Pneumatocele-induced pneumothorax after COVID-19 infection in a 45-day-old infant.

Throughout the literature, many pathologic lung lesions and complications following coronavirus disease 2019 (COVID-19) infection have been reported including pneumatocele formation which could potentially lead to pneumothorax development. This case report discusses the clinical course of a 45-day-old male with respiratory distress, whose condition worsened over time. Investigations revealed elevated COVID-19 immunoglobulin G (IgG) antibodies with negative COVID polymerase chain reaction (PCR) accompanied by radiologic evidence of pneumatocele formation, which was further complicated by pneumothorax. The clinical presentation of the patient was consistent with post-COVID infection but he had no history of contact with a sick individual which prompted further investigation of the source of the infection. Upon reviewing the history of the mother, symptoms consistent with COVID-19 around 32 weeks of pregnancy were revealed, which raises the possibility of maternal-fetal exchange of COVID-19 infection. This article presents the youngest reported patient with COVID-19 pneumonia that led to pneumatocele formation.

Pericardial effusion complicated by umbilical vein catheter in a preterm infant with respiratory distress syndrome: A case report.

Respiratory distress syndrome (RDS) is the most common respiratory illness in premature infants. This syndrome is characterized by a deficiency in surfactant, necessary for proper lung function. Serious complications of RDS include pericardial effusion and pulmonary hypertension. Although pericardial effusion is a rare complication of RDS, it is potentially fatal if not treated. The most common cause of pericardial effusion (PCE) is the placement of a central venous catheter (CVC), a widely used procedure in neonatal intensive care unit to support premature infants. In this paper, we report a case of a 36 + 4 weeks preterm male infant presenting for RDS. During his hospital stay, at 24 hours of life, the patient started to develop bradycardia where he was intubated. After 48 hours of birth, a central venous catheter was inserted, and on echocardiography results showed pericardial effusion, and pulmonary hypertension.

Erratum: Rotavirus Genotypes and Vaccine Effectiveness from a Sentinel, Hospital-Based, Surveillance Study for Three Consecutive Rotavirus Seasons in Lebanon.

[This corrects the article DOI: 10.1371/journal.pone.0161345.].

Wide Variability in the Sensitivity and Specificity of Rotavirus Immunoassay Diagnostic Kits in Practice.

INTRODUCTION: Most hospitals rely on rapid antigen-detection kits for the diagnosis of rotavirus infection. Several small studies reviewed the sensitivity and specificity of some of these kits. These studies showed discrepancy in results obtained for sensitivity and specificity that varied according to the type of kit used, area of study, and type of test used as standard for diagnosis of rotavirus infection. The objective of the study is to determine the sensitivity and specificity of five commonly used rotavirus immunoassay kits in comparison to RT-PCR as standard. METHODOLOGY: Stool samples (N = 1,414) collected from children under 5 years of age hospitalized with gastroenteritis were tested for rotavirus by immunoassay kits and RT-PCR in a prospective hospital-based surveillance study conducted at 7 centers in Lebanon. Concordance and discrepancy between the two methods was used to calculate sensitivity and specificity, using RT-PCR as the "gold standard". RESULTS: The sensitivity and specificity were respectively 95.08% and 86.62% for the SD Bioline® (Standard Diagnostics, Inc, South Korea) kit calculated on 645 samples, 65.86% and 45.90% for the VIROTECT® (Trinity Biotech, Ireland) kit calculated on 327 samples, 83.9% and 64.2% for the Rota-Strip (C-1001) (Coris Bioconcept, Belgium) calculated on 95 samples, 52.3% and 10.9% for the Acon® (Acon Laboratories, Inc, California, USA) kit calculated on 122 samples, 68.1% and 20% for the VIKIA® Rota-Adéno (Biomerieux, France) kit calculated on 32 samples. CONCLUSION: A wide discrepancy was detected between the calculated and advertised sensitivity and specificity for most of the kits.

