A Unique Mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene Causing Cystic Fibrosis in a Pakistani Child: A Case Highlighting the Need for More Awareness.

Cystic fibrosis (CF) is a recessively inherited disease most commonly seen in Caucasians. The mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for the condition, and to date, more than 2000 mutations have been published in the literature. The most common mutation worldwide is F508del. Here, we reported a five-year-old child who presented to the clinic with a chronic cough. Her newborn screening for CF was negative, including 139 mutation panels done in India. The sweat chloride test was positive, and CF gene sequencing was reported as c.2489dup p. (Glu831GLYFS *5) homozygotes mutation in the CFTR gene (Online Mendelian Inheritance in Man (OMIM) *602421). To the best of our knowledge, this gene was first described and published in the literature.

Effect of intravenous lipid therapy in critically ill pediatric patients with calcium channel blocker toxicity.

BACKGROUND: Overdose with calcium-channel blockers (CCBs) still maintain their importance with a high lethality rate after exposure. We report the intravenous lipid emulsion therapy (ILE) therapy in our CCB overdose patients. METHODS: We retrospectively analyzed the records of 6 patients with CCB intoxication from Batman Training and Research Hospital PICU between March 2021 and September 2022. Patients aged 0-18 years who received ILE treatment for CCB poisoning were included. RESULTS: All six patients ingested CCB with the intention of committing suicide and were followed up in the pediatric intensive care unit (PICU). All patients received ILE therapy due to hemodynamic instability despite intravenous fluid boluses, calcium, glucagon, insulin-dextrose, and vasoactive agents. Vasoactive-Inotropic Score (VIS) decreased after ILE treatment. All patients were transferred from the PICU after recovery. CONCLUSIONS: ILE therapy should be kept in mind as a salvage therapy in hemodynamically unstable CCB poisoning cases that do not respond to initial and advanced options.

Indications, Efficacy, and Complications of Pediatric Bronchoscopy: A Retrospective Study at a Tertiary Center.

Background Bronchoscopy is an essential procedure for evaluating, diagnosing, and treating pediatric respiratory diseases. In this study, we demonstrate the indications and contraindications of bronchoscopy done in a tertiary referral hospital, Al Qassimi Woman's and Children's Hospital (AQWCH) in Sharjah, United Arab Emirates (UAE), in order to achieve better service. This study aims to evaluate patients' characteristics, diagnostic and therapeutic indications, and complications of bronchoscopy. Material and method This retrospective chart review included children aged between one day and 13 years, admitted to AQWCH, who underwent bronchoscopy (rigid or flexible) procedures between January 2018 and December 2019. All patients were identified by using a computerized search of hospital discharge diagnosis, which was codified as "pediatric bronchoscopy, flexible, rigid, bronchoalveolar lavage". The main study outcome measure was to evaluate patients' characteristics, diagnostic or therapeutic indications, bronchoalveolar lavage (BAL) analysis, as well as complications of bronchoscopy at AQWCH.  Results There were 72 pediatric bronchoscopies (rigid and flexible) performed in patients aged less than 13 years old; the reason for bronchoscopy procedure was diagnostic in 51% and both diagnostic and therapeutic in 49%. Cough was the most common symptom (n=53; 74%), and chest recession was the most common clinical finding (n=46; 64%). Foreign body aspiration was the main indication (n=23; 32%), followed by stridor (26%). Consolidation was the most common radiological finding. Foreign body was the common finding, seen in 25% of bronchoscopies, followed by tracheomalacia in 17%. The suspected diagnosis was confirmed in 89%, and management change was needed in 54% of patients. The main complication during the procedure was desaturation (26%), and cough was the main post-bronchoscopy complication (14%). BAL was done for 28 (39%) patients, in which BAL culture was positive in 75%. Rigid bronchoscopy was done when foreign body aspiration was suspected based on positive history in 70%, abnormal physical examination in 60%, and chest X-ray abnormalities in 39% of patients. Sensitivity and specificity for patient history, physical examination, and chest X-ray were 80% and 83%, 66% and 60%, and 40% and 66 %, respectively. Conclusion Bronchoscopy is an important tool for evaluating, diagnosing, and treating pediatric respiratory diseases. While it is a safe procedure, it still needs a careful selection of patients as it is invasive.

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) in a Middle Eastern patient cohort.

