Transplanting the Liver for a New Life: Can the Kidney Throw in a Spanner?

How to cite this article: Parameswaran N. Transplanting the Liver for a New Life: Can the Kidney Throw in a Spanner? Indian J Crit Care Med 2024;28(1):13-14.

Etiology and outcomes of acute kidney disease in children: a cohort study.

BACKGROUND: There is paucity of information regarding the etiology and outcomes of Acute Kidney Disease (AKD) in children. METHODS: The objectives of this cohort study were to evaluate the etiology and outcomes of AKD; and analyze predictors of kidney survival (defined as free of CKD 2, 3a, 3b, 4 or 5). Patients aged 1 month to 18 years who developed AKD over a 4-year-period (January 2018-December 2021) were enrolled. Survivors were followed-up at the pediatric nephrology clinic, and screened for residual kidney injury. RESULTS: Among 5710 children who developed AKI, 200 who developed AKD were enrolled. The median (IQR) eGFR was 17.03 (10.98, 28) mL/min/1.73 m2. Acute glomerulonephritis, acute tubular necrosis (ATN), hemolytic uremic syndrome (HUS), sepsis-associated AKD, and snake envenomation comprised of 69 (34.5%), 39 (19.5%), 24 (12%), 23 (11.5%) and 15 (7.5%) of the patients respectively. Overall, 88 (44%) children required kidney replacement therapy (KRT). There were 37 (18.5%) deaths within the AKD period. At a follow-up of 90 days, 32 (16%) progressed to chronic kidney disease stage-G2 or greater. At a median (IQR) follow-up of 24 (6, 36.5) months (n = 154), 27 (17.5%) had subnormal eGFR, and 20 (12.9%) had persistent proteinuria and/or hypertension. Requirement of KRT predicted kidney survival (free of CKD 2, 3a, 3b, 4 or 5) in AKD (HR 6.7, 95% CI 1.2, 46.4) (p 0.04). CONCLUSIONS: Acute glomerulonephritis, ATN, HUS, sepsis-associated AKD and snake envenomation were common causes of AKD. Mortality in AKD was 18.5%, and 16% progressed to CKD-G2 or greater at 90-day follow-up.

Vitamin D and Its Myriad Disease Associations: Can the Heart be Left Behind?

How to cite this article: Parameswaran N. Vitamin D and Its Myriad Disease Associations: Can the Heart be Left Behind? Indian J Crit Care Med 2023;27(7):463-464.

Authors' Reply on: FOCUS more on POCUS.

How to cite this article: Subramani S, Parameswaran N. Authors' Reply on: FOCUS more on POCUS. Indian J Crit Care Med 2023;27(3):226-227.

Clinical profile and outcomes of multisystem inflammatory syndrome in children (MIS-C): Hospital-based prospective observational study from a tertiary care hospital in South India.

AIM: To study the clinical profile and outcomes in children with multisystem inflammatory syndrome in children (MIS-C). METHODS: Children aged 1 month to 15 years presenting with MIS-C (May 2020 to November 2021) were enrolled. Clinical, laboratory, echocardiography parameters and outcomes were analysed. RESULTS: Eighty-one children (median age 60 months (24-100)) were enrolled. Median duration of fever was 5 days (3-7). Twenty-nine (35.8%) had shock (severe MIS-C) including 23 (28.3%) requiring inotropes (median duration = 25 h (7.5-33)). Ten required mechanical ventilation, 12 had acute kidney injury and 1 child died. Left ventricular (LV) dysfunction was seen in 38 (46.9%), 16 (19.7%) had coronary artery abnormalities (CAA) and 13 (20%) had macrophage activation syndrome. Sixty-one (75.3%) were SARS CoV-2 positive (10 by RT-PCR and 51 by serology). Sixty-eight (83.9%) received immunomodulators. Younger age was significantly associated with CAA (P value = 0.05). Older age, LV dysfunction, SARS CoV-2 positivity, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C (univariate analysis). Younger age was an independent predictor of CAA (P = 0.05); older age (P = 0.043) and low platelet count (P = 0.032) were independent predictors of severe MIS-C (multivariate logistic regression analysis). CONCLUSION: Our patients had diverse clinical manifestations with a good outcome. Younger age was significantly associated with CAA. Older age, LV dysfunction, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C. Younger age is an independent predictor of CAA. Older age and low platelet count are independent predictors of severe MIS-C.

