Clinical and Immunological Profile of Systemic Lupus Erythematosus: A 5-year Retrospective Analysis from Northeast India.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with a wide range of clinical manifestations having considerable variation in clinical features that are influenced by ethnic, sociocultural, and geographical factors. This disease primarily affects young women aged between 18 and 35 years. The aim of this present study was to delineate the clinical manifestations and immunological patterns of SLE patients from the Northeastern (NE) region of India. MATERIALS AND METHODS: The study was carried out in a tertiary care hospital from January 2016 to January 2021. Adult patients of age >18 years fulfilling systemic lupus international collaborating clinic criteria (SLICC) for classification of SLE were included in this study. Immunology such as antinuclear antibodies (ANA) and double-stranded deoxyribonucleic acid (dsDNA) were also performed followed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Over a period of 5 years, 142 patients were recruited for the study, with an overall female-to-male ratio was 9.9:1, a median age at onset of 25 years (interquartile range age 21-32 years) and a mean disease duration was 15.25 months (range 2-60 months). Our study revealed that ANA was positive in 97.18% of patients while anti-dsDNA was positive in 78.68%, indicating that women from this region have higher positivity rates. CONCLUSION: Our findings support the notion that SLE is a multisystem disorder that predominantly affects young females, especially during the second and third decades of life. Hematological, mucocutaneous, and renal manifestations are common in our patients. Moreover, pulmonary, cardiovascular, and gastrointestinal (GI) manifestations were understudied in other cohorts, which is one of our study's strengths.

Natural Killer Cell Count in Systemic Lupus Erythematosus Patients: A Flow Cytometry-Based Study.

Background Natural killer cells (NK cells) are important mediators of innate immune regulation and literature has shown that they have a role in shaping the adaptive immune system. Objective The present study was undertaken to analyze the NK cell count in systemic lupus erythematosus (SLE) patients as compared to that of controls. Materials and methods Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index (SELENA-SLEDAI) score was assessed in 32 SLE cases. CD3(-) cells were identified as NK cells on flow cytometry, and then their subsets CD56(+) and CD16(+) cells were identified compared to 30 healthy controls. Receiver Operating Characteristic (ROC) curve analysis was performed on NK cells to attempt to determine a cut-off point. Results The CD3(-) NK cells, including the percentages of CD56(+) and CD16(+), were significantly (p<0.001) reduced in SLE patients (12.35%, and 18.7%) as compared to controls (24.67%, and 46.6%). On ROC curve analysis, cut-off values <481/cumm with sensitivity of 86.7% and specificity of 84.4% for CD3(-) NK cells (p<0.001), <23% with 60% sensitivity and 75% specificity for CD56(+) NK cells (p<0.001), and <29% with sensitivity of 70% and specificity of 87.5% for CD16(+) NK cells (p<0.001) were noted. Subsets of NK cells showed no association with the clinicopathological parameters like age, sex, disease activity, anti-nuclear antibodies (ANA), dsDNA, absolute lymphocyte count, and renal involvement. Conclusion NK cells, and their subpopulations of CD56(+) and CD16(+) cells, are decreased in patients with SLE as compared to controls.

Artificial Intelligence and Machine Learning Technology Driven Modern Drug Discovery and Development.

