Culture-independent identification of bloodstream infections from whole blood: prospective evaluation in specimens of known infection status.

Sepsis caused by bloodstream infection (BSI) is a major healthcare burden and a leading cause of morbidity and mortality worldwide. Timely diagnosis is critical to optimize clinical outcome, as mortality rates rise every hour treatment is delayed. Blood culture remains the "gold standard" for diagnosis but is limited by its long turnaround time (1-7 days depending on the organism) and its potential to provide false-negative results due to interference by antimicrobial therapy or the presence of mixed (i.e., polymicrobial) infections. In this paper, we evaluated the performance of resistance and pathogen ID/BSI, a direct-from-specimen molecular assay. To reduce the false-positivity rate common with molecular methods, this assay isolates and detects genomic material only from viable microorganisms in the blood by incorporating a novel precursor step to selectively lyse host and non-viable microbial cells and remove cell-free genomic material prior to lysis and analysis of microbial cells. Here, we demonstrate that the assay is free of interference from host immune cells and common antimicrobial agents at elevated concentrations. We also demonstrate the accuracy of this technology in a prospective cohort pilot study of individuals with known sepsis/BSI status, including samples from both positive and negative individuals. IMPORTANCE: Blood culture remains the "gold standard" for the diagnosis of sepsis/bloodstream infection (BSI) but has many limitations which may lead to a delay in appropriate and accurate treatment in patients. Molecular diagnostic methods have the potential for markedly improving the management of such patients through faster turnaround times and increased accuracy. But molecular diagnostic methods have not been widely adopted for the identification of BSIs. By incorporating a precursor step of selective lysis of host and non-viable microorganisms, our resistance and pathogen ID (RaPID)/BSI molecular assay addresses many limitations of blood culture and other molecular assay. The RaPID/BSI assay has an approximate turnaround time of 4 hours, thereby significantly reducing the time to appropriate and accurate diagnosis of causative microorganisms in such patients. The short turnaround time also allows for close to real-time tracking of pathogenic clearance of microorganisms from the blood of these patients or if a change of antimicrobial regimen is required. Thus, the RaPID/BSI molecular assay helps with optimization of antimicrobial stewardship; prompt and accurate diagnosis of sepsis/BSI could help target timely treatment and reduce mortality and morbidity in such patients.

Study of Pulmonary Function Test Abnormalities in Metabolic Syndrome.

INTRODUCTION: Metabolic Syndrome (MetS) is defined as a constellation of an interconnected physiological, biochemical, clinical, and metabolic factors that directly increases the risk of atherosclerotic cardiovascular disease and T2DM. Although the link between impaired lung function and cardiovascular events and T2DM has been recognized, the association between impaired lung function and MetS has not been comprehensively assessed. MATERIAL AND METHODS: A cross sectional prevalence study was done in tertiary care hospital in northern India on 100 patients of the age between 25-65 years who fulfilled the IDF criteria for MetS to evaluate pulmonary function test (Spirometry) abnormalities. RESULTS: Maximum number of patients were in 31-40 years of age group (45%) followed by those aged 41-50 year (26%), < 30 years (15%), >50 years (14%). Mean age of patients was 39.59±8.67 year. In this cross-sectional study, patients with Metabolic Syndrome showed significantly lower FVC % predicted (P< 0.001), FEV1 % predicted (P< 0.001) as compared to the group without Metabolic Syndrome. There was a strong linear decrease in FVC and FEV1 % predicted as the number of components of MetS increases. We observed that 28% of the male and 46.6% of female patients showed restrictive ventilatory pattern and 7% of male and 13.4% of female patients showed mixed pattern. CONCLUSION: All MetS components were associated with pulmonary function impairment. As the number of MetS components increases, patients had more severe decline in pulmonary functions.

Adhesion molecules, chemokines and matrix metallo-proteinases response after albendazole and albendazole plus steroid therapy in swine neurocysticercosis.

The treatment of neurocysticercosis (NCC) varies with location, number and stage of the Taenia solium cysticerci (cysts). Albendazole (ABZ) effectively kills cysticerci, and subsequently induces neuro-inflammation facilitated by leukocyte infiltration. We hypothesize that immune response varies around drug responder (degenerating/dying) and non-responder (viable) cysts after ABZ and ABZ plus steroid (ABZS) therapy, which may determine the disease pathogenesis. Twenty cysticercotic swine were treated with ABZ (n = 10; group1) and ABZS (n = 10; group2). Expression of adhesion molecules, chemokines and matrix metallo-proteinases (MMPs) was measured by qRT-PCR (quantitative reverse transcriptase-polymerase chain reaction) and ELISA. Gelatin gel zymography was performed to detect the activity of MMP-2 and -9. In group1, ABZ therapy induced higher expressions of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), E-selectin, MCP-1 (monocyte chemotactic protein-1), Eotaxin-1, MIP-1α (macrophage inflammatory protein-1α), RANTES (regulated on activation, normal T cell expressed and secreted), MMP-2 and MMP-9 around ABZ responder (AR) cysts. Three pigs with cyst burdens ≥10 died following ABZ therapy. However, in group2, moderate expressions of ICAM-1, VCAM-1, E-selectin, RANTES and MMP-9 were associated with ABZS responder (ASR), whereas low expressions of these molecules were associated with ABZS non-responder (ASNR) cysts. In conclusion, ABZ alone therapy is not safe since it causes death of pigs due to higher inflammatory immune response around dying cysts. However, combination therapy is an effective treatment regimen even with the high cyst burden.

