Acute liver failure in pregnancy.

Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and progress to acute liver failure (ALF). There is a discrete set of etiology for ALF in pregnancy and comprehensive understanding will help in urgent evaluation. Certain diseases such as acute fatty liver of pregnancy, hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome and pre-eclampsia are secondary to pregnant state and can present as ALF. Quick and targeted evaluation with urgent institution of etiology-specific management, especially urgent delivery in patients with pregnancy-associated liver diseases, is the key to avoiding maternal deaths. Pregnancy, as also the fetal life, imparts a further layer of complication in assessment, prognosis and management of these sick patients with ALF. Optimal management often requires a multidisciplinary approach in a well-equipped centre. In this review, we discuss evaluation, assessment and management of pregnant patients with ALF, focussing on approach to pregnancy-associated liver diseases.

Association of antibiotic duration and all-cause mortality in a prospective study of patients with ventilator-associated pneumonia in a tertiary-level critical care unit in Southern India.

OBJECTIVES: To estimate all-cause mortality in ventilator-associated pneumonia (VAP) and determine whether antibiotic duration beyond 8 days is associated with reduction in all-cause mortality in patients admitted with VAP in the intensive care unit. DESIGN: A prospective cohort study of patients diagnosed with VAP based on the National Healthcare Safety Network definition and clinical criteria. SETTING: Single tertiary care hospital in Southern India. PARTICIPANTS: 100 consecutive adult patients diagnosed with VAP were followed up for 28 days postdiagnosis or until discharge. OUTCOME MEASURES: The incidence of mortality at 28 days postdiagnosis was measured. Tests for association and predictors of mortality were determined using χ2 test and multivariate Cox regression analysis. Secondary outcomes included baseline clinical parameters such as age, underlying comorbidities as well as measuring total length of stay, number of ventilator-free days and antibiotic-free days. RESULTS: The overall case fatality rate due to VAP was 46%. There was no statistically significant difference in mortality rates between those receiving shorter antibiotic duration (5-8 days) and those on longer therapy. Among those who survived until day 9, the observed risk difference was 15.1% between both groups, with an HR of 1.057 (95% CI 0.26 to 4.28). In 70.4% of isolates, non-fermenting Gram-negative bacilli were identified, of which the most common pathogen isolated was Acinetobacter baumannii (62%). CONCLUSION: In this hospital-based cohort study, there is insufficient evidence to suggest that prolonging antibiotic duration beyond 8 days in patients with VAP improves survival.

Biomarkers of coagulation, endothelial, platelet function, and fibrinolysis in patients with COVID-19: a prospective study.

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7-14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26-4.55 ng/ml; Soluble P-selectin = 13.5-31.5 ng/ml; BTG = 0.034-1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.

UDHAVI Community Support During India's Second COVID-19 Wave: A Descriptive Study on a Tertiary Care Center's Pandemic Response Helpline.

BACKGROUND: In April 2021, during the peak of the second wave of the COVID-19 pandemic in India, hospitals overflowed with COVID-19 patients, and people hesitated to seek necessary care due to fear of contracting the disease. The UDHAVI helpline was set up by a tertiary care hospital in Vellore with the help of district administration, nongovernmental organizations, and various supporting agencies to provide general information, medical advice, counseling, and logistics support to the community. METHODS: This is a retrospective study of all the phone calls made to the UDHAVI helpline between mid-May and mid-June 2021 during the second wave of the COVID-19 pandemic. The calls were electronically captured as part of the process, and the information was subsequently retrieved and analyzed. RESULTS: In all, 677 calls were received. The lines for general information, medical advice, counseling, and logistics support received 168 (25%), 377 (56%), 15 (2%), and 117 (17%) calls, respectively. Home care kits, oxygen concentrators, and food were delivered by volunteers from local nongovernmental organizations and hospitals. CONCLUSION: We believe the details of our experience would be useful in the preparedness and mobilization of resources in the event of any public health emergency. As a result of this initiative, we propose an integrated partnership model for emergency response to any pandemic situation.

