-seq data and applied this workflow to 76 participants from the Religious Order Study and the Rush Memory and Aging Project (ROSMAP) cohort. We focused only on excitatory neurons, the dominant cell type in the scRNA-seq data. 196 sites were identified that harbored at least 1 individual with an excitatory neuron–specific somatic mutation (ENSM), and these 196 sites were mapped to 127 genes. The single base substitution (SBS) pattern of the putative ENSMs was best explained by signature SBS5 from the Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, a clock-like pattern correlating with the age of the individual. The count of ENSMs per individual also showed an increasing trend with age. Among the mutated sites, we found 2 sites tend to have more mutations in older individuals (16:6899517 [RBFOX1], p = 0.04; 4:21788463 [KCNIP4], p < lt; 0.05). In addition, 2 sites were found to have a higher odds ratio to detect a somatic mutation in AD samples (6:73374221 [KCNQ5], p = 0.01 and 13:36667102 [DCLK1], p = 0.02). Thirty-two genes that harbor somatic mutations unique to AD and the KCNQ5 and DCLK1 genes were used for gene ontology (GO)–term enrichment analysis. We found the AD-specific ENSMs enriched in the GO-term "vocalization behavior" and "intraspecies interaction between organisms." Of interest we observed both age-specific and AD-specific ENSMs enriched in the K+ channel–associated genes.

Copyright © American Academy of Neurology. All Rights Reserved.

Source: Zhang, M., Bouland, G. A., Holstege, H., et al. (2023). Identifying Aging and Alzheimer Disease-Associated Somatic Variations in Excitatory Neurons From the Human Frontal Cortex. Neuro Genetics. 2023; 9(3): e200066. Published: June, 2023. DOI: 10.1212/NXG.0000000000200066.

Summary

A Randomized Controlled Comparative Study

[Posted 19/May/2026]

AUDIENCE: General Surgery, Family Medicine

KEY FINDINGS: Early active treatment with isotretinoin and FMRF is safe and better than isotretinoin monotherapy over 44 weeks regarding severity, reduced erythema, and improved surface roughness in moderate-to-severe acne vulgaris. This encourages early and effective treatment of acne to mitigate acne scarring and improve patients' quality of life.

BACKGROUND: Oral isotretinoin is the standard therapy for severe acne. However, scarring may persist. Fractional microneedling radiofrequency (FMRF) improves both inflammatory lesions and scars with minimal downtime. In this study, we compare isotretinoin monotherapy and concurrent isotretinoin and FMRF for active acne regarding clinical outcomes. The GAGS scores of isotretinoin and FMRF were significantly lower than those of isotretinoin monotherapy from weeks 12-44 (-79.69% vs. -60.34% at week 44, respectively; p < 0.001). Isotretinoin and FMRF showed significantly greater lesion count reductions than isotretinoin monotherapy at follow-up visits from weeks 12-44. Isotretinoin and FMRF showed significantly lower hemoglobin levels than isotretinoin monotherapy at weeks 32 and 44 (p = 0.029 and p < 0.001, respectively). Skin surface roughness improved substantially and persistently from week 12-44.

DETAILS: In this parallel two-group comparative study, patients received either low-dose isotretinoin monotherapy for 20 weeks (n = 34) or low-dose isotretinoin concurrently with 5 monthly FMRF sessions (n = 36). Outcomes were assessed at baseline and weeks 12, 20, 24, 32, and 44. The primary endpoints were Global Acne Grading System (GAGS) scores and inflammatory/non-inflammatory lesion counts. Secondary endpoints were hemoglobin indices and skin roughness.

Copyright © Wiley Periodicals LLC. All rights reserved

Source: Disphanurat, W., Leeyangyuen, P,, and Srisantithum, B. Efficacy of Low-Dose Oral Isotretinoin Combined With Fractional Microneedle Radiofrequency Versus Low-Dose Oral Isotretinoin Monotherapy in the Treatment of Moderate-To-Severe Acne Vulgaris: A Randomized Controlled Comparative Study. Lasers in Surgery and Medicine. 2026; 58(4): 321-330. Published: April, 2026. DOI: 10.1002/lsm.70120.

