Pediatric Patients Research Articles

Impaired intestinal FXR signaling is involved in aberrant stem cell function leading to intestinal failure-associated liver disease in pediatric patients with short bowel syndrome.

Intestinal failure-associated liver disease (IFALD) is a serious complication of long-term parenteral nutrition in patients with short bowel syndrome (SBS), and is the main cause of death in SBS patients. Prevention of IFALD is one of the major challenges in the treatment of SBS. Impairment of intestinal barrier function is a key factor in triggering IFALD, therefore promoting intestinal repair is particularly important. Intestinal repair mainly relies on the function of intestinal stem cells (ISC), which require robust mitochondrial fatty acid oxidation (FAO) for self-renewal. Herein, we report that aberrant LGR5+ ISC function in IFALD may be attributed to impaired farnesoid X receptor (FXR) signaling, a transcriptional factor activated by steroids and bile acids. In both surgical biopsies and patient-derived organoids (PDOs), SBS patients with IFALD represented lower population of LGR5+ cells and decreased FXR expression. Moreover, treatment with T-βMCA in PDOs (an antagonist for FXR) dose-dependently reduced the population of LGR5+ cells and the proliferation rate of enterocytes, concomitant with decreased key genes involved in FAO including CPT1a. Interestingly, however, treatment with Tropifexor in PDOs (an agonist for FXR) only enhanced FAO capacity, without improvement in ISC function and enterocyte proliferation. In conclusion, these findings suggested that impaired FXR may accelerate the depletion of LGR5 + ISC population through disrupted FAO processes, which may serve as a new potential target of preventive interventions against IFALD for SBS patients.

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

Physeal Location on the Distal Femoral Cortical Surface Is Consistently Proximal to Apparent Location on the Perfect Lateral Radiograph: A 3-Dimensional Digitally Reconstructed Radiograph Study.

The perfect knee lateral radiograph visualizes anatomic landmarks on the distal femur for clinical and scientific purposes. However, radiographic imaging is a two-dimensional (2D) representation of a three-dimensional (3D) physis. The aim of this study was to characterize the perceived radiographic projection of the femoral physis using perfect lateral digitally reconstructed radiographs (DRRs) and to evaluate discrepancies from this projection to the physis at the lateral and medial cortices. Pediatric patients from a cohort of CT scans were analyzed. Inclusion criteria were an open physis; exclusion criteria were any implant or pathology affecting the physis. CT scans were imported into 3D imaging software and transformed into lateral DRRs and 3D renderings of the femur. The physis was divided into four equal segments, with fiducial markers placed at the "anterior," "midpoint," and "posterior" points. Lines extended from these points in the lateral and medial direction. The vertical distance from these lines, representing the radiographic projection of the physis, was measured relative to the physis at the lateral and medial cortex of the femur on coronal CT slices. Thirty-one patients were included. On the perfect lateral radiograph DRR, the physis on the medial cortex was located proximal to the visualized physis by 6.64 ± 1.74 mm, 11.95 ± 1.67 mm, and 14.30 ± 1.75 mm at the anterior (25%), midpoint (50%), and posterior (75%) locations, respectively. On the lateral side, the physis on the lateral cortex was proximal to the visualized physis by 2.19 ± 1.13 mm, 3.71 ± 1.19 mm, and 6.74 ± 1.25 mm at the anterior, midpoint, and posterior locations, respectively. In this cohort of pediatric patients, the location of the cortical physis was, in all areas measured, proximal to the projection of the visualized physis as seen on the perfect knee lateral DRR. The distance from radiographic physis to cortical physis was greater at the medial cortex compared with the lateral cortex. Descriptive laboratory study. III, observational radiographic anatomic study.

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА БОЛЕЗНИ БЛАУНТА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Lower extremities deformation is observed quite often in infants. One of the Blount's disease diagnosis features is the difficulty of its differential diagnosis of when excluded from other conditions such as rickets, rickets-like diseases and physiological curvature of the lower extremities in infants. Article represents the main diagnostic criteria for the abovementioned diseases. A clinical case of a patient with Blount's disease who had deviations in calcium-phosphorus metabolism that in their turn are uncommon for this pathology is described. The entire set of clinical and laboratory signs analysis was carried out in details, which then made it possible to carry out a differential diagnosis and exclude hereditary forms of rickets, primarily hypophosphatemic rickets as the reason for pronounced varus deformity of the legs in a 2.5 y/o pediatric patient. The tactics for further treatment by a specialized practitioner had been determined as well.