Awareness and Outcome of Changing Trends in Clinical Profile of Dengue Fever: A Retrospective Analysis of Dengue Epidemic from January to December 2014 at a Tertiary Care Hospital.

BACKGROUND: Dengue fever is caused by mosquito-borne arboviral infection that has become a public health concern globally. Recently, an alarming rise of dengue has also been seen in India. Hence the study was undertaken to know profile of clinical manifestations and laboratory findings during the evolution of dengue fever. METHODS: In this study, retrospective data analysis was done in 216 seropositive dengue patients admitted between January to December 2014 in department of medicine at a north Indian care hospital. The tests analyzed were blood counts, serum electrolytes, liver function tests, kidney function tests, chest x-ray and other relevant investigations. RESULTS: Males were commonly affected and the most exposed age group was found to be18-35 years. The seropositive case rate for dengue was 56% for NS1 antigen and 36% for IgM. There was rural dominancy of cases with a peak in September. Fever was the most common clinical feature followed by headache, myalgia, backache, nausea and abdominal pain. Petechia was most common haemorrhagic manifestation. Common laboratory findings included 89.35% decreased Platelet counts (<100 000/cmm), 67.59% increased hematocrit (>45%) and 58.33% deranged liver function test. There was no reported mortality in dengue. CONCLUSIONS: From prompt and proper treatment could prevent deaths in moderate and severe dengue. Atypical presentations of dengue should be kept in mind so as not to miss the cases. Increased community awareness and vector control measures need to be strengthened during peri-monsoon period to reduce burden of dengue cases.

Role of MRI in Evaluation of Malignant Lesions of Tongue and Oral Cavity.

BACKGROUND: Aim of the present study was to evaluate the role of MRI in staging of malignant lesions of the oral cavity and to correlate MRI findings with clinical/surgical and anatomical-pathological findings, wherever possible. MATERIAL/METHODS: The study included 50 patients who presented with malignant lesions of the oral cavity and were referred to radiology departments for MRI. All patients included were subjected to a detailed physical examination following which MRI was carried out on Philips Gyroscan Achieva 1.5 Tesla unit. RESULTS: In the study, the highest number of patients were found to have tongue malignancy (82%) followed by buccal mucosa and gingivobuccal sulcus malignancy (18%). The highest number of patients was in the age group of 51-60 years (32%). The incidence was higher in males (96%). There was moderate agreement (k=0.537) for T stage between the clinical and MRI staging assessments. The agreement for N stage between clinical and MRI staging assessments was fair (k=0.328). The final diagnosis was made by histopathology in 22 patients. The agreement for T stage was good/substantial (k=0.790) and for N stage was moderate (k=0.458) between MRI and histopathology staging assessments. CONCLUSIONS: MRI provides satisfactory accuracy for preoperative estimation of tumor thickness and predicting occult cervical nodal metastasis. MRI is the preferred modality in evaluation and staging of oral cavity malignancy which helps a clinician for planning of treatment.

Role and Correlation of High Resolution Ultrasound and Magnetic Resonance Imaging in Evaluation of Patients with Shoulder Pain.

BACKGROUND: The study aimed to evaluate of the role of high-resolution ultrasound and magnetic resonance imaging in patients with shoulder pain. MATERIAL/METHODS: This prospective study included 50 patients referred for ultrasound and MRI because of shoulder pain. All patients were examined clinically, followed by radiography of the affected shoulder. High-resolution ultrasound examination of the involved shoulder was performed together with an examination of the contralateral normal shoulder, followed by MRI of the symptomatic shoulder in all 50 patients. RESULTS: In the present study, the majority of patients were in age group 56-65 years, 56% were males and 44% were females (of a total of 50 patients). A total of 40 patients were diagnosed as having rotator cuff tears on ultrasound (USG) and MRI. USG showed complete-thickness tears in 25 patients and partial-thickness tears in 15 patients. MRI detected 28 complete- and 12 partial-thickness tears of the rotator cuff. In the diagnosis of rotator cuff tears, the strength of agreement between ultrasound and magnetic resonance imaging was good (kappa coefficient=0.79). CONCLUSIONS: Ultrasonography of the shoulder shows promising results in the diagnosis of rotator cuff tears and in differentiating partial from complete tears. A wide availability, cost effectiveness and better tolerability of ultrasonography make it a modality of first choice for evaluating rotator cuff tears.

