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Background: Extra-abdominal presentations are rarely seen in ovarian germ cell tumors (OGCT). We report a case of a patient with OGCT who presented with systemic venous thrombosis, pulmonary infarct, and chylothorax simultaneously. Case Presentation: A 13-year-old girl presented with dyspnea, fever, and cough of 1 week duration. She was detected to have left-sided chylothorax. Carcinoma Antigen 125 and alpha fetoprotein levels were raised. Computed tomography showed a large ovarian mass, and thrombi in superior vena cava, left brachiocephalic vein, and segmental branch of right pulmonary artery. She also had a peripheral opacity in the right lung with a reverse-halo sign, suggestive of pulmonary infarct. She was diagnosed with yolk-sac tumor and managed with anticoagulation and subsequently neo-adjuvant chemotherapy and surgery. Conclusion: Prothrombotic state in OGCT can lead to systemic thrombosis which may result in chylothorax due to obstruction of thoracic duct. The phenomenon, though rare, should be kept in mind during management of OGCT.

As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach.A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members.Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

Background Among patients hospitalized for severe pneumonia due to coronavirus disease (COVID-19), clinical stability and normal resting peripheral oxygen saturation (SpO

Sjogren syndrome is an autoimmune disease characterised by lymphocytic infiltration and inflammation of the exocrine glands resulting in decreased secretion of involved glands which manifests mostly as dry eye and dry mouth. The prevalence of the disease is reported to be about 10.3 per 10,000 population. It is more common in females with a male: female ratio of 16:1. Extra glandular manifestations are seen in up to 1/3rd of the cases. Renal involvement is seen in 4.9% of patients with Sjogren syndrome.Here we present three cases of Sjogren Syndrome who presented to our hospital with hypokalaemic quadriparesis.On evaluation all three of the patients were found to have renal tubular acidosis type 1. None of these patients had any symptom of Sjogren syndrome before the onset of quadriparesis. All of these patients had acute onset progressive areflexic quadriparesis with involvement of facial muscles and drooping of eyelids without sensory or bladder bowel involvement. One of these patients had respiratory muscle paralysis severe enough to mandate mechanical ventilation. Arterial Blood Gas analysis and urine electrolyte analysis were suggestive of type 1 renal tubular acidosis. ANA positive in 2 of the 3 patients. Anti-SSAamp; anti-SSB antibodies were positive in all three patients. Supportive measures and IV fluid and electrolyte correction was done. There was complete recovery of power in all three patients and were discharged on oral medications.Renal Tubular Acidosis is characterised by inability of the nephrons to maintain physiologic acid base balance. This usually results from a defect in the tubular transport mechanisms. Distal Renal tubular acidosis (as in these patients) is further defined by an alkalotic urinary pH(gt;5.5) and profound hypokalemia due to impairment in H+ secretion in ditstal tubular alpha-intercalated cells. Owing to this imbalance of ionic transport in distal tubules there can be nephrocalcinosis, nephrolithiasis, rickets and severe muscle weakness. Sjogren syndrome is one of the etiologies leading to development of T1RTA.T1RTA can be the presenting feature of Sjogren Syndrome.Though a rare manifestation of the disease if can be the presenting symptom. Work up for RTA (ABG, urine electrolytes, Urine PH and osmolarity etc) in patients with hypokalaemic paresis can help establish the etiological diagnosis(ANA, anti-SSA,anti-SSB) and help prevent future relapses of the disease.

Background Computed tomography (CT) scans and CT severity scores (CTSS) are widely used to assess the severity and prognosis in coronavirus disease 2019 (COVID-19). CTSS has performed well as a predictor in differentiating severe from non-severe cases. However, it is not known if CTSS performs similarly in hospitalized severe cases with hypoxia at admission. Methods We conducted a retrospective comparative study at a COVID-care center from Western India between 25th April and 31st May 2021, enrolling all consecutive severe COVID-19 patients with hypoxemia (peripheral oxygen saturation94%). Neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, ferritin, and CT thorax were done within 24h of admission before being initiated on any anti-COVID-19 therapy. CTSS was calculated by visual assessment and categorized into three severity categories and was correlated with laboratory markers and overall survival (OS). Statistical analysis was done using John's Macintosh Project (JMP) 15.0.0 ver. 3.0.0 (Cary, North Carolina). Results The median age of the study population (n-298) was 59 years (24-95) with a male preponderance (61.41%, n=183). The 15 and 30-day survivals were 67.64% and 59.90%, respectively. CTSS did not correlate with age, gender, time from vaccination, symptoms, or comorbidities but had a significant though weak correlation with LDH (p=0.009), D-dimer (p=0.006), and NLR (p=0.019). Comparing demographic and laboratory aspects using CT severity categories, only NLR (p=0.0146) and D-dimer (p=0.0006) had significant differences. The 15d-OS of mild, moderate, and severe CT categories were 88.62%, 70.39%, and 52.62%, respectively, while 30d-OS of three categories were 59.08%, 63.96%, and 49.12%, respectively. Conclusion Among hospitalized severe COVID-19 patients with hypoxemia at admission, CT severity categories correlate well with outcomes but not inflammatory markers at admission.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