Hawkinsinuria With Direct Hyperbilirubinemia in Egyptian-Lebanese Boy.

Tyrosinemia type III is the rarest type of tyrosinemia, because of a mutation in 4-OH-phenylpyruvate dioxygenase (HPD). This causes two different types of diseases with different modes of inheritance: tyrosinemia type III and hawkinsinuria. Hawkinsinuria is an autosomal dominant disease, which presents a failure to thrive and metabolic acidosis; however, the liver is not affected. P.A33T heterozygous mutation was reported by Tomoeda et al. to cause hawkinsinuria. This case report will present the first case of an Egyptian-Lebanese male who developed direct hyperbilirubinemia and was found to have tyrosinemia type III, due to elevated tyrosine levels in the blood and tyrosine derivatives in the urine, but genetic testing revealed a P.A33T heterozygous mutation, a cause of hawkinsinuria.

The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population.

BACKGROUND: The past few decades have witnessed a tremendous development in the field of genetics. The implementation of next generation sequencing (NGS) technologies revolutionized the field of molecular biology and made the genetic information accessible at a large scale. However, connecting a rare genetic variation to a complex phenotype remains challenging. Indeed, identifying the cause of a genetic disease requires a multidisciplinary approach, starting with the establishment of a clear phenotype with a detailed family history and ending, in some cases, with functional assays that are crucial for the validation of the pathogenicity of a mutation. METHODS: Two hundred Lebanese patients, presenting a wide spectrum of genetic disorders (neurodevelopmental, neuromuscular or metabolic disorders, etc.), sporadic or inherited, dominant or recessive, were referred, over the last three and a half years, to the Medical Genetics Unit (UGM) of Saint Joseph University (USJ). In order to identify the genetic basis of these diseases, Whole Exome Sequencing (WES), followed by a targeted analysis, was performed for each case. In order to improve the genetic diagnostic yield, WES data, generated during the first 2 years of this study, were reanalyzed for all patients who were left undiagnosed at the genetic level. Reanalysis was based on updated bioinformatics tools and novel gene discoveries. RESULTS: Our initial analysis allowed us to identify the specific genetic mutation causing the disease in 49.5% of the cases, in line with other international studies. Repeated WES analysis enabled us to increase the diagnostics yield to 56%. CONCLUSION: The present article reports the detailed results of both analysis and pinpoints the contribution of WES data reanalysis to an efficient genetic diagnosis. Lessons learned from WES reanalysis and interpretation are also shared.

The effect of regional anaesthesia versus general anaesthesia on behavioural functions in children.

PURPOSE: The primary objective was to assess the effect of general anaesthesia versus regional anaesthesia in a single exposure before the age of 2 years on the development of long-term behavioural changes in children. METHODS: The study was conducted between January 2014 and March 2015. Medical records of eligible children were reviewed. Then, parents of children who were included in the study were contacted and asked to visit the Outpatient Department to fill the Eyberg Child Behaviour Inventory questionnaire to measure behavioural changes in children. Children who were exposed to regional or general anaesthesia for surgery between January 2002 and December 2006 were included. Data collected were age and weight at the time of the first anaesthesia exposure and surgery duration. Chi-square test, t-test and multivariate analysis were used. RESULTS: In total, 394 children were exposed to anaesthesia before the age of 2 years. Among the 168 patients who were exposed to general anaesthesia, 44 children (26.2%) developed behavioural abnormalities compared to 12 out of 226 patients (5.3%) who were exposed to regional anaesthesia (P-value<0.0001). Exposure to anaesthesia before age of 2 years increases the risk of developing behavioural disorder when surgery is accompanied by general anaesthesia, younger age at time of exposure, and longer surgery duration (P-value<0.0001, 0.001, 0.038 respectively). CONCLUSION: Regional anaesthesia showed much lesser effect on children's behaviour compared to general anaesthesia. The incidence of behavioural disorder is increased with the use of general anaesthesia, younger age of the patient at time of exposure, and longer surgery duration.