The discovery and advances of medicines may be considered as the ultimate relevant translational science effort that adds to human invulnerability and happiness. But advancing a fresh medication is a quite convoluted, costly, and protracted operation, normally costing USD ~2.6 billion and consuming a mean time span of 12 years. Methods to cut back expenditure and hasten new drug discovery have prompted an arduous and compelling brainstorming exercise in the pharmaceutical industry. The engagement of Artificial Intelligence (AI), including the deep-learning (DL) component in particular, has been facilitated by the employment of classified big data, in concert with strikingly reinforced computing prowess and cloud storage, across all fields. AI has energized computer-facilitated drug discovery. An unrestricted espousing of machine learning (ML), especially DL, in many scientific specialties, and the technological refinements in computing hardware and software, in concert with various aspects of the problem, sustain this progress. ML algorithms have been extensively engaged for computer-facilitated drug discovery. DL methods, such as artificial neural networks (ANNs) comprising multiple buried processing layers, have of late seen a resurgence due to their capability to power automatic attribute elicitations from the input data, coupled with their ability to obtain nonlinear input-output pertinencies. Such features of DL methods augment classical ML techniques which bank on human-contrived molecular descriptors. A major part of the early reluctance concerning utility of AI in pharmaceutical discovery has begun to melt, thereby advancing medicinal chemistry. AI, along with modern experimental technical knowledge, is anticipated to invigorate the quest for new and improved pharmaceuticals in an expeditious, economical, and increasingly compelling manner. DL-facilitated methods have just initiated kickstarting for some integral issues in drug discovery. Many technological advances, such as "message-passing paradigms", "spatial-symmetry-preserving networks", "hybrid de novo design", and other ingenious ML exemplars, will definitely come to be pervasively widespread and help dissect many of the biggest, and most intriguing inquiries. Open data allocation and model augmentation will exert a decisive hold during the progress of drug discovery employing AI. This review will address the impending utilizations of AI to refine and bolster the drug discovery operation.

Immunoglobulin A Nephropathy in a SARS-CoV-2-Positive Patient With Coexistent Metabolic Syndrome.

SARS-CoV-2 viral infection though primarily affects the respiratory system, but concurrent renal involvement is been reported in the medical literature. Acute kidney injury (AKI) is a common finding in SARS-CoV-2-positive patients. An isolated case of IgA nephropathy in a SARS-CoV-2 virus-infected patient has been already reported in the medical literature. Incidence of metabolic syndromes is on the rise considering the change in lifestyle and food habits and the global pandemic of obesity. Renal manifestations of metabolic syndrome are myriad with IgA nephropathy being an occasional manifestation in such patients. We reported a case of IgA nephropathy in a patient in her fourth decade of life diagnosed as metabolic syndrome with concomitant SARS-CoV-2 infection that progressed to chronic kidney damage (CKD) subsequently. In this case report, we postulate that cytokine storm along with hypoxemia secondary to SARS-CoV-2 infection may accelerate the declining renal function however further studies are necessary to confirm this hypothesis considering the rarity of such cases.

Mycetism - A report of three cases with review of recent literature.

Wild mushroom grow abundantly in the tropical belts of India, and they form part of the diet among the ethnic tribes. However, wild mushrooms are toxic, and some cause organ failure, namely fulminant hepatitis and kidney injury. Mushroom poisoning is frequently diagnosed based on clinical suspicion, and death has been reported commonly because of the consumption of amatoxin-containing mushrooms. In this article, we discuss three cases of amatoxin-induced mushroom poisoning that resulted in acute kidney and liver failure, requiring intensive medical management and renal replacement therapy. One of these patients died from irreversible fulminant hepatitis.

Delayed liver toxicity and delayed gastroenteritis: A 5 year retrospective analysis of the cause of death in Mushroom poisoning.

