Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Omnipresent and The Omnipotent – Surveillance and Power: A Critical Analysis Of Suzanne Collins’ The Hunger Games

The objective of this paper is to trace the derivation of power through imperious surveillance upon the citizens of Panem and the consequent denial of citizen rights. The paper also analyses the nature of people’s fear of being watched and how the overbearing surveillance system in action can violate individual privacy. The act of being continuously watched or monitored and the knowledge of being under the control of power, a 'watchful eye', can create a huge impact upon the people under surveillance. In the modern world, people are being watched continuously and closely and are tracked through economic activities and electronic media. The paper aims to prove that surveillance in any form is a constraining force limiting people from being themselves. The Hunger Games by Suzanne Collins portray a dystopian post-apocalyptic land of Panem where the Capitol uses surveillance and the people’s fear of being watched as tools to assert their power over the citizens. After years of being watched and controlled, the people of Panem have forgotten basic citizen birthrights and the beauty of freedom in their lives. These people lose their real identity in this cage where they are devoid of any individual preferences. If the citizens are not completely aware of the value of privacy which is an inherent human right and much required for individual growth and development, the possibilities of losing the contemporary world to such a dystopian reality are high

Extra-adrenal retroperitoneal paraganglioma associated with duplication of inferior vena cava

Retroperitoneal paragangliomas arise from specialized neural crest cells symmetrically distributed along the aorta in association with the sympathetic chain. If this tissue aggregates in the adrenal medulla pheochromocytoma may arise. When it remains in the paraaortic sites it could develop into extra-adrenal, retroperitoneal paraganglioma. We report a case of extra-adrenal paraganglioma in the renal hilum intimately related to the left side of a double inferior vena cava. To the best of our knowledge such an association has never been described before. The clinical significance of this venous anomaly is reviewed

Bilineage T-lymphoblastic/myeloid extramedullary blast crisis in chronic myelogenous leukemia

The blast crisis of chronic myelogenous leukemia (CML) can be hematological or extramedullary. About 25% of these cases fulfill the criteria for mixed phenotype acute leukemia. We here report a case of a second blast crisis of CML which was extramedullary and was immunophenotypically bilineage T/myeloid

Our experience with papillary thyroid microcancer

Background: Papillary thyroid microcarcinoma (PTMC) describes a focus of papillary thyroid cancer that is less than 1 cm in size. These tumors are frequently found on histopathological examination of thyroid specimens, operated upon for an indication other than suspected malignancy. Materials and Methods: From 2005 to 2012, 94 of 1300 thyroidectomy specimens in our institution were found to have PTMC. Of these, 77 were isolated PTMC while the others were associated with other differentiated cancers. We studied their clinicopathologic features, treatment and long-term outcome. Results: There were 18 men and 59 women (the male: female ratio was 1:3), their mean age was 44 ± 10.5 years (range: 18-72 years). Multinodular goiter was the most common indication for surgery. Malignancy was suspected in only 31.4% cases. The mean tumor size was 4.1 ± 2.3 mm. Nearly 17% cases had slightly larger tumors measuring >6 but <10 mm. Multifocal tumor was found in 44.1% of cases and among these, multifocal disease restricted to a single lobe was found in 19.5%. Eleven patients (14.2%) had cervical lymph node metastasis, 3 (3.9%) had extra thyroid tumor extension and 2 (2.6%) had evidence of vascular invasion. One patient (1.3%) presented with bone metastasis.Majority of the patients (79.2%) underwent total thyroidectomy with or without lymph node dissection. Sixteen patients (20.7%) who had initially undergone hemithyroidectomy went on to have completion thyroidectomy. Twenty nine patients (36.8%) also received radioactive iodine.The mean duration of follow-up was 20.2 ± 13.5 months. On follow-up one patient developed cervical lymph node recurrence and one died due to a second malignancy. Conclusions: PTMC is often found as an incidental finding on the thyroidectomy specimen. Sometimes they present with regional lymph node metastasis and very rarely with distant metastasis. They have a good prognosis similar to papillary thyroid carcinoma