Эффективность использования новой роботической системы Versius для выполнения операций у детей: результаты клинических испытаний

Authors represent the Russia’s first research demonstrating the results of the use of the Versius modular & portable surgical robot by “CMR Surgical,” Ltd. (Cambridge, Cambridgeshire, United Kingdom) in surgical interventions on pediatric patients that they’ve obtained as part of the clinical trials complex approved by the Federal Service for Surveillance in Healthcare of Russia (“Roszdravnadzor”). The purpose of this research was to obtain practical evidence of the clinical safety and effectiveness of the use of the new Versius® Surgical Robotic System in minimally invasive surgical interventions on children. The criteria for the safety and effectiveness of the method were the absence of complications caused by the Surgical Robotic System (SRS) operation or the surgical technique as well as the absence of dropping into either laparoscopy or open surgery technique. Material and methods used: non-randomized single-center controlled trial had been carried out in children aged 1 to 18 y/o. Areas of application for surgical procedures included urology, abdominal and thoracic surgeries. Results: the number of patients who had undergone the robot-assisted surgeries had totaled 55 (27 (49%) m/28 (51%) f). The patient’s median age of the surgical intervention was 11.5 [7.0; 15.0] y/o; the median weight was 45.5 [27.0; 59.0] kilograms; the median surgical intervention duration was 140.0 [85.0; 175.0] minutes; patients’ stay in the intensive care unit had averaged for 23.0 [19.0; 24.0] hours; the average hospitalization duration was 8.0 [4.0; 14.0] days. Surgical interventions weren’t accompanied by any of the intraoperative complications such as bleeding, organ perforation and/or injury to adjacent anatomical structures. Conversions to either laparoscopic or open surgery technique also weren’t recorded. The equipment technical problems with SRS such as sudden system power-off, synchronous interaction of joysticks/manipulators interruption, robotic arms blocking, manipulators’ uncontrolled movement and/or traumatic effects on the tissues of the abdominal wall/chest weren’t recorded as well. Conclusion: the preliminary results obtained from the clinical trials complex affirm the potential ability of the Versius® Surgical Robotic System to performing robotic surgical interventions on pediatric patients aged 1 to 18 years old.

Генетически-фенотипический профиль детей с атипичным гемолитико-уремическим синдромом

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease caused by dysregulation of the alternative complement pathway as a result of mutations in complement genes or the formation of antibodies (AB) to some of the complement factors. Identification of the gene mutations incidence and the corresponding phenotypic features in pediatric patients with aHUS in Russia is aimed at improving the diagnosis and prognosis of the disease as well as treatment tactics planning for patient management. The purpose of this research was to determine the patterns of progression, prognosis and outcomes of aHUS in children depending on their genetic profile. Materials and methods used: the Article represents data from a retro- and prospective analyses of the characteristics of the course of aHUS in 172 children depending on their genetic profile performed in Jan. 2012-Feb. 2022. The sporadic form of aHUS was diagnosed after exclusion of the other forms of thrombotic microangiopathy (TMA), the familial form (in cases with the familial records), the acquired (CFH-Ab HUS) in cases with AB increase to factor H. AutoAb against factor H was determined by enzyme-linked immunosorbent assay (ELISA-VIDITEST anti-complement factor H). The search for mutations (n=167) was carried out using Next-generation Sequencing (NGS) and Sanger sequencing methods. Results: the sporadic form of aHUS was diagnosed in 96.9% of cases, familial in 3.1% and CFH-Ab HUS in 23.8%. The genetic nature of aHUS was confirmed in 53.4% of cases. Pathogenic mutations were detected in 8.6% of cases, probably pathogenic in 42.8% and those with unclear clinical significance in 46.8%. The complement genes mutations were detected in 88.5% of cases and mutations of genes not related to the complement system (ADAMTS13, DGKE, INF2) in 11.5%. The most frequently identified mutations were in the CFH (17.1%), C3 (12.9%) and CD46 (12.9%) genes and less frequently in CFI (7.1%), THBD (5.7%), CFHR5 (5.7%) and CFB (1.4%). In children with CFH-Ab HUS, the CFHR1/CFHR3 deletion was detected in 87.8% of cases, including in 19.4% in combination with mutations of unknown clinical significance. Multiple organ failure syndrome had developed in 77.8% of cases in children with pathogenic/probably pathogenic mutations, in 85.3% in patients with mutations of unknown clinical significance, in 91.8% in patients without mutations and in 83.3% in patients with CFHR1/CFHR3 deletion. Chronic kidney disease (CKD) stages 3 to 5 in sporadic/familial aHUS, regardless of genetic profile, had counted for 14.5% and 16.7% in CFH-Ab HUS. Lethal outcome occurred in 4.3% of cases in the presence of mutations, in 4.9% in the absence of mutations and in 2.8% in cases of CFHR1/CFHR3 deletion. Relapses of aHUS prior to the Eculizumab treatment had developed more often in the presence of CFHR1/CFHR3 mutations and deletion in comparison with children without mutations (31.4% v. 13.1%, p=0.0313 and 44.4% v. 13.1%, p= 0.004). Relapse of aHUS after discontinuation of the Eculizumab therapy had developed in 16.4% of cases. Risk factors for the relapse of aHUS were as follows: patient’s age above 12 months old at the time of the development of aHUS, severe arterial hypertension in the acute period, the use of Eculizumab at the fourth week after the onset of the disease and/or later, recurrent course of aHUS and the presence of CKD prior to the start of the Eculizumab therapy. Conclusion: The genetic profile of patients does not determine the severity and outcome of aHUS though it does affect the relapse rate. The prognosis and survival of patients with aHUS are determined by the severity of the acute period and the timeliness of the complement blocking therapy management.

