An epidemic of hepatitis D in the foothills of the Himalayas in south Kashmir

We have identified hepatitis D as an etiologic cause of an outbreak of 'hepatitis' in an endemic area for hepatitis B in South Kashmir, India. Thirty-five of the 51 patients with jaundice were hepatitis B virus carriers. Twenty-two of the 24 such patients tested had hepatitis D (hepatitis D virus superinfection). Two of the 3 patients with acute hepatitis B were coinfected with hepatitis D virus (HDV). Thirty-six asymptomatic household contacts of hepatitis D patients were assessed. Six were hepatitis B virus carriers, 3 of whom had HDV superinfection. Two contacts had acute hepatitis B, one with HDV coinfection. The disease occurred in adults with a mean age of 28.2 +/- 10.5 years (range 10-56 years) and was equally distributed between the sexes. Three patients with HDV superinfection presented with fulminant hepatic failure with a fatal outcome. All the patients with non-fulminant hepatitis D showed apparent clinical recovery. However, in the subsequent follow-up at 4 years, 7 patients with HDV superinfection had evidence of chronic hepatitis. One of these 7 patients died due to progressive chronic liver disease.     

Management of Complex Upper Extremity Trauma with Associated Vascular Injury

Introduction  Combined soft tissue and vascular injuries of the upper extremity pose several challenges at once to the plastic surgeon. Many decisions have to be taken urgently that will influence the salvage or amputation of the affected extremity. The aim of this article was to provide an evidence-based outline for the management of such injuries. Learning objectives of this article are as follows: (1) approach to a patient with upper extremity composite tissue and vascular injury presenting to the emergency, (2) decision-making as to when to salvage and when to go for amputation of the traumatized upper extremity, (3) role of imaging in emergency situation, (4) role of fasciotomy, (5) intraoperative sequencing of steps, and (6) options for vascular reconstruction and the flaps used for coverage. After reading this article, the reader should have a clear understanding of the management of vascular injury in a patient with composite defects of upper extremity.     

Genome-wide DNA hypermethylation opposes healing in patients with chronic wounds by impairing epithelial-mesenchymal transition

An extreme chronic wound tissue microenvironment causes epigenetic gene silencing. An unbiased whole-genome methylome was studied in the wound-edge tissue of patients with chronic wounds. A total of 4,689 differentially methylated regions (DMRs) were identified in chronic wound-edge skin compared with unwounded human skin. Hypermethylation was more frequently observed (3,661 DMRs) in the chronic wound-edge tissue compared with hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs were involved in epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation of a predicted specific upstream regulator TP53. RNA-Seq analysis was performed to qualify findings from methylome analysis. Analysis of the downregulated genes identified the TP53 signaling pathway as being significantly silenced. Direct comparison of hypermethylation and downregulated genes identified 4 genes, ADAM17, NOTCH, TWIST1, and SMURF1, that functionally represent the EMT pathway. Single-cell RNA-Seq studies revealed that these effects on gene expression were limited to the keratinocyte cell compartment. Experimental murine studies established that tissue ischemia potently induces wound-edge gene methylation and that 5′-azacytidine, inhibitor of methylation, improved wound closure. To specifically address the significance of TP53 methylation, keratinocyte-specific editing of TP53 methylation at the wound edge was achieved by a tissue nanotransfection-based CRISPR/dCas9 approach. This work identified that reversal of methylation-dependent keratinocyte gene silencing represents a productive therapeutic strategy to improve wound closure.     

Phagocytic function of monocytes of rhesus monkeys during Plasmodium knowlesi infection and the effect of treatment with chloroquine

The effect of chloroquine on the phagocytic function of monocytes was studied in normal and Plasmodium knowlesi-infected rhesus monkeys during a course of therapy. In normal animals, chloroquine inhibited phagocytic activity after three doses. The effect of the drug and concentration was greatest after six to eight days. Recovery in function of monocytes was noticed after the drug had been excreted. In P. knowlesi-infected monkeys, the degree of inhibition of phagocytosis depends on the level of parasitaemia. Chloroquine treatment reversed the trend of inhibition in the animals that received the drug when parasitaemia was less than 30%.     

Breakthrough COVID19 infections after vaccinations in healthcare and other workers in a chronic care medical facility in New Delhi,India

Background and aimsVaccinations for COVID19 are now open to all adults in India. However, spread of COVID19 infection continues unabated. We aimed to ascertain number of breakthrough COVID19 infections after vaccinations in a chronic care, diabetes-centric healthcare facility.MethodsWe reviewed rigorously maintained data of vaccinations, health status, symptoms of COVID19 & RT-PCR testing of all staff (doctors, nurses, paramedical workers, and other staff) in our health care facility from January 16, 2021 till date.ResultsOut of 123 employees, 113 were vaccinated (Covaxin, 28, Covishield, 85). Second dose was completed in 107 (94.7%) and first dose in 6 persons (5.3%). Symptomatic COVD19 infections occurred in 19 persons (16.9%) post any dose of vaccine. Symptomatic breakthrough infections > 14 days after second dose occurred in 15 persons (13.3%). Except one (required hospitalization), all 14 had mild COVID19 disease.ConclusionsWe report mild symptomatic breakthrough infections as seen in our health care facility. Research in breakthrough infections in India should be extended to other institutions and community to obtain larger data.     

Myopathy Associated With Statins and SGLT2 – A Review of Literature

Drug-induced myopathy is a well-described clinical entity characterized by muscle damage leading to symptoms ranging from myalgias to rhabdomyolysis and acute kidney injury. Many pharmacotherapies are known to precipitate myopathic symptoms. Recent case reports suggest a potential relationship between the use of sodium/glucose cotransport 2 (SGLT2) inhibitors and onset of myopathy. The pathogenesis of this has yet to be elucidated. The relevance of this association is augmented by the recent popularity of SGLT2 inhibitors as well as the tendency for them to be prescribed alongside statins. This study reviewed the literature on the incidence and mechanism of drug-induced myopathy in patients with type 2 diabetes mellitus who are taking SGLT2 inhibitors with and without the use of statins.