A PROSPECTIVE OBSERVATIONAL CASE SERIES OF OPHTHALMIC MANIFESTATIONS AND TREATMENT MODALITY OF RHINO-OCULO-CEREBRAL MUCORMYCOSIS DURING SECOND WAVE OF COVID PANDEMIC IN A TERTIARY CARE HOSPITAL.

Aim: During the second wave of the COVID-19 pandemic in India, there has been a significant increase in the prevalence of COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM). In this investigation, the primary objective was to ascertain the ocular manifestations of risk factors encompassing comorbidities and pharmacological interventions employed in the management of COVID-19. Methodology: This study presents a prospective, observational case series examining patients diagnosed with COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) who exhibited ocular manifestations. The patients included were seen at the eye outpatient department, admitted to the ear, nose, and throat department, and received treatment for COVID-19 at a designated COVID hospital. The study was conducted for a duration of three months, from 1st May 2021 to 30th August 2021. Results: The majority of cases developed ROCM symptoms between day 10 and day 15 after COVID-19 diagnosis, with 56% developing within 14 days and 44% developing beyond 14 days. Orbital involvement, with stage 3c, comprises the majority (27%) of the total. 73% received intravenous amphotericin B, 56% underwent pa: ranasal sinus (PNS) debridement/ functional endoscopic sinus surgery (FESS), 3% received both orbital exenteration and PNS/ FESS debridement, and 15% underwent orbital exenteration. Intraorbital amphotericin B injections were administered in 22% of cases. The final follow-up revealed a 14% mortality rate. Conclusion: Diabetes mellitus and corticosteroids are the most significant risk factors for COVID-19-associated ROCM development. COVID-19 patients must be followed even after recovery. A successful outcome requires a high index of clinical suspicion, awareness of red flag signs and symptoms, speedy diagnosis, early treatment initiation with amphotericin B, orbital exenteration when indicated, and aggressive surgical debridement of the PNS. Recommendation: In the case of COVID-19 patients who are suffering from diabetes mellitus and are treated with corticosteroids, physicians should be vigilant and monitor patients carefully for the occurrence of rhino-orbital-cerebral mucormycosis

Impact of various detergent-based immersion and perfusion decellularization strategies on the novel caprine pancreas derived extracellular matrix scaffold

Limited availability of the organs donors has facilitated the establishment of xenogeneic organ sources for transplantation. Numerous studies have decellularized several organs and assessed their implantability in order to provide such organs. Among all the decellularized organs studies for xenotransplantation, the pancreas has garnered very limited amount of research. The presently offered alternatives for pancreas transplantation are unable to liberate patients from donor dependence. The rat and mice pancreas are not of an accurate size for transplantation but can only be used for in-vitro studies mimicking in-vivo immune response in humans, while the porcine pancreas can cause zoonotic diseases as it carries porcine endogenous retrovirus (PERV- A/B/C). Therefore, we propose caprine pancreas as a substitute for these organs, which not only reduces donor dependence but also poses no risk of zoonosis. Upon decellularization the extracellular matrix (ECM) of different tissues responds differently to the detergents used for decellularization at physical and physiological level; this necessitates a comprehensive analysis of each tissue independently. This study investigates the impact of decellularization by ionic (SDS and SDC), non-ionic (Triton X-100 and Tween-20), and zwitterionic detergents (CHAPS). All these five detergents have been used to decellularize caprine pancreas via immersion (ID) and perfusion (PD) set-up. In this study, an extensive comparison of these two configurations (ID and PD) with regard to each detergent has been conducted. The final obtained scaffold with each set-up has been evaluated for the left-over cytosolic content, ECM components like sGAG, collagen, and fibronectin were estimated via Prussian blue and Immunohistochemical staining respectively, and finally for the tensile strength and antimicrobial activity. All the detergents performed consistently superior in PD than in ID. Conclusively, PD with SDS, SDC, and TX-100 successfully decellularizes caprine pancreatic tissue while retaining ECM architecture and mechanical properties. This research demonstrates the viability of caprine pancreatic tissue as a substitute scaffold for porcine organs and provides optimal decellularization protocol for this xenogeneic tissue. This research aims to establish a foundation for further investigations into potential regenerative strategies using this ECM in combination with other factors

Effectiveness of intermittent screening and treatment for the control of malaria in pregnancy: a cluster randomised trial in India.