Clinical and Genomic Evolution of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections over Two Time Periods at a Tertiary Care Hospital in South India: A Prospective Cohort Study.

INTRODUCTION: The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections and their impact at a tertiary care hospital in South India. METHODS: A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014-2015; C2, 2021-2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. RESULTS: A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p = 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p = 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-ß-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. CONCLUSIONS: CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Central nervous system manifestations of dengue infection: data from a tertiary care Centre in South India.

BACKGROUND: Dengue fever is the second most common mosquito-borne disease affecting human beings and neurological manifestations (NMs) of this arboviral infection are increasingly being reported. METHODS: In this retrospective study, conducted in a tertiary care centre in south India, we sought to describe the spectrum of NMs of dengue fever. The records of all patients admitted in the Department of Internal Medicine over 8 years, with a diagnosis of dengue-based on clinical symptoms and the detection of dengue IgM antibodies or detection of NS1 antigen or nucleic acid by reverse transcriptase-polymerase chain reaction (RT-PCR); with Glasgow coma score (GCS) ≤14, neck stiffness, focal neurological signs, seizures, or visual disturbances-were explored. RESULTS: Of 1121 patients admitted with dengue fever, 341 (30%) had severe dengue and 23 (2%) had NMs. Encephalopathy was seen in 9 patients (39%), encephalitis in 6 (27%), cerebellitis in 4 (17%), acute disseminated encephalomyelitis (ADEM) in 2 (9%), ischaemic stroke in 1 (4%) patient, and neuro-ophthalmological manifestations in 1 (4%) patient. The median duration of hospital stay was 7 days. Nine (39% of) patients required intensive care unit (ICU) admission and 5 (22%) had fatal outcomes. There was no association between thrombocytopenia, metabolic acidosis, transaminitis, hyponatremia, the type of dengue infection, and the various NMs described. CONCLUSIONS: The NMs of dengue infection are varied, and a high index of suspicion is needed to identify them in patients who present with lethargy or altered sensorium on the background of an acute febrile illness suggestive of dengue.

Pulmonary tuberculosis and diabetes mellitus: Clinical profile and outcomes.

Background: India is endemic for Tuberculosis (TB), contributing to the world's highest number of active cases. Diabetes (DM), with its increasing burden in India, could contribute to adverse outcomes among patients with TB. Methods: Consecutive patients with sputum smear positive pulmonary tuberculosis were included in the study. We defined cases as those patients with diabetes at recruitment. Controls were non diabetics (NDM). Sputum samples for AFB smears, AFB culture and Xpert PCR along with blood samples for glycosylated Haemoglobin and glucose levels were collected at recruitment and at 6 months from patients with sputum positive pulmonary TB. Blood glucose levels and sputum smears were repeated at 2 months and monthly till they tested negative. The primary outcome studied was mortality at 6 month follow-up. The secondary outcomes included the time to conversion of sputum smears and cure rates between cases and controls. Results: We recruited 124 patients of which 68 were cases. Mortality after therapy was 15% in cases and 7% in controls, however, the difference was not statistically significant. Equal proportions in each group (Diabetics: 9% vs. NDM 9%) had persistent smear positivity at 2 months. There was no association between delayed sputum conversion and uncontrolled diabetes. Only about 57% of cases and 50% of controls were documented to have completed treatment or been cured. A significant reduction in HbA1c after 6 months of Antituberculous therapy was noted among the cases. [Mean difference - 1.76, P-value - 0.001, 95% CI of difference - (1.01 - 2.52)]. Conclusions: Diabetes did not have adverse outcomes in the form of increased mortality or delayed sputum conversion rates. The high proportion of loss to follow-up seems to be a trend of concern, which should be addressed emergently.

Accuracy of Xpert MTB/RIF Ultra for the diagnosis of tuberculosis in adult patients: a retrospective cohort study.