Plasminogen activator inhibitor-1 stimulates macrophage activation through Toll-like Receptor-4.

While inflammation is often associated with increased Plasminogen Activator Inhibitor-1 (PAI-1), the functional consequences of PAI-1 in inflammation have yet to be fully determined. The aim of this study was to establish the in vivo relevance of PAI-1 in inflammation. A mouse model of systemic inflammation was employed in wild-type (WT) and PAI-1 deficient (PAI-1(-/-)) mice. Mice survival, macrophage infiltration into the lungs, and plasma levels of pro-inflammatory cytokines were assessed after lipopolysaccharide (LPS) infusion. In vitro experiments were conducted to examine changes in LPS-induced inflammatory responses after PAI-1 exposure. PAI-1 was shown to regulate inflammation, in vivo, and affect macrophage infiltration into lungs. Further, PAI-1 activated macrophages, and increased pro-inflammatory cytokines at both the mRNA and protein levels in these cells. The effect of PAI-1 on macrophage activation was dose-dependent and LPS-independent. Proteolytic inhibitory activity and Lipoprotein Receptor-related Protein (LRP) and vitronectin (VN) binding functions, were not involved in PAI-1-mediated activation of macrophages. However, the effect of PAI-1 on macrophage activation was partially blocked by a TLR4 neutralizing antibody. Furthermore, PAI-1-induced Tumor Necrosis Factor-alpha (TNF-α) and Macrophage Inflammatory Protein-2 (MIP-2) expression was reduced in TLR4(-/-) macrophages compared to WT macrophages. These results demonstrate that PAI-1 is involved in the regulation of host inflammatory responses through Toll-like Receptor-4 (TLR4)-mediated macrophage activation.

Promoting microtubule assembly: A hypothesis for the functional significance of the +TIP network.

Regulation of microtubule (MT) dynamics is essential for many cellular processes, but the machinery that controls MT dynamics remains poorly understood. MT plus-end tracking proteins (+TIPs) are a set of MT-associated proteins that dynamically track growing MT ends and are uniquely positioned to govern MT dynamics. +TIPs associate with each other in a complex array of inter- and intra-molecular interactions known as the "+TIP network." Why do so many +TIPs bind to other +TIPs? Typical answers include the ideas that these interactions localize proteins where they are needed, deliver proteins to the cortex, and/or create regulatory pathways. We propose an additional and more mechanistic hypothesis: that +TIPs bind each other to create a superstructure that promotes MT assembly by constraining the structural fluctuations of the MT tip, thus acting as a polymerization chaperone.

Mechanism for the catastrophe-promoting activity of the microtubule destabilizer Op18/stathmin.

Regulation of microtubule dynamic instability is crucial for cellular processes, ranging from mitosis to membrane transport. Stathmin (also known as oncoprotein 18/Op18) is a prominent microtubule destabilizer that acts preferentially on microtubule minus ends. Stathmin has been studied intensively because of its association with multiple types of cancer, but its mechanism of action remains controversial. Two models have been proposed. One model is that stathmin promotes microtubule catastrophe indirectly, and does so by sequestering tubulin; the other holds that stathmin alters microtubule dynamics by directly destabilizing growing microtubules. Stathmin's sequestration activity is well established, but the mechanism of any direct action is mysterious because stathmin binds to microtubules very weakly. To address these issues, we have studied interactions between stathmin and varied tubulin polymers. We show that stathmin binds tightly to Dolastatin-10 tubulin rings, which mimic curved tubulin protofilaments, and that stathmin depolymerizes stabilized protofilament-rich polymers. These observations lead us to propose that stathmin promotes catastrophe by binding to and acting upon protofilaments exposed at the tips of growing microtubules. Moreover, we suggest that stathmin's minus-end preference results from interactions between stathmin's N terminus and the surface of α-tubulin that is exposed only at the minus end. Using computational modeling of microtubule dynamics, we show that these mechanisms could account for stathmin's observed activities in vitro, but that both the direct and sequestering activities are likely to be relevant in a cellular context. Taken together, our results suggest that stathmin can promote catastrophe by direct action on protofilament structure and interactions.

Identification of species and genetic variation in Taenia isolates from human and swine of North India.

