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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

Clinical Inshorts by ClinicHours

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.

Clinical Inshorts by ClinicHours

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

Clinical Inshorts by ClinicHours

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
Clinical Rounds by ClinicHours

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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Naltrexone can be safely administered to patients with alcohol use disorder (AUD) and compensated cirrhosis to help them achieve abstinence and decrease craving, results of the first such randomized controlled trial show. The prospective, double-blind, single-center study at the ILBS, in New Delhi, enrolled 100 patients with alcohol dependence and cirrhosis between 2020 and 2022. Participants were randomly assigned in a 1:1 ratio to receive naltrexone (50 mg/d) or placebo for 12 weeks.

Clinical Inshorts by Clinic Hours