РАСПРОСТРАНЕННОСТЬ И КЛИНИЧЕСКИЕ ОСОБЕННОСТИ ВОДОРОДНО –МЕТАНОВОГО ВАРИАНТА ТЕЧЕНИЯ СИНДРОМА ИЗБЫТОЧНОГО БАКТЕРИАЛЬНОГО РОСТА У ДЕТЕЙ С ФУНКЦИОНАЛЬНОЙ ДИСПЕПСИЕЙ

Prevalence of small intestinal bacterial overgrowth (SIBO) syndrome, improved diagnostic accuracy and therapeutic approaches require further study. The purpose of this research was to evaluate the effect of hydrogen dominant or hydrogen-producing SIBO (H-SIBO) and methane dominant or methane-producing SIBO (M-SIBO) types on the severity of clinical manifestations in children with functional dyspepsia (FD). Materials and methods used: a single-center cross-sectional study of 90 pediatric patients: 41 (45.6%) aged 11.0 [9.0:13.0] y/o with FD, of which 20 (48.8%) girls/21 (51.2%) boys, and 49 (54.4%) evaluatively healthy children (“control group”) aged 12.0 [9.5:13.6] y/o, of whom 27 (55.1%) girls/22 (44.9%) boys. The SIBO was determined with the domestically-produced “Lactophan” hydrogen breathing test by AMA Co., Ltd. (Saint Petersburg, Russia) and the “GastroCH4ECK Gastrolyzer” CH4 & H2 monitor by Bedfont Scientific Ltd. (Harrietsham, Maidstone, Kent, England, UK). Results: SIBO (41/100% and 28/57.1%, p<0.001) and H-SIBO (29/70.7% and 18/36.7%, p=0.045) were statistically significantly more often detected in children with FD than in the control group. The M-SIBO incidence (12/29.3% and 10/20.4%, p=0.467) did not differ statistically significantly between the groups. The methane output at the 60th to 90th minutes of the breathing test was 1.7 to 1.8 times higher in FD patients. The hydrogen threshold values at the 60th minute of the breathing test in FD patients for predicting of complaints were as follows: above 35 ppm (ROC-AUC=0.88, 95% CI=0.61-1.00, SE 87.5%, SP 97.2%) for “Sour taste in the mouth,” and above 33 ppm (ROC-AUC=0.80, 95% CI=0.53-1.00, SE 80.6%, SP 75.0%) for “Diarrhea.” The hydrogen threshold value at the 90th minute of the breathing test for “Flatulence” symptom was 44 ppm (ROC-AUC=0.71, 95% CI=0.36-0.88, SE 60.9%, SP 75.0%). Conclusion: testing for methane had increased the accuracy of SIBO diagnosis by 29.3% in patients with FD, i.e. from 70.7% to 100%! The relationship between the hydrogen and the methane concentrations coupled with the presence of dyspeptic symptoms may require the correction of SIBO in patients with FD.