Taenia solium is the major cause of taeniasis and cysticercosis/neurocysticercosis (NCC) in the developing countries including India, but the existence of other Taenia species and genetic variation have not been studied in India. So, we studied the existence of different Taenia species, and sequence variation in Taenia isolates from human (proglottids and cysticerci) and swine (cysticerci) in North India. Amplification of cytochrome c oxidase subunit 1 gene (cox1) was done by polymerase chain reaction (PCR) followed by sequencing and phylogenetic analysis. We identified two species of Taenia i.e. T. solium and Taenia asiatica in our isolates. T. solium isolates showed similarity with Asian genotype and nucleotide variations from 0.25 to 1.01 %, whereas T. asiatica displayed nucleotide variations ranged from 0.25 to 0.5 %. These findings displayed the minimal genetic variations in North Indian isolates of T. solium and T. asiatica.

Design, synthesis and biological evaluation of di-substituted noscapine analogs as potent and microtubule-targeted anticancer agents.

Noscapine is an opium-derived kinder-gentler microtubule-modulating drug, currently in Phase I/II clinical trials for cancer chemotherapy. Here, we report the synthesis of four more potent di-substituted brominated derivatives of noscapine, 9-Br-7-OH-NOS (2), 9-Br-7-OCONHEt-NOS (3), 9-Br-7-OCONHBn-NOS (4), and 9-Br-7-OAc-NOS (5) and their chemotherapeutic efficacy on PC-3 and MDA-MB-231 cells. The four derivatives were observed to have higher tubulin binding activity than noscapine and significantly affect tubulin polymerization. The equilibrium dissociation constant (KD) for the interaction between tubulin and 2, 3, 4, 5 was found to be, 55±6µM, 44±6µM, 26±3µM, and 21±1µM respectively, which is comparable to parent analog. The effects of these di-substituted noscapine analogs on cell cycle parameters indicate that the cells enter a quiescent phase without undergoing further cell division. The varying biological activity of these analogs and bulk of substituent at position-7 of the benzofuranone ring system of the parent molecule was rationalized utilizing predictive in silico molecular modeling. Furthermore, the immunoblot analysis of protein lysates from cells treated with 4 and 5, revealed the induction of apoptosis and down-regulation of survivin levels. This result was further supported by the enhanced activity of caspase-3/7 enzymes in treated samples compared to the controls. Hence, these compounds showed a great potential for studying microtubule-mediated processes and as chemotherapeutic agents for the management of human cancers.

Comparison of a Novel Score "NOD-ACLF" to Other Established Prognostic Scores for Prediction of Mortality in APASL-ACLF Patients: A Cohort Study from a Tertiary Care Center of North India.

Background: Commonly used prognostic scores for acute on-chronic liver failure (ACLF) have complex calculations. We tried to compare the simple counting of numbers and types of organ dysfunction to these scores, to predict mortality in ACLF patients. Methods: In this prospective cohort study, ACLF patients diagnosed on the basis of Asia Pacific Association for Study of the Liver (APASL) definition were included. Severity scores were calculated. Prognostic factors for outcome were analysed. A new score, the Number of Organ Dysfunctions in Acute-on-Chronic Liver Failure (NOD-ACLF) score was developed. Results: Among 80 ACLF patients, 74 (92.5%) were male, and 6 were female (7.5%). The mean age was 41.0±10.7 (18-70) years. Profile of acute insult was; alcohol 48 (60%), sepsis 30 (37.5%), variceal bleeding 22 (27.5%), viral 8 (10%), and drug-induced 3 (3.8%). Profiles of chronic insults were alcohol 61 (76.3%), viral 20 (25%), autoimmune 3 (3.8%), and non-alcoholic steatohepatitis 2 (2.5%). Thirty-eight (47.5%) were discharged, and 42 (52.5%) expired. The mean number of organ dysfunction (NOD-ACLF score) was ->4.5, simple organ failure count (SOFC) score was >2.5, APASL ACLF Research Consortium score was >11.5, Model for End-Stage Liver Disease-Lactate (MELD-LA) score was >21.5, and presence of cardiovascular and respiratory dysfunctions were significantly associated with mortality. NOD-ACLF and SOFC scores had the highest area under the receiver operating characteristic to predict mortality among all these. Conclusion: The NOD-ACLF score is easy to calculate bedside and is a good predictor of mortality in ACLF patients performing similar or better to other scores.

Clinicopathologic review of epithelial tumors of the lacrimal gland.

