Assessing the accuracy of pleural puncture sites in patients with pleural effusion as determined by clinical examination versus ultrasound-A single-centre prospective study.

INTRODUCTION: This study aimed to ascertain the accuracy of clinical examination for the determination of pleural puncture sites as compared to the use of ultrasonography in patients with pleural effusion. MATERIAL AND METHODS: A single-centre, prospective, observational study was carried out amongst 115 patients with pleural effusion in a tertiary care hospital in western India. Patients were subjected to clinical assessment for determination of pleural puncture sites and the same were confirmed with ultrasonography. All physicians were blinded to the marking of the previous physician to prevent any influence on their assessment. RESULTS: The study had 345 physician observations. The overall accuracy of the clinical examination was 94.8%. Multivariate logistic regression of the factors responsible for the accuracy of clinical examination demonstrated a significant role of higher body mass index (BMI) (OR-1.19) and lower zone pleural effusions (OR-4.99) when adjusted for age, gender, side of effusion, and experience of examining doctors. When the effusions were classified according to their location, lower zone pleural effusions and loculated pleural effusions had an error rate of 15.9% and 8.33%, respectively. CONCLUSION: An ultrasound is the standard of care to assess all pleural effusions and guide the best point for aspiration.

Scorpion Sting Envenomation, a Neglected Tropical Disease: A Nationwide Survey Exploring Perspectives and Attitudes of Resident Doctors from India.

Scorpion sting envenomation (SSE) is a commonly encountered and a significant problem in the tropics, affecting rural and marginalized communities. However, it is not formally listed as a neglected tropical disease (NTD) by the WHO. We designed this cross-sectional study to explore medical graduates' and resident doctors' perspectives on SSE as an NTD and to assess their experiences, knowledge, and confidence in managing these patients. An online questionnaire was developed, validated, and administered to interns and resident doctors across India. Adjusted odds ratios were calculated for factors predicting high self-reported confidence scores for managing scorpion stings using multivariable logistic regression. The final questionnaire contained 26 items including participant background, perspectives about SSE being an NTD, experiences, knowledge, and skills needed to manage, and prevent stings effectively. Of 454 participants, 69% opined that SSE was an NTD, and > 60% felt that SSE was inadequately addressed within undergraduate training. Predictors of high self-reported confidence scores in management competencies were residency in a clinical branch that commonly encountered SSE (internal/emergency medicine or pediatrics, P < 0.0001), having ever managed an SSE patient alone or as a part of a team (P < 0.0001), and attending a class or teaching session on SSE during undergraduate training (P = 0.048). Our results suggest that residents across India believe that there is an urgent need to declare SSE an NTD to increase its visibility, further paving the way for innovative multilevel cross-cutting solutions for mitigation. Designing authentic learning experiences can help produce competent and empathetic physicians in managing and preventing SSE.

Delayed Compression Paralysis Following an Iliopsoas Hematoma 30 Days After Saw-Scaled Viper (Echis carinatus sochureki) Envenoming: A Case Report.

Snakebite envenoming is a neglected tropical disease disproportionately affecting the rural and marginalized population in low-middle-income countries. The saw-scaled viper (Echis carinatus) is a clinically important snake that causes serious morbidity and mortality in the Indian subcontinent. Even though it is within the so-called big-four snakes against which polyvalent antivenom is available throughout India, reports of antivenom ineffectiveness are emerging in saw-scaled viper envenoming, especially around Jodhpur, Rajasthan, India. This case report highlights a patient with saw-scaled viper envenoming with an ineffective antivenom response complicated by acute kidney injury as well as local and systemic bleeding complications, which subsequently resulted in a pelvic hematoma that compressed the lumbosacral nerves, causing lower-limb weakness and sensory deficits. He was successfully managed with hematoma aspiration and supportive care. This case brings into focus the challenges of managing saw-scaled viper envenoming in this region with antivenom ineffectiveness, resulting in delayed and significant coagulopathy and its complications leading to prolonged hospital stay and morbidity. Our report spotlights less emphasized aspects of long-term morbidity in snakebite survivors, such as loss of working days and productivity. We also highlight the need for an organized system of long-term follow-up of snakebite survivors to screen for possible complications and manage them early.

A clinical and in-silico study of microRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors. METHODS: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR. RESULTS: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients. CONCLUSIONS: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.

Use of rotational thromboelastometry to predict the outcome of COVID-19 patients: A retrospective observational study.

