The profile of epilepsy and its characteristics in children with neurocutaneous syndromes.

Objectives: The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes. Materials and Methods: Cross-sectional study over 18 months at a tertiary care pediatric hospital, including children with neurocutaneous syndromes aged between 1 and 15 years, using the 2017-International League Against Epilepsy classification. Results: In 119 children with neurocutaneous syndromes, 94 (79%) had epilepsy. In eight children with neurofibromatosis one with epilepsy, 5 (62.5%) had generalized motor tonic-clonic seizures, 1 (12.5%) had generalized motor epileptic spasms, 1 (12.5%) had generalized motor automatism, and 1 (12.5%) had a focal seizure. In 69 children with tuberous sclerosis complex with epilepsy, 30 (43.5%) had generalized motor epileptic spasms, 23 (33.3%) had focal seizures, and nine (13.0%) had generalized motor tonic-clonic seizures. In 14 children with Sturge-Weber syndrome with epilepsy, 13 (92.8%) had focal seizures, and 1 (7.2%) had generalized motor tonic seizures. Statistically significant associations were found between epilepsy and intellectual disability (P = 0.02) and behavioral problems (P = 0.00). Conclusion: Profiling seizures in children with neurocutaneous syndromes are paramount in devising target-specific treatments as the epileptogenesis in each syndrome differs in the molecular pathways leading to the hyperexcitability state. Further multicentric studies are required to unravel better insights into the epilepsy profile of neurocutaneous syndromes.

In-vitro antioxidant and anti-inflammatory potential along with p.o. pharmacokinetic profile of key bioactive phytocompounds of Snow Mountain Garlic: a comparative analysis vis-à-vis normal garlic.

Snow mountain garlic (SMG) is a trans-Himalayan medicinal plant used in the traditional medicine system for several ailments, including inflammatory arthritis. Research studies are insufficient to validate its folk medicinal applications. In the present study, the comparative abundance of its key bioactive phytocompounds, viz., S-allyl-L-cysteine (SAC), alliin, and S-methyl-L-cysteine (SMC) against normal garlic were assessed using the LC-MS/MS-MRM method. In addition, the study also explored the antioxidant and anti-inflammatory potency of crude extract of SMG and purified signature phytocompounds (i.e., SMC, SAC, and alliin) in comparison with normal garlic and dexamethasone in LPS-stimulated RAW264.7 macrophage cells. The LC-MS/MS-MRM study revealed significant differences among SMG and normal garlic, viz., alliin 22.8-fold higher in SMG, and SMC could be detected only in SMG. In the bioassays, SMG extract and purified signature phytocompounds significantly downregulated oxidative damage in activated macrophages, boosting endogenous antioxidants' activity. SMG extract-treated macrophages significantly suppressed NF-κB expression and related inflammatory indicators such as cytokines, COX-2, iNOS, and NO. Notably, the observed anti-inflammatory and antioxidant bioactivities of SMG extract were comparable to signature phytocompounds and dexamethasone. In addition, SAC being uniformly found in SMG and normal garlic, its comparative pharmacokinetics was studied to validate the pharmacodynamic superiority of SMG over normal garlic. Significantly higher plasma concentrations (Cmax), half-life (t1/2), and area under curve (AUC) of SAC following SMG extract administration than normal garlic validated the proposed hypothesis. Thus, the abundance of bioactive phytocompounds and their better pharmacokinetics in SMG extract might be underlying its medicinal merits over normal garlic.

To Study the Distress, Anxiety, Depression, and Sleep Effects of the COVID-19 Pandemic on Essential Workers.