Introduction: Mushroom poisoning occurs from consumption of the wild variants of mushroom containing varied forms of toxins. Among those toxins, amatoxin containing mushrooms are known for the significant morbidity and mortality from hepatic toxicity and delayed gastroenteritis. Although not a very common cause of poisoning, it is prevalent in the north-eastern region of India, especially during the rainy summer seasons when the wild variants are found abundantly and often confused with the edible variants. Aims and Objectives: To study the clinical and biochemical profiles and short term outcomes of patients with mushroom poisoning admitted to a tertiary care hospital. Materials and Methods: We analyzed the data of patients with mushroom poisoning admitted to a tertiary care institute in north-eastern India between January 2015 to December 2020 to study their clinical and biochemical profiles, and short-term outcomes. Their clinical features, biochemical parameters, management, and in-hospital outcomes were noted. All data was recorded in Microsoft MS Excel and analyses done using SPSS version 22. Results: Of the 44 patients with mushroom poisoning, 23 (52%) were male and 21 (47%) were female, with a mean age of 20.13 years. Seventeen patients (38%) had delayed liver failure and delayed gastroenteritis, 19 patients (43%) had acute gastroenteritis syndrome, 5 patients (11%) had cholinergic symptoms, one patient (2%) each had acute kidney injury and a disulfiram-type reaction with headache. The mean hospital stay of the patients was 5 days. In-hospital mortality occurred in 10 (58%) patients with delayed liver failure and none of the patients with the other complications died. Conclusion: This study revealed a high prevalence of mushroom poisoning that caused delayed liver toxicity and delayed gastroenteritis, probably amatoxin-induced, which is fatal, thus accounting for high mortality and poor outcomes in these patients.

Epidemiology, clinical, and laboratory profile of patients with hepatitis C: A prospective, observational study from north-eastern India.

Low and middle-income countries (LMICs) contribute to 80% of the global hepatitis C virus (HCV) infection burden. Intravenous drug use (IVDU) is not uncommon in Northeastern India, thus contributing to HCV. Its epidemiology, clinical, and laboratory profile were studied in a tertiary care centre in northeastern India.HCV patients (age >18) of either sex were prospectively assessed for demographic, virological, and genotype distributions. Most were male (M: F, 5.8:1) with a mean age of 37.1 ± 11.8 years. The most common risk factor was IVDU(77.69%), followed by concomitant alcohol use in 69.2%. Besides genotype 3 (59.2%), genotype 1 (26.1%) and genotype 6 were also common (14.6%). The demographics, liver disease severity, and biochemical parameters were similar across genotypes.

COVID-19 Vaccination Status Among Healthcare Workers and Its Effect on Disease Manifestations: A Study From Northeast India.

Background and objective Since being declared a global pandemic, coronavirus disease 2019 (COVID-19) has led to millions of cases and deaths worldwide. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to wreak havoc on individuals, healthcare systems, and economies, the intensive vaccination strategies adopted by several countries have significantly slowed the progress and the severity of the disease. In this study, we aimed to determine the COVID-19 vaccination status among healthcare workers (HCWs) and examine the effects of vaccination on disease manifestations. Materials and methods This cross-sectional study was conducted at a teaching hospital in Northeast India from April 2021 to September 2021, during the second phase of the COVID-19 pandemic. HCWs employed in the hospital who were laboratory-confirmed cases of COVID-19 based on semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) or cartridge-based nucleic acid amplification test (CBNAAT) on oropharyngeal samples were included in the study. Data analysis was performed using Microsoft Excel (Microsoft Office Professional Plus 2019, Microsoft Corp., Redmond, WA) Results A total of 178 HCWs reported positive for COVID-19 infection during the study period. Of these, 42 (23.59%) were males and 136 were females (76.40%). Among them, 86 (48.32%) HCWs were fully vaccinated, 58 (32.58%) were partially vaccinated, and 34 (19.10%) were not vaccinated. Most of the HCWs experienced mild disease (145, 81.46%), and only four (2.24%) reported moderate to severe disease. Compared with unvaccinated HCWs, individuals who have had either one or two doses of vaccines were less likely to have moderate to severe disease or seek treatment at the hospital. On symptoms analysis, shortness of breath was found to be more common in unvaccinated individuals than in vaccinated patients, and anosmia and loss of taste were more common in vaccinated than in unvaccinated individuals. No deaths were reported among the participants included in this study. Conclusions Following the first and second waves of the COVID-19 pandemic, a substantial proportion of HCWs were infected with SARS-CoV-2, likely as a result of the acquisition of the virus in the community during the early phase of local spread. Fully vaccinated individuals with COVID-19 were more likely to be completely asymptomatic or only mildly symptomatic compared to unvaccinated HCWs.