Background and Aims: The hypercoagulability occurring in COVID-19 patients is detected only by Rotational thromboelastometry (ROTEM). However, the benefit of performing ROTEM in the management of disease and predicting the outcome of COVID-19 patients is yet to be established. Material and Methods: The data of 23 critically ill and 11 stable COVID-19 adult patients were extracted from the hospital information system admitted between July and August 2020 and patient charts and analyzed retrospectively. The critically ill patients were divided as a survivor and non-survivor groups. The Intrinsic pathway part of ROTEM (INTEM) and Fibrinogen part of ROTEM (FIBTEM) were performed on day 0 for both critically ill and stable patients, and on day 10 for critically ill patients. The statistical package for social science (SPSS) version 26 was used for statistical analysis. Results: The median FIBTEM amplitude at 5 min (A5) and maximum clot firmness (MCF) were elevated in both stable and critically ill patients (24 vs 27 mm, P = 0.46 and 27.5 vs 40 mm, P = 0.011) with a significant difference in FIBTEM MCF. But there was no significant difference between number of survivors and non-survivors with FIBTEM MCF >25 at day 0 and day 10. Conclusion: The Hypercoagulability state as detected by ROTEM parameters at day 0 and day 10 had no association with the outcome (mortality) of critically ill COVID-19 patients. Hence it cannot be used as a prognostic test. The increasing age, comorbidities and D-dimer values were associated with a poor prognosis in COVID-19 patients.

Evaluation of Liver Histopathological Findings of Coronavirus Disease 2019 by Minimally Invasive Autopsies.

AIM: The severe acute respiratory syndrome coronavirus 2 outbreak resulted in severe health impact with the loss of many lives across the world. Pulmonary parenchyma suffers the most from the brunt of the infection. However, evidence suggested a systemic involvement during the course of illness. Information on morphological changes of the liver is sparse in the literature. We aimed to evaluate the pathological findings in the liver by minimally invasive autopsies. METHODS: Postmortem core biopsies of the liver obtained from patients who succumbed to coronavirus disease 2019 disease were studied. Demographic findings, comorbidities, and relevant laboratory tests were collected. Detailed histopathological changes were assessed. RESULTS: Liver function tests were available in 40 cases, and it was deranged in 80% cases. A spectrum of histological changes was observed. Macrovesicular steatosis and nonspecific portal inflammation of mild degree were the common morphological changes. Features suggestive of vascular alteration were noted in more than half of the cases. These included increased portal vein branches, irregular luminal dilation, and herniation of portal veins into the periportal hepatocytes. In addition, we observed morphological changes attributed to terminal shock-related changes. CONCLUSION: The present study results highlight that liver parenchyma changes may be related to multiple pathogenic mechanisms. The presence of vascular alteration in portal tracts suggests derangement of hepatic vasculature related to systemic hypercoagulable state induced by the viral infection. It remains to be established if the histological changes are related to direct viral insult or to the systemic response caused by the viral attack.

Evaluation of Bone Marrow Findings of COVID-19 by Minimally Invasive Autopsies: A Single Tertiary Care Centre Experience from India.

The 2019 novel coronavirus (2019-nCoV) originated in Wuhan City of China. In India, first confirmed case of coronavirus disease (COVID-19) was reported on January 30, 2020 and India is presently hit by second wave of COVID-19. The aim of the present study was to evaluate bone marrow findings of COVID-19 by minimally invasive autopsies to aid in understanding pathophysiology of the disease. This prospective study was conducted at tertiary care centre of Western Rajasthan. After obtaining approval from Institute's ethics committee and consent from next of kins, minimally invasive autopsies were conducted in 37 COVID-19 deceased patients within an hour after the death. The tissue specimens were processed with standard biosafety measures. Electronic medical records were reviewed retrospectively and patients' clinical details and results of laboratory investigations were noted. In this prospective study, bone marrow biopsies were collected from 37 COVID-19 minimally invasive autopsies. Mean age of these cases was 61.8 years and male: female ratio was 2.36. Comorbidities were observed in 25 (67.5%) of all cases. Histopathological analysis revealed hypercellular, normocellular and hypocellular marrow in 5, 25 and 5 cases respectively (two biopsies were inadequate). There was marked interstitial prominence of histiocytes in 24 (68.5%) cases. Out of these, evidence of haemophagocytosis was observed in 14 (40%) cases, marked increase of haemosiderin laden macrophages in 20 (57.1%) cases. There was prominence of plasma cells in 28 (80%) cases. The present study attempted to fill the gap of dearth of literature from our country in COVID-19 autopsy studies by highlighting bone marrow findings. The data support the evidence of development of secondary haemophagocytic lymphocytosis in COVID-19 cases.