Structural and optical properties of dysprosium-doped hydroxyapatite nanoparticles and the use as a bioimaging probe in human cells.

In this work, the hydroxyapatite nanoparticles doped with trivalent dysprosium ions were synthesized by a co-precipitation method. The characterization techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX) were carried out to determine the crystalline and structural properties. The Rietveld structural refinement of the XRD patterns confirmed the purity of the phase formation of the synthesized nanoparticles. The photoluminescence emission spectra exhibited intense emissions in the blue region at 450 nm and 476 nm along with less intense yellow emission at 573 nm which can be attributed to the magnetic dipole and electric dipole transitions of dysprosium respectively. In order to evaluate the colour tunability of the emitted light CIE chromaticity coordinate values were calculated. The intense blue emissions from the synthesized sample were found to be favourable for bioimaging. The images obtained from the fluorescence microscopy revealed that the dysprosium-doped hydroxyapatite nanoparticles are potential bioimaging probes in human cells.

Prevalence, clinico-laboratory features, and the functional outcome of children with scrub typhus meningoencephalitis-a cohort study.

Scrub typhus is being reported as the most common cause of childhood meningoencephalitis (ME) in India. Hence, we planned to estimate the proportion of scrub typhus infection among children aged 1 month to 12 years with the clinical diagnosis of ME and to evaluate their demographic, clinical and laboratory characteristics. This cohort study was conducted in the Department of Pediatrics of a tertiary care teaching hospital in south India. One hundred and twenty-seven consecutive children aged 1 month to 12 years with the clinical diagnosis of ME were the participants. Their socio-demographic factors, clinical details, laboratory reports and outcomes were analyzed. The etiological agent was identified in 71 (56%) children. Orientia tsutsugamushi (Scrub typhus) was the most common infection (24.4%), of all children with ME. Children aged ≥5 years were frequently affected by scrub typhus ME. Eschar, capillary leak, hepatomegaly and splenomegaly were the predominant clinical features of scrub typhus ME. Thrombocytopenia and deranged liver function tests were common in scrub typhus ME. To conclude, Orientia tsutsugamushi was the most common organism identified in our study. Prompt recognition of some tell-tale clinical signs of scrub typhus (such as eschar, thrombocytopenia and hepatosplenomegaly), and timely initiation of antibiotics would lead to better outcomes as evident from the study.

Respiratory Syncytial Virus Infection in the Aftermath of COVID-19: Is It a Case of Old Wine in a New Bottle?

How to cite this article: Parameswaran N. Respiratory Syncytial Virus Infection in the Aftermath of COVID-19: Is It a Case of Old Wine in a New Bottle? Indian J Crit Care Med 2022;26(11):1167-1168.

Assessment of the Endotracheal Tube Tip Position by Bedside Ultrasound in a Pediatric Intensive Care Unit: A Cross-sectional Study.

Introduction: The chest X-ray (CXR) is the standard of practice to assess the tip of the endotracheal tube (ETT) in ventilated children. In many hospitals, it takes hours to get a bedside CXR, and it has radiation exposure. The objective of this study was to find the utility of bedside ultrasound (USG), in assessing the ETT tip position in a Pediatric Intensive Care Unit (PICU). Methods: It was a prospective study conducted in the PICU of a tertiary care center involving 135 children aged from 1 month to 60 months, requiring endotracheal intubation. In this study, the authors compared the position of the ETT tip by the CXR (gold standard) and USG. The CXR was taken in children to assess the correct position of the tip of ETT. The USG was used to measure the distance between the tip of ETT and the arch of the aorta, thrice in the same patient. The mean of the three USG readings was compared with the distance between the tip of the ETT and carina in CXR. Results: The reliability of three USG readings was tested by absolute agreement coefficient in intraclass correlation (ICC), 0.986 (95% CI: 0.981-0.989). The sensitivity and specificity of the USG in identifying the correct position of the ETT tip in children when compared to CXR were 98.10% (95% CI: 93.297-99.71%) and 50.0% (95% CI: 31.30-68.70%), respectively. Conclusion: In ventilated children <60 months of age, identifying the tip of ETTs by bedside the USG has good sensitivity (98.10%) but poor specificity (50.0%). How to cite this article: Subramani S, Parameswaran N, Ananthkrishnan R, Abraham S, Chidambaram M, Rameshkumar R, et al. Assessment of the Endotracheal Tube Tip Position by Bedside Ultrasound in a Pediatric Intensive Care Unit: A Cross-sectional Study. Indian J Crit Care Med 2022;26(11):1218-1224.

