Senthilkumar Sankararaman

In the current era of cystic fibrosis (CF) transmembrane conductance regulator (CFTR)‐directed therapies (modulators), people with CF have significant improvement in pulmonary disease burden and overall survival. Extrapulmonary complications, including those affecting the gastrointestinal and renal systems, are gaining attention. Nephrolithiasis is increasingly recognized as a significant comorbidity in CF. The mechanisms underlying nephrolithiasis in CF are multifactorial and closely associated with altered gastrointestinal milieu in CF. Overt or residual fat malabsorption (due to exocrine pancreatic insufficiency along with other causes such as altered bile salt handling, acidic intestinal pH), and increased intestinal permeability collectively enhance enteric oxalate absorption. Renal stones in CF tend to present at a younger age, are associated with higher recurrence rates, and require more frequent procedural interventions compared with the general population with nephrolithiasis. With the increased survival in the post modulator era, the burden of renal complications in CF is expected to grow. There is lack of CF‐specific nephrolithiasis guidelines and more studies on this topic are needed. Also, given the paucity of pediatric studies, literature from adults can be carefully inferred. Clinicians should educate people with CF on preventative strategies such as optimizing pancreatic enzyme replacement therapy, enhancing hydration, nutritional management strategies such as optimizing dietary calcium intake particularly when consuming high‐oxalate foods, managing hypocitraturia, and minimization of nephrotoxic medication exposures. Multidisciplinary team approach is recommended to optimize outcomes from nephrolithiasis. In this review, the epidemiology, pathogenic mechanisms, and clinical management of nephrolithiasis in CF, with an emphasis on early‐life contributors and opportunities for improved prevention in CF management are detailed.

Non-cirrhotic portal hypertension (NCPHT) is defined as portal hypertension (PHT) occurring in the absence of cirrhosis. Major etiological causes of NCPHT include immunological disorders, chronic infections, exposure to medications or toxins, prothrombotic conditions, and several genetic syndromes, highlighting that NCPHT is not a single disease but a shared phenotype arising from diverse underlying pathways. NCPHT is frequently misdiagnosed, largely due to inconsistent nomenclature and limited scientific literature. The broader term non-cirrhotic portal fibrosis (NCPF) or porto-sinusoidal vascular disease (PSVD) includes patients in a preclinical stage who demonstrate histological features similar to NCPHT but lack clinical evidence of PHT. Early detection is linked to a favorable prognosis and improved clinical outcomes. Management strategies in pediatrics continue to rely on extrapolations from adult practice, with sparse evidence to guide pediatric care. Liver biopsy remains the cornerstone of diagnosis, demonstrating nodular regenerative hyperplasia, obliterative portal venopathy, or incomplete septal fibrosis. Management focuses on prophylactic and symptomatic care, with endoscopic therapy for controlling variceal bleeding. Porto-systemic shunts and, ultimately, liver transplantation therapies may be needed for advanced stages. A pressing need exists for standardized diagnostic criteria and multicenter studies to define natural history, refine risk stratification, and evaluate therapeutic approaches in the pediatric population. This review provides an overview of the pediatric causes of NCPHT, outlines the current understanding of pathophysiology, and discusses the clinical presentations and management strategies, while highlighting existing research gaps.

Vitamin A plays an important role in multiple homeostatic functions such as vision, immunity, epithelial cell integrity and differentiation, cell signaling, pulmonary function, reproduction, growth, and development. Vitamin A deficiency was described in people with cystic fibrosis (pwCF) due to a multitude of causes, such as suboptimally managed exocrine pancreatic insufficiency, advanced cystic fibrosis-related liver disease (aCFLD), and a history of intestinal resection, and is generally rare in contemporary practice. Apart from true vitamin A deficiency, low vitamin A levels may also be noted in various inflammatory states, as vitamin A is a negative acute-phase reactant. In the current era of cystic fibrosis (CF) transmembrane-conductance regulator (CFTR)-directed therapies, there is a paradigm shift in vitamin A status, with deficiency statuses becoming rarer, and instead higher serum vitamin levels (in some cases, even in the hypervitaminosis range) are increasingly reported. People with aCFLD, renal insufficiency, post-lung transplantation, and pregnancy are prone to vitamin A toxicity. Hence, CF clinicians should be proactive in evaluating these abnormalities and proficient in managing both deficiency and toxicity, as both these conditions can be associated with adverse outcomes. In this review, we detailed the basics of vitamin A metabolism, manifestations of both vitamin A deficiency and excess, and their clinical implications in pwCF.