Introduction: Very often in clinical biochemistry laboratory, lipemic samples are encountered which causes analytical interference in measurement of various biochemistry parameters. In routine practice, 8 to 10 hours of fasting is advised to overcome interference caused by lipemia. To minimize lipemic interference ultracentrifugation, high speed centrifugation, lipid clearing agent, dilution with normal saline or sample blanking can be used. Out of these, u ltracentrifugation is likely to cause least interference as there is minimal exposure to additional chemicals. Aims and Objectives: Aims and objectives of the study were to, identify lipemic samples, analyze liver function test in lipemic samples before ultracentrifugation, perform ultracentrifugation, analyze same analytes after ultracentrifugation and compare the results for any significant statistical and clinical difference. Materials and Methods: From 50 lipemic samples, 2 aliquots were prepared each having 500 microliter of serum. One aliquot was used to perform liver function test. Second aliquot was further subjected to the ultracentrifugation after which the same biochemical parameters were performed. Comparison of results obtained, was done by paired Student’s t-test in Microsoft Office 2007 to assess statically significant difference. Ratio of (lipemic bias in relation to ultracentrifuge samples) to (Biological Variation, CLIA acceptability criteria and laboratory CV %) were also calculated to see whether the difference is clinically significant or not. Results: Statistically significant difference between lipemic and ultracentrifuge samples was observed in alkaline phosphatase, alanine transaminase, total bilirubin, albumin and total protein while only total bilirubin, total protein and alanine transaminase showed clinically significant difference. Conclusions: Ultracentrifugation results in statistically significant difference in results obtained for all parameters of liver function test but clinic

Background High-altitude pulmonary edema (HAPE) is a common cause of hospitalization in high altitude areas with significant morbidity. The clinical presentation of HAPE can overlap with a broad spectrum of cardiopulmonary diseases. Also, it is associated with varied radiological manifestations mimicking other conditions and often leading to unnecessary and inappropriate treatment. Patients and methods The primary aim of the study was to study the various radiological manifestations of HAPE through real-world chest radiographs. We present six different chest X-ray patterns of HAPE as a pictorial assay, at initial presentation, and after the resolution of symptoms with supplemental oxygen therapy and bed rest alone. Results HAPE can present as bilateral symmetrical perihilar opacities, bilateral symmetrical diffuse opacities, unilateral diffuse opacities, bilateral asymmetrical focal opacities, and even lobar consolidation with lower zone or less commonly upper zonal predilection. These presentations can mimic many common conditions like heart failure, acute respiratory distress syndrome, pulmonary embolism, aspiration pneumonitis, pneumonia, malignancy, and tuberculosis. Conclusion A holistic clinical-radiological correlation coupled with analysis of the temporal course can help high-altitude physicians in differentiating true HAPE from its mimics. How to cite this article Yanamandra U, Vardhan V, Saxena P, Singh P, Gupta A, Mulajkar D, et al. Radiographical Spectrum of High-altitude Pulmonary Edema: A Pictorial Essay. Indian J Crit Care Med 2021;25(6):668-674.

Drugs that target human thymidylate synthase (hTS) are widely used in anti-cancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces its over-expression and the development of drug resistance. We thus pursued an alternative strategy that led to the discovery of TS-dimer disrupters that bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. We performed a structural, spectroscopic and kinetic investigation of the effects of these small molecules andthe best one, E7, accelerates the proteasomal degradation of hTS in cancer cells. E7 showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.

Scrub typhus is a rickettsial disease caused by gram negative coccobacilli and transmitted through the bite of larval stage of mite. The disease is notable in the Asia-Pacific belt with few sporadic and epidemic cases reported from India as well. The disease is well identified from North Western part of Rajasthan that are the areas with dense vegetation. The clinical scenario ranges from acute febrile illness to multiple organ dysfunction by virtue of haematogenous seedling. This case series highlights the neurological manifestations of scrub typhus that are diverse and life threatening but holding dearth of literature to convoy appropriately timed diagnosis and treatment.

