ADVANCING THE UNDERSTANDING OF CLINICAL SEPSIS USING GENE EXPRESSION-DRIVEN MACHINE LEARNING TO IMPROVE PATIENT OUTCOMES.

ABSTRACT: Sepsis remains a major challenge that necessitates improved approaches to enhance patient outcomes. This study explored the potential of machine learning (ML) techniques to bridge the gap between clinical data and gene expression information to better predict and understand sepsis. We discuss the application of ML algorithms, including neural networks, deep learning, and ensemble methods, to address key evidence gaps and overcome the challenges in sepsis research. The lack of a clear definition of sepsis is highlighted as a major hurdle, but ML models offer a workaround by focusing on endpoint prediction. We emphasize the significance of gene transcript information and its use in ML models to provide insights into sepsis pathophysiology and biomarker identification. Temporal analysis and integration of gene expression data further enhance the accuracy and predictive capabilities of ML models for sepsis. Although challenges such as interpretability and bias exist, ML research offers exciting prospects for addressing critical clinical problems, improving sepsis management, and advancing precision medicine approaches. Collaborative efforts between clinicians and data scientists are essential for the successful implementation and translation of ML models into clinical practice. Machine learning has the potential to revolutionize our understanding of sepsis and significantly improve patient outcomes. Further research and collaboration between clinicians and data scientists are needed to fully understand the potential of ML in sepsis management.

A TRANSCRIPTOMIC APPRECIATION OF CHILDHOOD MENINGOCOCCAL AND POLYMICROBIAL SEPSIS FROM A PRO-INFLAMMATORY AND TRAJECTORIAL PERSPECTIVE, A ROLE FOR VASCULAR ENDOTHELIAL GROWTH FACTOR A AND B MODULATION?

ABSTRACT: This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 gene expression also showed temporal changes in the MSS datasets. In the postmortem dataset comparing MSS cases to controls, VEGF-A was upregulated and VEGF-B downregulated. Renal tissue exhibited higher VEGF-A expression compared with other tissues. Similar VEGF-A upregulation and VEGF-B downregulation patterns were observed in the cross-sectional MSS datasets and the polymicrobial sepsis dataset. Hexagonal plots confirmed VEGF-R (VEGF receptor)-VEGF-R2 signaling pathway enrichment in the MSS cross-sectional studies. The polymicrobial sepsis dataset also showed enrichment of the VEGF pathway in septic shock day 3 and sepsis day 3 samples compared with controls. These findings provide unique insights into the dynamic nature of sepsis from a transcriptomic perspective and suggest potential implications for biomarker development. Future research should focus on larger-scale temporal transcriptomic studies with appropriate control groups and validate the identified gene combination as a potential biomarker panel for sepsis.

Gastrointestinal Issues in Critically Ill Children.

Due to lack of uniform diagnostic criteria, gastrointestinal (GI) complications in critically ill occur with variable frequency,1 and overall incidence of such complications seems to be less in children compared to adults. Major risk factors are use of catecholamines, sedatives, and muscle relaxants in patients with shock. GI dysmotility in critically ill patients is the main reason behind abdominal distension, increased gastric residual volume, and constipation. GI bleeding is described in about 10% of patients with critical illness with about 1.6% have clinically significant bleeding, particularly in patients with coagulopathy, respiratory failure, or PRISM scores >10.2 In this review, the most common GI issues encountered in children will be discussed as mentioned earlier. In addition management of acute GI bleeding will also be discussed. How to cite this article: Khilnani P, Rawal N, Singha C. Gastrointestinal Issues in Critically Ill Children. Indian J Crit Care Med 2020;24(Suppl 4):S201-S204.

Consensus Guidelines for Pediatric Intensive Care Units in India, 2020.

