Vancomycin Dosing and Its Association With Acute Kidney Injury in Pediatric Cardiac Intensive Care Patients Under 3 Months of Age.

BACKGROUND: The standard vancomycin regimen for term neonates is 45 mg/kg/day. However, the optimal starting vancomycin dosing for achieving therapeutic levels in young infants in cardiac intensive care units remains unknown. Moreover, data on the association of supratherapeutic vancomycin levels with acute kidney injury (AKI) are limited. METHODS: Retrospective study of infants ≤3 months old, receiving vancomycin following congenital heart surgery at postoperative intensive care unit admission. Assessed were vancomycin dosing, achievement of therapeutic trough concentration of 10-20 mg/L and development of AKI, based on the modified Kidney Disease Improving Global Outcomes criteria. RESULTS: Inclusion criteria were met by 109 patients with a median age of 8 days (IQR: 6-16). The mean (SD) vancomycin dose required for achieving therapeutic concentration was 28.9 (9.1) mg/kg at the first postoperative day. Multivariate logistic regression identified higher preoperative creatinine levels and shorter cardiopulmonary bypass time as predictors of supratherapeutic vancomycin concentrations (c-index 0.788). During the treatment course, 62 (56.9%) developed AKI. Length of stay and mortality were higher in those who developed AKI as compared with those who did not. Multivariate logistic regression identified higher vancomycin concentration as a predictor for postoperative AKI, OR, 3.391 (95% CI: 1.257-9.151), P = 0.016 (c-index 0.896). CONCLUSION: Our results support a lower starting vancomycin dose of ~30 mg/kg/day followed by an early personalized therapeutic approach, to achieve therapeutic trough concentrations of 10-20 mg/L in cardiac postoperative term infants. Supratherapeutic concentrations are associated with an increased risk for AKI, which is prevalent in this population and associated with adverse outcomes.

Pediatric thermal epiglottitis: insights from a tertiary center experience.

Thermal epiglottitis, a non-infectious cause of epiglottitis, is a rare entity that shares some clinical features with infectious epiglottitis. This study presents 16 years of experience in diagnosing and managing thermal epiglottitis. A retrospective descriptive study in a tertiary center in southern Israel included confirmed cases of thermal epiglottitis in children (0-18 years) between 2004 and 2020 by endoscopy. Of approximately 600,000 pediatric ER admissions between 2004 and 2020, seven children were diagnosed by endoscopy with thermal epiglottitis (mean age 24 months, 71% males). Clinical presentation included stridor, respiratory distress, and drooling. Four children had fever and elevated inflammatory markers at presentation and were treated with systemic antibiotics. All were treated with systemic steroids. The median length of stay in the PICU was five days, and four patients required intubations. All fully recovered without experiencing any sequelae.  Conclusion: Thermal epiglottitis stands as a potential contributor to acute upper airway obstruction. Although it's rarity, it should be discussed in any child with acute upper airway obstruction. It is essential to inquire directly about the accidental intake of hot beverages, particularly in cases lacking fever or elevated inflammatory markers. What is Known: • Thermal epiglottitis is a rare, non-infectious condition sharing clinical features with infectious epiglottitis. • Common presentations include stridor, respiratory distress, and drooling. What is New: • Thermal epiglottitis is a potential contributor to acute upper airway obstruction, urging consideration even in the absence of fever or elevated markers. • Direct inquiry about hot beverage intake for diagnosis is essential for diagnosis.

Pediatric Mechanical Circulatory Support: Introduction and Schneider's Experience.