Contribution of next generation sequencing in pediatric practice in Lebanon. A Study on 213 cases.

BACKGROUND: According to the Catalogue of Transmission Genetics in Arabs, less than half of diseases reported in Lebanese patients are mapped. In the recent years, Next Generation Sequencing (NGS) techniques have significantly improved clinical diagnosis, compared to traditional sequencing methods. METHODS: A total of 213 analyses by NGS (167 by whole exome sequencing (WES) and 46 by multigene panels tests) were performed on pediatric patients across different regions of Lebanon over a period of two years (December 2015-December 2017). RESULTS: Neurological disorders were the most frequent referral demand for both WES and gene panels (122/213). Pathogenic, likely pathogenic, or variants of unknown significance were identified in 69.5% of the WES and panel patients combined. Over half of the patients with such variants had an autosomal recessive disorder. A definite molecular diagnosis (pathogenic or likely pathogenic variants) was achieved in 34.1% and 47.8% of the patients studied by WES and the multigene panels, respectively. Thirty-three novel variants were found in the cases that were molecularly solved; 26 of these being identified by WES and seven by the multigene panels. In three consanguineous families, autosomal recessive inheritance of genes previously reported as showing dominant inheritance patterns were found. Biallelism was found in six cases, digenism in four cases, and one case was trigenic. CONCLUSION: Our study thus suggests that NGS tools are valuable for an improved clinical diagnosis, and highlights that the increased adoption of such techniques will significantly further improve our understanding of the genetic basis of inherited diseases in Lebanon.

Low rate of human papillomavirus vaccination among schoolgirls in Lebanon: barriers to vaccination with a focus on mothers' knowledge about available vaccines.

BACKGROUND: Human papillomavirus (HPV) infection is an established predisposing factor of cervical cancer. In this study, we assessed the awareness about genital warts, cervical cancer, and HPV vaccine among mothers having girls who are at the age of primary HPV vaccination attending a group of schools in Lebanon. We also assessed the rate of HPV vaccination among these girls and the barriers to vaccination in this community. SUBJECTS AND METHODS: This is a cross-sectional, school-based survey. A 23-item, self-administered, anonymous, pretested, structured questionnaire with closed-ended questions was used to obtain data. The questionnaire was sent to the mothers through their student girls, and they were asked to return it within a week. Data were analyzed using the Statistical Package for Social Sciences version 21.0. Bivariate analysis was performed using the chi-square test to compare categorical variables, whereas continuous variables were compared using the Student's t-test. Fisher's exact test was used when chi-square test could not be employed. RESULTS: The response rate in our survey was 39.4%. Among the responders, the rate of awareness about HPV infection was 34%, where 72% of the mothers had heard about cervical cancer, and 34% knew that a vaccine is available to prevent cervical cancer. HPV vaccination uptake rate was 2.5%. This lack of vaccination was primarily attributed to the low rate of mothers' awareness about the vaccine (34%). Factors significantly affecting awareness about the vaccine were the mothers' marital age, nationality, level of education, employment, and family income. Barriers to HPV vaccination, other than awareness, were uncertainty about safety or efficacy of the vaccine, conservative ideas of mothers regarding their girls' future sexual life, and relatively high price of the vaccine. CONCLUSION: Vaccine uptake is low among eligible girls attending this group of schools. The barriers to vaccination are multiple; the most important one is the mothers' lack of knowledge about HPV, cervical cancer, and the modes of prevention. Awareness campaigns along with a multimodal strategy that targets the identified barriers would be recommended to achieve higher rates of HPV vaccination.

Case report: Guillain-Barre syndrome with pneumococcus - A new association in pediatrics.

Guillain-Barre Syndrome, an acute flaccid paralysis known to be caused by recent Gastro-intestinal infections mainly campylobacter, and Respiratory infections mainly mycoplasma pneumoniae and influenza. One reported case of severe invasive pneumococcal disease in a 68 year old female, that presented with Austrian's triad of meningitis, pneumonia and endocarditis, and progressed to develop Guillain Barre syndrome, an association never been documented before. We present a case of 13 year old male, presented with hypoactivity and inability to bare his own weight, developed septic shock due to pneumococcus with Acute Respiratory Distress Syndrome, and was found to have neurological findings of Guillain-Barre Syndrome. A new association in pediatric age group, never been reported before.

