Diuretics in pregnancy: Data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC).

AIMS: Data on diuretic use in pregnancy are limited and inconsistent, and consequently it remains unclear whether they can be used safely. Our study aims to evaluate the perinatal outcomes after in-utero diuretic exposure. METHODS AND RESULTS: The Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital anomalies and foetal growth. Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (86%). Age >35 years (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0), other cardiac medication use (OR 5.4, 95% CI 4.2-6.9), signs of heart failure (OR 1.7, 95% CI 1.2-2.2), estimated left ventricular ejection fraction <40% (OR 2.9, 95% CI 2.0-4.2), New York Heart Association class >II (OR 3.4, 95% CI 2.3-5.1), valvular heart disease (OR 6.3, 95% CI 4.7-8.3) and cardiomyopathy (OR 3.9, 95% CI 2.6-5.7) were associated with diuretic use during pregnancy. In multivariable analysis, diuretic use during the first trimester was not significantly associated with foetal or neonatal congenital anomalies (OR 1.3, 95% CI 0.7-2.6), and diuretic use during pregnancy was also not significantly associated with small for gestational age (OR 1.4, 95% CI 1.0-1.9). CONCLUSIONS: Our study does not conclusively establish an association between diuretic use during pregnancy and adverse foetal outcomes. Given these findings, it is essential to assess the risk-benefit ratio on an individual basis to guide clinical decisions.

Prevalence of HIV, syphilis, hepatitis B, and hepatitis C in patients attending STI/RTI clinic of a tertiary care teaching hospital.

BACKGROUND: Patients attending Sexually transmitted infection/ Reproductive tract infection (STI/RTI) clinics are investigated for HIV and syphilis under the National AIDS Control Program (NACP). Although sexual contact is one of the modes of transmission of hepatitis B and C, they are not investigated under NACP. This study was planned to find the prevalence of HIV, syphilis, hepatitis B, and C in patients attending STI/RTI clinics and to identify the predictive risk factors. METHODS: A prospective cross-sectional study was carried out over 5 years on 500 consenting adults. 10 ml blood was collected and tests were performed as per standard protocol for HIV, syphilis, hepatitis B, and C. Risk factors for the sexually transmitted diseases were queried. RESULTS: 500 samples were tested, 117(23.4%) men and 383 (76.6%) women. 26(22.2%), 20(17.1%), 11(9.4%) and 01(0.9%) men and 8(2.1%), 36(9.4%), 01(0.3%) and 0(0%) women were positive for HIV, RPR, hepatitis B and C respectively. Dual infection for HIV and syphilis was detected in four (0.8%) men and HIV and hepatitis B in three (0.6%) men. CONCLUSION: To investigate all patients attending STI/RTI clinics for Hepatitis B and to integrate Hepatitis B testing into the National AIDS Control Program.

Comparison of gastric lavage/sputum and stool specimens in the diagnosis of pediatric pulmonary tuberculosis- A pilot study.

BACKGROUND AND OBJECTIVE: Global TB report 2021 mentions 11 % prevalence of pediatric TB, whereas 5.65% of the cases were reported from India in 2020. India features in the list of TB high burden countries, HIV-TB high burden and MDR-TB high burden countries. The diagnosis of pulmonary tuberculosis in children is difficult as they tend to swallow the sputum, invasive techniques of gastric aspirates needs to be followed and the disease itself is paucibacillary. The disease progresses rapidly in young children and hence rapid diagnosis is needed. Obtaining appropriate respiratory samples for diagnosis is difficult especially in primary care settings. Stool sample is easy to obtain and since children swallow sputum, it can be used to diagnose pulmonary tuberculosis. With this background, a pilot study was planned to evaluate the accuracy of the Xpert MTB/RIF assay for the detection of MTB in stool specimens obtained from pediatric pulmonary TB patients confirmed either by gastric lavage(GL) or sputum(SP) Xpert MTB/RIF assay. In addition, the results of microscopy of stool specimen were compared with that of gastric lavage/ sputum (GL/SP) specimen by Ziehl-Neelsen (ZN) and fluorescent light-emitting diode (LED) staining. MATERIAL AND METHODS: A prospective study was carried out on 50 GL/SP Xpert MTB/RIF assay positive children (0-14 years). Stool specimens from these children were processed for Xpert MTB/RIF assay. The GL/SP and stool specimens were processed for ZN and Auramine O fluorescent microscopy as well. RESULTS: Fluorescent staining detected acid fast bacilli (AFB) in 24 GL/SP and 16 stool specimens as compared to 20 GL/SP and 10 stool specimens by ZN staining. Stool Xpert MTB/ RIF assay was positive in 29 out of 50 children. Rifampicin resistance was detected in 13 of the 50 (26%) GL/SP specimens. Of these 13 children, rifampicin resistance was detected in 7 stool specimens, rifampicin indeterminate resistance was detected in one specimen and in the remaining 5 children, M.tuberculosis was not detected in stool. CONCLUSION: Stool is a good non-invasive specimen for the detection of pulmonary TB in children, especially in remote areas, where invasive techniques cannot be performed for sample collection.

