Functional dyspepsia: How to manage the burn and the bloat.

Functional dyspepsia is defined as persistent symptoms of postprandial bloating, early satiety, or pain in the center of the upper abdomen, without findings on upper endoscopy such as peptic ulcer disease to explain these symptoms. It is common, affecting up to 30% of the global population, but it often goes undiagnosed for years. There are 2 subtypes: epigastric pain syndrome (burning and pain) and postprandial distress syndrome (bloating and satiety). The authors discuss how to diagnose and treat both subtypes.

Combinatorially restricted computational design of protein-protein interfaces to produce IgG heterodimers.

Redesigning protein-protein interfaces is an important tool for developing therapeutic strategies. Interfaces can be redesigned by in silico screening, which allows for efficient sampling of a large protein space before experimental validation. However, computational costs limit the number of combinations that can be reasonably sampled. Here, we present combinatorial tyrosine (Y)/serine (S) selection (combYSelect), a computational approach combining in silico determination of the change in binding free energy (ΔΔG) of an interface with a highly restricted library composed of just two amino acids, tyrosine and serine. We used combYSelect to design two immunoglobulin G (IgG) heterodimers-combYSelect1 (L368S/D399Y-K409S/T411Y) and combYSelect2 (D399Y/K447S-K409S/T411Y)-that exhibit near-optimal heterodimerization, without affecting IgG stability or function. We solved the crystal structures of these heterodimers and found that dynamic π-stacking interactions and polar contacts drive preferential heterodimeric interactions. Finally, we demonstrated the utility of our combYSelect heterodimers by engineering both a bispecific antibody and a cytokine trap for two unique therapeutic applications.

Corrigendum: PCRRT Expert Committee ICONIC position paper on prescribing kidney replacement therapy in critically sick children with acute liver failure.

[This corrects the article DOI: 10.3389/fped.2021.833205.].

PCRRT-ICONIC critical care pediatric nephrology course: the global prevalence of COVID-19 and associated sequelae.

After nearly three years of the COVID-19 pandemic, research has affirmed that COVID-19 is more than just a respiratory virus. There have been significant breakthroughs made surrounding the development of acute kidney injury (AKI) and chronic kidney disease (CKD), in pediatric populations. Additionally, patient populations susceptible to renal complications consist of pediatric transplant recipients, multisystem inflammatory syndrome (MIS-C), and dialysis. Although research is gradually becoming more available surrounding this prevalent topic, knowledge is sparse on the deleterious effects of COVID-19 on pediatric patients with kidney disease and requires more in-depth analysis. The virtual international conference, Pediatric Critical Care Nephrology & Dialysis Course, on August 7th, 2021, reviewed the severe cases of COVID-19 in the global pediatric population. By integrating international perspectives, statistics, techniques, and treatments for managing renal complications, we further develop scientific understanding of the renal complications seen in children with COVID-19 globally.

Cardiovascular implications in adolescent and young adult hypertension.

Background: Hypertension is one of the most prevalent diseases in the United States, affecting an estimated 3.5% of children and adolescents. It can be adversely affect most organ systems but is particularly detrimental to the heart and vascular systems. The repercussions can be gauged through well-established measures of cardiovascular function including left ventricular mass index (LVMI), left ventricular hypertrophy (LVH), carotid intima media thickness (cIMT), and aortic stiffness. Cardiovascular function is also affected by underlying etiologies of hypertension including chronic kidney disease, polycystic kidney disease, coarctation of the aorta, adrenal disorders, renal artery stenosis, obstructive sleep apnea, as well as various drugs and medications (decongestants, stimulants, Non-steroidal Anti-inflammatory Drugs (NSAIDs), and steroids). Methods: An exhaustive literature search was conducted for clinical data regarding pediatric hypertension. Sixty-seven articles were incorporated with data on 189,477 subjects total. The data was then extracted and categorized as relating to hypertension incidence, LVMI, LVH, cIMT, and/or aortic stiffness. Results: The prevalence of pediatric ( < 18 years) hypertension extracted from 47 studies from 1994 to 2018 averaged 4%. The LVMI assessed over 7 studies (n = 661) averaged 39.3 g/ m 2.7 in the hypertensive cohort and 30.1 g/ m 2.7 in the control cohort. The cIMT assessed over 7 studies (n = 580) averaged 0.55 mm in the hypertensive cohort and 0.49 mm in the control cohort. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the normotensive cohort averaged 99.73 mmHg, 69.81 mmHg, 76.85 mmHg, and 46.90 mmHg, for SBP, DBP, MAP, and PP respectively. Ambulatory arterial stiffness parameters assessed over 5 studies (n = 573) in the hypertensive cohort averaged 129.56 mmHg, 73.69 mmHg, 95.08 mmHg, and 56.80 mmHg, for SBP, DBP, MAP, and PP respectively. Conclusions: The significance of pediatric hypertension is emphasized by evidence of early cardiovascular disease as demonstrated by non-invasive measures including cIMT and arterial stiffness parameters, and target organ damage and including LVH and LVMI factors. Thus, early diagnosis and treatment of high blood pressure is paramount for improving long term cardiovascular health and preventing long term morbidity and mortality.

Pediatric Atypical Hemolytic Uremic Syndrome Advances.

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by dysregulation of the alternate pathway. The diagnosis of aHUS is one of exclusion, which complicates its early detection and corresponding intervention to mitigate its high rate of mortality and associated morbidity. Heterozygous mutations in complement regulatory proteins linked to aHUS are not always phenotypically active, and may require a particular trigger for the disease to manifest. This list of triggers continues to expand as more data is aggregated, particularly centered around COVID-19 and pediatric vaccinations. Novel genetic mutations continue to be identified though advancements in technology as well as greater access to cohorts of interest, as in diacylglycerol kinase epsilon (DGKE). DGKE mutations associated with aHUS are the first non-complement regulatory proteins associated with the disease, drastically changing the established framework. Additional markers that are less understood, but continue to be acknowledged, include the unique autoantibodies to complement factor H and complement factor I which are pathogenic drivers in aHUS. Interventional therapeutics have undergone the most advancements, as pharmacokinetic and pharmacodynamic properties are modified as needed in addition to their as biosimilar counterparts. As data continues to be gathered in this field, future advancements will optimally decrease the mortality and morbidity of this disease in children.

PCRRT Expert Committee ICONIC Position Paper on Prescribing Kidney Replacement Therapy in Critically Sick Children With Acute Liver Failure.

Management of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in the pediatric population can be challenging. Kidney manifestations of liver failure, such as hepatorenal syndrome (HRS) and acute kidney injury (AKI), are increasingly prevalent and may portend a poor prognosis. The overall incidence of AKI in children with ALF has not been well-established, partially due to the difficulty of precisely estimating kidney function in these patients. The true incidence of AKI in pediatric patients may still be underestimated due to decreased creatinine production in patients with advanced liver dysfunction and those with critical conditions including shock and cardiovascular compromise with poor kidney perfusion. Current treatment for kidney dysfunction secondary to liver failure include conservative management, intravenous fluids, and kidney replacement therapy (KRT). Despite the paucity of evidence-based recommendations concerning the application of KRT in children with kidney dysfunction in the setting of ALF, expert clinical opinions have been evaluated regarding the optimal modalities and timing of KRT, dialysis/replacement solutions, blood and dialysate flow rates and dialysis dose, and anticoagulation methods.