Возможности консервативной тактики ведения пациентов с гипертрофией и воспалением глоточной миндалины

Patients who suffer from pharyngeal tonsil hypertrophy or inflammation are very common visitors in outpatient physicians’ practice. Hypertrophy of the pharyngeal tonsil may be accompanied by persistent difficulty in nasal breathing and complications whilst adenoditis in the absence of a significant impact on the child’s quality of life and associated complications had not been regarded as a ‘pathology’ in pediatric physicians’ practice until the patient is reached the age of 7 to 9 years old. The purpose of this research was to compare the regimens of the use of the homeopathic medications in patients with pharyngeal tonsil hypertrophy or inflammation. Materials and methods used: a single-center controlled randomized observation of the use of homeopathic medications of a single active substance had been conducted in pediatric patients aged 1 to 18 y/o with pharyngeal tonsil hypertrophy or inflammation. The study included patients with pharyngeal tonsil hypertrophy or inflammation who had previously taken homeopathic single-substance medications, including in combination with standard treatment. Depending on the choice of patients (repetition of the homeopathic single-substance medications intake or prophylactic regimen) the patients were then divided into comparison groups. All of the patients had undergone both the routine examination and the ENT endoscopy, the parents’/caregivers’ satisfaction with the treatment results was then assessed using the 5-point Likert scale as well as the incidence of acute respiratory infections (ARI) in children while taking homeopathic medicines (compared to the period without taking them) and the willingness to use homeopathic medicines in the future. Results: after the ENT endoscopy (reduction in the size of the pharyngeal tonsil in 38% of cases, p≤0.001) and the parents’/caregivers’ survey (reduction in the ARI frequency in 62% of cases and high satisfaction with the treatment results), the majority of parents/caregivers have assessed the repetition of the repetition of the homeopathic single-substance medications intake as rather more effective in treatment of patients with inflammation of the pharyngeal tonsil of varying degrees of hypertrophy. Conclusion: the use of homeopathic medicines in patients with pharyngeal tonsil hypertrophy or inflammation has showed good effectiveness. According to the ENT endoscopy results before v. after the treatment and the parents’/caregivers’ survey it is preferable to repeat the homeopathic single-substance medications intake in the next adenoiditis episode. The parents’/caregivers’ readiness to go on with the homeopathic medicines’ intake ranges from 50% to 78%.

Консервативная тактика ведения врожденного и инфантильного нефротического синдрома: опыт одного центра

Treatment tactics for patients with congenital nephrotic syndrome (CNS) varies from aggressive kinds, such as early nephrectomy, to conservative ones that include diuretic and nutritional support. The purpose of this research was to assess the effectiveness of conservative treatment of children with congenital and infantile nephrotic syndromes. Materials and methods used: a single-center retrospective study of 11 pediatric patients who had been manifested with NS within their first year of life and had required diuretic therapy, was conducted. The effectiveness of conservative therapy was assessed as preservation of the renal function according to glomerular filtration and satisfactory weight/height and height alone parameters’ dynamics that ensure the safety of kidney transplantation. Results: despite the molecular genetic study was conducted in all 250 children with NS, the described 11 have had verified pathogenic variants as follows: in the NPHS1 gene in 5 (45.5%, CI 16.8-76.6%), in the NPHS2 gene in another 5 (45.5%, CI 16.8-76.6%) and a single patient with none of a kind. It was revealed that despite the persistence of pronounced NS laboratory activity, the edema gradually disappeared against the background of conservative therapy, which in its turn had made it possible to refrain from early nephrectomy as well as to begin the renal replacement therapy over the age of 3 (4) y/o. 9 (81.8%, CI 48.2-97.7%) had satisfactory weight and height parameters at the age of 3 y/o. Only a single patient had undergone the early nephrectomy at the age of 4 months old, that was then followed by a successful kidney transplant at the age of 1 year and 4 months old, which, however, did not affect the then positive height prognosis. Conclusion: thus, reasonably selected conservative therapy for CNS can be effective against edematous syndrome and contribute to satisfactory weight/height growth parameters without early nephrectomy and, accordingly, the start of dialysis during the first year of life.