Potential of Y. lipolytica epoxide hydrolase for efficient production of enantiopure (R)-1,2-octanediol.

The recombinant Yleh from a tropical marine yeast Yarrowia lipolytica NCIM 3589 exhibited a high epoxide hydrolase activity of 9.34 ± 1.80 µmol min-1 mg-1 protein towards 1,2-epoxyoctane (EO), at pH 8.0 and 30 °C. The reaction product was identified as 1,2-Octanediol (OD) by GC-MS using EO and H2O18 as substrate, affirming the functionality of Yleh as an epoxide hydrolase. For EO, the Km, Vmax, and kcat/Km values were 0.43 ± 0.017 mM, 0.042 ± 0.003 mM min-1, and 467.17 ± 39.43 mM-1 min-1, respectively. To optimize the reaction conditions for conversion of racemic EO by Yleh catalyst to enantiopure (R)-1,2-octanediol, initially, Response Surface Methodology was employed. Under optimized reaction conditions of 15 mM EO, 150 µg purified Yleh at 30 °C a maximal diol production of 7.11 mM was attained in a short span of 65 min with a yield of 47.4%. Green technology using deep eutectic solvents for the hydrophobic substrate (EO) were tested as co-solvents in Yleh catalyzed EO hydrolysis. Choline chloride-Glycerol, produced 9.08 mM OD with an increased OD yield of 60.5%. Thus, results showed that deep eutectic solvents could be a promising solvent for Yleh-catalyzed reactions making Yleh a potential biocatalyst for the biosynthesis of enantiopure synthons.

Mist nebulizer versus heated humidifier on endotracheal tube patency in spontaneously breathing intubated patients: A prospective, randomized controlled trial.

Background and Aims: Using a humidifier in intubated patients is now a standard of care as the humidifying effect of the upper airway is lost. We conducted this study to compare the efficacy of a heated humidifier (HH) with the more commonly used conventional mist nebulizer on overnight intubated and spontaneously breathing post-operative patients. Material and Methods: This prospective, randomized control trial included 60 post-operative overnight intubated and spontaneously breathing patients, of which 30 patients were allocated to the HH group and 30 to the mist nebulizer group. The reduction of endotracheal tube (ETT) patency was measured quantitatively by the difference between the pre-intubation and immediate post-extubation ETT volume and compared between the two groups. Also, the characteristics of secretion, the temperature of inspired gas at the Y-piece, and the frequency of refilling the humidifier chamber were recorded and compared. Results: The reduction of ETT volume was significantly more in the mist nebulizer group compared to the HH group (P-value 0.00026). The mean temperature of the inspired gas (°C) was higher in the HH group (P-value < 0.0001). More patients in the mist nebulizer group had thicker (P-value 0.057) and drier secretions (P-value 0.005) compared to the HH group. None of the patients in the HH group required refilling of the humidifier chamber while the mean frequency of the refilling was 3.5 times per patient in the mist nebulizer group. Conclusion: HH may be preferred over mist nebulizer as the latter requires more frequent refilling which may not be practically possible in a busy recovery room rendering the patient at the risk of inhaling dry gas and consequent thick and dry secretions with decreased ETT patency.

TAKEN: A Traffic Knowledge-Based Navigation System for Connected and Autonomous Vehicles.

Connected and autonomous vehicles (CAVs) have witnessed significant attention from industries, and academia for research and developments towards the on-road realisation of the technology. State-of-the-art CAVs utilise existing navigation systems for mobility and travel path planning. However, reliable connectivity to navigation systems is not guaranteed, particularly in urban road traffic environments with high-rise buildings, nearby roads and multi-level flyovers. In this connection, this paper presents TAKEN-Traffic Knowledge-based Navigation for enabling CAVs in urban road traffic environments. A traffic analysis model is proposed for mining the sensor-oriented traffic data to generate a precise navigation path for the vehicle. A knowledge-sharing method is developed for collecting and generating new traffic knowledge from on-road vehicles. CAVs navigation is executed using the information enabled by traffic knowledge and analysis. The experimental performance evaluation results attest to the benefits of TAKEN in the precise navigation of CAVs in urban traffic environments.

