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In 1 min, Article

Semaglutide emerges as a potential treatment for MASH

Semaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction–associated steatohepatitis (MASH).

Methods: In this phase 3 trial, 1197 patients with biopsy-confirmed MASH and liver fibrosis (stage 2 or 3) were randomly assigned to weekly semaglutide 2.4 mg or placebo. Interim results at 72 weeks from the first 800 patients are reported. Primary goals were resolution of steatohepatitis without worsening fibrosis and improvement in fibrosis without worsening steatohepatitis.

Results: Semaglutide led to steatohepatitis resolution without fibrosis worsening in 62.9% of patients vs. 34.3% with placebo. Fibrosis improved without worsening steatohepatitis in 36.8% vs. 22.4%. Both outcomes occurred in 32.7% vs. 16.1%. Weight loss was greater with semaglutide (−10.5% vs. −2.0%). GI side effects were more common with semaglutide; pain scores were similar.

Conclusions: Semaglutide 2.4 mg weekly significantly improved liver histology in MASH patients with fibrosis.

Reference: NEJM
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In 1 min, Article

New guidelines prioritize Iron over Dopamine in Restless Legs Syndrome

Restless Legs Syndrome (RLS) affects 8% of the population, mainly women. It causes an overwhelming urge to move the legs, especially in the evening or during rest, often with tingling or electric sensations. Movement temporarily relieves symptoms.

Previously, dopamine agonists (e.g., pramipexole, rotigotine, ropinirole) were first-line treatment. However, the American Academy of Sleep Medicine (AASM) now recommends against them due to augmentation syndrome—a worsening of symptoms with long-term use. France still permits their use in severe cases, per 2019 guidelines.

At a recent neurology conference in Montpellier, Dr. Sofiène Chenini emphasized non-dopaminergic options and warned against overuse.

Updated First-Line Therapies:

  • IV iron supplementation (when ferritin <75 µg/L) is now first-line.
  • Antiepileptics (gabapentin, pregabalin) are preferred for mild-to-moderate RLS or in cases with insomnia.
  • Lifestyle changes—avoiding caffeine, alcohol, smoking; regular sleep habits; and daytime exercise—can help mild cases.

If oral iron fails, IV options like ferric carboxymaltose or ferric hydroxide-sucrose are recommended. Mild opioids(e.g., codeine, tramadol) may be added if symptoms persist.

Diagnosis Criteria (SFRMS 2016)

  1. Urge to move legs with unpleasant sensations
  2. Worsens at rest
  3. Relieved by movement
  4. Worse at night
  5. No other underlying cause

RLS is linked to brain iron deficiency—MRI studies suggest impaired iron transport and dopamine/glutamate overactivity. Contributing factors include aging, certain medications (especially serotonergic antidepressants and antihistamines), and genetic predisposition.

Alternative antidepressants like venlafaxine or duloxetine (shorter half-life) are preferred if needed.

Misuse Drives Change

A U.S. registry of 670,000 RLS patients revealed 60% received dopamine agonists, and 20% exceeded recommended doses, especially among neurologists. Overprescription—often modeled on Parkinson’s protocols—prompted AASM’s guideline update.

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In Article

OMI & NOMI concept: Replacing the STEMI/NSTEMI terminologies

In 2018, Meyers, Weingart and Smith introduced us to the concept of Occlusion Myocardial Infarction (OMI). The term STEMI equivalent is already in our vocabulary, but it actually refers to patients with clinical and ECG features concerning for acute coronary occlusion who would benefit from immediate PCI.

Definition of OMI?

An ongoing ischemia resulting in irreversible infarction caused by complete or near-complete occlusion of a culprit epicardial coronary artery, with inadequate collateral circulation, thus necessitating immediate reperfusion.

Definition of NOMI?

No occlusion, or sufficient collateral circulation to avoid active infarction.

What’s wrong with the STEMI label?