Background: People with cystic fibrosis (CF) are at increased risk of fat‐soluble vitamin (A, D, E, and K) deficiencies secondary to exocrine pancreatic insufficiency (EPI). Estimation of vitamin K deficiency in routine clinical practice is challenging, and no uniform consensus exists due to lack of an accurate clinical test for the evaluation of its status. We aimed to estimate vitamin K status in people with CF using des‐gamma‐carboxy‐prothrombin (DCP). Methodology: A single‐center retrospective chart review was done between 2022 and 2024. Ninety‐four (39 pediatric and 55 adult) people with CF were included for final review. Results: The median DCP value was 0.35 ng/mL (IQR 0.2–0.60; range was 0.1–11 ng/mL). Post hoc, we classified patients into low‐DCP (0–90th percentile values in DCP or ≤ 2 ng/mL) and high‐DCP (91–100th percentile in DCP or >2 ng/mL) groups. Eleven out of 94 (11.7%) patients had DCP > 2 ng/mL; three out of 11 (27%) had advanced CF liver disease (aCFLD), p = 0.011, and another three had other fat‐soluble vitamin deficiencies, and low adherence to pancreatic enzymes and/or vitamin supplementation was suspected, p = 0.011. There were no significant differences in demographics (age, gender) or other comorbidities between the groups. Conclusion: DCP can be used for estimating vitamin K status, and the prevalence of suboptimal vitamin K status was 11.7%. DCP levels were higher in aCFLD, as well as those with suspected low adherence to pancreatic enzymes and/or vitamin supplementation. Prospective, multicenter clinical trials are needed to evaluate this further.

Purpose of Review: Magnesium plays an indispensable role in human health and is intricately involved in many crucial physiological and metabolic pathways. True biochemical magnesium deficiency is rarely encountered in clinical practice but subclinical and functional deficiency of magnesium appears to be more common and is reported in many chronic health disorders. Recent Findings: Estimating magnesium status is challenging and best evaluated by a combination of serum magnesium, urinary magnesium, and dietary magnesium intake. Many randomized controlled trials (RCTs) have demonstrated the efficacy of magnesium supplementation in various chronic disorders such as constipation, dyspepsia, mood disorders, metabolic diseases, and bone health. However, magnesium supplements are heavily advertised for several purported and hyped benefits, which require more high-quality evidence to support these claims. Caution should be exerted when supplementing magnesium to people who are predisposed to adverse effects, such as in renal insufficiency. Summary: Studies noted the significant role of magnesium in the acute management of eclampsia, asthma, and migraine. RCTs have noted a significant role of magnesium supplements in many chronic disorders, such as constipation, gastroesophageal reflux disease, metabolic dysfunction (diabetes, hypertension, dyslipidemia, and obesity), and mood disorders.

Purpose of Review: Malnutrition, whether pre-existing or acquired in the ICU, is common in critically ill children. This narrative review synthesizes current evidence on nutritional assessment and therapy, highlighting how illness phase, underlying disease, and medical interventions influence energy expenditure and nutrient requirements. Recent Findings: International guidelines recommend comprehensive nutritional assessment and early initiation of enteral nutrition (EN) for all patients admitted to the Pediatric ICU. However, EN is frequently underutilized or insufficient to meet metabolic demands and sometimes contraindicated. Barriers to delivery persist, and parenteral nutrition (PN) may be required when EN is not feasible or adequate. Summary: Nutrition plays a crucial yet complex role in the care of critically ill children. Optimizing individualized nutrition strategies, including timely EN and appropriate PN use, is essential to improve clinical outcomes, support recovery, and enhance long-term rehabilitation, while highlighting the need for improved implementation and future research.