Postoperative complications and critical care management after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy: A systematic review of the literature.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment option performed for peritoneal surface malignancies. Postoperatively almost all patients are transferred to the intensive care unit electively. AIM: To describe the common and rare postoperative complications, postoperative mortality and their critical care management after CRS-HIPEC. METHODS: The authors assessed 54 articles for eligibility. Full text assessment identified 14 original articles regarding postoperative complications and critical care management for inclusion into the final review article. RESULTS: There is an exaggerated metabolic and inflammatory response after surgery which may be termed as physiological in view of the nature of surgery combined with the use of heated intraperitoneal chemotherapy with/out early postoperative intravenous chemotherapy. The expected postoperative course is further discussed. CRS-HIPEC is a complex procedure with some life-threatening complications in the immediate postoperative period, reported morbidity rates between 12%-60% and a mortality rate of 0.9%-5.8%. Over the years, since its inception in the 1980s, postoperative morbidity and survival have significantly improved. The commonest postoperative surgical complications and systemic toxicity due to chemotherapy as reported in the last decade are discussed. CONCLUSION: CRS-HIPEC is associated with a varying rate of postoperative complications including postoperative deaths and needs early suspicion and intensive care monitoring.

Classification of Rajayoga Meditators Based on the Duration of Practice Using Graph Theoretical Measures of Functional Connectivity from Task-Based Functional Magnetic Resonance Imaging.

Context: Functional magnetic resonance imaging (fMRI) studies on mental training techniques such as meditation have reported benefits like increased attention and concentration, better emotional regulation, as well as reduced stress and anxiety. Although several studies have examined functional activation and connectivity in long-term as well as short-term meditators from different meditation traditions, it is unclear if long-term meditation practice brings about distinct changes in network properties of brain functional connectivity that persist during task performance. Indeed, task-based functional connectivity studies of meditators are rare. Aims: This study aimed to differentiate between long-term and short-term Rajayoga meditators based on functional connectivity between regions of interest in the brain. Task-based fMRI was captured as the meditators performed an engaging task. The graph theoretical-based functional connectivity measures of task-based fMRI were calculated using CONN toolbox and were used as features to classify the two groups using Machine Learning models. Subjects and Methods: In this study, we recruited two age and sex-matched groups of Rajayoga meditators from the Brahma Kumaris tradition that differed in the duration of their meditation experience: Long-term practitioners (n = 12, mean 13,596 h) and short-term practitioners (n = 10, mean 1095 h). fMRI data were acquired as they performed an engaging task and functional connectivity metrics were calculated from this data. These metrics were used as features in training machine learning algorithms. Specifically, we used adjacency matrices generated from graph measures, global efficiency, and local efficiency, as features. We computed functional connectivity with 132 ROIs as well as 32 network ROIs. Statistical Analysis Used: Five machine learning models, such as logistic regression, SVM, decision tree, random forest, and gradient boosted tree, were trained to classify the two groups. Accuracy, precision, sensitivity, selectivity, area under the curve receiver operating characteristics curve were used as performance measures. Results: The graph measures were effective features, and tree-based algorithms such as decision tree, random forest, and gradient boosted tree yielded the best performance (test accuracy >84% with 132 ROIs) in classifying the two groups of meditators. Conclusions: Our results support the hypothesis that long-term meditative practices alter brain functional connectivity networks even in nonmeditative contexts. Further, the use of adjacency matrices from graph theoretical measures of high-dimensional fMRI data yields a promising feature set for machine learning classifiers.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a 2-YearOld Child with Abdominopelvic Rhabdomyosarcoma: A Case Report of Anaesthetic Concerns.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-established multimodal treatment in patients with peritoneal surface malignancies in adults. Children younger than 3 years rarely undergo such extensive surgeries with heated chemotherapy infusion intraoperatively. Only one such case is reported in the literature for CRS-HIPEC for an abdominopelvic rhabdomyosarcoma in a child of 2 years or less. We present the case of a 2-year-old child with abdominopelvic rhabdomyosarcoma undergoing CRS-HIPEC and discuss the perioperative concerns and challenges.

Epidemiology and Predictors of Hospital Outcomes of Critically Ill Pediatric Oncology Patients: A Retrospective Study.

