Children's Hospital Mansoura University

Caffeine is the most commonly used medication for treatment of apnea of prematurity. Its effect has been well established in reducing the frequency of apnea, intermittent hypoxemia, and extubation failure in mechanically ventilated preterm infants. Evidence for additional short-term benefits on reducing the incidence of bronchopulmonary dysplasia and patent ductus arteriosus has also been suggested. Controversies exist among various neonatal intensive care units in terms of drug efficacy compared to other methylxanthines, dosage regimen, time of initiation, duration of therapy, drug safety and value of therapeutic drug monitoring. In the current review, we will summarize the available evidence for the best practice in using caffeine therapy in preterm infants.

INTRODUCTION: Respiratory failure is a life threatening complication of Guillain Barré syndrome (GBS). There is no consensus on the specific treatment for this subset of children with GBS. METHODS: This was a prospective randomized study to compare the outcome of intravenous immunoglobulin (IVIG) and plasma exchange (PE) treatment in children with GBS requiring mechanical ventilation. Forty-one children with GBS requiring endotracheal mechanical ventilation (MV) within 14 days from disease onset were included. The ages of the children ranged from 49 to 143 months.Randomly, 20 children received a five-day course of IVIG (0.4 g/kg/day) and 21 children received a five-day course of one volume PE daily. Lumbar puncture (LP) was performed in 36 patients (18 in each group). RESULTS: Both groups had comparable age (p = 0.764), weight (p = 0.764), duration of illness prior to MV (p = 0.854), preceding diarrhea (p = 0.751), cranial nerve involvement (p = 0.756), muscle power using Medical Research Council (MRC) sum score (p = 0.266) and cerebrospinal fluid (CSF) protein (p = 0.606).Children in the PE group had a shorter period of MV (median 11 days, IQR 11.0 to 13.0) compared to IVIG group (median 13 days, IQR 11.3 to 14.5) with p = 0.037.Those in the PE group had a tendency for a shorter Pediatric Intensive Care Unit (PICU) stay (p = 0.094).A total of 20/21 (95.2%) and 18/20 (90%) children in the PE and IVIG groups respectively could walk unaided within four weeks after PICU discharge (p = 0.606).There was a negative correlation between CSF protein and duration of mechanical ventilation in the PE group (p = 0.037), but not in the IVIG group (p = 0.132). CONCLUSIONS: In children with GBS requiring MV, PE is superior to IVIG regarding the duration of MV but not PICU stay or the short term neurological outcome.The negative correlation between CSF protein values and duration of MV in PE group requires further evaluation of its clinical usefulness. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01306578.

BACKGROUND: Infantile cholestasis continues to represent a diagnostic challenge. It is very important to diagnose surgically correctable disorders, such as biliary atresia, in a timely manner to prevent progressive damage to the liver. It has been recently suggested that the triangular cord (TC) sign is a simple and useful tool in the diagnosis of biliary atresia. METHODS: We prospectively studied 65 infants presenting with conjugated hyperbilirubinemia (age range: 32-161 days). All patients underwent ultrasonographic examination with a 7.0-MHz transducer (Acuson, Mountain View, CA). The TC was defined as a triangular, or tubular, echogenic density seen immediately cranial to the portal vein bifurcation. RESULTS: The TC sign was identified in 25 infants, and all of them had histologic features suggestive of biliary atresia; the diagnosis was confirmed at surgery by gross morphology of hepatobiliary system, and liver biopsy, with or without intraoperative cholangiogram. Among the 40 patients who did not have the TC sign, 6 had paucity of the intrahepatic bile ducts. Three had alph-1-antitrypsin deficiency, and 31 had neonatal hepatitis. None of the 40 patients who did not have the TC sign developed acholic stools. Seven patients with biliary atresia were followed by ultrasonographic examination for 6 months after the Kasai procedure. The TC sign disappeared in all patients after the surgery; however, the TC sign reappeared in 3 patients who developed progressive cholestasis after the procedure. CONCLUSION: The TC sign is a simple, timesaving, and reliable diagnostic tool in the evaluation of infants with infantile cholestasis. The TC sign may also prove to be helpful in following patients after hepatoportoenterostomy. We suggest a new diagnostic strategy for patients suspected to have biliary atresia. When the TC sign is visualized, the patient should undergo intraoperative cholangiogram to confirm the diagnosis of biliary atresia, reserving percutaneous liver biopsy for those patients in whom the TC sign could not be detected.