Utility of reticulocyte indices in the diagnosis of pancytopenia.

Introduction: Pancytopenia is a hematological condition in which there is a reduction in all three cell lines of blood. This study aims to evaluate the utility of reticulocyte indices such as reticulocyte % (retic %), immature reticulocyte fraction (IRF), and mean reticulocyte volume (MRV) in identifying the cause of pancytopenia. Materials and Methods: Reticulocyte indices were measured by an automated coulter. These values were then correlated with relevant biochemical and bone marrow results and cases were stratified into different etiological groups. Receiver operator curve (ROC) analysis was performed and various cut-off values were derived based on the reticulocyte indices. ROC was repeated to further classify cut-off values at every level to help formulate a diagnostic algorithm. Results: A total of 154 cases of pancytopenia were obtained. Ages ranged from 7 months to 87 years with a mean of 42, the male:female ratio was 1.08:1. The majority of the cases were megaloblastic anemias in which the cut-off values for retic % was <0.91 with a sensitivity of 78.1% and specificity of 70%, IRF was 0.45 with a sensitivity of 76.7% and specificity of 64%, and MRV was >121.8 fl with a sensitivity of 83.6% and specificity of 80%. The values on ROC could segregate nutritional from nonnutritional causes. The IRF and MRV also helped to differentiate megaloblastic anemia from dual deficiency anemia. Conclusion: Reticulocyte indices help identify the cause of pancytopenia. They can segregate nutritional anemia from other causes of pancytopenia allowing presumptive treatment to be initiated and may obviate invasive procedures such as bone marrow examination.

Inflammation and Its Determinants in Patients With Chronic Kidney Disease: A Study From North Eastern Region of India.

Background and objective Chronic kidney disease (CKD) comprises a spectrum of pathophysiologic processes with increased cardiovascular disease (CVD) risk mediated mostly by endothelial dysfunction other than traditional risk factors. The present study is carried out to see the cardiovascular risk in CKD patients with special reference to the determinants of endothelial dysfunction. Materials and methods We enrolled 60 CKD patients along with 120 healthy controls in the age group 18-50 years belonging to the same ethnicity and localities. Demographic and clinico-laboratory information including markers of endothelial dysfunction were recorded followed by univariate and multivariate analyses to assess the relationship between CKD and CVD risk. Results Cases comprised of 60 CKD patients (mean age = 38.47±8.56 years) including 35 (58%) females and 25 (42%) males. Etiology in 43% of cases was idiopathically followed by diabetes and hypertension (42%) and obstructive uropathy (13%). On comparing the means of inflammatory markers between cases and controls, calcium phosphate product, c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil: lymphocyte (N:L) ratio was found to be significantly higher (p < 0.05) in cases as compared to controls but carotid intima-media thickness (CIMT) and low-density cholesterol (LDL) did not show a significant difference (p < 0.05). Conclusion Our study showed uniformly higher levels of inflammatory markers in cases irrespective of age and gender except for LDL and CIMT which uniquely showed a positive correlation with age. CKD patients require appropriate treatment and preventive measures for CVD with a high index of suspicion as endothelial dysfunction cannot be adequately gauged by traditional risk scoring methods.

Evaluation of Hematological Parameters in Predicting Intensive Care Unit Admission in COVID-19 Patients.

Hematological parameters like total leukocyte count (TLC), neutrophil, lymphocyte, and absolute eosinophil counts (AEC), and neutrophil-to-lymphocyte ratio (NLR) are known to predict the severity of novel coronavirus disease 2019 (COVID-19) patients. In the present study, we aimed to study the role of complete blood count parameters in triaging these patients requiring intensive care unit (ICU) admission. A retrospective study was done over a period of 2 months. Patients, who were ≥ 18 years of age with COVID-19 confirmed on SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) and whose routine hematology counts were sent within 24 h of admission, were included in the study. Cut-off values of 47.5 years for age, 11.3 × 109/L for TLC, and 9.1 for NLR were predictive of disease severity among COVID-19 patients. Relative neutrophilia ≥ 70% (p < 0.007), relative lymphopenia ≤ 20% (p < 0.002), AEC ≤ 40/cumm (p < 0.001), and NLR ≥ 9.1 (p < 0.001) were significantly associated with ICU admission. Routine hematological parameters are cost-effective and fast predictive markers for severe COVID-19 patients, especially in resource-constrained health care settings to utilize limited ICU resources more effectively.