Serious Adverse Reactions to Anti-snake Venom in Children with Snake Envenomation: An Underappreciated Contributor to Snakebite Mortality?

BACKGROUND: Deaths due to snakebites and serious adverse reactions to anti-snake venom (ASV) are both underreported in India. Serious adverse reactions to ASV are common, contributing significantly to mortality and morbidity. We conducted a study to determine the frequency of occurrence of severe adverse reactions to ASV in children and study the various risk factors and their outcomes. PATIENTS AND METHODS: We carried out a retrospective record review of all children of snake envenomation admitted in our tertiary care teaching hospital, from January 2013 to December 2016. Children aged 0 to 12 years admitted for snake envenomation and who received ASV as part of their treatment were included. Details about their management, including ASV usage and any adverse effects noted, were collected on a standard data collection form. RESULTS: Sixty-eight children were enrolled. Hemotoxic (52.9%) envenomation was more common than neurotoxic (35.2%). Severe adverse reactions were present in 42.6%, hypotension in 38.2%, and bronchospasm in 4.4% of the children. The overall mortality rate was 16.1%, anaphylaxis to ASV contributing to 36.3% of them. Mortality was significantly higher in cases with severe adverse reactions (p = 0.005). ASV reactions were also significantly different with different manufacturers. CONCLUSIONS: There is a high frequency of occurrence of severe adverse reactions to ASV resulting in significant morbidity and mortality. HOW TO CITE THIS ARTICLE: Hooda R, Parameswaran N, Subramanian M. Serious Adverse Reactions to Anti-snake Venom in Children with Snake Envenomation: An Underappreciated Contributor to Snakebite Mortality? Indian J Crit Care Med 2021;25(6):720-723.

Loss of interleukin-10 exacerbates early Type-1 diabetes-induced bone loss.

Type-1 diabetes (T1D) increases systemic inflammation, bone loss, and risk for bone fractures. Levels of the anti-inflammatory cytokine interleukin-10 (IL-10) are decreased in T1D, however their role in T1D-induced osteoporosis is unknown. To address this, diabetes was induced in male IL-10 knockout (KO) and wild-type (WT) mice. Analyses of femur and vertebral trabecular bone volume fraction identified bone loss in T1D-WT mice at 4 and 12 weeks, which in T1D-IL-10-KO mice was further reduced at 4 weeks but not 12 weeks. IL-10 deficiency also increased the negative effects of T1D on cortical bone. Osteoblast marker osterix was decreased, while osteoclast markers were unchanged, suggesting that IL-10 promotes anabolic processes. MC3T3-E1 osteoblasts cultured under high glucose conditions displayed a decrease in osterix which was prevented by addition of IL-10. Taken together, our results suggest that IL-10 is important for promoting osteoblast maturation and reducing bone loss during early stages of T1D.

Can Airway Abnormalities be the Elephant in the Room in Children with Congenital Heart Disease?

How to cite this article: Parameswaran N. Can Airway Abnormalities be the Elephant in the Room in Children with Congenital Heart Disease? Indian J Crit Care Med 2020;24(5):289-290.

Composite Outcomes for Clinical Trials in Critical Care: The Devil is in the Detail.

How to cite this article: Lalgudi Ganesan S, Parameswaran N. Composite Outcomes for Clinical Trials in Critical Care: The Devil is in the Detail. Indian J Crit Care Med 2020;24(10):903-904.

Altered Platelet Fatty Acids in Dengue Cases by Gas Chromatography-Mass Spectrometry Analysis.