OBJECTIVES: M-mode sonography is a noninvasive method for detection of diaphragmatic excursion and thickness. A few studies have assessed diaphragmatic kinetics in children with diaphragmatic paresis and paralysis, but to our knowledge, no data about normal values in pediatrics are available. The aims of this study were to determine reference values for diaphragmatic excursion and thickness, as evaluated by sonography in healthy infants and children, and identify correlations between them and anthropometric measurements, age, and sex. METHODS: A total of 400 healthy participants aged between 1 month and 16 years, divided into 4 equal groups (group 1, 1 month-2 years; group 2, 2-6 years; group 3, 6-12 years); and group 4, 12-16 years) were studied. M-mode sonography was used to measure the excursion and thickness of the right and left hemidiaphragms (using the liver and spleen as acoustic windows, respectively). RESULTS: Reference values for diaphragmatic excursion and thickness were determined in different age groups of healthy infants and children. There were no significant differences with respect to sex. Significant positive correlations were found between excursion of the right hemidiaphragm and body weight in all age groups (r = 0.52, 0.25, 0.27. and 0.20; P < .001, .013, .011, and .047 for groups 1-4, respectively). We plotted percentile curves for right diaphragmatic excursion against body weight. CONCLUSIONS: This study provides reference values for diaphragmatic excursion and thickness in healthy infants and children. Percentile curves for right diaphragmatic excursion plotted against body weight were plotted.

Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10 −4 ) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10 −4 ). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10 −3 ), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10 −8 ). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10 −5 ). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

In this study, Entamoeba histolytica had high prevalence and unusual presentation by affecting high proportion of infants under 1 year; severe clinical manifestations, and laboratory findings that were known to be usually encountered in invasive amebiasis as significant leukocytosis for age, neutrophilic leukocytosis for age, and positive C-reactive protein were found among more than 50% of admitted Saudi infants and children with E. histolytica infection in our locality. E. histolytica can be a re-emerging serious infection when it finds favorable environmental conditions and host factors which are mainly attributed to inadequate breastfeeding in this study. This may occur in any other area of the world with the same risk factors, so we must be ready to tackle it with effective and more powerful preventive measures.

OBJECTIVE: The geographical incidence of type 1 diabetes mellitus (T1DM) varies widely worldwide. Both genetic and environmental factors have been implicated, although environmental factors are still speculative and elusive. More epidemiological studies are needed to uncover such factors. To date, there are no reported studies on the epidemiology of childhood T1DM in Nile Delta, Egypt. We aimed to define the incidence, prevalence and demographic characteristics of T1DM in children (0-18 years) living in the Nile Delta region, one of the most densely populated areas in Egypt. METHODS: The study included all T1DM patients aged 0-18 years who lived in the Nile Delta region of Egypt and who were either diagnosed at or referred to Mansoura University Children's Hospital (MUCH) between 1 January 1994 and 31 December 2011. The hospital files of the patients were reviewed. General population data on the 0-18 year age group in the Nile Delta governorates were also presented. RESULTS: From a total of 1600 T1DM patients, 891 (55.7%) were females (p=0.000) and 935 (58.4%) were from rural areas (p=0.000). Calculated age-adjusted incidence of T1DM in 1996, 2006 and 2011 were 0.7, 2.0 and 3.1/10(5)/year, respectively, while calculated age-adjusted prevalence of T1DM in the same years were 1.9, 15.5 and 26.8/10(5)/year, respectively. Patients presented most frequently in the 5-10 year age group (p<0.000) and in winter months (p=0.009). CONCLUSION: In this first childhood T1DM epidemiology study in the Nile Delta region of Egypt, T1DM incidence and prevalence were found to show an increase over the past 18 years (1994-2011). Incidence and prevalence were higher in females and more cases were found to originate from rural areas.

BACKGROUND: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. METHODS: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. RESULTS: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). CONCLUSIONS: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation.