BACKGROUND: The number of pediatric oncology patients admitted to the intensive care unit (ICU) has increased, and their hospital outcomes are improving. Since scarce data are available about this patient population, we conducted this retrospective study to evaluate the epidemiology and predictors of hospital outcomes. MATERIALS AND METHODS: We included all children with cancers who were admitted to our ICU over 1 year. We excluded children admitted after elective surgery and those following bone marrow transplant. We collected data about demographics, admission diagnosis, type of malignancies, and ICU interventions. The primary outcome was the hospital outcome. The secondary outcomes were ICU length of stay (LOS), and ICU and hospital mortality. We analyzed the predictors of hospital outcome. RESULTS: Two hundred pediatric oncology patients were admitted from November 1, 2014 to October 30, 2015. Seventy-eight children had solid organ malignancies, and the rest had hematological malignancies. Hematooncology malignancy patients had significantly higher hospital mortality than those with solid organ malignancies. (61.5 vs 34.6%, p = 0.015). On multivariate regression analysis, mechanical ventilation [odds ratio (OR), 14.64; 95% confidence interval (CI): 1.23-165.05; p <0.030], inotropes (OR, 9.81; 95% CI: 1.222-78.66; p <0.032), and the presence of coagulopathy (OR, 3.86; 95% CI: 1.568-9.514; p <0.003) were independent predictors of hospital mortality. CONCLUSION: In this retrospective cohort of 200 children with malignancies, we found that children with hematologic cancer had significantly higher hospital mortality as compared to those with solid tumors. The need for mechanical ventilation, use of inotrope infusion, and coagulopathy were independent predictors of mortality. HOW TO CITE THIS ARTICLE: Bhosale SJ, Joshi M, Patil VP, Kothekar AT, Myatra SN, Divatia JV, et al. Epidemiology and Predictors of Hospital Outcomes of Critically Ill Pediatric Oncology Patients: A Retrospective Study. Indian J Crit Care Med 2021;25(10):1183-1188.

Tropical Infections in the Indian Intensive Care Units: The Tip of the Iceberg!

How to cite this article: Karnad DR, Patil VP, Kulkarni AP. Tropical Infections in the Indian Intensive Care Units: The Tip of the Iceberg! Indian J Crit Care Med 2021; 25(Suppl 2):S115-S117.

Does Presence of Sepsis by Itself Predispose the Patients to HCAIs?

How to cite this article: Gaikwad S, Patil VP. Does Presence of Sepsis by Itself Predispose the Patients to HCAIs? Indian J Crit Care Med 2021;25(3):253-254.

Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer.

Leukotrienes are one of the major eicosanoid lipid mediators produced due to an oxidative transformation of arachidonic acid. Subsequently, they get converted into various cellular signaling hormones by a series of enzymes of myeloid origin to mediate or debilitate inflammation. Interestingly, the available literature demonstrates the pivotal role of eicosanoids in neurodegenerative, obesity, diabetes, cardiovascular diseases, and cancers as well. The aberrant metabolism of arachidonic acid by the LOX pathway is a common feature of epithelial-derived malignancies and suggests the contributory role of dietary fats in carcinogenesis. The enzymes and receptors of the LOX pathway play a significant role in cell proliferation, differentiation and regulation of apoptosis through multiple signaling pathways and have been reported to be involved in various cancers, including prostate, colon, lung and pancreatic cancers. So far, leukotriene receptor antagonists and 5-LOX inhibitors have reached up to the clinical trials for treating various diseases. Keeping its various roles in cancer, the review highlights the components of the leukotriene synthesizing machinery, emerging opportunities for pharmacological intervention, and the probability of considering lipoxygenases and leukotriene receptors as good candidates for clinical chemoprevention studies.

Is Immature Granulocyte Count a Potential Prognostic Marker for Upper Gastrointestinal Tract Bleeding? A New Road to Explore.

How to cite this article: Prabu NR, Patil VP. Is Immature Granulocyte Count a Potential Prognostic Marker for Upper Gastrointestinal Tract Bleeding? A New Road to Explore. Indian J Crit Care Med 2020;24(9):750-752.

Apolipoprotein C2 - CD36 Promotes Leukemia Growth and Presents a Targetable Axis in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a devastating hematologic malignancy that affects the hematopoietic stem cells. The 5-year overall survival (OS) of patients with AML is less than 30%, highlighting the urgent need to identify new therapeutic targets. Here, we analyze gene expression datasets for genes that are differentially overexpressed in AML cells compared with healthy hematopoietic cells. We report that apolipoprotein C2 (APOC2) mRNA is significantly overexpressed in AML, particularly in patients with mixed-lineage leukemia rearrangements. By multivariate analysis, high APOC2 expression in leukemia blasts is significantly associated with decreased OS (HR: 2.51; 95% CI, 1.03-6.07; P = 0.04). APOC2 is a small secreted apolipoprotein that constitutes chylomicrons, very-low-density lipoproteins, and high-density lipoproteins with other apolipoproteins. APOC2 activates lipoprotein lipase and contributes to lipid metabolism. By gain and loss of function approaches in cultured AML cells, we demonstrate that APOC2 promotes leukemia growth via CD36-mediated LYN-ERK signaling activation. Knockdown or pharmacological inhibition of either APOC2 or CD36 reduces cell proliferation, induces apoptosis in vitro, and delays leukemia progression in mice. Altogether, this study establishes APOC2-CD36 axis as a potential therapeutic target in AML.