A Composite Study of Coagulation Milieu in Covid-19: Experience from a Tertiary Care Centre from India.

BACKGROUND: The understanding of pathogenesis is necessary for the development of effective treatment for COVID-19. Various studies have postulated that there is a complex interplay of mediators of coagulation and inflammation responsible for the pathogenesis of COVID-19. We did this study on coagulation parameters and inflammatory markers and their effect on outcome in patients with COVID-19. METHODS: This was a single centre observational cross-sectional study. Procoagulants [Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, lupus anticoagulant (LA), fibrinogen, factor-VIII (F-VIII)]; anticoagulants [protein-C (PC), protein-S (PS), antithrombin] and inflammatory markers [interleukin-6 (IL-6) and highly sensitive - C-reactive protein (hs-CRP)] were measured at the time of hospitalization and correlated with the severity of the disease. RESULTS: A total of 230 patients were enrolled, of which 61.3%, 20.0%, and 18.7% had asymptomatic/ mild, moderate, or severe disease, respectively. COVID-19 disease severity was associated with rising trends with coagulation parameters (PT, APTT, D-Dimer; p value 0.01, <0.0001, <0.0001, respectively). Falling trends of anticoagulant (PC, Antithrombin; p value <0.0001, 0.003 respectively) and rising trends of procoagulant (fibrinogen, F-VIII; p value 0.004, <0.0001 respectively) were observed with increasing COVID-19 disease severity. Multivariate logistic regression analysis found that advanced age, high D-Dimer, and high hs-CRP (p value 0.035, 0.018, <0.0001 respectively) were independent predictors of mortality in COVID-19. Procoagulant parameters (D-dimer, APTT, Factor VIII) were positively correlated with anticoagulant parameters (PC and PS) and inflammatory parameters (hs-CRP). CONCLUSION: This study revealed increased levels of coagulation and inflammatory parameters, which correlated with the severity of COVID-19. Age, D-dimer, IL-6, hs-CRP, APTT, fibrinogen, and Factor VIII were significantly higher in patients with moderate and severe disease as compared to asymptomatic/mild disease. Advanced age, high D-dimer, and high hs-CRP were significantly associated with poor outcomes.

Clinical Features, Radiological Findings, and Treatment Outcomes in Patients with Pulmonary Nocardiosis: A Retrospective Analysis.

Introduction Lack of specific clinical features makes the diagnosis of pulmonary nocardiosis difficult. A high index of suspicion is required for diagnosis especially in cohorts with pre-existing risk factors. This study aimed to study the clinical and radiological characteristics and outcomes in patients with pulmonary nocardiosis. Methods This was a retrospective observational study. Data of confirmed cases with pulmonary nocardiosis were collected from a digital patient management system. Results A total of eight cases of pulmonary nocardiosis were included. The mean age of patients was 50 ± 14.3 years with a female preponderance (62.5%). The most common co-morbidity was chronic lung disease (37.5%). The common clinical feature of pulmonary nocardiosis was cough with expectoration (50%) and the mean duration of symptoms was 18 days. The common radiological (CT thorax) findings were consolidation, bronchiectasis, mediastinal lymphadenopathy, and nodularity (50% each). One patient had an extension of pulmonary disease in the chest wall. Microbiological detection of Nocardia spp. was done in sputum samples (50%) and in bronchoalveolar lavage (BAL) samples (50%). Culture was positive in two BAL samples. Intravenous empirical antibiotics in combination with oral trimethoprim-sulfamethoxazole double standard (15 mg/kg trimethoprim) were started at the time of diagnosis. Ceftriaxone and amikacin were commonly used antimicrobials. Conclusion Nocardia spp. commonly causes disease in patients with pre-existing chronic disease. A high index of suspicion is required in patients with subacute to chronic respiratory symptoms, raised inflammatory markers, and the absence of common respiratory pathogens in evaluation.

Post-Discharge Prophylactic Anticoagulation in COVID-19 Patients: A Clinical Dilemma.

