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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
Clinical Inshorts by ClinicHours

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.

Clinical Inshorts by ClinicHours

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

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.

Clinical Inshorts by ClinicHours

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
Clinical Inshorts by ClinicHours

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
Clinical Rounds by
ClinicHours

Dichlorvos Ingestion – An OP poisoning case

History: A 27 yr old female brought to ED with A/H/O ingestion of 50ml of Dichlorvos solution at her home 35 minutes ago. On arrival primary survey was

A – Airway compromised

B – Breathing Laboured, Spo2 – 37% on RA, B/L crepts +nt

C – BP – 166/78 mmhg P – 90 bpm

D – E1V2M2 Pupils – B/L constricted, RBS – 112 mg/dl

ABG done shows ph 6.98 pco2 23 pO2 68 hco3 13 Lac 17 AG 22. What’s the diagnosis and how will you manage this patient?

Answer: Dichlorvos is an organophosphate compound.

Look for signs & symptoms of OP poisoning & ask the attendants to bring the sample  :

  • Muscarinic manifestations : DUMBELSDiarrhoea; Urinary incontinence; Miosis; Bradycardia, Bronchorrhea and Bronchospasm; Emesis; Lacrimation, Low blood pressure; Salivation and Sweating. Others include abdominal cramps, hypertension, fascicu­lations, muscle weakness, confusion, coma, seizures.
  • Nicotinic manifestations: Twitching, fasciculations, weakness, diminished respiratory effort, HTN & tachycardia.
  • CNS manifestations: Anxiety, restlessness, tremors, convulsions, confusion, weakness and coma.

Diagnosis:

  • Clinical diagnosis is based on the toxidrome
  • History of exposure
  • ABG, ECG (Prolong QT), CBC, LFT, KFT
  • Cholinesterase assay if available

Rx plan: 

  1. Evaluate ABCD.
  2. Stable patient: Decontamination (Healthcare workers should wear PPE).
  3. Unstable patient: Resuscitation first followed by decontamination. (Never use succinylcholine for intubation).
  4. Gastric lavage within first 1hr of ingestion (Seal GL sample for MLC) with NS & activated charcoal is given orally at a dose of 1-2 g/kg body weight.
  5. Inj. Atropine 1mg or 0.01 to 0.04 mg/kg IV. Double the dose every time and target end points is atropinisation (Clear chest on auscultation with no wheeze, HR>80, pupils no longer pinpoint, dry axilla & SBP >90 mmHg). Once atropinised set up an infusion of atropine at an hourly dose of 10-20% of the total dose of atropine given initially.
  6. Inj. Pralidoxime (2-PAM) is a cholinesterase reactivator. It is effective for nicotinic as well as muscarinic features of toxicity. 30 mg/kg initially over 20 mins followed by a constant infusion at 9 mg/kg/ hour. It is usually continued for 12-24 hrs.

Complications: 

  • Intermediate Syndrome – Syndrome of muscular paralysis occurs within 24-96 hours after ingestion of an organophosphate and following treat­ment of acute cholinergic syndrome. Muscle weakness affects predominantly neck flexors, proximal limb muscles, those supplied by cranial nerves & respiratory muscles.
  • Organophosphate-lnduced Delayed Polyneuropathy (OPIDN) – Cramping muscle pain in the lower limbs, distal numbness and paraesthesia followed by progressive weakness, depres­sion of deep tendon reflexes in the lower limbs > the upper limbs.

Ddx :

  • Carbamate toxicity
  • Nicotine toxicity
  • Methacholine toxicity
  • Arecoline toxicity
  • Bethanechol toxicity
  • Pilocarpine toxicity
  • Pyridostigmine toxicity
  • Neostigmine toxicity
  • Mushroom poisoning
  • Poison hemlock
Clinical Rounds by ClinicHours

Raccoon eyes case

History: A 60 yr female with history of fall from 5 stairs at her residence. No history of LOC/ ENT bleed/ seizure/ vomiting/ FND. On examination B/L periorbital discoloration can be noted. What’s the likely diagnosis?

Answer: Raccoon eyes sign aka panda eyes is periorbital ecchymosis with sparing of the tarsal plate and is a physical examination finding indicative of a base of skull fracture of the anterior cranial fossa. It has positive predictive value of 85%. Also seen in metastatic neuroblastoma, Kaposi sarcoma, multiple myeloma, and amyloidosis.

Clinical Rounds by ClinicHours

A Hydrofluoric acid burn case

History: A 35 yr old male working with germicides accidentally came in contact with hydrofluoric acid presented to ED with blue-gray appearance with surrounding erythema of skin with extreme pain. How will you manage this in your ED?

Answer:  Decontaminate the patient by removing contaminated clothing and do copious irrigation for 15-30 mins.

  • Apply 2.5 % Calcium gluconate gel LA.
  • Inj 10% Calcium gluconate ID at rate of 0.5mL/cm2 OR 40 ml D5 + 10 mL 10%  calcium gluconate infusion over 4 hrs.

Investigation: VBG, ECG, serum electrolytes.

Hydrofluoric acid (HF) quickly penetrates the skin, where fluoride ions react with calcium and magnesium, causing significant electrolyte disturbances such as hypocalcemia and hypomagnesemia. Additionally, HF inhibits potassium channels, leading to hyperkalemia. These abnormalities can trigger severe cardiac arrhythmias, including ventricular fibrillation, which can be fatal. A notable symptom of HF burns is intense pain disproportionate to the injury, attributed to potassium depletion from nerve endings.

Clinical Rounds by ClinicHours

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
Clinical Inshorts by ClinicHours
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