Role of Coagulation Profile in Predicting Disease Severity Among Patients of COVID-19.

Background Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), affects the coagulation cascade. In this retrospective study, we aimed to analyze the association of different coagulation parameters including that of D-dimer, fibrinogen, prothrombin time (PT), and activated partial thromboplastin time (aPTT) with severity in COVID-19 patients. Methodology A total of 90 patients positive for SARS-CoV-2 on real-time reverse transcription-polymerase chain reaction (rRT-PCR) were included in the study. The patients were categorized as severe and non-severe, and their D-dimer, fibrinogen, PT, and aPTT values on admission were evaluated. The association of the coagulation parameters with disease severity was analyzed by independent t-test and Chi-square test. The cut-off values of these parameters were calculated to predict the disease severity by receiver operator characteristic (ROC) curve. Results Out of 90 patients admitted, 42 patients were categorized as severe and the rest 48 patients were categorized as non-severe. D-dimer, fibrinogen, and PT in the severe group were significantly higher than the non-severe group with p-values of <0.001, 0.005, and <0.001, respectively. Cut-off values of 0.99 mg/L for D-dimer,349.5 mg/dL for fibrinogen, and 13.05 seconds for PT were predictive of disease severity among COVID-19 patients. Conclusion Severe COVID-19 patients showed significantly higher levels of D-dimer and fibrinogen and prolongation of PT as compared to non-severe COVID-19 patients. Higher levels of D-dimer and fibrinogen, and prolonged PT are predictive of increased disease severity among COVID-19 patients.

Methotrexate-Induced Septicemia With Severe Pancytopenia and Diffuse Cutaneous Ulcerative Lesions.

Methotrexate, a folate antimetabolite and one of the first few anti-neoplastic drugs, is now a commonly used drug in the treatment of many inflammatory disorders ranging from diseases like rheumatoid arthritis to psoriasis. The life-threatening toxicity of methotrexate in inflammatory diseases is not commonly encountered. Here we report a case of life-threatening multiorgan failure from methotrexate toxicity, which was given for skin lesions suspected to be psoriasis.

Tracheal Diverticulum in SARS-CoV-2 Patients on Non-Invasive Ventilation A not so "Spontaneous" Cause of Pneumomediastinum? An imaging Pictorial Presentation of Two Cases with Review of Literature.

Spontaneous pneumomediastinum is a rare but potentially life-threatening condition, the incidence of which has showed an increase in patients with SARS-CoV-2 pneumonia, especially when they are on positive pressure ventilation. None of the reported cases of covid related pneumomediastinum had an associated tracheal diverticulum. Also, to the best of our knowledge, tracheal diverticulum has not been reported in patients on NIV. We report 2 cases of COVID-19 pneumonia on NIV with pneumomediastinum, which also had associated tracheal diverticulum, one of which developed after NIV. Though the establishment of causality needs further research, early detection of a tracheal diverticulum, which might be a harbinger of pneumomediastinum, can be a timely alarm to prompt titration of the pressure settings and judicious use of NIV. The role of inverted grey scale CT images in mediastinal window is a simple, yet hardly utilised radiological tool to increase detection of 'mediastinal air', let it be free air or air within a diverticulum. Through this case report, we would like to highlight the role of conventional and inverted CT imaging of pneumomediastinum and tracheal diverticulum in general and in SARS-CoV-2 pneumonia in particular, and to call for more objective research to throw light on the plausible relationship between pneumomediastinum and tracheal diverticulum.