OBJECTIVES: The value of the "trace" result in Xpert Ultra for diagnosing active tuberculosis (TB) remains unclear. Our study evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) (Cepheid, Sunnyvale, USA) over Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, USA) and mycobacterial culture when compared with a composite reference standard (CRS). METHODS: A retrospective single-center observational study was conducted in a tertiary care hospital in South India. Over three months, patients (aged ≥15 years) data on Xpert Ultra tests and mycobacterial culture of pulmonary and extrapulmonary samples were extracted from their electronic medical records. Patients were defined as TB cases based on the CRS criteria. Sensitivity, specificity, positive and negative predictive values of diagnostic tests were calculated by comparing them to the CRS. RESULTS: Xpert Ultra was more sensitive (87.8%) than Xpert (72.1%) and culture (44.1%). The specificity of Xpert Ultra was lower (98.1%) than those of Xpert (100%) and culture (100%). The sensitivity (92%) and specificity (100%) of Xpert Ultra were highest when performed on pus samples. CONCLUSIONS: Xpert Ultra with the trace category is superior to the conventional Xpert, and mycobacterial culture in identifying TB.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Differentiating Cardiac and Pulmonary Causes of Dyspnea Using Ultrasonography and Dyspnea Discrimination Index.

BACKGROUND: One of the most common reasons for emergency room (ER) visits is acute dyspnea. The challenge is in differentiating a cardiac and pulmonary cause of acute breathlessness. Hence, we have studied the effectiveness of the dyspnea discrimination index (DDI) used in conjunction with ultrasonography (USG) in distinguishing between cardiac and pulmonary causes of dyspnea. METHODS: This was a prospective study conducted in the ER and general medicine wards to evaluate the efficacy of the DDI and USG in dyspneic patients. Data were entered in a standard data sheet and analysis was done using SPSS software. RESULTS: The majority of the patients were between the ages of 45 and 60, with a male predominance. Risk factors like smoking were more common in the pulmonary group (36%). Pulmonary cause of breathlessness was seen in 62% of patients and cardiac pathology was noted in 28%. The mean (SD) DDI value and DDI% are as follows: pulmonary group (DDI)-5.47 (SD: 2.82); cardiac group (DDI)-8.34 (SD: 3.75); pulmonary group (DDI%)-1.31 (SD: 0.68); cardiac group (DDI%)-2.34 (SD: 1.14). There was a significant difference in DDI% between the pulmonary and cardiac groups (p = 0.001). DDI was found to have a sensitivity and specificity of 77.3% and 70%, respectively. While for DDI%, sensitivity and specificity were 72.7% and 72%, respectively. Lung USG had 98% sensitivity and 95.5% specificity, with a narrow confidence interval. The positive likelihood ratio was noted to be 21.6, indicating a very high post-test probability. CONCLUSION: The DDI and USG in conjunction had good discriminative power, when it came to distinguishing between cardiac and pulmonary causes of dyspnea. USG had a high specificity and sensitivity, making it suitable for identifying the cause of dyspnea in a tertiary care ER setting. HOW TO CITE THIS ARTICLE: Chandy GM, Sathyendra S, Pichamuthu K, Hazra D, Abhilash KPP. Differentiating Cardiac and Pulmonary Causes of Dyspnea Using Ultrasonography and Dyspnea Discrimination Index. Indian J Crit Care Med 2022;26(1):33-38.

Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR): design and methodology.