OBJECTIVE: To study the clinicopathologic features of epithelial tumors of the lacrimal gland diagnosed at a tertiary care center in India during a 10-year period. METHODS: Medical records of cases with histopathologically proven epithelial tumors of the lacrimal gland were reviewed for demographic details and clinical features at the time of presentation. For histopathologic findings, slides with hemotoxylin and eosin-stained sections of the tumors were reviewed. Special stains, including histochemical and immunohistochemical stains, and additional sections were studied, whenever needed. RESULTS: Of 66 cases with epithelial tumors of the lacrimal gland identified during the study period, 50 (76%) cases were benign and 16 (24%) cases were malignant tumors. Histopathologic examination was consistent with the diagnosis of pleomorphic adenoma (PA) in all 50 cases of benign tumors. The mean age at diagnosis in PA cases was 37.7 years. Microscopic examination of PA tumors showed cystic degeneration in 18 (36%) cases, squamous metaplasia in 16 (32%) cases, calcification in 6 (12%) cases, and ossification in 1 (2%) case. Among malignant tumors, adenoid cystic carcinoma (ACC) was the most common tumor (n = 12, 18%), with an average age at diagnosis of 32.4 years. Microscopic examination of ACC revealed that most cases were grade I tumors. Solid areas were noted in 4 (33.3%) cases and perineural invasion was identified in 2 (16.7%) cases. Other malignant tumors included 1 case each of carcinoma ex-PA (1.5%), lacrimal duct carcinoma (1.5%), mucoepidermoid carcinoma (1.5%), and basal cell adenocarcinoma (1.5%). CONCLUSIONS: As far as the authors are aware, this is the largest series on clinicopathologic features of epithelial tumors of the lacrimal gland from South Asia. The incidence of PA was significantly higher in this study than reported in the Caucasian population. Among malignant tumors, ACCs were the most common, although rare tumors were also identified.

Fetal Epicardial Fat Thickness: Its Role as Marker for Gestational Diabetic Mellitus.

Background There are very few studies on the association between fetal epicardial fat thickness (EFT) and gestational diabetes mellitus (GDM). Aims To evaluate the role of fetal epicardial fat thickness as a marker and use it in pregnancies to screen for GDM. Settings and Design A cross-sectional analytical study was conducted in the Department of Radiodiagnosis and Imaging at Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, after the due clearance from the institutional research and ethics committee. Materials and Methods The study included pregnant patients at 24 + 0/6 to 28 + 0/6 weeks of gestation scheduled for a 75 g oral glucose tolerance test from December 1, 2020 to March 30, 2022. Antenatal ultrasound was performed on Voluson E8 Expert BT12 (Wipro GE) ultrasound machine. Out of 180 patients, 60 patients were selected, that is, 30 patients with raised 75 g OGTT results (cases of GDM) and 30 patients with normal 75 g OGTT results. Statistical Analysis The collected data were transformed into variables, coded, and entered into Microsoft Excel. Data were analyzed using the Shapiro-Wilk normality test, student's t -test or Mann-Whiney U test, chi-square test, or Fisher's exact test and statistically evaluated using the SPSS-PC-25 version. Results Fetal EFT was found to be significantly more in the GDM group in comparison to controls without GDM, and the increased fetal EFT was positively associated with 2-hour OGTT serum glucose values. The mean fetal epicardial fat thickness (EFT) in mothers with GDM was significantly larger, i.e., 0.17 ± 0.02 cm than in mothers without GDM, i.e., 0.12 ± 0.01 cm ( p < 0.001). The receiver operating characteristic (ROC) curve plotted from values calculated from our results shows high sensitivity (i.e., 96.67%) and specificity (i.e., 90%) of fetal EFT as a predictor for GDM with an AUROC value of 0.96 and 95% confidence interval of 0.92 to 1.0. Conclusions EFT was significantly higher in fetuses of diabetic versus nondiabetic mothers. The mean difference in EFT of GDM cases and controls was relatively small but was statistically significant. The study concluded that measuring the epicardial fat thickness in fetuses can serve as a novel marker in GDM.

Obstructive Sleep Apnea in Hypertension.

Introduction About one-half of patients who have essential hypertension have obstructive sleep apnea (OSA), and about one-half of patients who have obstructive sleep apnea have essential hypertension. OSA can cause even resistant hypertension if left untreated. These two entities often co-exist and are seen as a continuum of the same process. Eighty percent to 90% of OSA cases are undiagnosed mostly because of a lack of awareness. Material and methods This was a cross-sectional study done over a period of one year in a tertiary care hospital. After taking informed consent, 179 hypertensive patients of >18 years were included in the study. All patients were screened for OSA by the STOP-BANG questionnaire. Patients having scores of ≥3 were subjected to overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). Patients with a STOP-BANG score ≤2 or score ≥3 with AHI <5, were considered non-OSA. Results More than half (53.1%) of the patients enrolled in the study had OSA. Their age ranged from 18 to 78 years and the mean age was 52.07±11.40 years. The mean age of OSA cases was found to be slightly higher than that of non-OSA. The majority of OSA cases were males (73.7%). There was an increase in the prevalence, as well as the severity of OSA, with an increase in BMI. Most of the cases had snoring and a history of tiredness. Triglyceride (TG) and low-density lipoprotein (LDL) levels of the OSA group were found to be significantly higher and high-density lipoprotein (HDL) levels were significantly lower than that of the non-OSA group. Conclusion More than half of our hypertensive patients had OSA. These two conditions often co-exist and are known as a dangerous pair. Physicians ought to have increased suspicion for early diagnosis and treatment to improve cardiovascular outcomes, reduce road traffic accidents, and improve quality of life.