Fluid Overload and Acute Kidney Injury.

Commonest intervention in hospitalized patient is fluid therapy, and practically every critically ill patient receives fluid resuscitation. Commonest indication for fluid administration is to achieve hemodynamic stability and prevent or manage acute kidney injury (AKI). However, fluid administration is a two-edged sword, i.e., inadequate fluids give rise to hypoperfusion and organ injury and overzealous fluid therapy can give rise to fluid overload and related consequences. Though fluids are commonly given to prevent development of AKI, hypervolemia itself has the potential to cause AKI. HOW TO CITE THIS ARTICLE: Patil VP, Salunke BG. Fluid Overload and Acute Kidney Injury. Indian J Crit Care Med 2020;24(Suppl 3):S94-S97.

Protective effects of luteolin against oxidative stress and mitochondrial dysfunction in endothelial cells.

BACKGROUND AND AIMS: Luteolin is a common flavonoid that is abundantly present in various edible plants, it is known to exhibit beneficial effects on cardiovascular system. However, the mechanisms which underlie the protective effects of luteolin on endothelial cell damage caused by oxidative stress remains unclear. The purpose of this study is to test the hypothesis which states that luteolin protects against H2O2-induced oxidative stress via modulating ROS-mediated P38 MAPK/NF-κB and calcium-evoked mitochondrial apoptotic signalling pathways. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were pretreated with luteolin prior to being stimulated by 600 µM H2O2 for another 24 h. The expression of native and phosphorylated-P38, IκB, NF-κB, native eNOS, phosphorylated-eNOS, iNOS and several apoptosis-related proteins were analyzed by Western blot. In addition, intracellular calcium was determined by fura-2 AM and mitochondrial membrane potential was examined by using JC1. Using the data gathered, we found indications that H2O2 induced P38 MAPK/NF-κB activation. H2O2 downregulated the expression of eNOS and upregulated iNOS, which in turn contribute to an elevated NO generation and protein nitrosylation. However, pretreatment with luteolin markedly reversed all of these alterations dose-dependently. Additionally, an intracellular calcium rise and subsequent mitochondrial membrane potential collapse, P53 phosphorylation, reduced BcL-2/Bax ratio in the mitochondrial membrane, release cytochrome c from mitochondria, leading to the subsequent activation of caspase 3 activation by H2O2 were all markedly suppressed in the presence of luteolin. CONCLUSION: Results from this study may provide the possible molecular mechanisms underlying cardiovascular protective effects of luteolin.

Human Granulocyte-Macrophage Colony-Stimulating Factor Fused to Elastin-Like Polypeptides Assembles Biologically-Active Nanoparticles.

Human granulocyte-macrophage colony-stimulating factor (hGMCSF) is crucial in the immune system as it stimulates survival, proliferation, differentiation, and functional activation of myeloid hematopoietic cells. hGMCSF is integral to approved therapies, including monoclonal antibodies against checkpoint inhibitors, chimeric antigen receptors, and prevention of chemotherapy-induced neutropenia. Recombinant hGMCSF can be purified from Escherichia. coli; however, it forms inclusion bodies that require solubilization and refolding. Alternatively, this manuscript describes its fusion with an elastin-like polypeptide (ELP). Previously reported as purification tags and solubility enhancers, ELPs are recombinant polypeptides that undergo reversible temperature-dependent phase separation. This report is the first to show that fusion to an ELP enables direct purification of hGMCSF fusions from the soluble fraction of bacterial lysate. Surprisingly, these ELP-fusions assemble stable, small, spherical nanoparticles that maintain pro-mitotic activity of hGMCSF. These nanoparticles exhibit ELP-mediated phase separation; however, nanoparticle assembly significantly increases the entropic and enthalpic cost of phase separation compared to ELP alone. The attachment of a high molecular weight ELP to a difficult-to-express protein, like hGMCSF, appears to be a useful strategy to stabilize bioactive, protein-based nanoparticles, which may have broad applications in medicine and biology.