BACKGROUND: Cardiac disease in pregnancy is a major contributor to maternal mortality in high, middle and low-income countries. Availability of data on outcomes of pregnancy in women with heart disease is important for planning resources to reduce maternal mortality. Prospective data on outcomes and risk predictors of mortality in pregnant women with heart disease (PWWHD) from low- and middle-income countries are scarce. METHODS: The Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR) is a prospective, multicentric and multidisciplinary registry of PWWHD from 29 participating sites including both public and private sectors, across the state of Tamil Nadu in India. The TNPHDR is aimed to provide data on incidence of maternal and fetal outcomes, adverse outcome predictors, applicability of the modified World Health Organization (mWHO) classification of maternal cardiovascular risk and the International risk scoring systems (ZAHARA and CARPREG I & II) in Indian population and identify possible gaps in the existing management of PWWHD. Pregnancy and heart teams will be formed in all participating sites. Baseline demographic, clinical, laboratory and imaging parameters, data on counselling received, antenatal triage and management, peripartum management and postpartum care will be collected from 2500 eligible participants as part of the TNPHDR. Participants will be followed up at one, three and six-months after delivery/termination of pregnancy to document study outcomes. Predictors of maternal and foetal outcome will be identified. DISCUSSION: The TNPHDR will be the first representative registry from low- and middle-income countries aimed at providing crucial information on pregnancy outcomes and risk predictors in PWWHD. The results of TNPHDR could help to formulate steps for improved care and to generate a customised and practical guideline for managing pregnancy in women with heart disease in limited resource settings. TRIAL REGISTRATION: The TNPHDR is registered under Clinical Trials Registry-India ( CTRI/2020/01/022736 ).

Bedside lung ultrasonography: comparison with chest radiography (BLUR), a diagnostic study in a developing country.

BACKGROUND: This study determines the diagnostic utility of lung ultrasonography (LUS) in a medical ward in a developing country. In a low resource country like India, we hope that use of lung ultrasound in primary and secondary hospitals will assist in earlier and better bedside diagnosis. METHODS: This prospective diagnostic study was done to test the diagnostic accuracy of LUS against a composite reference standard, which included clinical history and examination, basic laboratory investigations, imaging and the diagnosis at discharge. We evaluated 321 consecutive patients, admitted in our medical wards with an LUS within 24 hours of the chest radiograph being done. FINDINGS: Between August 2016 and August 2017, we enrolled 321 patients. The sensitivity and specificity of the LUS for all pathologies were found to be 82.5% (76.50 to 87.20) and 78.2% (69.09 to 85.26) respectively. A subgroup analysis including the patients in whom CT was part of the composite reference standard showed sensitivity and specificity of 87.9% and 92.9% for all lung pathologies. It was found that there was superior sensitivity and specificity of LUS compared with chest radiograph in a subgroup analysis of pulmonary oedema and acute respiratory distress syndrome (ARDS). INTERPRETATION: We found that the LUS was better than chest radiograph and as good as CT in most pathologies, especially pulmonary oedema and ARDS. We believe that training in the basics of bedside LUS must be part of the medical curriculum and a low-cost ultrasound machine must be made available in medical wards, so that clinical diagnosis can be supplemented with this tool. In a low resource setting like India, where access to chest radiograph and CT may be difficult particularly in a rural setup, expertise in LUS would be helpful in easy bedside diagnosis and saving cost on a CT scan.

Utility of positron emission tomography-computed tomography in the evaluation of fever of unknown origin in a resource-limited tropical nation.

Positron emission tomography-computed tomography (PET-CT) has been used as an imaging modality in workup of fever of unknown origin (FUO). The aim of our study is to evaluate the diagnostic utility of PET-CT in FUO workup in a resource-limited setting. We also looked at laboratory parameters as predictors of contributory PET-CT scans and propose an algorithm for evaluation of FUO in resource-limited tropical regions. This retrospective observational study included patients admitted for FUO workup under general medicine in a teaching hospital in South India from June 2013 to May 2016. PET-CT was done when the patient remained undiagnosed after a detailed clinical assessment and first- and second-tier investigations. Among 43 patients included in our study, a definite diagnosis was established in 74% (32). Noninfectious inflammatory diseases, infections, malignancies, and miscellaneous diseases were diagnosed in 37.2% (16/43), 23.3% (10/43), 9.3% (4/43), and 4.7% (2/43), respectively. Tuberculosis was the single most common disease seen in 20.9% (9/43). PET-CT scans were contributory toward establishment of final diagnosis in 90.7% (39/43). High C-reactive protein (CRP) and aspartate aminotransferase (AST) levels were associated with contributory PET-CT scans (P = 0.006 and 0.011, respectively). PET-CT delineating organ/tissue for diagnostic biopsy was associated with final diagnosis of infectious disease (P = 0.001). Sensitivity, specificity, and positive and negative predictive value of PET-CT scans were 76.9% (20/26), 33.3% (2/6), 83% (20/24), and 25% (2/8), respectively. High CRP and AST were predictors of contributory PET-CT scans. PET-CT scans have high sensitivity and positive predictive value when used in evaluation of FUO. Although it is a useful tool in FUO workup, especially in the diagnosis of tropical infections, PET-CT should be done after a comprehensive clinical assessment and basic investigations.