BACKGROUND: Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy. OBJECTIVE: To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram-negative late-onset sepsis (GN-LOS). METHODS: A prospective, randomized clinical trial was conducted in neonates with GN-LOS admitted to neonatal intensive care unit (NICU), Mansoura University Children's Hospital, between August 2013 and June 2015. Patients were randomly assigned to receive either intravenous infusion of meropenem over 4 hours (infusion group) or 30 minutes (conventional group) at a dosing regimen of 20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection. Clinical and microbiologic success in eradication of infection were the primary outcomes. Neonatal mortality, meropenem-related (MR) duration of mechanical ventilation, MR length of NICU stay, total length of NICU stay, duration of respiratory support (RS), duration of mechanical ventilation, MR duration of inotropes and adverse effects were secondary outcomes. RESULTS: A total of 102 infants (51 in each group) were recruited. The infusion group demonstrated a significantly higher rate of clinical improvement and microbiologic eradication 7 days after starting meropenem therapy compared with the conventional group. Mortality and duration of RS were significantly less in the infusion group compared with conventional group. Acute kidney injury after meropenem treatment was significantly less in the infusion group compared with the conventional group. CONCLUSIONS: Prolonged infusion of meropenem in neonates with GN-LOS is associated with higher clinical improvement, microbiologic eradication, less neonatal mortality, shorter duration of RS and less acute kidney injury compared with the conventional strategy.

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.

Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

BACKGROUND: Oropharyngeal administration of mother's colostrum in early days has an immunoprotective effect in preterm infants. OBJECTIVES: Our aim was to study the effect of oropharyngeal administration of mother's milk (OPAMM) on decreasing the incidence of nosocomial sepsis. METHODS: In a pilot prospective randomized study on preterm (<32 weeks gestation and 1500 g weight) infants, we compared OPAMM practice (applying 0.2 mL of mother's colostrum or milk prior to gavage feeding until full oral feeding is reached) with regular gavage feeding. The primary outcome was incidence of culture-proven nosocomial sepsis. Secondary outcomes included bacterial colonization of the gastrointestinal tract, feeding intolerance, time to reach full feeding, incidence of necrotizing enterocolitis, ventilator-associated pneumonia, duration of respiratory support, incidence of bronchopulmonary dysplasia (BPD), length of hospital stay, and neonatal mortality. RESULTS: The outcomes of 200 neonates (100 in each group) were analyzed. OPAMM practice did not significantly reduce the incidence of culture proven nosocomial sepsis (8% vs 13%, P = 0.35). Infants in the OPAMM group had a significantly lower growth of Klebsiella species in the oropharyngeal pouch, borderline lower incidence of ventilator-associated pneumonia, shorter duration of oxygen therapy, less episodes of feeding intolerance, reached full feeding earlier, and had a shorter length of hospital stay. OPAMM practice did not affect the incidence of necrotizing enterocolitis, BPD, or neonatal mortality. CONCLUSION: OPAMM prior to gavage feeding does not reduce the incidence of nosocomial sepsis but had beneficial effects on early achievement of feeding, and early hospital discharge in preterm very low-birth-weight infants.

OBJECTIVES: To evaluate the effect of trace elements (TEs), when added to total parenteral nutrition (TPN) solutions, on peroxides load, and to test the hypothesis that protection of TPN from light can decrease peroxides load and is associated with improvement in oxidant-related clinical outcomes in preterm infants. SUBJECTS AND METHODS: A total of 80 preterm infants were randomized to 1 of 4 groups (n=20 each): group 1 received a mixture of dextrose and amino acids; group 2 received a mixture of dextrose, amino acids, and lipid emulsion; group 3 received dextrose, amino acids, lipid emulsion, and multivitamins (MVP); and group 4 received dextrose, amino acids, lipid emulsion, MVP, and TEs. Each group was subdivided into photo-protected and photo-exposed subgroups (n=10 each). Using ferrous oxidation of xylenol orange technique, we measured the baseline level of excreted urinary peroxides before and 48 hours after starting TPN. We examined the association among light protection, urinary peroxides, and clinical outcomes of these infants. RESULTS: Baseline urinary peroxides ranged between 5.5 and 24.8 micromol/L. A significant increase in urinary peroxides was observed in all groups after receiving TPN. The use of TEs did not affect peroxide production. In regression analysis, the addition of MVP (P<0.0001) and the exposure to light (P=0.02) were significantly associated with increased urinary peroxides. In the overall population, light exposure was associated with a significant increase in the incidence of chronic lung disease (adjusted OR 9.26, confidence interval 1.2-73; P=0.03) but had no effect on mortality, necrotizing enterocolitis, or sepsis. CONCLUSIONS: TEs in TPN solutions have no effect on the production of urinary peroxides. Addition of MVP and exposure of TPN to light are the 2 major sources of peroxides in TPN. Protection from ambient light is associated with a decrease in chronic lung disease.