BACKGROUND: Ventricular assist devices (VADs) play a critical and increasing role in treating end-stage heart failure in pediatric patients. A growing number of patients are supported by VADs as a bridge to heart transplantation. Experience with VADs in the pediatric population is limited, and experience in Israel has not been published. OBJECTIVES: To describe this life-saving technology and our experience with VAD implantation in children with heart failure, including characteristics and outcomes. METHODS: We conducted a retrospective chart review of all patients who underwent VAD implantation at Schneider Children's Medical Center from 2018 to 2023. RESULTS: We analyzed results of 15 children who underwent VAD implantation. The youngest was 2.5 years old and weighed 11 kg at implantation. In eight patients, HeartMate 3, a continuous-flow device, was implanted. Seven patients received Berlin Heart, a pulsatile-flow device. Three children required biventricular support; 11 underwent heart transplants after a median duration of 169 days. Two patients died due to complications while awaiting a transplant; two were still on VAD support at the time of submission of this article. Successful VAD support was achieved in 86.6% of patients. In the last 5 years,79% of our heart transplant patients received VAD support prior to transplant. CONCLUSIONS: Circulatory assist devices are an excellent bridge to transplantation for pediatric patients reaching end-stage heart failure. VADs should be carefully selected, and implantation techniques tailored to patient's weight and diagnosis at a centralized pediatric cardiac transplantation center. Israeli healthcare providers should be cognizant of this therapeutic alternative.

The role of anion gap normalization time in the management of pediatric diabetic ketoacidosis.

Introduction: Our aims were to determine whether anion gap normalization time (AGNT) correlates with risk factors related to the severity of diabetic ketoacidosis (DKA) in children, and to characterize AGNT as a criterion for DKA resolution in children admitted with moderate or severe disease. Methods: A ten-year retrospective cohort study of children admitted to the intensive care unit with DKA. We used a survival analysis approach to determine changes in serum glucose, bicarbonate, pH, and anion gap following admission. Using multivariate analysis, we examined associations between patients' demographic and laboratory characteristics with delayed normalization of the anion gap. Results: A total of 95 patients were analyzed. The median AGNT was 8 h. Delayed AGNT (>8 h) correlated with pH < 7.1 and serum glucose >500 mg/dL. In multivariate analysis, glucose >500 mg/dL was associated with an increased risk for delayed AGNT, by 3.41 fold. Each 25 mg/dL elevation in glucose was associated with a 10% increment in risk for delayed AGNT. Median AGNT preceded median PICU discharge by 15 h (8 vs. 23 h). Discussion: AGNT represents a return to normal glucose-based physiology and an improvement in dehydration. The correlation observed between delayed AGNT and markers of DKA severity supports the usefulness of AGNT for assessing DKA recovery.

Implementing a screening algorithm for early recognition of sepsis in hospitalized children: a quality improvement project.

Sepsis is a leading cause of mortality in children. Utilizing a screening tool for early recognition of sepsis is recommended. Our centre had no screening tool for sepsis nor a standardized protocol for sepsis management. In December 2020, a screening algorithm for sepsis was implemented. The algorithm consisted of vital signs measurements in children with an abnormal body temperature, a pop-up alert, nurse's and physician's evaluation, and activation of a workup protocol. The project's primary aim was to increase vital signs measurement rates in hospitalized children with abnormal body temperature from 40% to >90% within 6 months, by 1 June 2021, and sustain until 31 December 2021. Adherence to the algorithm and performance were monitored during 2021, and the outcomes were compared to the preceding 5 years and a control ward. The alert identified 324 children and 596 febrile episodes. Vital signs measurement adherence increased from 42.7% to >90% in 2 months. A nurse evaluated 86.4% of episodes, and a physician evaluated 83.0% of these. Paediatric intensive care unit (PICU) admission rates were lower in the intervention period vs. the pre-intervention period vs. the control ward (4.6% vs. 5.6% vs. 6.0%, respectively); the median PICU length of stay was shorter in the intervention vs. the control ward [2.0 (IQR 1, 4) vs. 5.5 (IQR 2, 7), respectively]. These differences were not statistically significant. During the intervention period, the adherence to vital signs measurements reached the goal of >90%. The alert system prompted an evaluation by caregivers and management according to the protocol. Further monitoring is needed to improve outcomes.

The horizon of pediatric cardiac critical care.

Pediatric Cardiac Critical Care (PCCC) is a challenging discipline where decisions require a high degree of preparation and clinical expertise. In the modern era, outcomes of neonates and children with congenital heart defects have dramatically improved, largely by transformative technologies and an expanding collection of pharmacotherapies. Exponential advances in science and technology are occurring at a breathtaking rate, and applying these advances to the PCCC patient is essential to further advancing the science and practice of the field. In this article, we identified and elaborate on seven key elements within the PCCC that will pave the way for the future.