Summary

[Posted 11/May/2026]

AUDIENCE: All Healthcare Professionals

KEY FINDINGS:

• Hantaviruses are a family of viruses that cause serious illness and sometimes death in people worldwide.
• The viruses are spread by infected rodents through their urine, feces, and saliva.
• Some hantaviruses cause hantavirus pulmonary syndrome (HPS).
• Early symptoms of HPS in people resemble many other respiratory illnesses, making HPS difficult to diagnose at illness onset.
• Healthcare providers should test a person for hantavirus if they have HPS-compatible symptoms and have had contact with rodents.

BACKGROUND: Hantaviruses are spread by rodents' body fluids and excrement. People mostly contract hantavirus by breathing in the virus. Most hantaviruses found in North, Central, and South America can cause hantavirus pulmonary syndrome (HPS). Andes virus, which is found in South America, has reportedly had person-to-person transmission.

DETAILS: Different hantaviruses are found in the United States. Most of these cause HPS, which primarily affects the lungs. Non-HPS hantavirus infection can also occur, where patients experience non-specific viral symptoms, but no cardiopulmonary symptoms. The hantaviruses that are found throughout the United States are not known to spread between people.

HPS initially causes flu-like symptoms that can progress to more severe illness where people have trouble breathing. It's important for people with HPS to begin treatment as early as possible to improve their chances of recovery. HPS is fatal in nearly 4 in 10 people who are infected.

Exposure risks

Anyone who has contact with hantavirus-carrying rodents, or their droppings, urine, saliva or nesting material is at risk of HPS. Rodent infestation in and around the home remains the primary risk for hantavirus exposure. Even healthy individuals are at risk for HPS infection if they have contact with the virus.

Andes virus can cause HPS and is the only type of hantavirus that is known to spread person-to-person.

How it spreads

Each hantavirus has one primary rodent that carries the disease. The most common hantavirus that causes HPS in the U.S. is spread by the deer mouse.

People can contract hantavirus if they have contact with urine, feces or saliva of a rodent carrying the virus. This can occur when people:

1. Breathe in hantavirus-contaminated air when cleaning up after rodents.
2. Touch contaminated objects and then touch their nose or mouth.
3. Are bitten or scratched by an infected rodent.
4. Eat food contaminated with hantavirus.

Cases normally occur in rural areas where forests, fields, and farms offer habitats for rodents. The animals can get into homes and barns, where they may leave urine or feces.

Dogs and cats are not known to become infected with hantavirus in the United States. Pets may bring infected rodents to people or into homes.

Testing and diagnosis

Assessing patients for hantavirus can be difficult early in the infection because symptoms are non-specific and resemble many other viral infections like influenza, legionnaire's, leptospirosis, mycoplasma, and Q fever. Because hantavirus resembles these infections, a blood test is often the only way to officially diagnose it.

To diagnose hantavirus or HPS, clinicians should understand:

• Disease symptoms and rodent exposure history
• Testing guidelines to identify the virus
• How to request testing support from CDC if needed, and
• How to report cases to CDC

Clinicians with a patient experiencing symptoms compatible with HPS and a potential rodent exposure should contact their state, tribal, local, or territorial health department.

Testing

CDC uses an enzyme-linked immunosorbent assay (ELISA) to detect IgM antibodies and diagnose acute infections with hantaviruses. This diagnostic method is used to diagnose both HPS and HFRS. Diagnostic testing can be performed at:

1. CDC
2. State labs running the CDC-developed assay
3. State public health labs using other diagnostic assays
4. Commercial labs

The criteria to report hantavirus-positive cases are based on the national case definition, which includes clinical symptoms (HPS or non-HPS) and acute laboratory diagnostic results, such as:

1. IgM positive
2. IgG positive with rising titers
3. Immunohistochemistry positive, or
4. PCR positive

Treatment and recovery

There is no specific treatment for hantavirus infection. If HPS is suspected, the patient needs emergency medical care immediately, preferably in the intensive care unit, even before diagnosis.

Early intensive medical care is critical because patients who have sudden acute disease can rapidly become severely sick and die. If a patient is experiencing full distress, it is less likely the treatment will be effective.