Peripartum cardiomyopathy: An analysis of clinical profiles and outcomes from a tertiary care centre in southern India.

Peripartum cardiomyopathy is a syndrome of maternal heart failure with decreased left ventricular ejection fraction affecting maternal and fetal well-being. We analysed clinical profiles and outcomes in women with peripartum cardiomyopathy enrolled retrospectively from a tertiary care centre in southern India (1 January 2008-31 December 2014). The incidence of peripartum cardiomyopathy was one case per 1541 live births. Fifty-four women with a mean age of 25.5 years and mean gestational age of 35.4 weeks were recruited; 35 were primigravidae. Maternal and fetal deaths occurred in 9.3% and 24.1% of subjects, respectively. Mild-to-moderate maternal anaemia (80-110 g/L) was associated with fetal mortality (p = 0.02). Reduced left ventricular ejection fraction (<30%, p = 0.04) and cardiogenic shock (p = 0.01) were significantly associated with adverse maternal outcomes. Forty per cent of women were followed up after 24.2 ± 17.7 months, and in these women a significant increase in left ventricular ejection fraction was seen (mean 16.4%, p < 0.01); all were asymptomatic. Peripartum cardiomyopathy with poor left ventricular ejection fraction and shock is associated with adverse maternal outcomes, while non-severe maternal anaemia predisposes to adverse fetal outcomes. Significant left ventricular ejection fraction recovery occurred on follow-up.

Gram-negative infective endocarditis: a retrospective analysis of 10 years data on clinical spectrum, risk factor and outcome.

Infective endocarditis (IE) is a significant cause of morbidity and mortality. Underlying congenital heart disease and acquired valvular disease significantly increases the IE risk, which is still prevalent in developing countries. Gram-negative organism related IE prevalence appears to be rising with limited data on their presentation and outcomes. This study hopes to shed further light on this subject. This retrospective cross-sectional study occurred in a tertiary care center in South India. A retrospective cross-sectional study performed in a single tertiary care center in South India. All patients with IE from 2006 to 2016 were included in this study. The details of clinical presentation, laboratory investigations, clinical course, microbiology, and outcomes were obtained. Patients fulfilling the modified Duke's criteria and a culture-proven diagnosis of gram-negative IE were eligible for inclusion. A total of 27 patients were enrolled from Jan 2006 to Dec 2016, among whom 78% were male. Prior structural heart disease was common in our cohort (41%) with renal (55%) and embolic (51%) complications being the most common systemic complications. A comparison of mortality with survivors found that congenital and acquired structural heart disease had a higher risk of mortality. Non-fermenting GNB accounted for 52% of the cohort, with Pseudomonas accounting for 19%. E. coli was the most common bacilli isolated, constituting 37% of the cohort. Assessment of risk factors for adverse outcomes found that renal dysfunction and intravascular device were significant with multivariate-logarithmic analysis showing renal dysfunction as an independent risk factor. In-hospital mortality in this series was 30%. In conclusion, gram-negative IE was more prevalent among males. Underlying structural heart disease was the most common risk factor associated with the disease. Renal dysfunction and embolic complications were the most common complications in this cohort. E. coli and NFGNB accounted for 70% of the offending organisms. In-hospital mortality was similar to patients with IE secondary to common organisms. The presence of renal dysfunction was an independent risk factor for an adverse outcome.