BACKGROUND: Consensus Guidelines for Pediatric Intensive Care Units (PICUs) were published in Indian Pediatrics in 2002. OBJECTIVE: The current document represents a recent update in the Indian context, regarding unit design, equipment, organization, staffing as well as admission and discharge criteria for different levels of Pediatric Intensive Care and teaching units with PICU training programs, as well as nonteaching units. PROCESS: The Pediatric Intensive Care College Council (PICC), an academic wing of the Indian Academy of Pediatrics (IAP) Intensive Care Chapter took the initiative to update the guidelines with members of the PICU guidelines Committee writing group. After a great deal of discussion at conferences and through mailing and feedback with listed members, as well as with the guidance and feedback of senior PICU guidelines advisory committee members, The consensus is now updated. These guidelines are intended to serve as a reference for health Care institutions wishing to establish a new PICU or to modify an existing PICU. As a resource, experience of those members who have worked extensively in western PICUs was also taken into consideration, in addition to published guidelines in the medical literature. PICUs with teaching programs run by the IAP Intensive Care Chapter must follow these criteria for unit accreditation and teaching curricula as applicable. RECOMMENDATIONS: Unit design, equipment, organization, staffing as well as admission and discharge criteria for different levels of pediatric intensive care are updated.

Pediatric Critical Care Medicine Training in India: Past, Present, and Future.

Pediatric critical care services in India have grown with leaps and bounds. There has been a growing need of physicians specially trained in pediatric critical care medicine (PCCM) in India. Physicians returning to India after their formal training in PCCM abroad have partly supported this growing need. Development of formal PCCM training programs in India has been a huge step toward supporting the growing clinical needs. This article focuses on advances in pediatric critical care training in India and its future directions.

Guillain-Barre syndrome masquerading as acute respiratory failure in an infant.

Guillain-Barré syndrome (GBS) is a rare entity in infants. We report a case of GBS in a 5-month-old girl. The child presented with cough, loose stools, breathing difficulty, and listlessness. The child was treated as pneumonia with respiratory failure. Due to difficulty in weaning from ventilation with areflexia, marked hypotonia, and reduced power in all four limbs; possibilities of spinal muscular atrophy, poliomyelitis, and myopathies were kept. Nerve conduction velocity study was suggestive of mixed sensory-motor, severe axonal, and demyelinating polyradiculoneuropathy. Cerebrospinal fluid study revealed albuminocytological dissociation. Child was diagnosed as GBS and treated with intravenous immunoglobulin. Child recovered completely on follow-up. GBS should be considered as a differential diagnosis in acute onset respiratory failure with neuromuscular weakness in infants.

Prevalence and outcome of diastolic dysfunction in children with fluid refractory septic shock--a prospective observational study.

OBJECTIVES: Our primary objective was to determine the prevalence and outcome of diastolic dysfunction in children with fluid refractory septic shock. The secondary objective was to determine possible early predictors of diastolic dysfunction. DESIGN: Prospective observational study. SETTING: PICU of a tertiary care teaching hospital. PATIENTS: Consecutive children 17 years old or younger with fluid refractory septic shock and not on mechanical ventilation admitted to our ICU from June 2011 to August 2012 were included. Survivors were followed up till 1 year of discharge (July 2013). INTERVENTIONS: Children were subjected to 2D echocardiography and qualitative cardiac troponin-T test within the first 6 hours of admission. MEASUREMENTS AND MAIN RESULTS: A total of 56 children were included. Median age was 7 years (interquartile range, 1.5, 14) and majority (52%) were males. Most common underlying diagnoses were meningitis and pneumonia. The prevalence of diastolic dysfunction was 41.1% (95% CI, 27.8-54.4), and mortality rate was 43% in those with diastolic dysfunction. At 1-year follow-up, residual dysfunction was present in only one of 11 of the survivors (11%). On univariable analysis of possible early predictors of diastolic dysfunction, we observed that these children tended to have higher mean central venous pressure (13 vs 6; p < 0.0001) and greater positivity for cardiac troponin-T (70% vs 36%; p = 0.01) compared with others. Although factors such as duration of illness and diastolic blood pressure were also lower in children with diastolic dysfunction compared with others, the difference was not statistically significant. On multivariable analysis, only the variable central venous pressure remained significant (adjusted odds ratio, 1.6; 95% CI, 1.12-2.14; p = 0.008). CONCLUSIONS: Diastolic dysfunction is common in children with fluid refractory septic shock, and immediate outcomes may be poorer in such patients. Increased central venous pressure after initial fluid resuscitation may be an early indicator of diastolic dysfunction and warrant urgent bedside echocardiography to guide further management.