Patient management should include:

1. Monitoring and adjustment of cardiac function
2. Carefully administering fluids
3. Providing supplemental oxygen
4. Intubating and ventilating if needed

Suspected HPS patients should receive appropriate broad-spectrum antibiotic therapy, even if you're still waiting for diagnosis. Care should also include fever reducers and pain relievers.

While HPS can be quite severe, it has a short duration of critical disease. The cardiopulmonary dysfunction seen in HPS is most likely due to circulating inflammatory mediators. Autopsies performed on fatal cases did not show significant tissue damage.

Initiating extracorporeal membrane oxygenation (ECMO) at the earliest sign of decompensation has an 80 percent survival rate in patients despite cardiopulmonary collapse.

Within 24 hours of initial evaluation, most HPS patients develop some degree of hypotension. They also experience progressive evidence of pulmonary edema and hypoxia, usually requiring mechanical ventilation.

Patients with fatal infections often appear to have severe myocardial depression that progresses to sinus bradycardia with subsequent electromechanical dissociation, ventricular tachycardia, or fibrillation.

In patients with HPS, poor prognostic indicators include a plasma lactate of greater than 4.0 mmol/L or a cardiac index of less than 2.2 L/min/m2.

Pulmonary edema and pleural effusions are common, but multiorgan dysfunction syndrome is rarely seen. However, HPS patients sometimes have mildly impaired renal function. Survivors frequently become polyuric during convalescence and improve rapidly.

Intravenous ribavirin, a guanosine analogue, has been tested in patients with HPS. However, it was not shown to be effective for treatment of HPS.

Without adequate treatment, most deaths occur in patients with HPS within 24 to 48 hours of the cardiopulmonary phase onset.

Related diseases

Some hantaviruses cause kidney symptoms more than lung damage. When this occurs, it is called hemorrhagic fever with renal syndrome (HFRS).

Source: Clinician Brief: Hantavirus Pulmonary Syndrome (HPS). CDC. Published: May 8, 2026.

Summary

[Posted 8/May/2026]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: In two open-label trials, nirmatrelvir-ritonavir did not reduce the incidence of hospitalization or death among vaccinated higher-risk participants with SARS-CoV-2 infection.

BACKGROUND: Nirmatrelvir-ritonavir has been shown to reduce progression to severe illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unvaccinated high-risk outpatients. The effectiveness of nirmatrelvir-ritonavir in persons who have been vaccinated, infected naturally, or both is unclear.

DETAILS: In two open-label platform trials (PANORAMIC in the United Kingdom and CanTreatCOVID in Canada), we enrolled higher-risk adults (>=50 years of age or >=18 years of age with coexisting conditions) in the community who tested positive for SARS-CoV-2 and had been unwell for 5 days or less. The participants were randomly assigned to receive usual care plus nirmatrelvir (300 mg)-ritonavir (100 mg) twice a day for 5 days or to receive usual care alone. The primary outcome was hospitalization or death from any cause within 28 days after randomization. From December 8, 2021, to September 30, 2024, a total of 3516 participants in the PANORAMIC trial and 716 participants in the CanTreatCOVID trial underwent randomization. In the PANORAMIC trial, 14 of 1698 participants (0.8%) in the nirmatrelvir-ritonavir group and 11 of 1673 participants (0.7%) in the usual-care group were hospitalized or died (adjusted odds ratio, 1.18; 95% Bayesian credible interval, 0.55 to 2.62; probability of superiority, 0.334). In the CanTreatCOVID trial, 2 of 343 participants (0.6%) in the nirmatrelvir-ritonavir group and 4 of 324 participants (1.2%) in the usual-care group were hospitalized or died (adjusted odds ratio, 0.48; 95% Bayesian credible interval, 0.08 to 2.23; probability of superiority, 0.830). In a substudy involving 634 participants, viral load was reduced by the end of treatment with nirmatrelvir-ritonavir. Serious adverse events with nirmatrelvir-ritonavir were reported in 9 participants in the PANORAMIC trial and in 4 participants in the CanTreatCOVID trial.

Copyright © Massachusetts Medical Society. All rights reserved.