Brain lesions induced in newborn mice or rats by the glutamatergic agonists ibotenate (acting on NMDA and metabotropic receptors) or S-bromowillardiine (acting on AMPA-kainate receptors) mimic some aspects of white matter cysts and transcortical necrosis observed in human perinatal brain damage associated with cerebral palsy. Exogenous and endogenous cannabinoids have received increasing attention as potential neuroprotective agents in a number of neurodegenerative disorders of the adult. One recent study showed neuroprotection by the cannabinoid agonist WIN-55212 in a newborn rat model of acute severe asphyxia. The present study was designed to assess the neuroprotective effects of the endogenous cannabinoid anandamide using a well-defined rodent model of neonatal excitotoxic brain lesions. In this model, anandamide provided dose-dependent and long-lasting protection of developing white matter and cortical plate reducing the size of lesions induced by S-bromowillardiine. Anandamide had only marginal neuroprotective effect against ibotenate-induced cortical grey matter lesions. Anandamide-induced neuroprotection against AMPA-kainate receptor-mediated brain lesions were blocked by a CB1 antagonist but not by a CB2 antagonist. Furthermore, anandamide effects were mimicked by a CB1 agonist but not by a CB2 agonist. Real-time PCR confirmed the expression of CB1 receptors, but not CB2 receptors, in the untreated newborn neocortex. Finally, neuroprotective effects of anandamide in white matter involved increased survival of preoligodendrocytes and better preservation of myelination. The present study provides experimental support for the role of endocannabinoids as a candidate therapy for excitotoxic perinatal brain lesions.

We aimed to review computed tomography and magnetic resonance angiography of congenital anomalies of pulmonary veins. Total anomalous pulmonary venous return shows all pulmonary veins drain abnormally in another site rather than left atrium. Imaging can detect anomalous veins either supracardiac, infracardiac, or mixed. Partial anomalous pulmonary venous return shows some pulmonary vein have abnormal drainage that well delineated with computed tomography angiography. Scimitar syndrome is a type of partial anomalous pulmonary venous return where the pulmonary veins of the right lung drain infracardiac and is associated with right lung hypoplasia and dextrocardia. Pseudoscimitar show anomalous vein that takes a tortuous course and drains into the left atrium producing a false-positive scimitar sign. Cor triatriatum shows septum divide left atrium with proximal chamber receives blood flow from the pulmonary veins. Levoatriocardinal vein is an anomalous connection between the left atrium and anomalous vein from systemic venous system that is embryo logically derived from the cardinal veins. Computed tomography angiography can detect pulmonary vein stenosis, atresia, hypoplasia, and varix. Imaging is important for intimal diagnosis and detects the anomalous vessels and its connection, presence of stenosis, and associated other congenital cardiac anomalies. Also, it is a great role in assessment of patients after surgery.