Transcript-Based Diagnosis and Expanded Phenotype of an Intronic Mutation in TPM3 Myopathy.

INTRODUCTION: Congenital myopathies are a broad group of inborn muscle disorders caused by a multitude of genetic factors, often characterized by muscle atrophy and hypotonia. METHODS: Clinical studies, imaging, histology, whole-exome sequencing (WES) and muscle tissue RNA studies. RESULTS: We describe a severe congenital myopathy manifesting at birth with bilateral clubfeet, delayed motor development and hypotonia, becoming evident by 4 months of age. At 3 years of age, the patient had tongue fasciculations, was bedridden, and was chronically ventilated via tracheostomy. Imaging studies demonstrated severe muscle atrophy and, surprisingly, cerebral atrophy; electromyography demonstrated a myasthenic pattern and histological evaluation did not facilitate a definitive diagnosis. Trio WES did not identify a causative variant, except for a non-canonical intronic TPM3 c.118-12G>A variant of uncertain significance. Transcript analysis of muscle tissue from the patient proved the pathogenicity of this homozygous variant, with a 97% reduction in the muscle-specific TPM3.12 transcript. DISCUSSION: This study broadens the phenotypic spectrum of recessive TPM3 disease, highlighting tongue fasciculations and bilateral clubfoot, as well as possibly-related cerebral atrophy. It also shows the importance of a broad approach to genetic analysis and the utility of RNA-based studies, demonstrating efficacy of early genome and transcriptome queries in facilitating rapid and cost-effective diagnosis of congenital myopathies.

Severe Pneumonia Caused by Methicillin-Resistant Staphylococcus pseudintermedius in an Oncology Patient: Case Report and Literature Review.

Staphylococcus pseudintermedius is usually a commensal bacterium of microbiota of dogs and cats that can become pathogenic in these animals. In the past two decades, an increasing number of human infections caused by this pathogen was reported; only two pediatric cases were due to methicillin-susceptible isolates. We describe the first case of methicillin-resistant S. pseudintermedius diagnosed in a 12-year-old immunocompromised girl with refractory anaplastic ependymoma, presented with life-threatening pneumonia and bacteremia. The girl had close contact with her two pet dogs. This case emphasizes that immunocompromised children should be advised on proper handling of household pets to minimize the risk of infection, which could be life threatening.

Successful management of spinal cord ischemia in a pediatric patient with fibrocartilaginous embolism: illustrative case.

BACKGROUND: Fibrocartilaginous embolism (FCE) is a rare cause of ischemic myelopathy that occurs when the material of the nucleus pulposus migrates into vessels supplying the spinal cord. The authors presented a case of pediatric FCE that was successfully managed by adapting evidence-based recommendations used for spinal cord neuroprotection in aortic surgery. OBSERVATIONS: A 7-year-old boy presented to the emergency department with acute quadriplegia and hemodynamic instability that quickly progressed to cardiac arrest. After stabilization, the patient regained consciousness but remained in a locked-in state with no spontaneous breathing. The patient presented a diagnostic challenge. Traumatic, inflammatory, infectious, and ischemic etiologies were considered. Eventually, the clinical and radiological findings led to the presumed diagnosis of FCE. Treatment with continuous cerebrospinal fluid drainage (CSFD), pulse steroids, and mean arterial pressure augmentation was applied, with subsequent considerable and consistent neurological improvement. LESSONS: The authors proposed consideration of the adaptation of spinal cord neuroprotection principles used routinely in aortic surgery for the management of traumatic spinal cord ischemia (FCE-related in particular), namely, permissive arterial hypertension and CSFD. This is hypothesized to allow for the maintenance of sufficient spinal cord perfusion until adequate physiological blood perfusion is reestablished (remodeling of the collateral arterial network and/or clearing/absorption of the emboli).