OBJECTIVE: This is a comprehensive characteristic study of Kawasaki disease (KD) and Multi system inflammatory syndrome in children (MIS-C) in the Middle East that creates a formula to differentiate between the two. METHODS: We conducted a descriptive comparative study of KD and MIS-C in the United Arab Emirates. Retrospective MIS-C and KD cohorts were recruited between January 2017 until August 2021.We compared clinical and laboratory characteristics between both groups. Our data were compared with 87 patients with KD or MIS-C from the literature. RESULTS: We report on123 patients. Sixty-seven (54%) met the criteria for KD (36 male, 43 Arab), and fifty-six (46%) met the criteria for MIS-C (28 male, 35 Arab). The median age was 2.2 years range (0.15-10.7) in the KD group and 7.3 years (0.7-15.2) in the MIS-C group (P < 0.001). The clinical features on admission showed an increase in gastrointestinal manifestations in MIS-C compared with KD (84% vs. 31%, P < 0.001). Laboratory tests on admission revealed a significant increase in the following tests in KD compared with MIS-C; white blood cells (mean 16.30 10(3) µcL vs. 11.56 10(3) µcL, P < 0.001), absolute neutrophils (mean 10.72 10(3) µcL vs. 8.21 10(3) µcL, P 0.008), absolute lymphocytes (mean 3.92 10(3) µcL vs. 2.59 10(3) µcL, P 0.003), erythrocyte sedimentation rate (mean 73 mm/hr vs. 51 mm/hr, P < 0.001) and platelets (median {390 10(3) µcL vs. 236 10(3) µcL, P < 0.001}). In contrast, procalcitonin and ferritin were increased in the MIS-C group (2.4 )ng/mL, 370 ng/mL; P < 0.001). Cardiac dysfunction and admission to the pediatric intensive care unit were higher in MIS-C than in KD (21% vs. 8% and 33% vs. 7.5%, respectively, P < 0.001). CONCLUSION: This study showed vast similarities between KD and MIS-C, suggesting that they lie along the same clinical spectrum. However, there are several differences between the two disease entities suggesting that MIS-C most likely represents a new severe variant of KD. Based on our findings in this study, we created a formula to differentiate between KD and MIS-C.

A Case of Coexistent Sarcoidosis and Tuberculosis: A Diagnostic Dilemma.

Sarcoidosis and tuberculosis (TB) are chronic granulomatous diseases with similar radiological, clinical, and histopathological presentations. Although rare, both conditions can coexist together. Case reports of concomitant incidence have been published in the literature. The classic manifestations of both diseases overlap, making it difficult for clinicians to reach a final diagnosis. While TB is responsible for the majority of necrotizing granuloma cases, necrotizing sarcoidosis should be considered a possible diagnosis, especially in the absence of mycobacterial antigen isolation or when a remarkable improvement isn't achieved after administering anti-tb medications. We report a rare case of a 12-year-old female exhibiting an atypical form of the granulomatous disease (concomitant incidence of tuberculosis and sarcoidosis), who presented with respiratory distress, cough, fever, weight loss, and generalized fatigue that was initially diagnosed as Tuberculosis which was supported by radiological and biological findings. Initially, the patient had shown some clinical improvement with anti-tubercular treatment, but nonetheless, she experienced progressively increasing mediastinal lymphadenopathy. Subsequently, she developed new granulomatous skin findings. Further investigations supported the diagnosis of coexisting sarcoidosis.

Subcutaneous Fat Necrosis of the Newborn After Whole-Body Cooling for Birth Asphyxia.

Therapeutic hypothermia (TH) is a challenging treatment for a neonate who suffers from hypoxic-ischemic encephalopathy. It has been shown to improve neurodevelopmental outcomes and survival in infants with moderate-to-severe hypoxic-ischemic encephalopathy. However, it has severe adverse effects such as subcutaneous fat necrosis (SCFN). SCFN is a rare disorder that affects term neonates. It is a self-limited disorder but can have severe complications such as hypercalcemia, hypoglycemia, metastatic calcifications, and thrombocytopenia. In this case report, we present a term newborn who developed SCFN after whole-body cooling.

Beyond the Local Basic Panel: Full CFTR Gene Analysis Identifies Novel CF Mutation Missed on Standard Testing in an Arabic Child.

Cystic fibrosis (CF) is an autosomal recessive disease caused by different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It is the most common inherited disorder in the Caucasian population, with around 2000 mutations identified for the CFTR gene. The precise prevalence of CF in Arab countries remains unknown, with the prevalence of F508 del found to be a common type with other endemic mutations. We describe the case of a CF patient who was diagnosed at the age of seven years. She presented post-cardiac surgery for further evaluation for a recurrent chest infection and subtle dysmorphic features. CF genetic testing for the most common 31 mutations (CF panel) was negative, and a novel mutation was identified on CFTR gene sequencing.

Bayesian Dynamic Borrowing of Historical Information with Applications to the Analysis of Large-Scale Assessments.