Homozygous microdeletion of the ERI1 and MFHAS1 genes in a patient with intellectual disability, limb abnormalities, and cardiac malformation.

A male child, born from consanguineous parents and having intellectual disability, short stature, dysmorphic facial features, synpolydactyly, and cardiac malformations is reported. Chromosomal microarray analysis showed that the patient presents with an 8p23.1 homozygous deletion, containing the microRNA miR-4660, the exoribonuclease 1 (ERI1), and malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) genes. The microRNA miR-4660 has no known function. MFHAS1 is an immunomodulatory protein involved in Toll-like receptor signaling, erythropoiesis, and cancer. ERI1 is a ribonuclease involved in RNA metabolism and is required for the correct patterning of the skeleton by defining the HOXC8 expression. We discuss the involvement of these deleted genes to the patient's features and highlight differential diagnoses with syndromes implicating limb extremity abnormalities such as synpolydactyly, including the monosomy 8p.

Seven-Digit Creatine Kinase in Acute Rhabdomyolysis in a Child.

Rhabdomyolysis is an acute life-threatening condition that can occur in childhood secondary to many causes. The authors report the case of a 3-year-old male child who presented with acute rhabdomyolysis. The peak plasma creatine kinase level was extremely high. The 2 main causes of rhabdomyolysis in childhood are viral myositis and trauma, which can sometimes lead to acute renal failure. The highest creatine kinase levels reported in the literature so far was a 6-digit level in 2014 case report. In this study, the authors report the case of a 7-digit creatine kinase level in a child secondary to viral myositis who did not require renal dialysis.

Characterization of astrovirus-associated gastroenteritis in hospitalized children under five years of age.

PURPOSE: The aim of this study was to determine the incidence and genetic diversity of astrovirus (AstV) detected in children hospitalized for gastroenteritis (GE). METHODS: A multi-center, hospital-based surveillance study was conducted across Lebanon to investigate the incidence of AstV among diarrheal hospitalizations. Viral RNA was extracted from stool samples collected between 2011 and 2013 from children, below the age of 5years, hospitalized for GE at six medical centers across Lebanon. Demographic and clinical data were collected and analyzed. RNA of eligible samples (n=739) was screened by two AstV-specific PCR assays followed by genotype-specific PCR. Sanger sequencing and phylogenetic analysis were performed for genotypic characterization. RESULTS: Overall, 5.5% (41/739) of rotavirus-negative stool samples collected from hospitalized children <5years old tested positive for AstV infection. AstV infections were detected all year long. Diarrhea, dehydration, vomiting and fever were the most common symptoms associated with AstV infections. Children aged 48-59months had the highest incidence of AstV. Using the Vesikari Scoring System to assess clinical severity, 85.4% of children with AstV had a score>11, indicating severe GE. Genotype-specific PCR identified 22 classical and 4 MLB-like AstV specimens. Further sequencing and phylogenetic analysis of orf1b and orf2 genes revealed that AstV classical 1-3, 5, 6, and 8, MLB-1, VA-1 and -2 genotypes circulated in Lebanon. Recombination between classical AstV strains was detected in several cases as evident by the lack of congruency in the tree topologies of the orf1b and orf2. Two cases of mixed infections between classical and non-classical genotypic strains were recorded. CONCLUSION: High genetic diversity was detected among AstVs in Lebanon. AstVs are associated with 5.5% of non-rotavirus GE-associated hospitalizations in children under five years in Lebanon.

The effect of IV dexamethasone versus local anesthetic infiltration technique in postoperative nausea and vomiting after tonsillectomy in children: A randomized double-blind clinical trial.