Informe de Rotación Electiva

Dentro del programa de la Residencia Interdisciplinaria de Educación y Promoción de la Salud (RIEPS) se encuentran pautadas la realización de rotaciones electivas. Estas rotaciones están pensadas para residentes en su tercer año de formación, con el objetivo de que lx residente pueda ahondar en un tema que supere el desarrollo científico técnico de los Servicios del Gobierno de la Ciudad de Buenos Aires y del país, y en un lugar que sea referente en la materia (Cabral, Di Lorenzo, Lorusso, Rodríguez, 2003). En este marco, se realizó la rotación en los Servicios de Trabajo Social y Cuidados Paliativos del Hospital Zonal de Bariloche "Dr. Ramón Carrillo" desde el 1 de Marzo al 31 de Mayo del 2021. El presente informe pretende dar cuenta de las actividades realizadas durante la rotación electiva a fin de lograr los objetivos propuestos. También señalará los aprendizajes más significativos y los aportes realizados desde la antropología como desde la educación y promoción de la salud. (AU)

Characterization of children younger than 5 Years of age with severe community-acquired alveolar pneumonia (CAAP) requiring Pediatric Intensive Care Unit (PICU) admission.

BACKGROUND: The purpose of this study was to determine factors characterizing children admitted to the Pediatric Intensive Care Unit (PICU) with community-acquired alveolar pneumonia (CAAP) to help clinicians assess disease severity upon initial assessment in the emergency department. METHODS: We prospectively collected demographic, clinical, and laboratory data of children <5 years with radiologically confirmed CAAP referred to the Soroka University Medical Center during 2001-2011. Three groups of children were compared: 1) those hospitalized in the PICU (PICU-CAAP); 2) those treated in the emergency department and discharged (ED-CAAP); and 3) those hospitalized in a pediatric ward (Hosp-CAAP). RESULTS: Of 9722 CAAP episodes, 367 (3.8%) were PICU-CAAP, 5552 (57.1%) Hosp-CAAP and 3803 (39.1%) ED-CAAP. In a univariate analysis, respiratory syncytial virus (RSV) was detected more commonly among PICU-CAAP than in Hosp-CAAP (P = 0.02) and ED-CAAP patients (P < 0.001). In a multivariate analysis, several factors were associated with PICU hospitalization versus ED-CAAP and Hosp-CAAP: Younger age (ORs: 1.04, [95%CI: 1.02-1.05] and 0.97 [0.96-0.98], respectively); prematurity (ORs: 2.16 [1.28-3.64] and 1.61 [1.15-2.26], respectively), lower O2 saturation (ORs: 1.32 [1.25-1.41] and 0.94[0.92-0.96]), higher respiratory rate (ORs: 1.06 [1.04-1.07] and 1.00 [1-1.01], respectively). CONCLUSION: Children admitted to PICU were younger, had more respiratory syncytial virus (RSV) detection, were premature, had lower O2 saturation, and had a higher respiratory rate than those admitted to the general ward or those visiting the emergency department and subsequently discharged.

Variability of Care of Infants With Severe Respiratory Syncytial Virus Bronchiolitis: A Multicenter Study.

BACKGROUND: Viral bronchiolitis caused by respiratory syncytial virus (RSV) is a common childhood disease accounting for many hospitalizations worldwide. Some infants may clinically deteriorate, requiring admission to an intensive care unit. We aimed to describe diagnostic and therapeutic measures of bronchiolitis in Israeli pediatric intensive care units (PICUs) and evaluate intercenter variability of care. METHODS: Medical records of all RSV-infected infants admitted to 5 Israeli PICUs over 4 RSV seasons were retrospectively reviewed. RESULTS: Data on 276 infants with RSV-positive bronchiolitis, admitted to the participating PICUs were analyzed. Most of the infants were males with a mean admission age of 4.7 months. Approximately half of the infants had pre-existing conditions such as prematurity, cardiac disease or chronic lung disease. Respiratory distress was the most common symptom at presentation followed by hypoxemia and fever. There was significant variation in the methods used for RSV diagnosis, medical management and respiratory support of the infants. Furthermore, utilization of inhalational therapy and transfusion of blood products differed significantly between the centers. Although a bacterial pathogen was isolated in only 13.4% of the infants, 82.6% of the cohort was treated with antibiotics. CONCLUSIONS: Significant variation was found between the different PICUs regarding RSV bronchiolitis diagnosis, medical management and respiratory support, which may not be accounted for by the differences in baseline and clinical characteristics of the infants. Some of these differences may be explained by uneven resource allocations. This diversity and the documented routine use of medications with weak evidence of efficacy calls for national guidelines for bronchiolitis management.