Source: Butler, C. C., Pinto, A. D., Harris, V., et al. Oral Nirmatrelvir-Ritonavir for Covid-19 in Higher-Risk Outpatients. N Engl J Med. 2026; 394(16): 1583-1594. Published: April 22, 2026. DOI: 10.1056/NEJMoa2502457

Summary

[Posted 7/May/2026]

AUDIENCE: Ob/Gyn, Oncology

KEY FINDINGS: Recent actions by the U.S. Food and Drug Administration to update labeling for menopausal hormone therapy (MHT) represent an important shift toward evidence-based risk communication. By removing certain risks - cardiovascular disease, breast cancer, and probable dementia - from boxed warnings while retaining them in the Warnings and Precautions section, the FDA aims to provide a more balanced and clinically contextualized understanding of therapy risks and benefits.

BACKGROUND: The effects of menopause can make a woman's daily life much harder, and therapies approved by the U.S. Food and Drug Administration can help. But too many women might not use these treatments to lessen their menopause symptoms because of the risks associated with these drugs described in the drug labels' boxed warnings (the FDA's most prominent warnings).

DETAILS: The FDA has requested that drug companies remove risk statements about cardiovascular diseases, breast cancer, and probable dementia from boxed warnings for menopausal hormone therapy (MHT) - also called hormone replacement therapy (HRT). The FDA has requested that companies make changes to update information about the risks of these drugs so women and their health care providers can make the best decisions for their health. Several companies have already made, and FDA has approved, changes to their drug labels, and more companies may make changes.

Menopause and Symptoms Menopause is a natural stage in a woman's life when her menstrual periods permanently stop, marking the end of her reproductive years. This usually happens between ages 45 and 55.

When women go through menopause, their bodies produce less estrogen and progesterone. These lower hormone levels often cause symptoms that can significantly and adversely impact women's quality of life, including:

• Hot flashes (“hot flushes”), getting warm in the face, neck, or chest, with and without sweating.
• Night sweats, which may lead to problems sleeping and feeling tired, stressed, or tense.
• Vaginal changes, such as vaginal dryness and painful sex.
• Thinning of bones (osteoporosis), which may lead to loss of height and bone breaks.
• Treatments for menopausal symptoms include hormone therapy and non-hormonal therapy. The FDA has approved hormone therapies to help relieve hot flashes, night sweats, vaginal dryness, or dyspareunia (pain with sexual activity) - and that may reduce chances of getting osteoporosis. For women who cannot or choose not to take hormone treatments, the FDA has also approved three nonhormone therapies.

Types of Hormone Replacement Therapy There are four primary types of hormone replacement therapy: systemic combination therapy (estrogen and progestogen), systemic estrogen-alone therapy, systemic progestogen-alone therapy for women with a uterus using systemic estrogen-alone therapy, and topical vaginal estrogen therapy. Your health care provider can help you decide the best treatment based on your individual symptoms, medical history, and preferences.

Combination Therapy (Estrogen Progestogen Therapy or EPT): This therapy combines doses of estrogen and progestin (hormones that act like progesterone) or progesterone and is used in women with a uterus. Combination therapy most commonly comes in pills or skin patches.

Systemic Estrogen-Alone Therapy: This therapy contains only estrogen and comes in pills, skin patches, spray, gel, and vaginal ring. It is usually used in women who have had their uterus removed (hysterectomy). It can also be used in women with a uterus if progesterone-alone therapy is also added.

Progestogen-Alone Therapy: This therapy contains only progesterone or progestin and comes in pills. It is added to systemic estrogen-alone therapy in women with a uterus to protect against cancer of the uterus.

Topical Vaginal Estrogen Therapy: This therapy involves using estrogen applied topically to the vaginal area to treat vaginal symptoms. Forms of topical estrogen therapy include vaginal cream, tablet, insert, and ring.

What's a Boxed Warning? A boxed warning is the most prominent safety warning for FDA-approved prescription drugs. A boxed warning can be used to inform health care providers and patients about potentially serious or life-threatening risks essential to consider when patients and their health care providers assess a drug's risks and benefits.

Why the FDA Is Taking This Action Based on the FDA's analysis, the agency has requested drug sponsors of all HRT products that contain estrogen or progestogen and in all dose forms to remove language about the risk of cardiovascular disease, breast cancer, and probable dementia from the boxed warning, as well as make other safety-related labeling changes. FDA has not requested that drug sponsors remove the risks of cardiovascular disease and breast cancer from the Warnings and Precautions section of the labeling.