Nontubercular bacterial and fungal infections in patients of chronic obstructive pulmonary disease.

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (COPD), frequently due to respiratory tract infection is the major cause of morbidity and mortality, and estimate suggests that it is currently the third leading cause of death worldwide. Aims and Objectives: This study aims to study the prevalence of nontubercular bacterial and fungal infections in patients of COPD. Materials and Methods: It is an observational study done for 1-year period from August 2017 to July 2018. A total of 100 COPD patients who fulfilled the inclusion and exclusion criteria were analyzed in the present study. These cases were classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) combined assessment criteria and subjected to sputum or in some cases Bronchoalveolar lavage (BAL) fluid examination for nontubercular bacterial and fungal pathogens. Serum galactomannan assay, bronchoscopy, and computed tomography chest were done in selected cases. Results: The age of the study population ranged from 40 to 85 years and the mean age was 60.01 ± 9.85 years. Majority of the patients were male (81.0%) and most (78.0%) of them were smokers. Most of the patients belonged to GOLD Grades 2 and 3. Forty-six percent of the patients did show pathogenic organisms in sputum examination. Out of these, 80.4% were bacterial, mainly Gram-negative organisms (Acinetobacter, Pseudomonas, Escherichia coli, Enterobacter, Proteus, and Citrobacter) and 19.6% of cases were having fungal infections (Candida and Aspergillus). Conclusions: Increasing patient age, smoking habit, and severity of COPD were related to an increasing frequency of bacterial and fungal infections. Early detection and proper treatment could help in preventing the morbidity and mortality related to COPD.

Résumé Introduction: L'exacerbation aiguë de la maladie pulmonaire obstructive chronique (MPOC), souvent en raison de l'infection des voies respiratoires, est la principale cause de morbidité et de mortalité, et l'estimation suggère qu'il s'agit actuellement de la troisième cause de décès dans le monde. Objectifs et objectifs: Cette étude vise à étudier la prévalence des infections bactériennes et fongiques non tubulaires chez les patients de la MPOC. Matériaux et méthodes: Il s'agit d'une étude d'observation réalisée pour une période de 1 an d'août 2017 à juillet 2018. Un total de 100 patients atteints de MPOC qui remplissaient les critères d'inclusion et d'exclusion ont été analysés dans la présente étude. Ces cas ont été classés selon l'initiative globale des critères d'évaluation combinés chroniques obstructifs (OR) et soumis à des expectorations ou dans certains cas examen des liquides de lavage bronchoalvéolaire (BAL) pour les agents pathogènes bactéries et fongiques non tubulaires. Le test de galactomannane sérique, la bronchoscopie et le poitrine de tomodensitométrie ont été effectués dans certains cas. Résultats: L'âge de la population d'étude variait de 40 à 85 ans et l'âge moyen était de 60,01 ± 9,85 ans. La majorité des patients étaient des hommes (81,0%) et la plupart (78,0%) d'entre eux étaient des fumeurs. La plupart des patients appartenaient à GOLD GRADES 2 et 3. Quarante-six pour cent des patients ont montré des organismes pathogènes à l'examen des expectorations. Parmi ceux-ci, 80,4% étaient des organismes bactériens, principalement à Gram - négatifs (Acinetobacter, Pseudomonas, Escherichia coli, Enterobacter, Proteus et Citrobacter) et 19,6% des cas avaient des infections fongiques (Candida et 23 aspergillus). Conclusions: L'âge croissant du patient, l'habitude du tabagisme et la gravité de la MPOC étaient liés à une fréquence croissante des infections bactériennes et fongiques. La détection précoce et le traitement approprié pourraient aider à prévenir la morbidité et la mortalité liées à la MPOC. Mots-clés: Maladie pulmonaire obstructive chronique, infection fongique, initiative mondiale pour la maladie pulmonaire obstructive chronique, infection bactérienne non tuberculeuse.

KGHeBTA (King George's Medical University Hepatitis B Therapeutic Algorithm): A New Diagnostic and Therapeutic Algorithm and Clinico-epidemiological Spectrum of Hepatitis B.