The original version of this article unfortunately contained mistakes. In Table 2, under the column 'Lead to death' in Row 5 [CheckMate-026], the figures should read as '0.7' for Experimental Arm and '1.1' for Comparator. Right now, these are printed as 0.007 and 0.011 respectively.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic and selected cases of unresectable advanced non-small cell lung cancer (NSCLC). Importantly for patients, this implies that in the absence of a targetable oncogenic driver [especially epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements] and in the presence of high programmed death-ligand 1 (PD-L1) expression (≥ 50%), they are eligible for mono-therapy with pembrolizumab thereby avoiding chemotherapy as the first line of treatment. This mono-immunotherapy approach for high PD-L1 metastatic NSCLC is associated with improved overall survival (OS) and radiological responses (RR) with lesser toxicity as compared with conventional platinum doublet chemotherapy for both non-squamous and squamous histological types. However, majority of NSCLC patients either have no or low expression of PD-L1 (

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase that plays a key role in HCV replication, and, hence, NS5B is an attractive target for hepatitis C drug discovery. Hepatitis C is a chronic liver disease affecting the global population significantly. Many NS5B inhibitors targeting active site were launched in recent years, however, still there exists a pressing need for cost-effective therapies with pan genotypic activity and therapies targeting niche HCV population with comorbities and resistant to earlier therapies. The objective of the current study is to identify potential anti-HCV agents from FDA approved drugs that are already in the market for a different disease-Drug repurposing approach. A combination of computational chemistry and computational biology techniques was used to discover potential therapies for hepatitis C targeting the NS5B Thumb I allosteric site. Computational chemistry analysis emphasized the fact that fluvastatin, a lipid lowering agent, and olopatadine, an antihistamine, exhibited good binding affinity to NS5B. In addition, gene set enrichment analysis brought to light the significant overlap between disease characteristic features and the mechanism of action of fluvastatin and olopatadine. The current study concludes the potentially beneficial use of fluvastatin in niche hepatitis C patient population suffering from nonalcoholic fatty liver diseases.

LR and [d-Gln4]LR peptides bind the monomer-monomer interface of human thymidylate synthase and inhibit cancer cell growth. Here, proline-mutated LR peptides were synthesized. Molecular dynamics calculations and circular dichroism spectra have provided a consistent picture of the conformational propensities of the [Pro n]-peptides. [Pro3]LR and [Pro4]LR show improved cell growth inhibition and similar intracellular protein modulation compared with LR. These represent a step forward to the identification of more rigid and metabolically stable peptides.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is an idiosyncratic drug reaction following a characteristic long latency period. It is previously known as drug induced delayed multiorgan hypersensitivity syndrome (DIDMOHS) or drug induced hypersensitivity (DIHS). The syndrome is manifested by wide range of clinical symptomatology that hold a potential to be life threatening but still is under recognised. The major drugs that cause DRESS syndrome are anticonvulsants, followed by sulfonamides and many anti-in˜ ammatory drugs.Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is an idiosyncratic drug reaction following a characteristic long latency period. It is previously known as drug induced delayed multiorgan hypersensitivity syndrome (DIDMOHS) or drug induced hypersensitivity (DIHS). The syndrome is manifested by wide range of clinical symptomatology that hold a potential to be life threatening but still is under recognised. The major drugs that cause DRESS syndrome are anticonvulsants, followed by sulfonamides and many anti-inflammatory drugs.

Rhabdomyolysis is a serious medical condition, encountered in the intensive care unit (ICU). The etiology of rhabdomyolysis is often multifactorial. It leads to complications like acute kidney injury and life-threatening electrolyte abnormalities. A high index of suspicion and early institution of therapy is required to prevent complications and improve patient outcomes. Herein, we present the case of a young man with alcohol dependence who presented with fever and altered sensorium. He was found to have rhabdomyolysis and was managed successfully. We also discuss the common causes of rhabdomyolysis and a bedside approach to its management in the ICU. How to cite this article: Saxena P, Dhooria S, Agarwal R, Prasad KT, Sehgal IS. Rhabdomyolysis in Intensive Care Unit: More than One Cause. Indian J Crit Care Med 2019;23(9):427–429.

Background The ideal criteria for diagnosing allergic bronchopulmonary aspergillosis (ABPA) remain unknown because of the lack of a criterion standard. Latent class analysis using a probabilistic modeling technique can circumvent the need for a reference standard. Objective To compare the diagnostic performance of various criteria used for evaluating ABPA. Methods We prospectively enrolled consecutive cases of bronchial asthma and performed a series of investigations used for the diagnosis of ABPA. We used latent class analysis to analyze the performance of various existing and novel diagnostic criteria. Results Of the 543 subjects (mean age, 37 years; 319 women), 338 (62.2%) and 205 (37.8%) were labeled as “mild-to-moderate” and “severe” asthma cases, respectively. The subjects with severe asthma had a longer duration of asthma and a higher number of exacerbations in the previous year. The prevalence of Aspergillus fumigatus sensitization was 41% and 30%, using the A fumigatus–specific IgE and skin test, respectively. The prevalence of ABPA was 16%, using both the Rosenberg-Patterson and the International Society for Human and Animal Mycology (ISHAM)-ABPA Working Group criteria. The ISHAM criteria were slightly more sensitive (89% vs 81%) and specific (99% vs 98%) than the Patterson criteria. We obtained optimal diagnostic performance by altering the existing ISHAM criteria (serum total IgE >500 international units/mL, excluding the skin test, and using computed tomography of thorax instead of chest radiograph). Conclusions The ISHAM-ABPA Working Group criteria were only marginally better than the Patterson criteria in diagnosing ABPA among patients with asthma younger than 66 years. The diagnostic performance however improved by modifying the prevailing ISHAM criteria, but with increased cost.