BACKGROUND: The control of malaria in pregnancy (MiP) in India relies on testing women who present with symptoms or signs suggestive of malaria. We hypothesised that intermittent screening and treatment for malaria at each antenatal care visit (ISTp) would improve on this approach and reduce the adverse effects of MiP. METHODS: A cluster randomised controlled trial comparing ISTp versus passive case detection (PCD) was conducted in Jharkhand state. Pregnant women of all parities with a gestational age of 18-28 weeks were enrolled. Women in the ISTp group were screened with a rapid diagnostic test (RDT) for malaria at each antenatal clinic visit and those in the PCD group were screened only if they had symptoms or signs suggestive of malaria. All RDT positive women were treated with artesunate/sulfadoxine-pyrimethamine. The primary endpoint was placental malaria, determined by placental histology, and the key secondary endpoints were birth weight, gestational age, vital status of the newborn baby and maternal anaemia. RESULTS: Between April 2012 and September 2015, 6868 women were enrolled; 3300 in 46 ISTp clusters and 3568 in 41 PCD clusters. In the ISTp arm, 4.9% of women were tested malaria positive and 0.6% in the PCD arm. There was no difference in the prevalence of placental malaria in the ISTp (87/1454, 6.0%) and PCD (65/1560, 4.2%) groups (6.0% vs 4.2%; OR 1.34, 95% CI 0.78 to 2.29, p=0.29) or in any of the secondary endpoints. CONCLUSION: ISTp detected more infections than PCD, but monthly ISTp with the current generation of RDT is unlikely to reduce placental malaria or impact on pregnancy outcomes. ISTp trials with more sensitive point-of-care diagnostic tests are needed

Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood-brain barrier in cerebral malaria.

Cerebral malaria (CM) is caused by the binding of Plasmodium falciparum-infected erythrocytes (IEs) to the brain microvasculature, leading to inflammation, vessel occlusion, and cerebral swelling. We have previously linked dual intercellular adhesion molecule-1 (ICAM-1)- and endothelial protein C receptor (EPCR)-binding P. falciparum parasites to these symptoms, but the mechanism driving the pathogenesis has not been identified. Here, we used a 3D spheroid model of the blood-brain barrier (BBB) to determine unexpected new features of IEs expressing the dual-receptor binding PfEMP1 parasite proteins. Analysis of multiple parasite lines shows that IEs are taken up by brain endothelial cells in an ICAM-1-dependent manner, resulting in breakdown of the BBB and swelling of the endothelial cells. Via ex vivo analysis of postmortem tissue samples from CM patients, we confirmed the presence of parasites within brain endothelial cells. Importantly, this discovery points to parasite ingress into the brain endothelium as a contributing factor to the pathology of human CM

Primary Appendiceal Mucinous Adenocarcinoma

Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as having acute appendicitis. All the routine investigations were within normal limit. USG of abdomen showed dilated appendix with little fluid collection adjacent to it and no other abnormality was seen which suggested acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy was done as a second stage procedure. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory

Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis

International audiencePlasmodium falciparum gametocytes, the sexual stages responsible for malaria parasites transmission from humans to mosquitoes, are key targets for malaria elimination. Immature gametocytes develop in the human bone marrow parenchyma, where they accumulate around erythroblastic islands. Notably though, the interactions between gametocytes and this hematopoietic niche have not been investigated. Here we identify late erythroblasts as a new host cell for P.falciparum sexual stages and show that gametocytes can fully develop inside these nucleated cells in vitro and in vivo, leading to infectious mature gametocytes within reticulocytes. Strikingly, we found that infection of erythroblasts by gametocytes and parasite-derived extracellular vesicles delay the erythroid differentiation, thereby allowing gametocyte maturation to coincide with the release of their host cell from the bone marrow. Taken together, our findings highlight new mechanisms that are pivotal for the maintenance of immature gametocytes in the bone marrow, and provide further insights on how Plasmodium parasites interfere with erythropoiesis and contribute to anemia in malaria patients