Background: Diagnostic and therapeutic algorithms given by various societies for hepatitis B are fragmented and complex. The clinico-epidemiologic spectrum of hepatitis B is not studied with large-scale data from our region. We aimed to develop a comprehensive algorithm for the treatment of hepatitis B and study its clinico-epidemiological spectrum. Methods: From 2014-2019, the clinico-laboratory data of hepatitis B surface antigen (HbsAg)-positive patients were prospectively recorded. King George's Medical University hepatitis B therapeutic algorithm (KGHeBTA) was developed on the basis of the standard existing guidelines. The prevalence of different clinical stages of HBsAg-positive patients was calculated and their treatment records reviewed. Testing circumstances and risk factors were noted. Results: Among 1,508 data record sheets, 421 were complete. According to the KGHeBTA algorithm, 221 had detectable hepatitis B virus DNA. 21% were cirrhotic and 79% non-cirrhotic. 72% were incidentally detected asymptomatic hepatitis B, 7% were hepatitis B with acute symptoms, 0.7% were acute hepatitis B, and 22% were chronic hepatitis B. 20% patients were eligible for antivirals and 80% patients were not eligible. 32% patients were actually treated with antivirals due to the inclusion of some special indications as pregnancy and family history. Screening during various medical illnesses (40%) was the most common and during health camps (0.2%), the least common testing approach. Road-side shaving (52%) was the most common and intravenous drug abuse (0.2%) and the least common risk factor for the detection of hepatitis B in our data pool. Conclusions: HBsAg-positive patients can be easily worked up and treated based on the proposed algorithm (KGHeBTA). About one fourth to one fifth of all HBsAg-positive patients were eligible and treated with oral antivirals. Most of the patients were incidentally detected asymptomatic hepatitis B screened during medical illnesses. Roadside shaving and intravenous drug abuse were the most and the least common risk factors.

Amphotericin B induced pancytopenia.

Amphotericin B (AMB) has been the irreplaceable drug of choice for countless fungal and protozoal infections. One of the lesser-known adverse effects of AMB is Pancytopenia - very rare with very few cases reported - most commonly observed following prolonged administration. We report the case of a patient suffering from visceral leishmaniasis, who developed worsening pancytopenia four to five days after being administered a single bolus dose of Liposomal Amphotericin B (L-AMB). The diagnosis was clinical and management involved supportive care, and granulocyte-macrophage colony-stimulating factor (GM-CSF). AMB is an effective drug, but is also associated with numerous side effects. Physicians are well-versed with the more frequently seen adverse drug reactions and their management. However, pancytopenia, being a rare adverse reaction to AMB, is less known and can be easily overlooked. This case report aims to ensure that the physicians must be aware of such possibilities in the first place to make swift diagnoses and management. The condition itself is seemingly self-limiting, although GM-CSF may be needed in refractory cases. It's true that few previous case reports have indicated pancytopenia in association with prolonged AMB exposure, but we believe certain conditions may predispose a patient to a more acute presentation - as seen in our case.

Scrub Typhus and its co-infection with Leptospirosis at a tertiary care hospital in Uttar Pradesh.

The diagnosis of Scrub Typhus is now improving with the availability of an array of serological tests at the majority of diagnostic centres and of molecular tests at advanced laboratories. Our study focuses on evaluating the spectrum of Scrub Typhus and its coinfection with Leptospirosis in patients presenting with acute febrile illness. A total of 1743 blood samples were collected from both In and Out Patient Department (OPD) patients and analyzed for anti Orientia tsutsugamushi and anti-Leptospira IgM antibodies. Our study showed the presence of Scrub Typhus IgM antibodies in 20.7% of all the cases of acute febrile illness. We also found an interesting correlation of Scrub Typhus with Leptospirosis owing to the presence of co-infection in 8.4% of Scrub Typhus cases paving a way for future research in this regard.

Obstructive sleep apnea in hypothyroidism.

Introduction: Obstructive sleep apnea (OSA) and hypothyroidism are closely linked as hypothyroidism has been shown to lead to the development of OSA through multiple mechanisms. With the changing lifestyle patterns worldwide and increased prevalence of obesity, the burden of OSA has substantially increased. The association of OSA with hypothyroidism is essential to establish. If identified early, treatment of OSA and associated hypothyroidism can be done timely to minimize the potential harmful complications of OSA on all aspects of the patient's health. Aims: This study was done to find out the prevalence of OSA in hypothyroidism patients. Setting and Designs: It was a cross-sectional study, done over a period of 1 year in a tertiary care hospital. Materials and Methods: A total of 100 hypothyroidism patients were enrolled after taking written consent. All patients were subjected to STOP-Bang questionnaire and patient falling in intermediate-high risk (score3-8), were taken for overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). Statistical Analysis Used: The Statistical Package for the Social Sciences version 21.0 statistical analysis software. Results: Out of 100 patients, who underwent polysomnography, 74 (74%) cases had OSA (AHI ≥5). Out of total 74 OSA cases, 29 (39.2%) cases had mild OSA (AHI 5-14), 15 (20.3%) cases had moderate OSA (AHI 15-30), and 30 (40.5%) cases had severe OSA. The age of the study population ranged between 24 and 78 years and the mean age was 58.28 ± 11.22 years. The mean age of the patients in the OSA group (59.27 ± 11.17 years) was higher than the non-OSA group (55.46 ± 11.09 years). Majority (64%) of our cases were male, and the proportion of males was found to be higher than females in both the groups (OSA/non-OSA). The body mass index (BMI) of the OSA group was found to be statistically higher as compared to that of the non-OSA group (P = 0.040). The BMI was found to be higher in severe OSA, but it was not statistically significant (P = 0.128). The mean value of FT4 was lower and thyroid-stimulating hormone (TSH) was higher in the OSA group as compared with the non-OSA group. However, no significant association was found between FT4 and TSH values in both the groups. Out of 100 cases, 41 patients were treatment naïve with mean TSH value of 13.1 ± 7 and 59 were on treatment with mean TSH of 8.3 ± 4. Treatment-naïve patients had a statistically higher number (85.3%) of OSA cases in comparison to patients on treatment (66.1) (P = 0.030). Conclusions: Prevalence of OSA is quite high in hypothyroidism. Patients with hypothyroidism should be screened for OSA for early diagnosis, especially in individuals with higher BMI. Treatment of hypothyroidism reduces the prevalence of OSA.