BACKGROUND: Nasal continuous positive airway pressure is frequently used to support preterm infants with respiratory distress syndrome. Little is known about the hemodynamic changes that occur, particularly during the weaning phase when lung compliance has improved and most of the airway pressure can be transmitted to the heart and major blood vessels. METHODS: We conducted a prospective study on preterm infants (gestational age <or=32 weeks) with resolving respiratory distress syndrome, who were receiving nasal continuous positive airway pressure of 5 cm H(2)O and 21% oxygen. While cycling nasal continuous positive airway pressure, we performed 2-dimensional M-mode and pulsed Doppler echocardiography on all infants during nasal continuous positive airway pressure and 1 hour after being off nasal continuous positive airway pressure. RESULTS: A total of 25 preterm infant were studied. The use of nasal continuous positive airway pressure significantly decreased right ventricular output (320 +/- 22.7 vs 410.5 +/- 44.1 mL/kg per min); right ventricular end diastolic diameter (6 +/- 0.7 vs 6.4 +/- 0.4 mm), left ventricular end diastolic diameter (11.6 +/- 0.9 vs 13.6 +/- 0.7 mm), left ventricular end systolic diameter (7.1 +/- 0.6 vs 8.3 +/- 0.4 mm), left atrial diameter (6.3 +/- 0.5 vs 8 +/- 0.5 mm), aortic root diameter (6.4 +/- 0.3 vs 6.6 +/- 0.4 mm), superior vena cava flow (70.2 +/- 8.5 vs 91.1 +/- 4 mL/kg per minute), and pulmonary maximum velocity (0.6 +/- 0.1 vs 0.7 +/- 0.1 m/seconds). It significantly increased mean inferior vena cava diameter (4.3 +/- 0.5 vs 3.5 +/- 0.6 mm), whereas nasal continuous positive airway pressure did not influence left ventricular output, aortic maximum velocity, fractional shortening, heart rate, or mean arterial blood pressure. Changes associated with nasal continuous positive airway pressure were similar in infants with (n = 8) and without (n = 17) patent ductus arteriosus. CONCLUSIONS: In infants with resolving respiratory distress syndrome, nasal continuous positive airway pressure can impede systemic and pulmonary venous return, but it does not compromise systemic arterial pressure or heart rate. It is not clear whether the degree of these hemodynamic changes can affect the success of weaning off nasal continuous positive airway pressure.

INTRODUCTION: This study was conducted to determine characteristics of Candida colonization and candidemia in the pediatric intensive care unit (PICU) of a tertiary care children's hospital. METHODOLOGY: Patients between 6 months and 15 years of age consecutively admitted to the PICU of Mansoura University Children's Hospital in Mansoura, Egypt, during one year period, were evaluated for Candida colonization and candidemia. Susceptibility of Candida species isolated from blood to fluconazole and amphotericin B was determined by Etest. RESULTS: Sixty-six patients without prior fluconazole prophylaxis had 88 episodes of candidemia, representing 19% of all cases with blood stream infections (BSIs). Candida albicans (CA) and non-albicans Candida (NAC) species accounted for 40% and 60% of candidemia episodes respectively. C. parapsilosis, C. tropicalis, and C. glabrata accounted for 25%, 17%, and 8% of NAC candidemias respectively. Fluconazole resistance was detected in 11.4% and 18.9% of CA and NAC isolates respectively. Of the fluconazole resistant NAC isolates, four were C. krusei. Amphotericin B resistance was detected in 17% of NAC isolates. Candida colonization was detected in 78.8% of patients. Compared to CA candidemia, higher risk for NAC candidemia was associated with age older than 1 year, Candida isolation from endotracheal tube (ETT) and from central venous catheter. Mortality rate was 42.4%, attributable mortality of candidemia was 16.7%. Regression analysis showed that the most significant independent predictors of death were ETT and mechanical ventilation (MV), MV longer than 7 days, and candiduria. CONCLUSIONS: This study presents important epidemiological features of Candida BSIs in a non-neonatal population.