BACKGROUND: Local anesthetic infiltration and corticosteroids had shown effectiveness in reducing post tonsillectomy nausea, vomiting and pain. OBJECTIVES: To compare the effect of intravenous dexamethasone versus pre-incision infiltration of local anesthesia in pediatric tonsillectomy on postoperative nausea and vomiting (PONV). The secondary objective was postoperative pain. METHODS: A randomized double-blind clinical trial was conducted at a tertiary care teaching hospital. Children admitted to undergo tonsillectomy aged between 4 and 13 years from January 2015 to August 2015 were enrolled and divided into two groups. Both groups had general anesthesia. Group I received intravenous dexamethasone 0.5 mg/kg (maximum dose 16 mg) with placebo pre-incision infiltration. Group II received pre-incision infiltration a total of 2-4 ml local anesthesia mixture with saline and an equivalent volume of intravenous saline. RESULTS: Group I consisted of 64 patients while group II had 65 patients. In the PACU, 15.6% of patients in group I experienced vomiting compared to 3.1% in group II (p-value = 0.032). After 24 h, the incidence of PONV was significantly higher in group I compared to group II (26.6% vs. 9.2% respectively, p-value = 0.019). At 48 h postoperatively, PONV was significantly higher in group I (p-value = 0.013). The incidence was similar in both groups after three, four and five postoperative days. Baseline pain and pain during swallowing were significantly different at 6, 12 and 24 h as well as days 1 through 5. Pain upon jaw opening was significantly different at 6, 12 and 24 h between the two groups. Pain while eating soft food was significantly different at 24 h and days 2 through 5. In the PACU, 20.3% of patients in group I received diclofenac compared to 3.1% in group II (p-value = 0.005). From day 1 till day 5, analgesic consumption was significantly higher in group I. CONCLUSION: Local anesthetic infiltration in addition to NSAIDS and paracetamol could serve as a multimodal analgesia and decrease PONV. TRIAL REGISTRATION: NCT02355678.

Nerve stimulator-guided pudendal nerve block vs general anesthesia for postoperative pain management after anterior and posterior vaginal wall repair: a prospective randomized trial.

STUDY OBJECTIVE: Compare the effectiveness of nerve stimulator-guided pudendal nerve block (PNB) vs general anesthesia (GA) for anterior and posterior (AP) colporrhaphy in terms of pain relief and analgesic consumption within 24 and 48 hours postoperatively. DESIGN: Prospective randomized trial. PATIENTS: Fifty-seven patients whose ages ranged between 20 and 53 years scheduled to undergo AP colporrhaphy due to the presence of cystorectocele. INTERVENTIONS: Patients were randomly assigned into 2 groups receiving either nerve stimulator-guided PNB (n = 28) or GA (n = 29). A total volume of 0.7 mL/kg of the local anesthetic mixture was injected at 4 sites. MAIN RESULTS: Both groups were similar with respect to age, weight, height, and surgery duration. There was a significant difference in average pain scores within the first and second postoperative days (P values = .005 and .004, respectively). Total analgesic consumption (ketoprofen and tramadol) was significantly lower in the PNB within the first (P values = .018 and .010) and second postoperative days (P values = .041 and .011), respectively. Return to normal daily activity was significantly (P< .0001) shorter in the PNB group compared with the GA group (3.6 days vs 12.2 days). A total of 71.4% of the patients in the PNB group were satisfied compared with 27.8% in the GA group (P< .0001). Surgeon satisfaction was significantly higher in the PNB group (82.1% vs 34.5%, P< .0001). CONCLUSION: This randomized controlled trial demonstrated that nerve stimulator-guided PNB could be used as an alternative to GA for AP repair of stages I and II prolapse because it is associated with less postoperative pain and analgesic consumption, in addition to shorter duration of recovery.

Mutations in pyrin masquerading as a primary immunodeficiency.