Résumé Introduction: L'apnée obstructive du sommeil (OSA) et l'hypothyroïdie sont étroitement liées car l'hypothyroïdie s'est avérée conduire au développement de l'AOS à travers de multiples mécanismes. Avec l'évolution des modèles de style de vie dans le monde et une prévalence accrue de l'obésité, le fardeau de l'AOS a considérablement augmenté. L'association de l'AOS avec l'hypothyroïdie est essentielle à établir. S'il est identifié tôt, le traitement de l'AOS et de l'hypothyroïdie associée peuvent être effectués en temps opportun pour minimiser les complications nocives potentielles de l'AOS sur tous les aspects de la santé du patient. Aims: Cette étude a été réalisée pour découvrir la prévalence de l'AOS chez les patients hypothyroïdiennes. Cadre et conception: C'était une étude transversale, réalisée sur une période de 1 an dans un hôpital de soins tertiaires. Matériaux et méthodes: Un total de 100 patients hypothyroïdiennes ont été inscrits après avoir pris consentement écrit. Tous les patients ont été soumis à un questionnaire d'arrêt de bang et à la chute des patients à risque élevé (score3-8), ont été pris pour la polysomnographie d'une nuit pour confirmer le diagnostic de l'AOS (AHI ≥5). Analyse statistique utilisée: Le logiciel Statistical Package for the Social Sciences Version 21.0 Analyse statistique. Résultats: Sur 100 patients, qui ont subi une polysomnographie, 74 (74%) cas avaient une OSA (AHI ≥5). Sur le total de 74 cas d'ASA, 29 (39,2%) avaient des cas légers de l'ASA (AHI 5­14), 15 (20,3%) avaient des cas d'ASA modérés (AHI 15-30), et 20 (40,5%) avaient une OSA sévère. L'âge de la population d'étude variait entre 24 et 78 ans et l'âge moyen était de 58,28 ± 11,22 ans. L'âge moyen des patients du groupe OSA (59,27 ± 11,17 ans) était plus élevé que le groupe non-OSA (55,46 ± 11,09 ans). La majorité (64%) de nos cas étaient des hommes, et la proportion d'hommes s'est révélée plus élevée que les femmes dans les deux groupes (OSA / non-OSA). L'indice de masse corporelle (IMC) du groupe OSA s'est avéré statistiquement plus élevé par rapport à celui du groupe non-OSA (P = 0,040). L'IMC s'est avéré être plus élevé dans l'OSA sévère, mais il n'était pas statistiquement significatif (p = 0,128). La valeur moyenne de FT4 était inférieure et l'hormone stimulante thyroïdienne (TSH) était plus élevée dans le groupe OSA par rapport au groupe non-OSA. Cependant, aucune association significative n'a été trouvée entre les valeurs FT4 et TSH dans les deux groupes. Sur 100 cas, 41 patients étaient naïfs de traitement avec une valeur TSH moyenne de 13,1 ± 7 et 59 étaient sous traitement avec une TSH moyenne de 8,3 ± 4. Les patients naïfs de traitement avaient un nombre statistiquement plus élevé (85,3%) des cas d'AOS par rapport à patients sous traitement (66,1) (p = 0,030). Conclusions: La prévalence de l'AOS est assez élevée en hypothyroïdie. Les patients atteints d'hypothyroïdie doivent être dépistés pour l'AOS pour un diagnostic précoce, en particulier chez les personnes atteintes d'IMC plus élevée. Le traitement de l'hypothyroïdie réduit la prévalence de l'AOS. Mots-clés: Indice d'apnée - hypene, indice de masse corporelle, hypothyroïdie, apnée obstructive du sommeil, polysomnographie, ronflement, fatigue pendant la journée, apnée observée et hypertension, indice.