INTRODUCTION: The COVID-19 pandemic resulted in quarantine/lockdown measures in most countries. Quarantine may create intense psychological problems including post-traumatic stress disorder (PTSD) especially for the vulnerable critically developing children/adolescents. Few studies evaluated PTSD associated with infectious disasters but no Saudi study investigated PTSD associated with COVID-19 in children/adolescents. This study was undertaken to screen for PTSD in children/adolescent in Saudi Arabia to identify its prevalence/risk factors during COVID-19 pandemic and its quarantine. METHODS: A cross-sectional survey was conducted after 2 months form start of quarantine for COVID-19 pandemic utilizing the original English version and an Arabic translated version for the University of California at Los Angeles Brief COVID-19 Screen for Child/Adolescent PTSD that can be parent-reported or self-completed by older children/adolescents. Participants (Saudi citizens/non-Saudi residents) were approached online via social media. RESULTS: Five hundred and thirty seven participants were enrolled. The participants were 262 boys and 275 girls with a mean age of 12.25±3.77 years. Symptoms of no, minimal, mild and potential PTSD were identified in 15.5%, 44.1%, 27.4% and 13.0% of children/adolescents, respectively. The age, gender, school grade, and residence were not predictive of PTSD symptoms. Univariate analysis of risk factors for PTSD revealed that work of a close relative around people who might be infected was significantly different between groups of PTSD symptoms, but this difference disappeared during multivariate analysis. Children/adolescents of Saudi citizens had significantly lower median total PTSD score than children/adolescents of expatriate families (p = 0.002). CONCLUSION: PTSD associated with the COVID-19 and its resultant quarantine shouldn't be overlooked in different populations as it is expected in a considerable proportion of children/adolescents with variable prevalence, risk factors and severity. Parents/healthcare providers must be aware of PTSD associated with COVID-19 or similar disasters, so, they can provide children/adolescent with effective coping mechanisms.

OBJECTIVES: To assess myocardial performance in septic full-term infants and to correlate it with serum cardiac troponin T concentrations. DESIGN: Prospective, case-control, clinical study. SETTING: Neonatal intensive care unit in a university hospital. PATIENTS: Twenty septic and 20 nonseptic full-term neonates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Conventional echocardiography, tissue Doppler imaging, and serum cardiac troponin T concentration tests were performed as soon as diagnosis was made. On tissue Doppler imaging measurements, right ventricular and left ventricular Tei indexes were significantly higher in septic neonates compared to nonseptic neonates (mean ± SD: 0.51 ± 0.09 vs. 0.28 ± 0.05, p < .001, and 0.56 ± 0.07 vs. 0.39 ± 0.04, p < .001, respectively). Mitral and tricuspid peak annular systolic velocities were significantly lower in septic neonates (mean ± SD: 4.35 ± 0.68 vs. 6.89 ± 0.94 cm/sec, p < .0001, and 5.55 ± 0.66 vs. 6.69 ± 0.87 cm/second, p < .0001, respectively). On conventional echocardiography measurements, left ventricular internal diameter at end-diastole was significantly higher in septic neonates (p = .04), whereas cardiac index and left ventricular and right ventricular diastolic functions were not significantly different between septic and nonseptic neonates. Cardiac troponin T concentrations were significantly higher in septic neonates (median [range], 0.19 [0.12- 0.32] vs. 0.03 [0-0.07] mg/L, p < .0001), and they correlated positively with left ventricular Tei index (r = .80; p < .0001) and right ventricular Tei index (r = .73; p < .0001), and correlated negatively with mitral peak annular systolic velocity (r = -.70; p < .0001) and tricuspid peak annular systolic (r = -.39, p = .012). Nonsurvivors had significantly higher serum cardiac troponin T concentrations and left ventricular Tei index. CONCLUSIONS: Neonatal sepsis is associated with systolic and diastolic myocardial dysfunction. This study provides proof-of-concept data for the use of tissue Doppler imaging in assessment of myocardial dysfunction in septic neonates. Tissue Doppler imaging appears to be more sensitive than conventional echocardiography in the detection of this dysfunction. Serum cardiac troponin T and left ventricular Tei index may have prognostic value in these patients.

Identifying genes linked to extreme phenotypes in humans has the potential to highlight biological processes not shared with all other mammals. Here, we report the identification of homozygous loss-of-function variants in the primate-specific gene ZNF808 as a cause of pancreatic agenesis. ZNF808 is a member of the KRAB zinc finger protein family, a large and rapidly evolving group of epigenetic silencers which target transposable elements. We show that loss of ZNF808 in vitro results in aberrant activation of regulatory potential contained in the primate-specific transposable elements it represses during early pancreas development. This leads to inappropriate specification of cell fate with induction of genes associated with liver identity. Our results highlight the essential role of ZNF808 in pancreatic development in humans and the contribution of primate-specific regions of the human genome to congenital developmental disease.