BACKGROUND: The role of dengue virus in altering the functional properties of platelets remains poorly understood. Few studies have observed that changes in fatty acids are found to have an effect on platelet activation and aggregation. Also, platelet fatty acids have not been extensively studied in dengue so far. So, we aimed to study the fatty acids of platelet membranes in patients with dengue. METHODS: Gas chromatography-mass spectrometry (GC-MS) method was used to analyze fatty acids in the lipid extracts of platelets isolated from the study participants. RESULTS: GC-MS analysis of platelet lipids identified and quantified nearly 23 unique lipid molecules on platelet membrane. We observed significant alterations with some of the fatty acids in patients with dengue compared to controls. Within dengue cases, increase in unsaturated fatty acids in severe dengue was observed compared to non-severe dengue. From baseline to defervescence, no difference in fatty acids was observed in dengue platelets. This indicates that in dengue, platelet physiology remains altered even after the febrile phase. CONCLUSION: To the best of our knowledge, this is the first study characterizing the differential expression of platelet fatty acids in dengue infection. However, further studies are warranted to expound the underlying cause for thrombocytopenia and platelet dysfunction in dengue.

An unusual presentation of early congenital syphilis with annular configuration of blisters resembling "string-of-pearls".

Skin lesions in early congenital syphilis can show considerable variability. A 35-day-old infant presented with rhinitis, desquamation of palms and soles, pseudoparalysis of the right upper limb, and annular lesions with peripheral blistering over the chest and abdomen, resembling a "string-of-pearls." A diagnosis of congenital syphilis was made on the basis of radiologic evaluation and reactive Venereal Disease Research Laboratory (VDRL) in both mother and child. We report this case to highlight the unusual presentation of congenital syphilis with annular configuration of blisters, mimicking a "string-of-pearls."

G protein-coupled receptor kinase-2-deficient mice are protected from dextran sodium sulfate-induced acute colitis.

G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase and plays a key role in different disease processes. Previously, we showed that GRK2 knockdown enhances wound healing in colonic epithelial cells. Therefore, we hypothesized that ablation of GRK2 would protect mice from dextran sodium sulfate (DSS)-induced acute colitis. To test this, we administered DSS to wild-type (GRK2+/+) and GRK2 heterozygous (GRK+/-) mice in their drinking water for 7 days. As predicted, GRK2+/- mice were protected from colitis as demonstrated by decreased weight loss (20% loss in GRK2+/+ vs. 11% loss in GRK2+/-). lower disease activity index (GRK2+/+ 9.1 vs GRK2+/- 4.1), and increased colon lengths (GRK2+/+ 4.7 cm vs GRK2+/- 5.3 cm). To examine the mechanisms by which GRK2+/- mice are protected from colitis, we investigated expression of inflammatory genes in the colon as well as immune cell profiles in colonic lamina propria, mesenteric lymph node, and in bone marrow. Our results did not reveal differences in immune cell profiles between the two genotypes. However, expression of inflammatory genes was significantly decreased in DSS-treated GRK2+/- mice compared with GRK2+/+. To understand the mechanisms, we generated myeloid-specific GRK2 knockout mice and subjected them to DSS-induced colitis. Similar to whole body GRK2 heterozygous knockout mice, myeloid-specific knockout of GRK2 was sufficient for the protection from DSS-induced colitis. Together our results indicate that deficiency of GRK2 protects mice from DSS-induced colitis and further suggests that the mechanism of this effect is likely via GRK2 regulation of inflammatory genes in the myeloid cells.

Advances in Probiotic Regulation of Bone and Mineral Metabolism.

Probiotics have been consumed by humans for thousands of years because they are beneficial for long-term storage of foods and promote the health of their host. Ingested probiotics reside in the gastrointestinal tract where they have many effects including modifying the microbiota composition, intestinal barrier function, and the immune system which result in systemic benefits to the host, including bone health. Probiotics benefit bone growth, density, and structure under conditions of dysbiosis, intestinal permeability, and inflammation (recognized mediators of bone loss and osteoporosis). It is likely that multiple mechanisms are involved in mediating probiotic signals from the gut to the bone. Studies indicate a role for the microbiota (composition and activity), intestinal barrier function, and immune cells in the signaling process. These mechanisms are not mutually exclusive, but rather, may synergize to provide benefits to the skeletal system of the host and serve as a starting point for investigation. Given that probiotics hold great promise for supporting bone health and are generally regarded as safe, future studies identifying mechanisms are warranted.

Antiquitin Deficiency with Adolescent Onset Epilepsy: Molecular Diagnosis in a Mother of Affected Offsprings.

