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Mild cortisol excess increases mortality in adrenal incidentaloma

Mortality is two to three times higher in patients with adrenal incidentalomas who have autonomous cortisol secretion levels of 83 nmol/L (3 µg/dL) or more after a 1 mg dexamethasone suppression test (DST) compared with those with levels below this, new research finds.

Autonomous cortisol secretion (ACS) has been linked to hypertension, cardiovascular disease, type 2 diabetes, and early mortality, and risks vary by cortisol level.

Source: Annals of Internal Medicine

A novel drug most effective in sickest HFrEF patients

The greatest relative benefit from omecamtiv mecarbil, a novel myotropic drug class that improves cardiac performance, is produced in heart failure patients with the lowest left ventricular ejection fraction (LVEF), a new analysis of the recently published phase 3 GALACTIC-HF trial has found.

The phase 3 multinational GALACTIC-HF trial, published earlier this year, linked omecamtiv mecarbil with an 8% reduction in the risk of a heart failure-related events or cardiovascular death, relative to placebo, which was the primary outcome. For entry, HFrEF patients were required to have a LVEF of 35% or less.

Source: Medscape

Sotagliflozin improves clinical outcomes in patients with HFpEF

The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST–WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions.

Source: Medscape

Management protocol for Mucormycosis by AIIMS Rishikesh

Management by Inj Liposomal amphotericin B (LAmB):

Test dose

•Inj. Liposomal Amphotericin- B 1 vial (50 mg) to be diluted in 12 ml of the diluent and 0.25ml (1 mg) of a solution made, to be mixed in 100ml Dextrose and to be infused in 30 minutes.
•Observe for fever and reactions

Pre-hydration

•500 mL NS over 30 minutes
•To reduce the risk of renal toxicity and hypokalaemia:- 500ml Normal Saline + 1 Amp (20mmol) KCL

Therapeutic dose

•5mg-10 mg /kg/day Amphotericin B in 500 mL D5 with 10 Units HIR over 3 hrs (To be covered in black sheet)

PostHydration

•500 mL NS over 30 minutes

Postdose

•KFT with Serum electrolytes after Every dose of Amphotericin B
•Fill Amphotericin monitoring chart

Duration: Continue for 14 to 21 days depending on severity/till clinical resolution and radiological stabilization; after 14days of therapy, shift to oral Posaconazole (200mg four times a day) if clinically stable.

Download Full Protocol ›

Source: AIIMS

Novel IL-6 antibody reduces CRP up to 92% in High-risk ASCVD

Inhibition of interleukin (IL)-6 with ziltivekimab reduces multiple biomarkers of inflammation and thrombosis in patients at high atherosclerotic risk with moderate to severe chronic kidney disease (CKD) and elevated C-reactive protein, results of the phase 2 RESCUE trial show.

At 12 weeks, median levels of high-sensitivity C-reactive protein (hsCRP) were reduced by 77%, 88%, and 92% with 7.5 mg, 15 mg, and 30 mg doses of ziltivekimab, respectively, every 4 weeks, compared with a 4% reduction with placebo.

Source: Medscape

Antibody status & incidence of SARS-CoV-2 infection in health care workers

The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear.

The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. Positive baseline anti-spike antibody assays were associated with lower rates of PCR-positive tests.

Full study: NEJM

ICMR releases guidelines for COVID-19 associated Mucormycosis

The correlation between COVID-19 and Mucormycosis isn’t surprising, as the biggest risk factors are uncontrolled diabetes and immune suppressant steroids. Rhino-orbital-cerebral and pulmonary infections are the most common syndromes caused by these fungi. The genera most commonly found in human infections are Rhizopus, Mucor, and Rhizomucor; Cunninghamella, Absidia (now reclassified as Lichtheimia), Saksenaea, and Apophysomyces are genera that are less commonly implicated in infection.

Source: ICMR

Statins: A potential treatment in COVID-19?

In the HARP-2 trial of simvastatin in acute respiratory distress syndrome (ARDS), published a few years ago, the main results were neutral, but in the subgroup of patients with hyperinflammatory ARDS, there was a reduction in mortality with simvastatin in comparison with placebo.

Moreover, in a series of observational studies of patients with COVID-19, use of statins was associated with a reduction in mortality among hospitalized patients. However, there are limited high-quality data to guide clinical practice.

Source: Medscape

Trastuzumab Deruxtecan has promising activity in Advanced Colorectal Cancer

Trastuzumab deruxtecan, an antibody-drug conjugate, showed “promising and durable activity” in HER2-positive metastatic colorectal cancer (CRC) refractory to standard treatment in an open-label phase-2 trial.

HER2 amplification is seen in 2% to 3% of colorectal tumors, but there are currently no approved HER2-targeted therapies for colorectal cancer.

The DESTINY-CRC01 trial evaluated trastuzumab deruxtecan in 78 patients with HER2-expressing metastatic CRC that had progressed on two or more previous regimens, including HER2-targeted therapies other than trastuzumab deruxtecan.

Patients were grouped by HER2-expression level: cohort A (HER2-positive, immunohistochemistry (IHC) 3+ or IHC2+ and in-situ hybridization (ISH)-positive; 53 patients); cohort B (IHC2+ and ISH-negative, seven patients); cohort C (IHC1+, 18 patients).

They received 6.4 mg/kg trastuzumab deruxtecan intravenously every three weeks until disease progression, unacceptable side effects, withdrawal of consent, or death.

After median follow up of 27 weeks, the objective response rate in cohort A (the primary endpoint) was 45.3% (24 of 53 patients). There was one (2%) complete response (2%) and 23 partial responses (43%), Dr. Salvatore Siena of the University of Milan, in Italy, and colleagues report in The Lancet Oncology.

Within cohort A, a greater proportion of patients with high levels of HER2 expression (IHC3+) had an objective response than did patients with IHC2+ and ISH-positive tumors (57.5% vs. 7.7%). “However, due to the low number of patients enrolled with IHC2+ and ISH-positive tumors, further studies are needed,” the investigators say.

“Although trastuzumab deruxtecan has shown antitumour activity in HER2-low breast tumors, no responses were seen among patients with HER2-low metastatic colorectal cancer tumors (cohort B, IHC2+ and ISH-negative; cohort C, IHC1+),” they note.

Source: Medscape

Varenicline nasal spray trial for Dry Eye

An experimental varenicline nasal spray can reduce signs and symptoms of dry eye disease, the results of a phase 3 trial suggest. That’s because Oyster Point’s OC-01 works by stimulating the trigeminal nerve through the nasal passage, causing the eyes to tear. By contrast, most current treatments are either anti-inflammatories or artificial tears that don’t include all the components of natural ones.

OC-01 also improves symptoms relatively fast — in as few as 14 days, rather than the 3-6 months needed for some other dry eye treatments.

Source: Medscape

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