Methotrexate monotherapy is a common management strategy in rheumatoid arthritis (RA). Treatment with immunosuppression can lead to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). The treatment options for PJP include cotrimoxazole, clindamycin-primaquine and dapsone. Though these drugs are generally well tolerated, they can result in potentially severe adverse effects. Sometimes several undesired events may occur in a single patient, reminding us of Murphy's law. Herein, we report a case which exemplifies this adage. A 50-year-old female developed PJP, while on methotrexate therapy for RA and was treated with cotrimoxazole. The latter resulted in painful peripheral neuropathy, which improved after cotrimoxazole was stopped. Salvage therapy for PJP with primaquine-clindamycin, lead to another serious adverse event, methemoglobinemia. Withdrawing the offending drug resulted in dramatic improvement.

Community-acquired pneumonia refers to an infection of the lung parenchyma acquired outside a healthcare setting. The term severe CAP (SCAP) signifies a more serious form of community-acquired pneumonia that requires admission to the intensive care unit and has a high risk of mortality. SCAP is an important cause of morbidity and mortality in both the developed and the developing world. The common causative pathogens of SCAP include pneumococcus, Hemophilus influenzae, and atypical bacterial organisms, and less commonly, gram-negative bacilli and Staphylococcus aureus, particularly in hosts with risk factors for these pathogens. An initial diagnosis can usually be made clinically based on the presentation, and confirmed with the help of a chest radiograph. Scoring systems may be used to assess the severity, mortality risk and requirement of admission to the intensive care unit. Empirical antibiotic treatment must be instituted at the earliest after sending blood and respiratory samples for microbiological analysis and antibiotics may be changed according to the results. Supportive and adjunctive treatments are instituted, as required. Personalized management based on various novel strategies may improve the management of SCAP in the future. In this chapter, we present a detailed discussion of the epidemiology, pathogenesis, diagnostic evaluation and treatment of SCAP.

It is accepted that metabolic syndrome increases the relative risk of cardiovascular disease and visceral adiposity lies at root of the cardio-metabolic risk. Upper body fat distribution has long been recognized as associated with metabolic syndrome and increased cardiovascular risk; hence the present study was conducted with the objective to evaluate the association of neck circumference with metabolic syndrome and cardiovascular risk factors.The present study was a hospital based observational, Descriptive and comparative analysis, conducted at Department of General Medicine at a tertiary care centre of west India after Ethical clearance from the institute's ethical committee and written informed consent. A total of 405 subjects aged 18 - 60 years were selected consecutively after inclusion and exclusion criteria. Subjects were evaluated for metabolic syndrome components and cardiovascular risk factors. Neck circumference of ≥ 37 cm in males and ≥ 34 cm in females was considered abnormal.Metabolic syndrome was seen in 189 (46.7%) subjects. Raised triglyceride level was the most common (52.8%) component. Neck circumference was found to be statistically significant associated with metabolic syndrome (p0.001) as well as cardiovascular risk factors like BMI, Waist circumference, Hypertension, Fasting blood sugar, TG and HDL were also found to be statistically significant associated with neck circumference.Neck Circumference can be used as a sensitive tool for metabolic syndrome and cardiovascular risk factors. Patients with abnormal Neck circumference should be screened for cardiovascular risk factors to detect abnormality for early and appropriate intervention.

Human thymidylate synthase (hTS), a target for antiproliferative drugs, is an obligate homodimer. Single-point mutations to alanine at the monomer–monomer interface may enable the identification of specific residues that delineate sites for drugs aimed at perturbing the protein–protein interactions critical for activity. We computationally identified putative hotspot residues at the interface and designed mutants to perturb the intersubunit interaction. Dimer dissociation constants measured by a FRET-based assay range from 60 nM for wild-type hTS up to about 1 mM for single-point mutants and agree with computational predictions of the effects of these mutations. Mutations that are remote from the active site retain full or partial activity, although the substrate KM values were generally higher and the dimer was less stable. The lower dimer stability of the mutants can facilitate access to the dimer interface by small molecules and thereby aid the design of inhibitors that bind at the dimer interface.Graphical abstract