Patients with acute occlusion not meeting STEMI criteria may be an underserved, underidentified subgroup of ACS patients who would benefit from emergent intervention, whereby classification of AMI by occlusion vs. no occlusion may be more appropriate than classification by ST elevation on the ECG. Meyers et al 2020

Example: A 70 year old female presents to ED with atypical chest pain. ECG done.


Explanation:

This ECG may appear normal to most of us, but it actually indicates an OMI. This ECG from @tbouthillet shows small hyperacute T waves in inferior leads concerning for early inferior OMI, demonstrated best by their size relative to the preceding QRS Complex.


OMI ECG Patterns not meeting STEMI criteria:

  • Wellens pattern A
  • Wellens pattern B
  • De Winter T-wave
  • New-onset bifascicular block
  • Modified Sgarbossa – Smith
  • Aslanger pattern
  • Posterior OMI
  • Precordial Swirl
  • Hyperacute T-wave
  • South African flag sign
  • Northern OMI

Mimics of OMI with ST Elevation:

References: https://omiguide.org/ | https://litfl.com/omi-replacing-the-stemi-misnomer/
Clinical Inshorts by ClinicHours
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In Article

Human Metapneumovirus (HMPV) symptoms, diagnosis & treatment

Human metapneumovirus (HMPV) is a negative-sense ss RNA virus of the family Pneumoviridae. It was isolated for the first time in 2001 in the Netherlands. It is the second most common cause after RSV of acute respiratory tract illness.

Subtypes: Four lineages – A1, A2, B1 and B2.

Virology: HMPV infects airway epithelial cells in the nose and lung. It attaches to the target cell via the glycoprotein protein interactions with heparan sulfate and other glycosaminoglycans.

Incubation period: 3-6 days

Transmission: Contact with contaminated secretions, via droplet, aerosol, or  hospital acquired infections.

Symptoms: Cough, fever, runny or stuffy nose, sore throat, wheezing, SOB (dyspnea), rash.

Diagnosis: RT-PCR, Immunofluorescence assays, NAAT.

Rx: Supportive care, Ribavirin showed effectiveness in an animal model.

Prognosis: Most people with HMPV have mild URTI similar to the common cold and recover from HMPV in about 7 to 10 days without any complications.

Complications: Viral pneumonia, Bronchiolitis, A/E COPD, secondary bacterial infections.

HMPV outbreak in East Asia began with an outbreak of cases Beijing, China in December 2024. It was linked to 5.4 % of respiratory illness hospitalisations in China, more than COVID-19, rhinovirus or adenovirus. Cases were also reported in Malaysia, India, Pakistan and Kazakhstan.

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In 1 min, Article

Indian Health Ministry approves BPaLM regimen for MDR TB

Indian Health Ministry approves introduction of new shorter and more efficacious treatment regimen for drug-resistant TB. BPaLM regimen consisting of 4 drug combination.


In December 2022 WHO also released a new treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) guideline.

A 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended in place of the 9-month or longer (18-month) regimens in MDR/RR-TB patients, now including extensive pulmonary TB and extrapulmonary TB (except TB involving central nervous system, miliary TB and osteoarticular TB).

Use of 9-month all-oral regimen rather than 18-months regimen is suggested in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded.

Longer (18-month) treatments remain a valid option in all cases in which shorter regimens cannot be implemented due to intolerance, drug-drug interactions, extensively drug-resistant tuberculosis, extensive forms of extrapulmonary TB, or previous failure.