Performance of molecular and serologic tests for the diagnosis of scrub typhus.

Diagnosis of scrub typhus, caused by the bacterium Orientia tsutsugamushi, is challenging because of the overlap of its non-specific symptoms with other infections coupled with the lack of sufficient data on the performance of diagnostic tests. Early diagnosis of scrub typhus is crucial to improve outcomes and this study evaluates the diagnostic performance of various tests. The present study aims at assessing the accuracy of various rapid diagnostic tests, serologic tests, and nucleic acid amplification methods on well-characterized patient samples. Adult patients with acute febrile illness and manifestations suggestive of scrub typhus confirmed by positive PCR in the blood, eschar or tissue were characterized as cases. Patients with acute febrile illness and a confirmed alternate etiology such as culture-confirmed typhoid, smear/PCR positive for malaria, PCR/NS1 antigen positive for dengue, PCR positive for influenza, PCR/MAT positive for leptospirosis, PCR positive for spotted fever were characterized as controls with other infections. The healthy controls consisted of subjects from the same geographic region. We performed the following tests on blood samples for scrub typhus and calculated the sensitivity, specificity, positive predictive value, and negative predictive value: (1) Quantitative real time PCR using 47kDa gene (qPCR); (2) Conventional PCR using 56kDa gene (cPCR); (3) Loop-mediated isothermal amplification assay (LAMP assay); (4) Immunofluorescence assay (IFA); (5) Enzyme-linked immunosorbent assay (ELISA); (6) Weil-Felix test(WF test); and (7) Immunochromatographic Rapid Diagnostic Test (RDT).Among the 316 participants, 158 had confirmed scrub typhus (cases) and 158 were controls. ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies had excellent discriminative potential with sensitivities and specificities of 92%, 94% and 92%, 92% respectively. The sensitivity and specificity of IFA were found to be 95% and 74% respectively. IgM serology had a false positivity rate of 8% with other acute febrile illnesses such as dengue, leptospirosis and spotted fever due to the nonspecific binding of the pentavalent IgM. LAMP assay had 91.7% sensitivity and 77.2% specificity while qPCR provided excellent sensitivity (97%) and perfect specificity. In conclusion, ELISA and RDT detecting Orientia tsutsugamushi specific IgM antibodies have excellent sensitivity and specificity while the accuracy of IFA is suboptimal for the diagnosis of scrub typhus. Given its perfect specificity and superior sensitivity, qPCR is preferred for diagnostic confirmation in reference laboratories particularly for diagnosis of early disease with less than 7 days duration. This study provides a comprehensive evaluation of all currently available diagnostic tests for scrub typhus.

Treatment outcomes with daily self-administered treatment and thrice-weekly directly-observed treatment in two cohorts of newly-diagnosed, sputum-positive adults with pulmonary tuberculosis.

BACKGROUND: The Revised National Tuberculosis Control Program (RNTCP) envisages shifting from thrice-weekly to a daily anti-tuberculosis treatment (ATT) regimen. The potential merits and demerits of both regimens continue to be debated. METHODS: This retrospective study compared treatment outcomes in 191 HIV-negative, newly diagnosed, sputum-positive adults with pulmonary tuberculosis from Vellore district of Tamil Nadu who were treated at a private medical college during 2009 to 2012 with intermittent Directly Observed Treatment Short Course (intermittent DOTS cohort, n=132) or who opted for daily Self-Administered Treatment (daily SAT cohort, n=59). Treatment outcomes obtained from medical records were supplemented by interviews with consenting, traceable patients. RESULTS: The rates for the RNTCP-recommended sputum smear examinations were suboptimal (42% for daily SAT and 72% for intermittent DOTS). However, treatment success with daily SAT and intermittent DOTS (76.2% vs. 70.4%); default (11.9% vs. 18.2%); death (6.8% vs. 5.3%); treatment failure (5.1% vs. 4.6%); and relapse (0% vs. 1.5%) did not significantly differ. CONCLUSIONS: While evaluable treatment outcomes were not significantly different with daily SAT and intermittent DOTS, rates for timely smear examinations and for treatment success were lower, and for default higher, in both cohorts than comparable RNTCP data from Vellore district. Further strengthening of RNTCP facilities within private medical colleges and regular, real-time audits of performance and outcomes are needed if daily ATT regimen under the RNTCP is to succeed.