The purpose of this paper is to demonstrate and evaluate the use of Bayesian dynamic borrowing (Viele et al, in Pharm Stat 13:41-54, 2014) as a means of systematically utilizing historical information with specific applications to large-scale educational assessments. Dynamic borrowing via Bayesian hierarchical models is a special case of a general framework of historical borrowing where the degree of borrowing depends on the heterogeneity among historical data and current data. A joint prior distribution over the historical and current data sets is specified with the degree of heterogeneity across the data sets controlled by the variance of the joint distribution. We apply Bayesian dynamic borrowing to both single-level and multilevel models and compare this approach to other historical borrowing methods such as complete pooling, Bayesian synthesis, and power priors. Two case studies using data from the Program for International Student Assessment reveal the utility of Bayesian dynamic borrowing in terms of predictive accuracy. This is followed by two simulation studies that reveal the utility of Bayesian dynamic borrowing over simple pooling and power priors in cases where the historical data is heterogeneous compared to the current data based on bias, mean squared error, and predictive accuracy. In cases of homogeneous historical data, Bayesian dynamic borrowing performs similarly to data pooling, Bayesian synthesis, and power priors. In contrast, for heterogeneous historical data, Bayesian dynamic borrowing performed at least as well, if not better, than other methods of borrowing with respect to mean squared error, percent bias, and leave-one-out cross-validation.

A rare presentation of childhood interstitial lung disease attributed to KDM3B gene mutation: a case report.

Childhood Interstitial Lung Disease (chILD) encompasses various respiratory conditions affecting children's lung airspaces and tissues, with diverse causes. One rare cause involves structural vascular changes. We describe a case of a 10-year-old boy diagnosed with chILD who exhibited specific dysmorphic features, developmental delay, and intellectual disability. He was diagnosed with severe pulmonary arterial hypertension (PAH) due to venous thromboembolic disease, an unusual underlying condition for chILD. A Whole Exome Sequence showed mutations in KDM3B and SIN3A genes, respectively responsible for Diets-Jongmans syndrome (DIJOS) and Witteveen-Kolk syndrome (WITKOS). Both syndromes can explain our patient´s phenotype and KDM3B mutation has been previously described to be associated with PAH. Our case suggests a potential association between KDM3B mutation and PAH leading to chILD. It also enriches the knowledge of genotypic diversity in KDM3B and SIN3A genes as well as the spectrum of clinical associations with DIJOS and WITKOS syndromes.

A Retrospective Chart Review of Pediatric Complicated Community-Acquired Pneumonia: An Experience in the Al Qassimi Women and Children Hospital.

Background Community-acquired pneumonia (CAP) is one of the most common global health issues. Even though many vaccinations and new diagnostic tools are available, CAP has a higher mortality rate, especially in children less than five years of age. Complicated CAP (CCAP) in a healthy child is a severe disease characterized by a combination of local complications, such as parapneumonic effusion (PPE), empyema (EMP), necrotizing pneumonia (NP), abscess, pneumothorax, and bronchopleural fistula, and systemic complications, such as bacteremia, metastatic infection, multiorgan failure, acute respiratory distress syndrome, disseminated intravascular coagulation, and, rarely, death. This study describes the demographic features, clinical presentation, management, and outcomes of patients diagnosed with CCAP at the Al Qassimi Women's and Children's Hospital (AQWCH). Methodology This retrospective chart review aims to collect and explore the data of all previously healthy children admitted with CCAP between the ages of one month and 13 years at AQWCH from January 2018 to December 2020. The primary study outcome measure is to provide clinicians with the diagnostics, evaluation, and management required to treat complicated pneumonia. Results A total of 195 patients were diagnosed with CAP, of whom 30 (15.3%) were diagnosed with CCAP. Of these, 14 (46.6%) patients had NP, eight (26.7%) had PPE, and eight (26.7%) had EMP. The median age of patients was 2.5 years, with 13 (43%) males and 17 (57%) females. The median duration of their stay in the hospital was 16 days. All patients were vaccinated with Hib, PCV13, or PCV7, and 57% of the patients received antibiotics before admission. The most common findings were consolidation and pleural effusion. Blood culture was negative in all cases, and pleural culture was positive only in three cases. A total of 17 (57%) patients underwent video-assisted thoracoscopic surgery (VATS), and post-VATS surgical emphysema was found to be the most common complication. Chest X-rays normalized after three months in 65% of patients. On comparing patients who were admitted to the Pediatric Intensive Care Unit (PICU) before any surgical intervention with those who were not, it was found that patients who required PICU admission were young (median = 2 years; interquartile range (IQR) = 1-4.5; p = 0.044) and had higher respiratory rate (mean = 49 breaths/per minute, standard deviation (SD) = 11; p = 0.000). In addition, they had lower median albumin (median = 2 g/L; IQR = 1.8-2.23; p = 0.004). On comparing patients who required VATS and those who did not require VATS, it was found that the former had a higher median respiratory rate (48 per min; range = 42-54; p = 0.01). A cavity in the chest computed tomography (CT) was found in 86% of patients with VATS (p = 0.017), and they had lower median albumin (median = 2 g/L; IQR = 1.92-2.24; p = 0.012), as well as longer median duration of using oral antibiotics (median = 21 days; IQR = 19-26; p = 0.025). Patients with complicated NP had a higher respiratory rate and higher PICU admission, and more cavity in the chest was found in the CT study. Most NP patients also underwent VATS and had longer median days of using oral antibiotics. One patient developed a bronchopleural fistula, and one patient diagnosed with NP died. Conclusions CCAP is a major cause of hospitalization in children. It is important to suspect CCAP in all CAP patients not responding to treatment after 48-72 hours.