Essential care workers like police personnel, social workers, and office and administrative staff of health institutions are also at increased risk of coronavirus disease 2019 (COVID-19) exposure along with healthcare workers. The present study aims to estimate the distress, anxiety, depression, and sleep impact of COVID-19 pandemic on essential workers through an online survey. This cross-sectional study (included 369 participants) was conducted in Chandigarh through an online survey using three psychological scales: Peritraumatic Distress Inventory (PDI), Insomnia Severity Index, and Depression Anxiety Stress Scale. Three-hundred-sixty-nine frontline warriors from hospital and community settings were included in the study. The respondents include police personnel (274; 73.66%), office staff (24; 6.45%), social workers (53; 14.24%), and media staff (21; 5.65%). Maximum distress was reported by media/transport officials on duty (85.7%). The majority of them scored high (>14), and slightly less than one-fourth (23.8%) scored significantly abnormal (>23) on PDI. About 42.9% reported moderate insomnia, 52.4% exhibited severe anxiety, and 33.3% of media/transport participants reported severe depression. Psychological morbidity is high in media/transport and social workers working in the community during the COVID-19 pandemic.

Exploring the combined effect of heavy metals on accumulation efficiency of Salix alba raised on lead and cadmium contaminated soils.

The present study illustrated that Salix alba can accumulate high level of Pb and Cd in different plant parts, with maximum accumulation in roots followed by stem and leaves in the order Cd > Pb > Cd + Pb. The phytoremediation evaluation factors such as bioconcentration factor (BCF) and translocation factor (TF) was higher for Cd over Pb in all plant parts, further the BCF for both Pb and Cd was maximum in root (BCF > 1) followed by stem and leaves. Higher accumulation of Cd over the Pb was observed inside the plant tissues due to Cd mimics with other elements and gets transported through respective transporters. The combined treatment of Pb and Cd affected the bioaccumulation at every treatment level suggesting the negative effect among both elements. Higher survival rate (>85%) was recorded up to 200mgPb/kg and 15mgCd/kg, while further increase in metal concentration reduced the plant efficiency to remediate contaminated soils, hence results in declined survival rate. The FTIR analysis revealed that Pb and Cd accumulation in plants induced changes in carboxy, amino, hydroxyl and phosphate groups that ultimately caused alteration in physiological and biochemical processes of plant and thus provided an insight to the interaction, binding and accumulation of heavy metals.

The present study conferred that Salix alba is a heavy metal (Pb and Cd) excluder plant on the basis of phytoremediation efficiency evaluation factors such BCF >1 (root) and TF <1. The correlation studies suggested the negative correlation among Pb and Cd accumulation and morphological traits. Physiological studies indicated that Pb and Cd accumulation negatively affect chlorophyll concentration and the antioxidant mechanism of plants gets activated, further these results are confirmed with FTIR studies, which reported the alteration in functional groups and associated compounds in plant tissues under Pb and Cd stress.

X-Linked Lymphoproliferative Syndrome: A Spectrum of Clinical and Immunological Profile and Novel Pathogenic Variants from Chandigarh, India.

INTRODUCTION: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. METHODS: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. RESULTS: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. DISCUSSION/CONCLUSIONS: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.

Tolvaptan for Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in a Child with Corpus Callosum Agenesis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the common causes of euvolemic hyponatremia (serum Na+ < 135 mEq/L) in hospitalized children. It is characterized by increased serum ADH, leading to water retention via its action on V2 receptors in the distal renal tubules. Various conditions such as pain, the postoperative state, drugs, central nervous system infections, tumors, malformations, and pneumonia can predispose a person to SIADH. The conventional treatment of SIADH includes fluid restriction and salt supplementation. Occasionally, this may fail to control hyponatremia, mandating pharmacological therapy. V2-receptor antagonists are an FDA-approved therapy for adults with euvolemic and hypervolemic hyponatremia. However, there is limited experience with their use in the pediatric population. Here, the authors present a girl with corpus callosum agenesis with severe symptomatic hyponatremia due to SIADH who was successfully managed with the V2-receptor antagonist tolvaptan.

A self-heuristic inquiry: Unpacking the use of "Decolonization" in therapy and mental health care with and for racialized communities.