Acute oleander poisoning: A study of clinical profile from a tertiary care center in South India.

INTRODUCTION: Yellow oleander (Thevetia peruviana), which belongs to the Apocyanaceae family, is a common shrub seen throughout the tropics. All parts of the plant contain high concentrations of cardiac glycosides which are toxic to cardiac muscle and the autonomic nervous system. Here, we describe the clinical profile of patients with oleander poisoning and their outcomes. METHODS AND MATERIALS: This retrospective study was conducted over a period of 12 months (March 2016 to February 2017). The data was extracted from the inpatient electronic medical records. Adult patients with a diagnosis of acute yellow oleander poisoning were included in the study. Descriptive statistics were obtained for all variables in the study and appropriate statistical tests were employed to ascertain their significance. RESULTS: The study comprised 30 patients aged 30.77 ± 12.31 (mean ± SD) who presented at 12.29 ± 8.48 hours after consumption of yellow oleander. Vomiting (80%) was the most common presenting symptom. Metabolic abnormalities at presentation included hyperchloremia in 22 patients and metabolic acidosis (bicarbonate <24 mmol/L) in 29 patients. Fifteen (50%) patients had abnormal ECG, of which second-degree AV block was the commonest ECG abnormality seen in 4 (13.3%). Fifteen (50%) patients had transvenous temporary pacemaker insertion (TPI). Having a TPI significantly prolonged the duration of hospital stay (OR 1.85, 95% CI 1.06-3.21, P 0.03). The mortality in the cohort was 2 (6.7%). CONCLUSION: In patients with yellow oleander poisoning, dyselectrolytemia with ECG abnormalities was common. TPI prolonged the duration of hospital stay. Further studies are required to know the indication for and to ascertain the effect of temporary pacing on survival.

First Indian report on genome-wide comparison of multidrug-resistant Escherichia coli from blood stream infections.

BACKGROUND: Multidrug-resistant (MDR) E. coli with extended-spectrum ß-lactamases (ESBLs) is becoming endemic in health care settings around the world. Baseline data on virulence and antimicrobial resistance (AMR) of specific lineages of E. coli circulating in developing countries like India is currently lacking. METHODS: Whole-genome sequencing was performed for 60 MDR E. coli isolates. The analysis was performed at single nucleotide polymorphism (SNP) level resolution to identify the presence of their virulence and AMR genes. RESULTS: Genome comparison revealed the presence of ST-131 global MDR and ST410 as emerging-MDR clades of E. coli in India. AMR gene profile for cephalosporin and carbapenem resistance differed between the clades. Genotypes blaCTX-M-15 and blaNDM-5 were common among cephalosporinases and carbapenemases, respectively. For aminoglycoside resistance, rmtB was positive for 31.7% of the isolates, of which 95% were co-harboring carbapenemases. In addition, the FimH types and virulence gene profile positively correlated with the SNP based phylogeny, and also revealed the evolution of MDR clones among the study population with temporal accumulation of SNPs. The predominant clone was ST167 (blaNDM lineage) followed by ST405 (global clone ST131 equivalent) and ST410 (fast spreading high risk clone). CONCLUSIONS: This is the first report on the whole genome analysis of MDR E. coli lineages circulating in India. Data from this study will provide public health agencies with baseline information on AMR and virulent genes in pathogenic E. coli in the region.