Effect of peritoneal drainage on the prognosis following appendectomy in pediatric patients with appendicitis: a retrospective study based on appendicitis grade.

This study aimed to assess the impact of peritoneal drainage and its type on prognosis, encompassing postoperative recovery and complications, in pediatric patients (≤ 16years old) following appendectomy based on the grade of appendicitis. In this retrospective study, we analyzed pediatric patients (≤ 16years old) with appendicitis who met the inclusion and exclusion criteria in our center from January 2017 to January 2024 and classified them into grade I-V based on the grade of appendicitis, with V representing the most serious cases. The patients were grouped according to drainage status and type. The main clinical outcomes included postoperative rehabilitation indexes such as time to resume a soft diet, time to remove the drain, duration of postoperative antibiotic use and length of hospitalization (LOH), as well as postoperative complications including intra-abdominal abscess (IAA), ileus and wound infection (WI), and readmission within 30days after surgery. A total of 385 pediatric patients with appendicitis were included in the study and divided into No-drainage (ND) group (n = 74), Passive drainage (PD) group (n = 246) and Active drainage (AD) group (n = 65) according to drainage status and type. Compared to the other two groups, the ND group had a significantly shorter time to resume a soft diet, duration of postoperative antibiotic use and LOH, and these differences were statistically significant. Similar findings were observed in grade I patients too (P < 0.05). In all cases examined here, the AD group had a significantly shorter time for drain removal compared to the PD group (3.04 [1-12] vs 2.74 [1-15], P = 0.049); this difference was also evident among grade I patients (2.80 [1-6] vs 2.47 [1-9], P = 0.019). Furthermore, within the same grade, only in grade IV did the AD group exhibit a shorter duration of postoperative antibiotic use compared to the PD group (4.75 [4-5] vs 8.33 [5-15], P = 0.009). Additionally, the LOH in the AD group was longer than that in the PD group (8.00 [4-13] vs 4.75 [4-5], P = 0.025). Among all cases, the ND group exhibited significantly lower incidences of overall complications and WI compared to the other two groups (P < 0.05). Additionally, the incidence of IAA in the ND group was significantly lower than that in the PD group (0% vs 5.3%, P = 0.008 < 0.0167). Furthermore, although there were no statistically significant differences in the incidence of overall complications, IAA, ileus, and WI between the PD and AD groups during grade ≥ II analysis (P > 0.05), a higher readmission rate within 30days was observed in the PD group compared to the AD group; however, these differences were not statistically significant (P > 0.05). Moreover, multivariate analysis revealed that a higher grade of appendicitis was associated with an increased risk of overall complications and IAA as well as a longer duration of postoperative antibiotic use and LOH. The appendicitis grade is a crucial indicator for predicting postoperative IAA and LOH. In patients with grade I appendicitis, peritoneal drainage, even if active drainage, is not recommended; For patients with grade ≥ II appendicitis, active drainage may be more effective than passive drainage in reducing the duration of postoperative antibiotic use and LOH.

Effect of parenteral lipids on essential fatty acid deficiency in pediatric intestinal failure: A retrospective cohort study.

Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure. This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences. A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels. This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure.

Diffuse alveolar hemorrhage in pediatrics: Etiologies and outcomes.

Many conditions, including autoimmune disease and idiopathic pulmonary hemosiderosis (IPH), can cause diffuse alveolar hemorrhage (DAH). Little is known about the epidemiology and outcomes in children. This retrospective cohort study sought to describe the etiologies and outcomes of DAH in pediatric patients at a tertiary care center. This study involved review of patient records with diagnostic codes or bronchoscopy reports suggestive of pulmonary hemorrhage at a large children's hospital over 11 years (2010-2020). Patients were included if they met criteria for DAH, defined as bilateral pulmonary infiltrates and at least one of the following: (1) hemoptysis, (2) blood visible on bronchoscopic exam without apparent airway source, or (3) DAH noted on biopsy or autopsy. Infants less than 10 days corrected gestational age were excluded. Seventy-one children with DAH were included in the analysis. Cardiovascular disease was the most common etiology. Bleeding diathesis was common, but all patients had other causes of DAH. Patients with IPH were younger than those with autoimmune disease (p < .001). Most (77%) patients required mechanical ventilation, though this was less common among patients with autoimmune disease. Overall mortality was high (37%) but varied based on underlying etiology; mortality was higher in patients with cardiovascular disease (65%) while no deaths were seen in patients with autoimmune disease or IPH (p = .002). Survivors of DAH who performed pulmonary function tests had normal lung function. DAH frequently causes respiratory failure in children. In our cohort, mortality was highest in patients with cardiovascular disease.