As a registered psychotherapist and art therapist, my clinical training was primarily based on North American clinical approaches influenced by traditional Euro and western-centric clinical theories of human behavior. I completed my training feeling certain that traditional clinical mental health practices were not an appropriate fit for racialized communities and could have negative implications for their healing and well-being. As clinicians, it is our moral obligation to support and enhance the quality of life for marginalized groups. We can do this by challenging our values and knowledge that have been defined and influenced by structures (i.e., education, training, etc.) embedded in these colonial teachings. For this paper, I used a heuristic self-inquiry research method to investigate these concerns. I interviewed other racialized psychotherapists practicing in Turtle Island (currently mostly occupied by the political entities of Canada and the United States) with the aim to learn how and if decolonization can be used in therapy practice. With this research, I (1) identified a gap in care for racialized communities, (2) questioned if or how a decolonizing approach to care should be considered, (3) explored my discomfort with practitioners in the field that claim their position on decolonizing therapy, practice, and approaches, and lastly (4) propose other ways of knowing that can inform new ways of practicing therapy. The results of this research helped to problematize the language and use of decolonizing therapeutic practices while learning about other concepts that may be relevant yet distinct, such as principles of coloniality/decoloniality. Those of us, therapists or researchers, wanting to disrupt the current practice of therapy need to work together, share knowledge, and challenge each other, so that we can transform the way we practice as psychotherapists. This paper is my contribution to this conversation.

Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India.

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Delay in diagnosis is the most important proximate reason for mortality in hereditary angio-oedema: our experience at Chandigarh, India.

BACKGROUND: Hereditary angio-oedema (HAE) is a rare autosomal dominant disorder characterized clinically by recurrent episodes of nonpruritic subcutaneous and/or submucosal oedema. Laryngeal oedema is the commonest cause of mortality in patients with HAE. Prior to the availability of first-line treatment options for the management of HAE, mortality was as high as 30%. Mortality has significantly declined in countries where first-line treatment options are available and patients can access these therapies. There is a paucity of literature on the outcomes of patients with HAE in developing countries where availability of and access to first-line treatment options are still a challenge. OBJECTIVES: To report our experience on mortality in patients with HAE and to report factors associated with the death of these patients. METHODS: We carried out a record review of all patients diagnosed with HAE between January 1996 and August 2022. Families with HAE who had reported the death of at least one family member/relative from laryngeal oedema were studied in detail. RESULTS: Of the 65 families (170 patients) registered in the clinic, 16 families reported the death of at least one family member/relative from laryngeal oedema (total of 36 deaths). Of these 16 families, 14 reported that 1 or more family members had experienced at least 1 attack of laryngeal oedema. One patient died during follow-up when she was taking long-term prophylaxis with stanozolol and tranexamic acid, while the remaining 35 patients were not diagnosed with HAE at the time of their death. At the time of death of all 36 patients, at least 1 other family member had symptoms suggestive of HAE, but the diagnosis was not established for the family. CONCLUSIONS: To our knowledge, this is the largest single-centre cohort of patients with HAE in India reporting mortality data and factors associated with death in these families. The delay in diagnosis is the most important reason for mortality.

Cognitive Function in Early Onset Type 1 Diabetes in Children.

OBJECTIVES: To assess cognitive function and factors affecting it in Indian children with early-onset type 1 diabetes (T1D) (less than 6 y). METHODS: This cross-sectional, single-centre study recruited children diagnosed with T1D before 6 y of age and having a disease duration of at least 2 y, as cases. Controls were age- and sex-matched apparently healthy children or siblings. Children with birth asphyxia, intellectual disability, syndromic children, or pre-existing psychiatric illness were excluded. Enrolled children underwent cognitive assessment using Malin's Intelligence Scale for Indian Children (MISIC), and scores in various subtests were compared between cases and controls. RESULTS: A total of 60 children were enrolled in each group. When compared to controls, cases had significantly lower scores on most subtests, verbal, performance and overall Intelligence Quotient (IQ- 100.62 ± 3.26 vs. 103.23 ± 1.22). HbA1c >9%, severe hypoglycemia and lesser duration since the last diabetic ketoacidosis (DKA) episode significantly correlated with lower neurocognitive scores. CONCLUSIONS: Children with early onset T1D showed significant deficits in various cognitive domains and IQ. Poor glycemic control, higher glycemic variability and exposure to severe hypoglycemia are risk factors for poor cognitive outcomes in these children. Further longitudinal studies could potentially aid in a finer understanding of factors affecting cognitive functioning in T1D children in developing countries.