Whole exome sequencing is increasingly used in the diagnosis of primary immunodeficiencies due to the overlapping and atypical presentations of these disorders. We report two patients who presented with recurrent infections and early onset colitis. They were investigated by whole exome sequencing due to suspicion of primary immunodeficiency and found to have mutations in pyrin known to cause familial Mediterranean fever.

Rotavirus Genotypes and Vaccine Effectiveness from a Sentinel, Hospital-Based, Surveillance Study for Three Consecutive Rotavirus Seasons in Lebanon.

INTRODUCTION: Globally, rotavirus (RV) is the leading cause of gastroenteritis (GE) in children. Longitudinal data about changes in RV genotype distribution and vaccine effectiveness (VE) are scarce. This study was conducted in Lebanon over 3 consecutive RV seasons to estimate the rate of RVGE hospitalization, identify RV genotypes, determine the seasonal and geographical variations, and calculate RV VE. MATERIALS AND METHODS: This prospective, multicenter, hospital-based surveillance study was conducted between 2011 and 2013 and enrolled children (<5 years) admitted for GE. Socio-demographic and clinical data about the current episode of GE at admission were collected. Genotypes were determined from stool samples testing positive for RV by PCR. RESULTS: Of 1,414 cases included in the final analysis, 83% were <2 years old and 55.6% were boys. Median duration of hospitalization was 4 days and 91.6% of GE cases were severe (Vesikari score ≥11). PCR testing showed that 30.3% of subjects were RV-positive of which 62.1% had fever versus 71.1% of RV-negative subjects (P = 0.001). RV was predominantly detected in the cold season from November till March (69.9%). G and P genotype pairs for all RV-positive stool specimens showed a predominance of G1P[8] in 36% (n = 154) of specimens, G9P[8] in 26.4% (n = 113), and G2P[4] in 17.8% (n = 76). RV-negative subjects were more likely to be RV-vaccinated (21%) compared to the RV-positive subjects (11.3%) (P<0.001), with a vaccine breakthrough rate of 18.8%. The ratio of RV1-vaccinated for each RV5-vaccinated subject was 7.8 and VE against RV disease was 68.4% (95%CI, 49.6%-80.2%). CONCLUSION: RV is a major cause of GE requiring hospitalization of children under 5 years of age in Lebanon. A few genotypes predominated over the three RV seasons studied. Mass RV vaccination will likely decrease the burden of hospitalization due to RV. VE is similar to what has been observed for other middle-income countries.

A Rare Case of Congenital Ranula in an Infant.

Ranula is a mucus extravasation cyst originating from the sublingual gland on the floor of the mouth. Congenital ranula is very rare. We report a case of a 4-month-old girl with a congenital ranula in the floor of mouth. The ranula was treated first by marsupialization, but the cyst recurred after 1 week. Excision of the ranula was done and was successful.

Clinical and epidemiological characteristics of norovirus gastroenteritis among hospitalized children in Lebanon.

AIM: To assess the burden of norovirus (NoV) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS: Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software. RESULTS: Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for NoV genogroups I (GI) and II (GII). GII accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GI (0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GI gastroenteritis cases were designated GI.3 and one case as GI.4. GII.4 was predominantly detected in stool of our study participants (68%). We report a JB-15/KOR/2008 GII.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GII.4 Sydney 2012 and Sydney 2012/FRA GII.4 strains. We also report the co-circulation of non-GII.4 genotypes among hospitalized children. Our data show that NoV gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months. CONCLUSION: The majority of NoV-associated viral gastroenteritis cases among our participants are attributable to GII.4, which is compatible with results reported worldwide.

Spectrum of Phenotypes Associated with Mutations in LRBA.

To date, several germline mutations have been identified in the LRBA gene in patients suffering from a variety of clinical symptoms. These mutations abolish the expression of the LRBA protein, leading to autoimmunity, chronic diarrhea, B-cell deficiency, hypogammaglobulinemia, functional T-cell defects and aberrant autophagy. We review the clinical and laboratory features of patients with LRBA mutations and present five novel mutations in eight patients suffering from a multitude of clinical features.