Bogota Bag Temporary Abdominal Closure Surgical Technique in Children: A 15-Year Single Center Experience.

BACKGROUND: Temporary abdominal closure (TAC) surgical technique relates to a procedure in which the post-surgical abdominal wall remains open in certain indications. The Bogota bag (BB) technique is a tension-free TAC method that covers the abdominal contents with a sterilized fluid bag. There are very few reports of pediatric patients treated with this technique. OBJECTIVES: To describe our institution's 15 years of experience using the BB technique on pediatric patients. METHODS: A retrospective cohort study describing our experience treating patients with BB was conducted. The medical files of 17 pediatric patients aged 0-18 years were reviewed. RESULTS: Between January 2000 and December 2014, 17 patients were treated with BB at our medical center (6 females, median age 12 years). Indications for BB were a need for a surgical site re-exploration, mechanical inability for primary abdominal closure, and high risk for ACS development. Median BB duration was 5 days and median bag replacement was 2 days. Median ICU length of stay (LOS) was 10 days and hospital LOS was 27 days. The ICU admission and BB procedure was tolerated well by 6 patients who were discharged home without complications. Of the remaining 11 patients, 6 patients died during the admission (35%) and the others presented with major complications not related to the BB but to the patient's primary disease. CONCLUSIONS: This report represents the largest series of children treated with BB. The technique is simple to perform, inexpensive, and has very few complications.

The Inadequate Oxygen Delivery Index and Low Cardiac Output Syndrome Score As Predictors of Adverse Events Associated With Low Cardiac Output Syndrome Early After Cardiac Bypass.

OBJECTIVES: To evaluate the effectiveness of two scoring systems, the inadequate oxygen delivery index, a risk analytics algorithm (Etiometry, Boston, MA) and the Low Cardiac Output Syndrome Score, in predicting adverse events recognized as indicative of low cardiac output syndrome within 72 hours of surgery. DESIGN: A retrospective observational pair-matched study. SETTING: Tertiary pediatric cardiac ICU. PATIENTS: Children undergoing cardiac bypass for congenital heart defects. Cases experienced an adverse event linked to low cardiac output syndrome in the 72 hours following surgery (extracorporeal membrane oxygenation, renal replacement therapy, cardiopulmonary resuscitation, and necrotizing enterocolitis) and were matched with a control patient on criteria of procedure, diagnosis, and age who experienced no such event. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of a total 536 bypass operations in the study period, 38 patients experienced one of the defined events. Twenty-eight cases were included in the study after removing patients who suffered an event after 72 hours or who had insufficient data. Clinical and laboratory data were collected to derive scores for the first 12 hours after surgery. The inadequate oxygen delivery index was calculated by Etiometry using vital signs and laboratory data. A modified Low Cardiac Output Syndrome Score was calculated from clinical and therapeutic markers. The mean inadequate oxygen delivery and modified Low Cardiac Output Syndrome Score were compared within each matched pair using the Wilcoxon signed-rank test. Inadequate oxygen delivery correctly differentiated adverse events in 13 of 28 matched pairs, with no evidence of inadequate oxygen delivery being higher in cases (p = 0.71). Modified Low Cardiac Output Syndrome Score correctly differentiated adverse events in 23 of 28 matched pairs, with strong evidence of a raised score in low cardiac output syndrome cases (p < 0.01). CONCLUSIONS: Although inadequate oxygen delivery is an Food and Drug Administration approved indicator of risk for low mixed venous oxygen saturation, early postoperative average values were not linked with medium-term adverse events. The indicators included in the modified Low Cardiac Output Syndrome Score had a much stronger association with the specified adverse events.

Feasibility and Acceptability of Methods to Collect Follow-Up Information From Parents 12 Months After Their Child's Emergency Admission to Pediatric Intensive Care.