Nonspecific Interstitial Pneumonitis in a Child Associated With Hashimoto Thyroiditis.

Interstitial lung disease (ILD) is a rare disease defined as a specific type of chronic fibrosing interstitial pneumonitis whose effects are limited to the lung. Nonspecific interstitial pneumonia (NSIP) was defined as a histopathological form that can be seen in the presence of large different clinical and radiological features. The exact role of thyroid hormone in the pathogenetic mechanism of idiopathic interstitial pneumonitis (IIP) is unclear. But there is a suggestion that the thyroid hormone plays a role in pulmonary inflammation and fibrosis. In this case report, we described the presentation of NSIP which was associated with Hashimoto thyroiditis.

Prevalence and Time Course of Thiamine Deficiency in Critically Ill Children: A Multicenter, Prospective Cohort Study in Turkey.

OBJECTIVES: To determine the prevalence and time course of thiamine deficiency (TD) in PICU patients. DESIGN: Multicenter, prospective, cohort study between May 2019 and November 2019. SETTING: Three university-based tertiary care, mixed medical-surgical PICUs in Ankara, Turkey. PATIENTS: PICU patients 1 month to 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 476 patients and grouped them by TD status on days 1 and 3 of the PICU admission. There might be a risk of unintended bias since we excluded 386 patients because of the absence of consent, inadequate blood samples, loss of identifier information, and recent vitamin supplementation. On day 1, TD was present in 53 of 476 patients (11.1%) and median (minimum-maximum) thiamine levels were 65.5 ng/mL (5-431 ng/mL). On day 3, TD was present in 27 of 199 patients (13.6%) with repeated measurement. The median (minimum-maximum) thiamine levels were 63 ng/mL (13-357 ng/mL). The time course of TD from day 1 to day 3 in these 199 patients was as follows. In 21 of 199 patients (10.6%) with TD on day 1, 11 of 21 (52%) continued to have TD on day 3 and the other 10 of 21 patients (48%) improved to no longer having TD. In 178 of 199 patients (89.4%) without TD on day 1, 16 of 178 (9%) went on to develop TD by day 3, and the other 162 of 178 (91%) continued to have normal thiamine status. CONCLUSIONS: In the PICU population in three centers in Turkey, the prevalence of TD in the sample of patients was 11.1%. In those TD patients who had serial studies, we also identified that by day 3 some continued to be TD, and some patients improved to normal thiamine status. Of concern, however, is the population who develop TD over the course of PICU stay.

Are platelet indices promising ratios for predicting pediatric septic shock prognosis?

OBJECTIVES: The aim of the present study was to determine the prognostic value of thrombocytopenia, platelet indices (MPV/PLT and PDW/PLT) in children with septic shock. BACKGROUND: Septic shock is one of the major causes of mortality among children worldwide. METHODS: A retrospective analysis was made of children admitted to the pediatric intensive care unit between November 2010 and December 2019. Two hundred four children were included; they were diagnosed with septic shock according to the international pediatric sepsis consensus conference criteria. The MPV/platelet ratio and PDW/platelet ratios were estimated as the MPV and PDW values divided by the platelet count on the first three days of hospitalization. The clinical outcome was 28-day mortality. RESULTS: MPV/PLT and PDW/PLT ratios were found to be significantly higher in the non-survivors than survivor (p≤0.001). In the multivariate logistic regression analysis, higher MPV/platelet ratios at 72h (OR: 7.41; 95% CI: 1.25-43.7; p=0.027) and PDW/platelet ratios at 72h (OR: 2.9; 95% CI: 1.13-7.50; p=0.027) were significant risk factors for mortality. CONCLUSIONS: Platelet indices are useful laboratory parameters in septic shock. MPV/PLT and PDW/PLT ratios can be promising reliable markers for 28-day mortality in children with septic shock (Tab. 4, Fig. 1, Ref. 29).