Pediatric Toy-Related Ocular Injuries in the United States: A National Electronic Injury Surveillance System Study

ABSTRACT Purpose The purpose of this study is to evaluate the epidemiological trends, primary ocular diagnosis, and degree of injury severity in pediatric patients after a toy-related ocular trauma. Methods A cross-sectional analysis was conducted using data from the National Electronic Injury Surveillance System Study (NEISS), encompassing patients who visited emergency departments over a 5-year period from January 1, 2017, to December 31, 2021, with toy-related ocular injuries. Descriptive statistics were employed using Microsoft Excel. Results Among the 1439 toy-related ocular injuries identified, the mean age of injury was 6.67 ± 4.36 years. The highest proportion of injuries occurred in the 2–5 years age group (27.2%). The NEISS database classified the severity of injury – the majority of which were minor anterior segment injuries. Toy guns with projectiles were identified as the most common type of toy associated with ocular eye injury. While most injuries were minor, a small percentage was severe. Conclusion Age-appropriate toy selection and adult supervision during playtime are recommended preventive measures to mitigate the incidence and severity of traumatic eye injuries in children.

Perioperative Management of Pediatric Combined Heart and Liver Transplantation: A 17 year single center experience.

An increasing number of centers are undertaking combined heart and liver transplantation in adult and pediatric patients with congenital heart disease. The primary aim of this study was to describe the perioperative management of a single center cohort, identifying challenges and potential solutions. We conducted a retrospective review of all patients undergoing combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022. Preoperative information included cardiac diagnosis, hemodynamics, and severity of liver disease. Intraoperative data included length of surgery, cardiopulmonary bypass time, and blood products transfused. Postoperative data included blood products transfused in the intensive care unit, time to extubation, length of intensive care unit stay, survival outcomes and 30-day adverse events. Eighteen patients underwent en bloc combined heart and liver transplantation at Stanford Children's Hospital from 2006 to 2022, and the majority 15 (83%) were transplanted for failing Fontan circulation with Fontan Associated Liver Disease. Median surgical procedure time was 13.4 [11.5, 14.5] h with a cardiopulmonary bypass time of 4.3 [3.9, 5.8] h. Median total blood products transfused in the operating room post cardiopulmonary bypass was 89.4 [63.9, 127.0] mLs/kg. Nine patients (50%) had vasoplegia during cardiopulmonary bypass. Activated prothrombin complex concentrates were used post cardiopulmonary bypass in 15 (83%) patients with a 30-day thromboembolism rate of 22%. Median time to extubation was 4.0 [2.8, 6.5] days, median intensive care unit length of stay 20.0 [7.8, 48.3] days and median hospital length of stay 54.0 [30.5, 68.3] days. Incidence of renal replacement therapy was 11%; however, none required renal replacement therapy by the time of hospital discharge. Neurological events within 30 days were 17% and the 30 day and 1 year survival was 89%. Perioperative challenges include major perioperative bleeding, unstable hemodynamics, and end organ injury including acute kidney injury and neurological events. Successful outcomes for en bloc combined heart and liver transplantation are possible with careful multidisciplinary planning, communication, patient selection, and integrated peri-operative management.

Immunoglobulin prophylaxis prevents hospital admissions for fever in pediatric acute lymphoblastic leukemia: results of a multicenter randomized trial.

Infections lead to substantial morbidity during treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system gets severely affected, leading to declining serum immunoglobulin levels. The aim of this trial was to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL prevents admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium risk (MR) ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every three weeks, starting day 22 after diagnosis) or well defined standard of care (control group). Between October 2012 until March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (p=0.011). IVIG prophylaxis was not associated with bacteremia. However, IVIG prophylaxis was associated with significantly less admissions for fever with negative blood cultures compared to the control group (N=113 versus 200, p.