Occult Esophageal Squamous Cell Carcinoma Presenting with Multiple Bony Osteolytic Lesions Clinically Mimicking Multiple Myeloma: A Diagnostic Dilemma.

Bone metastasis as an initial presentation of esophageal carcinoma is uncommon. In the absence of typical presentations like dysphagia, these cases may lead to diagnostic dilemmas both for the clinicians and pathologists. Here, we report a case of disseminated metastasis of esophageal squamous cell carcinoma to the bone in a 47-year-old female, who presented with multiple osteolytic lesions and clinically mimicking multiple myeloma. A detailed diagnostic work-up established the diagnosis of esophageal squamous cell carcinoma.

Granulomatous interstitial nephritis in granulomatosis with polyangiitis mimicking leprosy: A case report.

Granulomatous polyangiitis (GPA) is a small vessel vasculitis commonly affecting the upper and lower respiratory tracts and kidneys. About 90% of the cases are associated with ANCA, namely, PR3-ANCA and MPO-ANCA. Herein, we describe a patient of GPA who presented with anasarca, sensory neuropathy, recurrent upper airway congestion, epistaxis, and rapidly progressive glomerulonephritis. Granulomatous interstitial nephritis and necrotizing granulomatous inflammation of the nasal septum were found on biopsy of the kidney and nasal septum, respectively both of which are rare findings. PR3-ANCA and MPO-ANCA were negative. Fulfilling the ACR criteria, this case of GPA proves that biopsy is still the gold standard of diagnosis.

Kikuchi's disease (histiocytic necrotizing lymphadenitis): A rare presentation with acute kidney injury, peripheral neuropathy, and aseptic meningitis with cutaneous involvement.

Kikuchi's disease (KD) also known as histiocytic necrotizing lymphadenitis is rare, idiopathic, generally self-limited cause of lymphadenitis. We present a case of twenty year young female who presented in critically ill state with fever, cervical and axillary lymphadenopathy, rash, vomiting and altered sensorium and found to have neurological, hepatic, renal and dermatological involvement. Kikuchi's disease should be considered in differential diagnosis of fever and lymphadenopathy and though benign can sometimes present with multi-organ involvement. It is because of rarity of this disease with unusual complications, present case is reported.

Miliary tuberculosis with pulmonary and extrapulmonary component complicated with acute respiratory distress syndrome.

Miliary tuberculosis results from the lymphohematogenous spread of the tubercle bacilli to the vascular beds in the lungs and other organs. Diagnosis is made by clinical judgment and chest X-ray showing miliary mottling of the lung fields. Another imaging study like computed tomography imaging of the lungs and abdomen can also be supportive in diagnosing miliary tuberculosis. We present a case of miliary tuberculosis in an immunocompetent young male with atypical manifestation of a left-sided pleural effusion and a life-threatening complication of acute respiratory distress syndrome during hospital stay which required noninvasive mechanical ventilation and steroids therapy, along with antitubercular medication.

Scrub typhus complicated by acute respiratory distress syndrome and multiorgan failure; an unrecognized alarming entity in central India: a report of two cases.

Scrub typhus is an acute infectious illness, distributed throughout the Asia Pacific rim. In India, it has been reported from northern, eastern, and southern India. However, cases of scrub typhus have not been well-documented from Vidarbha, an eastern region of Maharashtra state in central India. We report two cases of complicated scrub typhus from Vidarbha region. These cases admitted in unconscious state with 8-10 days history of fever, body ache, cough, and progressive breathlessness. The diagnosis in both cases was based on presence of eschar, a positive Weil-Felix test, and a positive rapid diagnostic test (immunochromatographic assay). Both cases were complicated by acute respiratory distress syndrome (ARDS) and multiorgan failure. Both of them presented in their 2(nd) week of illness and died during the hospital course in spite of intensive supportive care. The main cause of mortality was delayed referral leading to delay in diagnosis and treatment.