Incidence of Central Line-Associated Bloodstream Infection in a Tertiary Care Hospital in Northern India: A Prospective Study.

Background Central line-associated bloodstream infection is the most common hospital-acquired infection and is associated with high morbidity and mortality along with increased healthcare cost. However, studies on the incidence of nosocomial infections are very limited in India. Aims To determine the incidence of central line-associate bloodstream infection (CLABSI), microorganisms associated and their antimicrobial sensitivity profile in the medical ICU of a tertiary care hospital. Material and methods A total of 186 patients who were admitted to the medical ICU and had a non-tunneled central venous catheter (CVC) implanted at admission in the emergency department or in the medical ICU for longer than 48 hours were monitored. By examining the blood culture reports, the patients were monitored every day for the emergence of new-onset sepsis after 48 hours following CVC insertion. The data were evaluated statistically using Microsoft Excel and SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Result Out of 186 catheterized patients, 37 developed CLABSI. The incidence of CLABSI was 9.3 per 1000 catheter days and 6.7 per 1000 inpatient days with a 0.7 device utilization ratio. The most common organism isolated was Acinetobacter species (22%) followed by K. pneumoniae (16%) and E. aerogenes (16%). The highest sensitivity was displayed by polymyxin B (100%) followed by tigecycline (85.48%) and minocycline (50.82%) in Gram-negative organisms. In Gram-positive organisms, the highest sensitivity was observed in S. aureus (100%) for vancomycin, linezolid and teicoplanin whereas Enterococcus species showed linezolid (100%) followed by vancomycin (93.75%) and teicoplanin (93.75%). Conclusion The prevention of CLABSI requires knowledge of the infection rates and of the sources, the pathogens involved as well as their antimicrobial profile. Due to rising antimicrobial resistance, surveillance programs are crucial in establishing the species distribution and resistance patterns of bacteria causing BSIs and thus providing the basis for appropriate empirical therapy.

Carbohydrate Counting vs. Fixed Meal Plan in Indian Children with Type 1 Diabetes Mellitus: A Randomized Controlled Trial.

OBJECTIVES: To study the impact of carbohydrate counting vs. fixed-meal plan on glycemic control, quality of life (QoL) and diabetes-related emotional distress in children with Type 1 diabetes mellitus (T1DM). METHODS: Children aged 6-18 y with T1DM of duration >1 y were eligible for the study if they were on multiple daily injections of insulin and regularly monitoring blood glucose. Those with celiac disease, hypothyroidism, any underlying chronic renal/liver/systemic disease or HbA1c >13% were excluded. Both groups received education on diabetes management and healthy diet. In the intervention arm, parents were taught to quantify carbohydrate content and modify insulin doses according to insulin-carbohydrate ratio. The control arm had dietary prescription according to recommended dietary allowance and food exchange list. Standard validated questionnaires were used to assess the QoL and emotional distress related to diabetes. RESULTS: One hundred twenty five patients (61 intervention, 64 controls) were enrolled and 91.8% and 84.3%, respectively, completed 6-mo follow-up. There was a reduction in HbA1c in both the groups, but was not statistically significant within or between groups {Intervention: 8.9 (1.4) to 8.6 (1.5) vs. control: 9.1 (1.6) to 8.8 (1.9), [95% CI 8.3-9.3 vs. 8.3-9.0, intention to treat (ITT), p = 0.63]}. There was a significant reduction in diabetes distress in the intervention group; DAWN Problem Areas in Diabetes Questionnaire (PAID) score with a median (interquartile range) of 21 (11-33) vs. control: 27 (20-40), (p = 0.04). CONCLUSIONS: Patients in the carbohydrate-counting group demonstrated lower diabetes distress scores and less emotional burnout compared to fixed-meal plan over a 6 mo period though overall glycemic control was comparable between groups.