Characterization of a cohort of patients with hypercalcemia in a tertiary pediatric hospital.

Introduction. Hypercalcemia is infrequent in pediatrics, of diverse etiology, and with multiorgan morbidity. Objective. Describe the etiology, biochemistry, clinical, and treatment in pediatric patients with hypercalcemia. Population and methods. Retrospective and descriptive study of a cohort of patients with hypercalcemia between 2008 and 2022. They were classified into three groups (G): hypercalcemia of iatrogenic cause (G1), parathyroid hormone (PTH) independent (G2), or PTH-dependent (G3). Results. One hundred forty-seven patients were included; 57% were male, with a median age of 3.7 years, median calcemia of 11.8 mg/dl, and mean phosphatemia of 4.9 mg/dl. Symptoms were present in 29% of patients, and 28.6% required additional treatments to those of the first line. In G1, 76 patients (51.7%) were included; in G2, 58 (39.4%), and in G3, 13 (8.8%). Median calcemia was lower in G1 vs. G2 and G3 (11.6 mg/dl, 12.6 mg/dl, and 12.3 mg/dl), and mean phosphatemia was lower in G3 vs. G1 and G2 (3.7 mg/dl, 5.3 mg/dl, and 4.9 mg/dl). Most of the patients with hypercalcemia were asymptomatic and did not require additional treatments. The percentage of symptomatic patients and the percentage requiring additional treatment were lower in G1 than in the other two groups. Conclusions. Iatrogenesis was the most frequent cause, presenting lower calcemia, while PTH-dependent causes presented the lowest phosphatemia. PTH-independent causes represented a diagnostic and therapeutic challenge due to lacking a characteristic biochemical profile.

Echocardiographic estimation of pulmonary arterial and right atrial pressures in children with congenital heart disease: a comprehensive prospective study and introduction of novel equations

BackgroundPediatric pulmonary hypertension (PH) is characterized by a mean pulmonary arterial pressure exceeding 20 mmHg. There is limited research on the suitability of adult-based methods for estimating PH in pediatric populations. Using established formulas for adults, this study aimed to evaluate the correlation between echocardiographic estimates of systolic, diastolic, and mean pulmonary arterial pressures, and mean right atrial pressures in children with congenital heart disease (CHD).MethodsA prospective study was conducted involving children with CHD undergoing cardiac catheterization without prior cardiac surgery. We used echocardiography to estimate pulmonary and right atrial pressures and compared these with invasively measured values. Four reliable regression equations were developed to estimate systolic, diastolic, and mean pulmonary arterial pressures, and mean right atrial pressures. Cutoff values were determined to predict the occurrence of PH. Linear regression, Bland–Altman analysis, and receiver operating characteristic curve analysis were performed to assess the accuracy of echocardiography and establish diagnostic thresholds for PH.ResultsThe study involved 55 children (23 with normal pulmonary arterial pressure and 32 with PH) with acyanotic CHD aged 1 to 192 months. Four equations were developed to detect high pulmonary arterial pressures, with cutoff values of 32.9 for systolic pulmonary arterial pressure, 14.95 for diastolic pulmonary arterial pressure, and 20.7 for mean pulmonary arterial pressure. The results showed high sensitivity and moderate specificity but a tendency to underestimate systolic and mean pulmonary arterial pressures at higher pressures.ConclusionsThe study provides valuable insights into the use of adult-based echocardiographic formulas for estimating PH in pediatric patients with acyanotic CHD.

Experience in a PHTS Expertise Centre: Yield of Thyroid Ultrasound Surveillance in Children with PTEN Hamartoma Tumor Syndrome.