Genetic analysis in Bartter syndrome from India.

Bartter syndrome is a group of inherited, salt-losing tubulopathies presenting as hypokalemic metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. Around 150 cases have been reported in literature till now. Mutations leading to salt losing tubulopathies are not routinely tested in Indian population. The authors have done the genetic analysis for the first time in the Bartter syndrome on two cases from India. First case was antenatal Bartter syndrome presenting with massive polyuria and hyperkalemia. Mutational analysis revealed compound heterozygous mutations in KCNJ1(ROMK) gene [p(Leu220Phe), p(Thr191Pro)]. Second case had a phenotypic presentation of classical Bartter syndrome however, genetic analysis revealed only heterozygous novel mutation in SLC12A gene p(Ala232Thr). Bartter syndrome is a clinical diagnosis and genetic analysis is recommended for prognostication and genetic counseling.

Intensive care unit acquired weakness in children: Critical illness polyneuropathy and myopathy.

BACKGROUND AND AIMS: Intensive care unit acquired weakness (ICUAW) is a common occurrence in patients who are critically ill. It is most often due to critical illness polyneuropathy (CIP) or to critical illness myopathy (CIM). ICUAW is increasingly being recognized partly as a consequence of improved survival in patients with severe sepsis and multi-organ failure, partly related to commonly used agents such as steroids and muscle relaxants. There have been occasional reports of CIP and CIM in children, but little is known about their prevalence or clinical impact in the pediatric population. This review summarizes the current understanding of pathophysiology, clinical presentation, diagnosis and treatment of CIP and CIM in general with special reference to published literature in the pediatric age group. SUBJECTS AND METHODS: Studies were identified through MedLine and Embase using relevant MeSH and Key words. Both adult and pediatric studies were included. RESULTS: ICUAW in children is a poorly described entity with unknown incidence, etiology and unclear long-term prognosis. CONCLUSIONS: Critical illness polyneuropathy and myopathy is relatively rare, but clinically significant sequelae of multifactorial origin affecting morbidity, length of intensive care unit (ICU) stay and possibly mortality in critically ill children admitted to pediatric ICU.

Isolated severe bilateral bronchomalacia.

Airway malacia is uncommon condition having symptoms similar to common respiratory illnesses. Any child having persistent wheeze during infancy should be evaluated for airway malacia. The authors report a case of isolated severe bilateral bronchomalacia managed with tracheostomy and continuous positive pressure ventilation.

Pachymeningitis in a young child responded to antitubercular therapy: a case report.

Pachymeningitis is a rare disease of diverse etiology mainly affecting the adult population. Only 4 pediatric cases have been reported till now. We report the youngest child with pachymeningitis from India. Our case responded very well to antitubercular therapy with near complete recovery. Antitubercular therapy can be considered in children from endemic countries with hypertrophic pachymeningitis before labeling their condition as idiopathic hypertrophic pachymeningitis.

Ventriculo-peritoneal shunt: A rare cause of basal ganglia and thalamic abscess.

We report an 18-month-old female child with ventriculo-peritoneal shunt related thalamic abscess treated with stereotactic aspiration. Deep seated abscesses are complex due to difficult access and are associated with an increased risk of intra-ventricular rupture as well as antibiotic resistance, a fact which justifies a more aggressive and immediate neurosurgical management.

Pediatric Sepsis Guidelines: Summary for resource-limited countries.

JUSTIFICATION: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. PROCESS: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. OBJECTIVE: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. RECOMMENDATIONS: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3-5 years as new body of evidence accumulates.