A Two-Year Surveillance of Central Line-Associated Bloodstream Infections in the Trauma ICU of a Tertiary Care Hospital in India.

Aim The aim of the study is to identify the risk factors and mortality associated with central line-associated bloodstream infection (CLABSI) and to investigate the incidence and associated etiology in trauma patients admitted to the trauma ICU (TICU) of a tertiary care teaching hospital in Northern India. Materials and methods The study was a prospective study conducted in the trauma ICU of a tertiary care teaching hospital in India from November 2020 to October 2022. Adult patients >18 years of age who were on central line for >48 hours were included in the study. The automated blood culture system BacT/ALERT 3D (bioMérieux, Durham, NC) was used for microbial detection from blood samples. We recorded patients' daily progress, and catheter-related data was collected and used as variables. All the data was analyzed using the Statistical Package for Social Sciences (SPSS) version 22.0 (IBM SPSS Statistics, Armonk, NY) to evaluate the risk factors associated with CLABSI. Result A total of 516 admissions occurred during the surveillance period, out of which 352 patients fulfilled the inclusion criteria and were enrolled in the study. Out of these 352 patients, a total of 74 patients developed central line-associated bloodstream infection (CLABSI). Thus, the incidence of CLABSI was 16.4 per 1000 central line days and 13.2 per 1000 inpatient days with a 0.8 device utilization ratio (DUR). The most common organisms isolated from these CLABSI cases were Acinetobacter species (23%), followed by Escherichia coli (16.5%) and Staphylococcus aureus (15.6%). The independent healthcare-associated risk factors for CLABSI were longer length of ICU stay and prolonged duration of central venous catheterization. The most common comorbidity associated with CLABSI was diabetes mellitus (20.3%), followed by hypertension (14.8%), and the mortality rate was 41.9%. Conclusion The healthcare-associated risk factors such as longer length of ICU stay and prolonged duration of central venous catheterization are the risk factors for developing central line-associated bloodstream infections (BSI).

Post-ischemic inactivation of HIF prolyl hydroxylases in endothelium promotes maladaptive kidney repair by inducing glycolysis.

Ischemic acute kidney injury (AKI) is common in hospitalized patients and increases the risk for chronic kidney disease (CKD). Impaired endothelial cell (EC) functions are thought to contribute in AKI to CKD transition, but the underlying mechanisms remain unclear. Here, we identify a critical role for endothelial oxygen sensing prolyl hydroxylase domain (PHD) enzymes 1-3 in regulating post-ischemic kidney repair. In renal endothelium, we observed compartment-specific differences in the expression of the three PHD isoforms in both mice and humans. We found that post-ischemic concurrent inactivation of endothelial PHD1, PHD2, and PHD3 but not PHD2 alone promoted maladaptive kidney repair characterized by exacerbated tissue injury, fibrosis, and inflammation. Single-cell RNA-seq analysis of the post-ischemic endothelial PHD1, PHD2 and PHD3 deficient (PHDTiEC) kidney revealed an endothelial glycolytic transcriptional signature, also observed in human kidneys with severe AKI. This metabolic program was coupled to upregulation of the SLC16A3 gene encoding the lactate exporter monocarboxylate transporter 4 (MCT4). Strikingly, treatment with the MCT4 inhibitor syrosingopine restored adaptive kidney repair in PHDTiEC mice. Mechanistically, MCT4 inhibition suppressed pro-inflammatory EC activation reducing monocyte-endothelial cell interaction. Our findings suggest avenues for halting AKI to CKD transition based on selectively targeting the endothelial hypoxia-driven glycolysis/MCT4 axis.

Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant.

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.

Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study.