The FDA is not requesting removal of the boxed warning for endometrial cancer for systemic estrogen-alone products.

Millions of women have avoided hormone replacement therapy since the early 2000s because of fears about cancer and heart disease risks. The FDA is asking for these labeling changes so women and their doctors have access to updated information on the benefits and risks of these medications so they can make informed decisions.

Source: Hormone Replacement Therapies Can Help Women with Bothersome Menopausal Symptoms. FDA. Published: February 13, 2026.

Summary

[Posted 6/May/2026]

AUDIENCE: Neurology, Psychiatry

KEY FINDINGS: The FDA approval of Auvelity for agitation in Alzheimer’s dementia represents a clinically meaningful advancement, introducing the first non-antipsychotic pharmacologic option for this challenging condition. Supported by randomized clinical trials demonstrating both symptomatic improvement and relapse prevention, Auvelity offers a promising alternative for managing agitation while potentially avoiding risks associated with antipsychotics. Careful patient selection and monitoring remain essential given its safety profile.

BACKGROUND: The U.S. Food and Drug Administration today approved an expanded use for Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride) extended-release tablets to treat agitation associated with dementia due to Alzheimer's disease in adults. The drug is the first FDA-approved treatment for this condition that is not an antipsychotic. FDA initially approved Auvelity in 2022 to treat major depressive disorder in adults.

DETAILS: "This approval represents a significant advancement in our ability to help patients and families dealing with one of the most challenging aspects of Alzheimer's disease," said FDA Commissioner Marty Makary, M.D., M.P.H. "With today's action, patients and their families have access to an additional important treatment for complications of this devastating disease."

Agitation is a common and distressing symptom in patients with Alzheimer's disease dementia, characterized by excessive motor activity, or verbal or physical aggression. It can significantly impact quality of life for patients and caregivers.

"Auvelity was found to be efficacious for treating agitation in Alzheimer's disease in two randomized trials and now represents an additional option to address one of the most difficult sequelae of the disease, especially as it progresses,” said Tracy Beth Hoeg, M.D., Ph.D., Acting Director of the FDA's Center for Drug Evaluation and Research. "We hope this approval will provide meaningful benefit to patients, their families, and caregivers."

The first randomized study (NCT 03226522) was a five-week trial in which participants received either Auvelity or a placebo. The primary endpoint was the change from baseline to week five in the total score of the Cohen-Mansfield Agitation Inventory (CMAI), a survey that assesses the frequency of manifestations of agitated behaviors in elderly patients, based on caregiver reports. Auvelity was significantly superior to placebo in The Cohen-Mansfield Agitation Inventory score improvements.

The second randomized study (NCT 04947553) was a withdrawal study in participants who responded to Auvelity. Upon reaching a sustained clinical response to Auvelity, patients were randomly assigned to continue treatment with Auvelity or switch to placebo. The primary endpoint was time to relapse. Participants who continued Auvelity treatment had a significantly longer time to relapse of agitation symptoms compared to patients receiving the placebo.

The most common side effects include dizziness, upset stomach, headache, diarrhea, drowsiness, dry mouth, sexual dysfunction, and uncontrolled sweating. Auvelity has a Boxed Warning about increased risk of suicidal thoughts and behaviors in adolescents and young adults taking antidepressants. Health care providers should monitor patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during initial treatment. The medicine can cause seizures, with risk increasing with dose. It can also cause elevated blood pressure and hypertension, and may activate mania or hypomania (irritable mood) in susceptible patients.

Before starting Auvelity, health care providers should assess blood pressure, screen for personal or family history of bipolar disorder, and determine if patients are taking other medications containing bupropion or dextromethorphan.

The FDA granted breakthrough therapy designation and priority review designation for this action. The approval of Auvelity for agitation associated with dementia due to Alzheimer's disease was granted to Axsome Therapeutics.

Source: FDA Approves First Non-Antipsychotic Drug to Treat Agitation Associated with Dementia. FDA. Published: April 30, 2026.