Low dose aspirin prevents duodenoesophageal reflux induced mucosal changes in wistar rat esophagus by MAP kinase mediated pathways

AbstractBackgroundInvestigations of molecular mechanisms behind the progression of neoplastic changes in the esophagus have uncovered the role of the COX & 5-Lox pathways. Human squamous esophageal mucosa produces relatively large amounts of eicosanoids in the presence of inflammation. Laboratory and epidemiological data suggest that aspirin and non-steroidal anti-inflammatory drugs may be chemo preventive through their inhibitory effect on COX25, 10. Cell culture studies have shown that the members of the mitogen activated protein (MAP) kinase family plays an important role in the development of bile acid-induced carcinogenesis. Differences in MAPK pathways activated by bile exposure were also noted in esophageal squamous cell lines and biopsies from patients with GERD. The protective role of aspirin and its molecular mechanism is not well understood.Aims1.The effect of duodenal reflux on esophageal mucosa.2.The role of aspirin in preventing duodenal reflux induced esophageal mucosa changes.3.If it is proven to be preventive, the mechanism of its action. A duodenal reflux rat animal model was used by an end- to-side esophago duodenostomy.MethodsTotal of 56 rats was included. 3 were "Naive control" animals which did not undergo the surgical procedure. The remaining animals were divided into two groups: Surgery alone (experimental) and Surgery + aspirin [therapy group], esophagoduodenostomy. At 40 weeks, the rats were euthanized and appropriate esophageal samples were analysed for histopathology and p38 & ERK MAP kinases, VEGF, protease activity and caspase 3 activities.ResultsThe presence of gross mucosal nodularity was seen in 21 and 10 rats of the experimental and therapy group respectively (p = 0.03; Table 1). Reflux-associated changes such as basal cell hyperplasia were more common in the experimental group, however this association did not reach statistical significance (p = 0.15; Table 1). Epithelial hyperplasia was seen more in the experimental group, which was prevented by aspirin [p < 0.01]. Papillomatosis, as shown in Fig. 4 was more common in the experimental group (p = 0.02). Activation of p38 & ERK MAP kinases was prevented in aspirin group (p < 0.05, CI −1.796–−0.014). Examination of protease activity by zymographic analysis of the esophageal samples revealed a number of gelatinolytic bands in 50% rats of the experimental group, not observed in the therapy group. No significant changes were seen in Caspase 3 [Normal areas −99.74 & nodular areas – 100.34 percent of controls] or VEGF [mean 0.64, sd ± 0.76 Vs 0.69 ± 0.96] activity.ConclusionsOur data demonstrated that low dose aspirin reduced the incidence of duodenoesophageal reflux induced histological changes in the esophagus by preventing activation of proliferative & anti-apoptotic MAP kinases such as p38 & ER as well as protease activity. Though Barretts’ changes and adenocarcinoma have not developed, it could explain the role of duodenoesophageal reflux in the development of different histological but potential premalignant lesions and molecular level changes which are prevented by low dose aspirin

Recurrent cutaneous eosinophilic vasculitis: A rare entity

Recurrent cutaneous necrotizing eosinophilic vasculitis is a rare entity described by Chen et al. It has a benign course without any systemic involvement. However, often long-term treatment with systemic steroids is required. The exact etiopathogenesis remains unknown. We report a female patient, who presented with recurrent pruritic purpuric papules and plaques affecting different body parts of long duration. Disease was well controlled with low dose systemic steroids, but invariably recurred on its withdrawal. Histology revealed the features of eosinophilic vasculitis. Subsequent detailed evaluation ruled out systemic involvement, underlying diseases, and any precipitating factors. Hence, a diagnosis of recurrent cutaneous eosinophilic vasculitis was made. Patient showed excellent response to prednisolone, and on tapering the drug, it was found that she needed a maintenance dose of 5 mg/day. We did not come across any previous reports of recurrent cutaneous eosinophilic vasculitis from India