Objective: Loss of Wilms tumor-1 (WT1) protein, a podocytopathy marker, through urine exosome (uE), could be an early indication of kidney injury. We examined WT1 in uE (uE-WT1), along with other urine markers of glomerular and kidney tubule injury, in individuals without chronic kidney disease (CKD). Methodology: The cross-sectional study included individuals who reported having no evidence of chronic kidney disease (CKD). Albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to assess kidney function. eGFR was calculated using the 2009 CKD-EPI (CKD-Epidemiological) equation. WT1 was analyzed in uE from humans and Wistar rats (before and after the 9th week of diabetes, n = 20). uE-WT1, urinary neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were estimated using ELISA. The Kruskal-Wallis H test, Mann-Whitney U test, and stepwise multivariable linear regression were performed. Results: Urine NGAL and ACR increase with uE-WT1 quartiles (n = 146/quarter). Similarly, uE-WT1, KIM-1, and NGAL were positively associated with ACR. Furthermore, KIM-1, NGAL, and uE-WT1 correlated with ACR. uE-WT1 outperformed KMI-1 and NGAL to explain ACR variability (25% vs. 6% or 9%, respectively). Kidney injury in streptozotocin-induced diabetic rats was associated with a significant rise in uE-WT1. Moreover, the findings were confirmed by the histopathology of kidney tissues from rats. Conclusion: uE-WT1 was strongly associated with kidney function in rats. In individuals without CKD, uE-WT1 outperformed NGAL as a determinant of differences in ACR.

An Observational Study from Northern India to Evaluate Catheter-associated Urinary Tract Infection in Medical Intensive Care Unit at a Tertiary Care Center.

Background: Healthcare-associated infections are the leading cause of morbidity and mortality in hospitalized patients. Catheter-associated urinary tract infection (CAUTI) is a leading infection in ICU settings. This study aims to evaluate the patient and catheter-related factors contributing to the urinary tract infection as well as implementing the preventive measures ultimately curbing down the burden of healthcare-associated infections. Material and methods: This is a hospital-based observational study conducted in Department of Microbiology, from October 2020 to September 2021. A total of 150 patients admitted to Medical Intensive Care Unit (MICU) with the indwelling urinary catheter were included. Urine samples were collected with proper aseptic precautions and processed within 2 hours of collection. Identification and antimicrobial susceptibility testing of the isolated pathogens was done as per CLSI guidelines 2019. Results: In this study, the CAUTI rate was 9.4 per 1000 urinary catheter days, while the overall magnitude was 14.67%. It was predominantly reported in 51-70-years age group (34%), and females (63.63%) outnumbered males (36.36%), with Escherichia coli being the commonest pathogen. The highest incidence was reported in the 3rd week of catheterization with diabetes being a predominant risk factor (17.24%). Conclusion: This study provides baseline data on CAUTI rate, pathogens isolated, and risk factors at our institute. The overall goal is to identify, educate, and implement best-practice measures for prevention and curbing down the incidence rates of catheter-associated urinary tract infections. How to cite this article: Parihar S, Sharma R, Kinimi SV, Choudhary S. An Observational Study from Northern India to Evaluate Catheter-associated Urinary Tract Infection in Medical Intensive Care Unit at a Tertiary Care Center. Indian J Crit Care Med 2023;27(9):642-646.

Management protocol and surgical techniques for MRI-Negative Cushing's disease: a series of 6 cases.

Up to 40% of Cushing's disease (CD) patients show no evidence of an adenoma on dynamic contrast-enhanced MRI. Inferior petrosal sinus sampling (IPSS) remains the gold standard for diagnosis in these patients. Remission rates in MRI-Negative CD are far less at 50%-71%, compared with patients in whom an adenoma is identified on MRI. Endoscopic endonasal transsphenoidal surgery is the surgical approach of choice in these cases. Various adjuncts can be used to localize an adenoma. In this video, the authors highlight their additional usage of pituitary perfusion MRI for identification of the adenoma. They present their stepwise management algorithm and surgical techniques for sellar and suprasellar exploration in 6 cases of MRI-Negative CD operated on by the senior author (A.S.). The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2318.