Children with PTEN hamartoma tumor syndrome (PHTS) are at increased risk for developing thyroid abnormalities, including differentiated thyroid carcinoma (DTC). The Dutch PHTS guideline recommends ultrasound surveillance starting from age 18. Since the literature describes PHTS patients who developed DTC before age 18, the Dutch PHTS expertise centre has initiated annual ultrasound surveillance starting from age 12. The purpose of this study was to identify the yield of thyroid ultrasound surveillance in children. A retrospective single centre cohort study was conducted. Pediatric PHTS patients who received thyroid ultrasound surveillance before age 18 between 2016-2023 were included. Patients' medical records have been reviewed. Primary outcomes included prevalence and time to develop thyroid nodules ≥10mm, nodular growth, goiter, thyroiditis and DTC. Descriptive statistics and Kaplan-Meier analyses were performed. Forty-three patients were included. Two patients (5%) were diagnosed with DTC at ages 12 and 17. Both DTCs were identified as minimally invasive follicular carcinoma at stages pT3NxMx and pT1NxMx respectively. A total of 84% were diagnosed with thyroid abnormalities at a median age of 12 years (range 9-18). Most common findings were benign, including nodular disease (74%), goiter (30%) and autoimmune thyroiditis (12%). Nodular growth was observed in 14 patients (33%) resulting in (hemi)thyroidectomy in 7 patients (16%). Thyroid ultrasound surveillance resulted in the detection of DTC in 2/43 PHTS patients before age 18. These findings support the recommendation to initiate thyroid ultrasound surveillance in children at least from age 12, preferably within an expertise centre.

Endocrine Disorders in Children with Primary Mitochondrial Diseases: Single-Center Experience.

Endocrine abnormalities may represent the only clinical manifestation of primary mitochondrial disorders. This study aimed to evaluate the endocrinological characteristics of mitochondrial disease in our cohort. A total of twenty-six pediatric patients diagnosed with mitochondrial disease were categorized on the basis of their specific genetic abnormalities. The auxologic data, pubertal development, and, based on their clinical symptoms, hormonal profiles were obtained. Twelve of the cohort of 26 patients (46%) were female. In 15 of the patients (57.6%), their mitochondrial disease (MD) was caused by nuclear DNA mutations (nDNA group). Four patients had Leigh syndrome, 2 patients had LHON syndrome, 2 patients had MELAS, and 1 patient had KSS clinical phenotype. The median age at diagnosis was 2.91 (0.59-16.8) years, and the median age at first endocrinologic evaluation was 4.62 (1.26-18) years. The mean height SDS was -1.34 ± 2.12, and the mean BMI SDS was -0.82 ± 1.96 for all patients. Of the 26 patients, 6 (23%) had a range of hormonal deficits. Ovarian insufficiency, central adrenal insufficiency, central hypothyroidism, diabetes mellitus, and critical illness-related adrenal insufficiency were all observed. Three of the patients were initially monitored in the endocrine clinic for hormone deficiencies but it was later determined that the hormonal abnormalities were caused by underlying mitochondrial disease. Individuals diagnosed with mitochondrial disease, particularly those with specific genetic abnormalities, are considered a high-risk group for developing hormonal deficits. Endocrine diseases could be one of the primary mitochondrial disorders' early warning symptoms.

Long-term outcomes of a cultured autologous dermo-epidermal skin substitute in children: 5 year results of a phase I clinical trial.

Limited donor sites and poor long-term outcomes with standard treatment for large skin defects remain a huge problem. An autologous, bilayered, laboratory-grown skin substitute (denovoSkin™) was developed to overcome this problem and has shown to be safe in ten pediatric patients in a phase I clinical trial after transplantation. The goal of this article is to report on 48 months long-term results. The pediatric participants of the phase I clinical trial were followed at yearly visits up to five years after transplantation. Safety parameters including occurrence of adverse events, possible deviations of vital signs and changes in concomitant therapy as well as additional parameters regarding skin stability, scar quality and tumor formation were assessed. Furthermore, scar maturation was photographically documented. From the ten patients treated with denovoSkinTM in this phase I clinical trial, seven completed the five-year follow-up period. Skin substitutes continued to be deemed safe, remained stable and practically unchanged, with no sign of fragility, and no tumor formation at clinical examination. Scar quality, captured by applying the Patient and Observer Scar Assessment Scale, was evaluated as close to normal skin. Transplantation of this laboratory-grown skin substitute in children is to date considered safe and shows encouraging functional and aesthetical long-term results close to normal skin. These results are promising and highlight the potential of a life-saving therapy for large skin defects. A multicentre, prospective, randomized phase II clinical trial to further evaluate the safety and efficacy of this novel skin substitute is currently ongoing.