BACKGROUND: COVID-19 pandemic has taken a great toll on the health care system worldwide. Along with the pandemic, there is also a concern regarding post COVID-19 complications in recovered patients. Thromboembolism (TE) has been reported as a fatal complication in recovered patients with COVID-19. There is still a great dilemma in post-discharge TE prophylaxis and its long-term benefits. CASE DESCRIPTION: We reported three cases of post COVID-19 with complications related to both diseases as well as post discharge anticoagulant therapy. The first case is about a 60-yr-old male who developed Covid-19 pneumonia (moderate disease) and was discharged on rivaroxaban after initial improvement. 3 weeks later, the patient was readmitted with lower gastro-intestinal bleeding. The other two cases developed pulmonary thromboembolism within a span of 2-3 months (after recovered from COVID-19 pneumonia). Both these patients were not prescribed anticoagulants for TE prophylaxis. CONCLUSION: There is an imperative need for effective guidelines for post discharge TE prophylaxis in COVID-19.

The Indian Society for Bone and Mineral Research (ISBMR) position statement for the diagnosis and treatment of osteoporosis in adults.

The Indian Society for Bone and Mineral Research (ISBMR) has herein drafted clinical practice guidelines for the diagnosis and management of osteoporosis for the people of India. Implementation of the position statement in clinical practice is expected to improve the overall care of patients with osteoporosis in India. PURPOSE: In India, osteoporosis is a major public health problem. However, in the absence of any robust regional guidelines, the screening, treatment, and follow-up of patients with osteoporosis are lagging behind in the country. METHODS: The Indian Society for Bone and Mineral Research (ISBMR), which is a multidisciplinary group of physicians, researchers, dietitians, and epidemiologists and who study bone and related tissues, in their annual meeting, drafted the guidelines for the diagnosis and management of osteoporosis that would be appropriate in a resource constraint setting like India. RESULTS: Diagnosis of osteoporosis can be made in a patient with minimal trauma fracture without the aid of any other diagnostic tools. In others, bone mineral density measured by dual-energy X-ray absorptiometry remains the modality of choice. Data indicates that osteoporotic fractures occur at an earlier age in Indians than in the West; hence, screening for osteoporosis should begin at an earlier age. FRAX can be used for fracture risk estimation; however, it may underestimate the risk of future fractures in our population and still needs validation. Maintaining optimum serum 25-hydroxyvitamin D levels is essential, which, in most cases, would require regular vitamin D supplementation. Pharmacotherapy should be guided by the presence/absence of vertebral/hip fractures or the severity of risk based on clinical factors, although bisphosphonates remain the first choice in most cases. Regular follow-up is essential to ensure adherence and response to therapy. CONCLUSIONS: Implementation of the position statement in clinical practice is expected to improve the overall care of patients with osteoporosis in India.

Effect of plasma glucose at admission on COVID-19 mortality: experience from a tertiary hospital.

OBJECTIVE: Plasma glucose has been correlated with in-hospital mortality among many diseases including infections. We aimed to study the plasma glucose at the admission of hospitalized patients with COVID-19 at a tertiary care referral hospital at Jodhpur, India and its relation with mortality. DESIGN: A hospital-based clinical study of plasma glucose of COVID-19 patients conducted from May 15 to June 30, 2020 after ethical approval. MEASUREMENTS: Random blood samples at admission were collected for plasma glucose, interleukin-6 (IL6) and high sensitivity C-reactive protein (hsCRP) after written informed consent was obtained. Plasma glucose was analyzed by the automated analyzer, IL6 by chemiluminescent immunoassay and hsCRP by immune-turbidimetric assay. RESULTS: A total of 386 patients were studied (female 39.6%); 11.1% had severe disease and 4.1% expired. There were 67 (17.4%) patients with known diabetes mellitus (DM). Patients with a history of DM had three times higher mortality (6/67, 9%) than those without DM (10/309, 3.1%). Patients with moderate and severe disease according to ICMR and WHO grading had higher plasma glucose than those with asymptomatic or mild disease (P < 0.0001). Plasma glucose levels at admission were significantly higher in non-survivors when compared to those who survived (297 ± 117 vs 131 ± 73; P < 0.0001). COVID-19 patients showed increased mortality with incremental plasma glucose levels. The hazard ratio for mortality was 1.128 (95% CI 0.86-14.860), 1.883 (95% CI 0.209-16.970), and 4.005 (95% CI 0.503-32.677) in random plasma glucose group of >100-200, >200-300 and >300 mg/dL, respectively, compared to those with random plasma glucose of <100 mg/dL at admission. Plasma glucose was strongly correlated with hsCRP (P < 0.001) and IL6 (P < 0.0001). CONCLUSIONS: Plasma glucose at admission in hospitalized COVID-19 patients is a strong predictor of mortality.