OBJECTIVES: To evaluate the feasibility and acceptability of different methods of collecting follow-up data from parents 12 months after their child's emergency admission to a PICU. DESIGN: Mixed-methods explanatory sequential design. SETTING: One regional PICU transport service and three PICUs in England. PATIENTS: Children undergoing emergency transport to PICU recruited to an ongoing biomarker study whose parents consented to be contacted for follow-up 12 months after PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Parents or guardians who consented were asked to complete three questionnaires about their child's functional status, quality of life, and behavior 12 months after PICU admission. Parents were given a choice about method of questionnaire completion: postal, online, or telephone interview and also asked for telephone feedback about the process and the reasons for their choice. Of 486 parents who consented to be contacted at 12 months, 232 were successfully contacted. Consent to receive questionnaires was obtained in 218 of 232 (94%). Of the 218 parents, 102 (47%) chose to complete questionnaires online (with 77% completion rate), 91 (42%) chose to complete postal questionnaires (48% completion rate), and 25 (11%) chose to complete questionnaires by telephone interview (44% completion rate). CONCLUSIONS: Parents expressed different preferences for follow-up questionnaire completion. Response rates varied by completion method. Understanding and catering for parental preferences is an important factor in maximizing response rates for follow-up studies in intensive care.

Cohort profile of the Biomarkers of Acute Serious Illness in Children (BASIC) study: a prospective multicentre cohort study in critically ill children.

PURPOSE: Despite significant progress, challenges remain in the management of critically ill children, including early identification of infection and organ failure and robust early risk stratification to predict poor outcome. The Biomarkers of Acute Serious Illness in Children study aims to identify genetic and biological pathways underlying the development of critical illness in infections and organ failure and those leading to poor outcome (death or severe disability) in children requiring emergency intensive care. PARTICIPANTS: We recruited a prospective cohort of critically ill children undergoing emergency transport to four paediatric intensive care units (PICUs) in Southeast England between April 2014 and December 2016. FINDINGS TO DATE: During the study period, 1017 patients were recruited by the regional PICU transport team, and blood and urine samples were obtained at/around first contact with the patient by the transport team. Consent for participation in the study was deferred until after PICU admission and 674 parents/carers were consented. Further samples (blood, urine, stool and throat swabs) were collected after consent. Samples were processed and stored for genomic, transcriptomic, proteomic and metabolomic analyses. Demographic, clinical and laboratory data at first contact, during PICU stay and at discharge, were collected, as were detailed data regarding infectious or non-infectious aetiology. In addition, 115 families have completed 12-month validated follow-up questionnaires to assess quality of life and child behaviour.The first phase of sample analyses (transcriptomic profiling) is currently in progress. FUTURE PLANS: Stored samples will be analysed using genomic, proteomic and metabolic profiling. Advanced bioinformatics techniques will be used to identify biomarkers for early diagnosis of infection, identification of organ failure and risk stratification to predict poor outcome (death/severe disability). TRIAL REGISTRATION NUMBER: NCT03238040.

Nitric oxide inhalations in bronchiolitis: A pilot, randomized, double-blinded, controlled trial.

AIM: The aims of this pilot study were to determine safety, tolerability (primary outcome) and efficacy (secondary outcome) of high-dose inhaled nitric oxide for the treatment of infants with moderately severe bronchiolitis. METHODS: This was a pilot, double-blinded, randomized controlled study (phase IIa). Intermittent inhalations of nitric oxide 160 ppm for 30 min or oxygen/air (control) were given 5 times/day to hospitalized infants (2-11 months) with acute bronchiolitis. Oxygen saturation, methemoglobin, and nitric dioxide (NO2 ) levels and vital signs were monitored. RESULTS: Forty-three infants were enrolled. Baseline characteristics were comparable in both study groups. Mean clinical score, comprised of four components: respiratory rate, use of accessory muscles, wheezes and crackles, and % room-air oxygen saturation, was 7.86 (±1.1) and 8.09 (±1.2) in the NO and control groups, respectively, consistent with moderate severity. The overall frequency of adverse events was similar between the groups. Repeated nitric oxide inhalations did not result in increased inhaled NO2 levels or cumulative effect on methemoglobin levels. Secondary outcomes of efficacy were measured by length of hospitalization (LOS) in hours: LOS did not differ between groups. However, in a post-hoc analysis of a subgroup of infants hospitalized for >24 h (n = 24), the median LOS was shorter in the nitric oxide (41.9 h) than in the control group (62.5 h) (P = 0.014). CONCLUSION: Our study was unable to detect a difference in side effects using intermittent high-dose nitric-oxide inhalation or supportive treatment alone, in infants with moderate bronchiolitis. Preliminary efficacy outcomes are encouraging.