Metastatic colorectal cancer in both sides of Aegean sea: practice patterns and outcome.

OBJECTIVE: The successful results obtained in trials may not necessarily translate into prolonged survival of metastatic colorectal cancer (mCRC) patients in real life. This multinational registry study aimed to evaluate the real-life data effecting the survival of patients with mCRC. METHODS: This is a multinational, retrospective registry study. Turkish and Greek mCRC patients diagnosed between 2005 and 2012, with at least 3 years of follow-up data or who died before 3 years of follow-up were included in the study. RESULTS: A total of 364 were included in the study. RAS and BRAF mutation rates were found to be 36% and 39%, respectively. As first-line therapy, 196 (54%) patients received bevacizumab and Anti-EGFR treatments in combination with chemotherapy. The objective response rate was 42% (n = 152) and 32% (n = 78) for 1st line and 2nd line treatments, respectively. While the median progression-free survival (PFS) with the 1st line treatment was 10 months, it was 7 months with the 2nd line treatments. In the total study population median PFS and overall survival (OS) were 10 (95% CI, 8.3-11.6) and 35 (95% CI, 30.7-39.2) months, respectively. In Turkish and Greek patients, median OS (36 months versus 29 months, p = .81) and PFS (10.2 versus 9.2, p = .42) were not different. In multivariate analysis, ECOG PS of ≥2 and having metastases in more than one region decreased overall survival (p = .002 and p = .003), it was found that wild RAS and BRAF mutations and second metastasectomy contributed to overall survival (p = .047 and p < .001). CONCLUSION: In conclusion, it seems that the patient's performance status, tumor location, number of metastatic lesions at the time of diagnosis affect the prognosis of mCRC. Although access to molecular tests and first-line treatments differ between Greece and Turkey, no significant difference was found in survival times.

Childhood Interstitial Lung Disease Masquerading as Post COVID-19 Respiratory Distress.

Childhood interstitial lung diseases (chILD) are a set of illnesses affecting the bronchoalveolar spaces and the cellular compartment of the lungs. In the neonatal period, they are mainly classified under disorders of development, growth, surfactant dysfunction, and others of unknown causes distinctive in infancy. One of the most common causes is the deficiency of triphosphate binding cassette transporter A3 (ABCA3) protein. It activates impairment in the function of surfactants, resulting in respiratory distress in term infants, which is lethal in many cases and in some other cases leads to interstitial lung disease. We herein present a case of a 14-month-old boy with a peculiar case of ABCA3 protein deficiency that was masked at birth with COVID-19 infection and then presented with shortness of breath and poor feeding at the age of three months. The child was treated with macrolides, steroids, and hydroxychloroquine, with which he survived beyond the age of one year.

Pulmonary Arterial Hypertension as a Fatal Complication of Neurofibromatosis Type 1 in a Neonate: A Diagnostic Dilemma.

Neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is a genetically transmitted autosomal dominant disease, with a prevalence of one per 4000 live births. Pulmonary arterial hypertension (PAH) is a rare but potentially life-threatening complication of NF1. There are no confirmatory data about the congenital association between PAH and NF1. However, in most cases, PAH is observed in late childhood or adulthood. Herein, we present a preterm baby with genetically confirmed NF1 who presented with PAH.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

An Approach to Addressing Multiple Imputation Model Uncertainty Using Bayesian Model Averaging.

This paper considers the problem of imputation model uncertainty in the context of missing data problems. We argue that so-called "Bayesianly proper" approaches to multiple imputation, although correctly accounting for uncertainty in imputation model parameters, ignore the uncertainty in the imputation model itself. We address imputation model uncertainty by implementing Bayesian model averaging as part of the imputation process. Bayesian model averaging accounts for both model and parameter uncertainty, and thus we argue is fully Bayesianly proper. We apply Bayesian model averaging to multiple imputation under the fully conditional specification approach. An extensive simulation study is conducted comparing our Bayesian model averaging approach against normal theory-based Bayesian imputation not accounting for model uncertainty. Across almost all conditions of the simulation study, the results reveal the extent of model uncertainty in multiple imputation and a consistent advantage to our Bayesian model averaging approach over normal-theory multiple imputation under missing-at-random and missing-completely-at random in terms of Kullback-Liebler divergence and mean squared prediction error. A small case study is also presented. Directions for future research are discussed.