Role of interleukin-2 and interleukin-18 in newly diagnosed type 2 diabetes mellitus.

OBJECTIVES: The study aimed to compare the levels of anti-inflammatory interleukin-2 (IL-2) and proinflammatory interleukin-18 (IL-18) among newly diagnosed type 2 diabetes mellitus (T2DM) and nondiabetic volunteers, to predict their roles as markers in the diagnosis of newly diagnosed T2DM. METHODS: In the study, 60 subjects were enrolled (30 T2DM cases and 30 non-diabetic controls). Biochemical parameters such as fasting plasma glucose (FBS), glycated haemoglobin (HbA1c), high sensitivity C-reactive protein (hs-CRP) and lipid profile were estimated in auto-analyser. Serum IL-2 and IL-18 levels were assessed by enzyme-linked immune sorbent assay (ELISA). RESULTS: Significant differences were observed in the levels of interleukins among study groups. The median (95% confidence interval) of IL-2 in cases and controls were 8.55 (6.07-47.23) and 45.87 (12.81-145.4) (p=0.02). The median (95% CI) of IL-18 on the other hand in cases and controls were 691.6 (580.3-872.6) and 511.1 (452.6-557.5) (p=0.0014). CONCLUSIONS: Our study is the first to correlate IL-2 and IL-18 in newly diagnosed T2DM patients. Findings from this study highlight the anti-inflammatory role of IL-2 and proinflammatory role of IL-18 in T2DM. ROC analysis helped predict their role as markers in T2DM diagnosis.

Swift contact tracing can prevent transmission-Case report of an early COVID-19 positive case.

This is a case study of a positive COVID-19 case who was diagnosed and isolated early on in the infection. However, her seventeen close contacts who were quarantined and under observation remained negative indicating no viable chain of transmission despite high-risk contact. We further discuss the importance of effective contact tracing coupled with strict isolation or quarantine in breaking the chain of transmission.

Short Stature: Understanding the Stature of Ethnicity in Height Determination.

Height is a polygenic trait with a high degree of heritability. Most (95%) children with short stature (defined as height below the third percentile) and poor growth (growth velocity <5 cm/year) do not have an endocrine disorder. The genetic basis for stature potential has been evaluated in recent years and is increasingly being recognized as a major basis for variation in height between different ethnic populations. Numerous genome-wide association studies have identified hundreds of loci linked to human growth. Apart from the genetic factors, various environmental, nutritional, hormonal, and socioeconomic factors also influence the height, and stature of individuals varies between different geographical locations and ethnic groups. Ethnically different populations might respond differently to the same environmental factors and thus the final height in different ethnic groups is different. This review covers in detail the short stature of African Pygmies and Andamanese Islanders along with the possible causative factors responsible for the variation in height in these ethnic groups.

An atypical presentation of multiple myeloma in a young patient with pathological fracture.

We report a case of a 34-year-old male with a history of pulmonary tuberculosis and pathological fracture of shaft of long bone presented with symptoms of lower respiratory tract infection. The patient did not have any typical symptoms of multiple myeloma or hypercalcemia on presentation. Throughout his hospitalization, his serum globulin level was very high along with mild normocytic normochromic anemia and mild renal function derangement without apparent cause. Acute phase markers of inflammation, for example, erythrocyte sedimentation rate (ESR) were not elevated in this patient and there was no lytic lesion in bone radiographs. He was eventually diagnosed as a case of stage 3 multiple myeloma by immuno-fixation electrophoresis and bone marrow study. Multiple myeloma represents a pathology of diverse distribution and has varied unusual presenting symptoms. We consider it an underdiagnosed disease often missed especially in young because it is not considered by clinicians.

Triple A syndrome (Allgrove syndrome) - A journey from clinical symptoms to a syndrome.

Triple A syndrome (Allgrove syndrome) is characterized by a triad of specific features, namely, alacrimia, adrenal insufficiency, and achalasia cardia. It is a rare autosomal recessive disorder. In the present study, an 18-year-old boy was presented with complaints of decreased tears, darkening of the skin, difficulty in walking and standing up from sitting position, and difficulty in swallowing liquids. Adrenal insufficiency, alacrimia, achalasia, and neurological manifestations were confirmed with relevant laboratory investigations. His condition improved with steroids and artificial teardrops. However, a vigilant eye of the clinician for clinical clues of syndromic manifestation will help in early diagnosis and proper management.