Summary

[Posted 11/Nov/2022]

AUDIENCE: Nephrology, Internal Medicine

KEY FINDINGS: Although NMR-quantified metabolites did not improve discrimination, several urine metabolic profiles were identified that may improve understanding of kidney stone pathogenesis.

BACKGROUND: The urine metabolites and chemistries that contribute to kidney stone formation are not fully understood. This study examined differences between the urine metabolic and chemistries profiles of first-time stone formers and controls.

DETAILS: High-resolution ¹H-nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was performed in 24-hour urine samples from a prospective cohort of 418 first-time symptomatic kidney stone formers and 440 controls. In total, 48 NMR-quantified metabolites in addition to 12 standard urine chemistries were assayed. Analysis of covariance was used to determine the association of stone former status with urine metabolites or chemistries after adjusting for age and sex and correcting for the false discovery rate. Gradient-boosted machine methods with nested cross-validation were applied to predict stone former status. Among the standard urine chemistries, stone formers had lower urine oxalate and potassium and higher urine calcium, phosphate, and creatinine. Among NMR urine metabolites, stone formers had lower hippuric acid, trigonelline, 2-furoylglycine, imidazole, and citrate and higher creatine and alanine. A cross-validated model using urine chemistries, age, and sex yielded a mean AUC of 0.76 (95% CI, 0.73 to 0.79). A cross-validated model using urine chemistries, NMR-quantified metabolites, age, and sex did not meaningfully improve the discrimination (mean AUC, 0.78; 95% CI, 0.75 to 0.81). In this combined model, among the top ten discriminating features, four were urine chemistries and six NMR-quantified metabolites.

Copyright © American Society of Nephrology. All rights reserved.

Source: Thongprayoon, C., Vuckovic, I., Vuckovic, L. E., et al. (2022). Nuclear Magnetic Resonance Metabolomic Profiling and Urine Chemistries in Incident Kidney Stone Formers Compared with Controls. JASN. 2022, 33(11): 2071-2086. Published: November, 2022. DOI: 10.1681/ASN.2022040416.

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

A Multicountry, Randomised, Open-Label, Non-Inferiority Trial

[Posted 23/Apr/2026]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: In people with advanced HIV disease, bictegravir, emtricitabine, and tenofovir alafenamide was shown to be non-inferior to darunavir, cobicistat, emtricitabine, and tenofovir alafenamide and resulted in fewer adverse events, supporting its use as a preferred first-line antiretroviral regimen in this vulnerable population.

BACKGROUND: To date, clinical trials have been underpowered to assess which antiretrovirals perform best in people with advanced HIV disease. We aimed to investigate the efficacy and safety of an integrase inhibitor-containing versus a boosted protease inhibitor-containing regimen for this population.

DETAILS: In this open-label, multicentre, non-inferiority trial in seven European countries (Spain, France, Italy, Germany, Belgium, Ireland, and the UK), therapy-naive adults with advanced HIV disease were randomly allocated (1:1) to receive either bictegravir, emtricitabine, and tenofovir alafenamide (integrase inhibitor group) or darunavir, cobicistat, emtricitabine, and tenofovir alafenamide (boosted protease inhibitor group) for 48 weeks. Randomisation was computer generated in permuted blocks within strata with block sizes of four and stratified by country and baseline CD4 cell count. The primary composite outcome (time to first occurrence of specified virological or clinical events) and its components were evaluated by Kaplan-Meier and Cox regression analyses in both modified intention-to-treat (mITT) and per-protocol populations. The mITT population included all randomly allocated participants who received at least one dose of the study drug, whereas the per-protocol population excluded those who received incorrect treatment. Non-inferiority of the integrase inhibitor-based regimen versus the boosted protease inhibitor-containing regimen was declared if the upper limit of the 95% CI of the hazard ratio (HR) for the primary composite endpoint was less than 1.606, corresponding to a 12% difference in the cumulative probability of the composite primary endpoint. Adverse events, a secondary endpoint, were recorded at eight visits in all participants. Between May 13, 2019, and June 26, 2023, 222 people were randomly assigned to the integrase inhibitor group and 225 to the boosted protease inhibitor group. Of these 447 recruited participants, 442 (99%) participants with a median CD4 count of 41 cells per μL (IQR 17-79) received at least one dose. 358 (81%) of the 442 treated participants self-reported as male and 84 (19%) female, and 276 (62%) were of White ethnicity, 83 (19%) Black, and 83 (19%) other. In the mITT analysis, the 48-week composite primary outcome event occurred in 49 (22%) of 220 participants in the integrase inhibitor group versus 70 (32%) of 222 participants in the boosted protease inhibitor group (adjusted HR 0.70 [95% CI 0.48-1.00]; non-inferiority shown). The per-protocol analysis gave a similar estimated adjusted HR of 0.69 (0.48-1.00; non-inferiority shown). By mITT, drug-related adverse events (grade >=2) occurred in 16 (7%) of 220 participants in the integrase inhibitor group versus 32 (14%) of 222 in the boosted protease inhibitor group (p=0.043). The rates of serious adverse events or adverse events leading to study discontinuation did not differ between groups. 12 deaths occurred during the study (nine in the integrase inhibitor group and three in the boosted protease inhibitor group), not related to the study drugs.

Copyright © Elsevier Ltd. All rights reserved.

Source: Behrens, G. M. N., Assoumou, L., Liegeon, G., et al. Integrase Versus Protease Inhibitor Therapy in Advanced HIV Disease (LAPTOP): A Multicountry, Randomised, Open-Label, Non-Inferiority Trial. The Lancet Infectious Diseases. 2025; 26, 510-521. Published: March, 2026. DOI: 10.1016/S1473-3099(25)00681-4

Summary

A Multicenter Cohort Study

[Posted 1/Apr/2026]

AUDIENCE: Endocrinology, Internal Medicine

KEY FINDINGS: A 30-unit increase in GGT over time was associated with a substantially higher risk of developing type 2 diabetes in children with MASLD. Together with AST, GGT may provide clinicians with concrete, routinely available parameters to monitor for early risk stratification. Further validation in independent cohorts is needed to confirm these findings and inform clinical application.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children and is linked to type 2 diabetes. This study evaluates whether longitudinal changes in liver chemistries - γ-glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) - can serve as biomarkers of increased type 2 diabetes risk in children with MASLD.

DETAILS: This multicenter longitudinal cohort study followed 1,035 children with biopsy-confirmed MASLD, without type 2 diabetes at baseline, for a mean of 3.9 years. Liver chemistries were measured annually, and type 2 diabetes was diagnosed based on fasting glucose, HbA1c, and clinical diagnosis. Extended Cox models with inverse probability weighting were used to evaluate associations between liver enzyme trajectories and type 2 diabetes risk. The cumulative incidence of type 2 diabetes was 12.3%. Increases in GGT (hazard ratio [HR] 1.55; 95% CI 1.34-1.80), AST (HR 1.31; 95% CI 1.20-1.43), and ALT (HR 1.13; 95% CI 1.07-1.20) were associated with a higher risk of developing type 2 diabetes in the independent models. In the mutual model with all three liver chemistries, only GGT and AST remained significant.

Copyright © American Diabetes Association. All rights reserved.

Source: Thai, N. Q. N., Chun, L. F., Newton, K. P., et al. Longitudinal Analysis of Liver Chemistry Trajectories and Risk of Type 2 Diabetes in Children With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Multicenter Cohort Study. Diabetes Care . 2026; 598-606. 49(4): Published: April, 2026. DOI: 10.2337/dc25-1532