Background: In people with cystic fibrosis (pwCF), identification of exocrine pancreatic insufficiency (EPI) is essential to prevent steatorrhea and, if not managed actively, can lead to catastrophic consequences. Fecal elastase‐1 (FE‐1) is a widely used test to screen for EPI in cystic fibrosis (CF). Once thought permanent, some patients with EPI on CF transmembrane conductance regulator (CFTR)‐directed therapies (modulators) have been noted to show improvement in EPI. Here, we evaluated the utility of FE‐1 in pwCF. Methodology: We performed a scoping review and searched several databases for the terms/concepts of “cystic fibrosis” and “fecal elastase‐1” and their synonyms. The search period was from 1‐1‐2003 to 7‐31‐2025. We included all age groups and used a web‐based platform for compiling and sorting out the articles. Results: We combined the eligible studies to synthesize information on four questions: Utilization of FE‐1 in CF (when to screen for EPI, how often to screen); Comparison of diagnostic accuracy of FE‐1 versus other tests; Definition of ideal cut‐off for FE‐1 in evaluating EPI in CF; Utilization of FE‐1 in pwCF managed on CFTR‐directed therapies. Conclusion: All pwCF should have EPI evaluated at diagnosis. Among various tests, FE‐1 is the most commonly utilized test for screening EPI. A value of < 200 μg/g of stool is consistent with EPI and is highly sensitive for EPI diagnosis. A value of < 100 μg/g is highly specific for severe EPI. Repeating FE‐1 should be considered in the current era of modulators, especially with a change in clinical status.

Chronic intestinal pseudo‐obstruction (CIPO) is a rare, heterogeneous, and debilitating disorder characterized by profound intestinal dysmotility and severe nutrition challenges. Its presentation resembles that of mechanical bowel obstruction, but CIPO occurs in the absence of luminal obstruction. Pediatric‐onset CIPO has higher morbidity and mortality and is termed pediatric intestinal pseudo‐obstruction (PIPO) to differentiate it from adult‐onset CIPO. PIPO often presents with vague abdominal symptoms such as abdominal pain, distension, bloating, constipation, and diarrhea. Nutrition therapy is the mainstay of the management of PIPO. The main management goals include maintaining an adequate caloric intake, avoiding fluid and electrolyte imbalance, minimizing/managing malnutrition, treating gastrointestinal symptoms, enhancing intestinal motility using pharmacological interventions, and managing complications such as small intestinal bacterial overgrowth. Surgical interventions are reserved for severe cases. Various modalities of nutrition intervention include modification of oral diet, enteral feeding, and parenteral nutrition. Most children with PIPO have a poor quality of life, and the prognosis is variable based on the underlying condition. Prognosis is better in an interdisciplinary team setting in specialized centers of excellence.

Background: Acute pancreatitis (AP) is one of the serious complications among patients with hematopoietic stem cell transplantation (HSCT). We aimed to evaluate the impact of AP on hospitalization outcomes in pediatric HSCT recipients. Methods: We retrospectively queried the PHIS database to include all pediatric patients who underwent HSCT between 2005-2024. The study population was divided into those with and without AP, and compared for various demographic and clinical variables. The primary outcome was in-hospital mortality, and secondary outcomes included healthcare resource utilization. Results: A total of 33,439 HSCT recipients were identified, and the prevalence rate of AP was 1.1%. The AP group had a significantly higher in-hospital mortality rate (22.7% vs. 4.6%), higher median hospitalization costs (USD 698,372 vs. 187,583), and higher median length of stay (138.5 vs. 60 days) (all p < 0.001). Our risk stratification model predicted a 2.7 (95% CI: 2.2 to 3.4) increased risk of AP for a score of >10, with an AUC of 0.85 (95% CI: 0.84 to 0.88). Conclusion: AP in HSCT prognosticates adverse outcomes with increased in-hospital mortality, prolonged length of stay, and higher hospitalization costs. Clinicians need to be vigilant in preventing and aggressively managing AP in HSCT. Category of study: Population study Impact: Acute pancreatitis (AP) in pediatric hemopoietic stem cell transplant (HSCT) recipients prognosticates adverse outcomes with increased mortality, prolonged length of stay, and higher hospitalization costs. The risk stratification model predicted a 2.7 (95% CI: 2.2 to 3.4) times increased risk of AP for a score of >10, with an AUC of 0.85 (95% CI: 0.84 to 0.88). Multivariable analysis showed AP was associated with 1.5 (CI:1.2 to 2, p = 0.001) times increased risk of mortality in pediatric population.