Reference: WHO, MoHFW
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In 1 min, Article

Causes of sudden cardiac arrest

Causes of sudden cardiac arrest:

1. Cardiovascular pathology

  • Coronary artery disease (MC – 80% of all cases)
  • Severe left ventricular dysfunction

2. Cardiomyopathy (10-15% of all cases)

  • Hypertrophic cardiomyopathy
  • Arrhythmogenic right ventricular cardiomyopathy

3. Congenital heart disease

  • Anomalous left coronary artery from the pulmonary artery [ALCAPA] syndrome
  • Aortic stenosis
  • Aortic coarctation
  • Tetralogy of Fallot
  • Transposition of the great arteries
  • Ebstein’s anomaly
  • Single ventricle

4. Valvular heart disease

5. Cardiac pacemaker

6. Conducting system disease

  • Lenegre’s disease
  • Lev’s disease

7. Hereditary channelopathies (5-10% of all cases)

  • Brugada syndrome
  • Early repolarization syndrome
  • Long QT syndrome
  • Short QT syndrome
  • Catecholaminergic polymorphic ventricular tachycardia
Reference: Page 53-55, Tintinalli’s Emergency Medicine 9th Edition
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In FDA Updates

FDA approves novel drug for resistant hypertension based on PRECISION trial

The USA FDA has approved Aprocitentan (Brand name TRYVIO) for the treatment of resistant hypertension in combination with other antihypertensive drugs.

Dose: 12.5 mg 1OD PO.

MOA: Dual endothelin receptor antagonist.

Contraindications: Pregnancy, Hypersensitivity.

Adverse effects: Edema, anemia, ⬇️ sperm count.

Warning & precautions: ERAs cause hepatotoxicity & liver failure.

Trial: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 studydone in Europe, North America, Asia &  Australia in June 18, 2018, to April 25, 2022 by Prof Markus P Schlaich, MD et al.

Inclusion criteria: Patients with SBP > 140 mmhg who were on 3 different anti hypertensive medications including diuretics.

Objectives: The primary endpoints were changes in SBP from baseline to 4 week & from withdrawal baseline to 40 week. Secondary endpoints included 24-h ambulatory blood pressure changes.

Methods: Study consisted of 3 sequential parts:

Part 1 was 4-week double-blind, randomised, & placebo-controlled part, in which patients received aprocitentan 12·5 mg, 25 mg, or placebo in a 1:1:1 ratio.

Part 2 was a 32-week single patient blind part, in which all patients received aprocitentan 25 mg.

Part 3 was a 12-week double-blind, randomised, placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio.

Findings: In patients with resistant hypertension, aprocitentan was well tolerated & superior to placebo in lowering blood pressure at 4 week with a sustained effect at 40 week.

Reference: http://clinicaltrials.gov/show/NCT03541174
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In Article, FDA Updates

FDA approves Nivolumab for resected stage IIB/C melanoma

The US FDA has approved nivolumab for the treatment of completely resected stage IIB/C melanoma for patients aged 12 years and older, expanding the melanoma indication for the programmed death receptor-1 (PD-1) inhibitor.

Dose – For patients >40 kg,  480 mg every 4 weeks or 240 mg every 2 weeks until disease recurrence or unacceptable toxicity for up to 1 year. For pediatric patients < 40 kg, 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year.

Adverse reactions – fatigue, musculoskeletal pain, rash, diarrhea &  pruritis.

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In Article, New Drug

Ritlecitinib for severe alopecia areata by European Commission

The European Commission has approved ritlecitinib to treat adults and adolescents 12 years of age and older with severe alopecia areata. Ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3. According to results from ALLEGRO-LT phase 3 trial, the most common adverse reactions included diarrhea (9.2%), acne (6.2%), URTI (6.2%), urticaria (4.6%), rash (3.8%), folliculitis (3.1%), and dizziness (2.3%).

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In 1 min, Article

Elon Musk’s Neuralink to start human trial of brain implant for paralysis patients

Elon Musk’s brain-chip startup Neuralink has received approval to begin recruitment for the first human trial of its brain implant for paralysis patients. Those with paralysis due to cervical spinal cord injury or amyotrophic lateral sclerosis may qualify for the study. The study will use a robot to surgically place a brain-computer interface (BCI) implant in a region of the brain that controls the intention to move, Neuralink said, adding that its initial goal is to enable people to control a computer cursor or keyboard using their thoughts alone.

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