Antiquitin deficiency is the most prevalent form of pyridoxine-dependent epilepsy. While most patients present with neonatal onset of therapy-resistant seizures, a few cases with late-onset during infancy have been described. Here, we describe the juvenile onset of epilepsy at the age of 17 years due to antiquitin deficiency in an Indian female with homozygosity for the most prevalent ALDH7A1 missense mutation, c.1279G > C; p.Glu427Gln in exon 14. The diagnosis was established along familial cosegregation analysis for an affected offspring, that had neonatal pyridoxine responsive seizures and had been found to be compound heterozygous for c.1279G > C; p.Glu427Gln in exon 14 and a nonsense mutation c.796C > T; p.Arg266* in exon 9. While seizures in the mother had been incompletely controlled by levetiracetam, she remained seizure-free on pyridoxine monotherapy, 200 mg/day. Her fourth pregnancy resulted in a female affected offspring, who was treated prospectively and never developed seizures with a normal outcome at age 2 years while on pyridoxine. This report illustrates that the phenotypic spectrum of antiquitin deficiency is still underestimated and that this treatable inborn error of metabolism has to be considered in case of therapy-resistant seizures even at older age. It furthermore supports prospective in utero treatment with pyridoxine in forthcoming pregnancies at risk.

G-protein-coupled receptor kinase-2 is a critical regulator of TNFα signaling in colon epithelial cells.

G-protein-coupled receptor kinase-2 (GRK2) belongs to the GRK family of serine/threonine protein kinases critical in the regulation of G-protein-coupled receptors. Apart from this canonical role, GRK2 is also involved in several signaling pathways via distinct intracellular interactomes. In the present study, we examined the role of GRK2 in TNFα signaling in colon epithelial cell-biological processes including wound healing, proliferation, apoptosis, and gene expression. Knockdown of GRK2 in the SW480 human colonic cells significantly enhanced TNFα-induced epithelial cell wound healing without any effect on apoptosis/proliferation. Consistent with wound-healing effects, GRK2 knockdown augmented TNFα-induced matrix metalloproteinases (MMPs) 7 and 9, as well as urokinase plasminogen activator (uPA; factors involved in cell migration and wound healing). To assess the mechanism by which GRK2 affects these physiological processes, we examined the role of GRK2 in TNFα-induced MAPK and NF-κB pathways. Our results demonstrate that while GRK2 knockdown inhibited TNFα-induced IκBα phosphorylation, activation of ERK was significantly enhanced in GRK2 knockdown cells. Our results further demonstrate that GRK2 inhibits TNFα-induced ERK activation by inhibiting generation of reactive oxygen species (ROS). Together, these data suggest that GRK2 plays a critical role in TNFα-induced wound healing by modulating MMP7 and 9 and uPA levels via the ROS-ERK pathway. Consistent with in vitro findings, GRK2 heterozygous mice exhibited enhanced intestinal wound healing. Together, our results identify a novel role for GRK2 in TNFα signaling in intestinal epithelial cells.

Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice.

G protein-coupled receptor kinase-6 (GRK6) is a serine/threonine kinase that is important in inflammatory processes. In this study, we examined the role of GRK6 in Escherichia coli-induced lung infection and inflammation using GRK6 knockout (KO) and wild-type (WT) mice. Intratracheal instillation of E. coli significantly enhanced bacterial load in the bronchoalveolar lavage (BAL) of KO compared with WT mice. Reduced bacterial clearance in the KO mice was not due to an intrinsic defect in neutrophil phagocytosis or killing but as a result of reduced neutrophil numbers in the KO BAL. Interestingly, neutrophil numbers in the lung were increased in the KO compared with WT mice, suggesting a potential dysfunction in transepithelial migration of neutrophils from the lungs to the bronchoalveolar space. This effect was selective for lung tissue because peritoneal neutrophil numbers were similar between the two genotypes following peritoneal infection. Although neutrophil expression of CXCR2/CXCR3 was similar between WT and KO, IL-17A expression was higher in the KO compared with WT mice. These results suggest that enhanced neutrophil count in the KO lungs but reduced numbers in BAL are likely due to transepithelial migration defect and/or altered chemokines/cytokines. Together, our studies suggest a previously unrecognized and novel role for GRK6 in neutrophil migration specific to pulmonary tissue during bacterial infection.