Natural history and clinical manifestations of hyponatremia and hyperchlorhidrosis due to carbonic anhydrase XII deficiency.

INTRODUCTION: We identified patients of Bedouin origin with a mutation in carbonic anhydrase XII (CA XII) leading to hyponatremia due to excessive salt loss via sweat. METHODS: The medical records of patients were reviewed for clinical and laboratory data. RESULTS: A total of 11 subjects were identified; 7 symptomatic patients presented with hyponatremic dehydration in infancy. Screening of the entire kindred identified 4 asymptomatic individuals with elevated sweat chloride. All symptomatic patients had failure to thrive and moderate-severe hyponatremia (106-124 mmol·l(-1)); 6 had hypochloremia (79-94 mmol·l(-1)). All asymptomatic subjects had normal or near-normal serum sodium and chloride concentrations. Both symptomatic and asymptomatic subjects had normal renal functions and normal cortisol response on low-dose ACTH test. All symptomatic patients were treated by dietary salt, which prevents episodes of hyponatremic dehydration and promotes growth. At follow-up, the chief complaints remained heat intolerance, accumulation of salt precipitates on the face and hyperhidrosis. No evidence for chronic renal, respiratory, gastrointestinal or fertility abnormalities was found. CONCLUSION: Recognizing this newly described entity and differentiating it from cystic fibrosis and pseudohypoaldosteronism are important. Patients with CA XII mutations should be followed even after early childhood, especially in hot temperatures and intense physical activity.

Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12.

Genetic disorders of excessive salt loss from sweat glands have been observed in pseudohypoaldosteronism type I (PHA) and cystic fibrosis that result from mutations in genes encoding epithelial Na+ channel (ENaC) subunits and the transmembrane conductance regulator (CFTR), respectively. We identified a novel autosomal recessive form of isolated salt wasting in sweat, which leads to severe infantile hyponatremic dehydration. Three affected individuals from a small Bedouin clan presented with failure to thrive, hyponatremic dehydration and hyperkalemia with isolated sweat salt wasting. Using positional cloning, we identified the association of a Glu143Lys mutation in carbonic anhydrase 12 (CA12) with the disease. Carbonic anhydrase is a zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide to form a bicarbonate anion and a proton. Glu143 in CA12 is essential for zinc coordination in this metalloenzyme and lowering of the protein-metal affinity reduces its catalytic activity. This is the first presentation of an isolated loss of salt from sweat gland mimicking PHA, associated with a mutation in the CA12 gene not previously implicated in human disorders. Our data demonstrate the importance of bicarbonate anion and proton production on salt concentration in sweat and its significance for sodium homeostasis.

Acute pericarditis caused by Streptococcus pneumoniae in young infants and children: three case reports and a literature review.

We present three cases of pericarditis caused by Streptococcus pneumoniae diagnosed in children. The presenting symptoms were fever, dyspnea, tachycardia, and hepatomegaly. Chest X-rays showed an enlarged heart silhouette and echocardiographic examination revealed a pericardial effusion in all cases. S. pneumoniae was recovered from the pericardial fluid and/or blood in all cases. Systemic antibiotic treatment and dopaminergic agents were used; all patients recovered completely. Another 10 cases of S. pneumoniae pericarditis in children reported since 1980 are presented. Most cases had preceding respiratory symptoms and had a good outcome. While rare and life-threatening, pericarditis caused by S. pneumoniae has a good outcome if diagnosed early and treated adequately.