Necrotizing Enterocolitis Complicating Severe RSV Bronchiolitis in PICU Settings.

This retrospective study aims to analyze the baseline characteristics and factors associated with poor outcomes in patients with necrotizing enterocolitis (NEC) complicating respiratory syncytial virus (RSV) infection. Using the Virtual Pediatric Systems data registry, patients under 2 years admitted to the pediatric intensive care unit (PICU) were screened. Patients with documented RSV infection and NEC, intestinal perforation, noninfectious gastroenteritis/colitis, or pneumatosis intestinalis occurring around the timing of RSV bronchiolitis diagnosis were included. Out of the screened patients, 41 were analyzed. Most patients (93%) were aged 30 days to 2 years, one-third had baseline anatomical cardiac defects, and 20% history of prematurity. Median PICU length of stay was 11.7 days. Seven patients died before hospital discharge. While not statistically significant, nonsurvivors tended to exhibit higher PRISM-3 scores, more acidemia, and lower systolic blood pressure. These findings emphasize the need for cautious assessment of gastrointestinal symptoms in critically ill patients with RSV infection.

Enhancing mitosis quantification and detection in meningiomas with computational digital pathology.

Mitosis is a critical criterion for meningioma grading. However, pathologists' assessment of mitoses is subject to significant inter-observer variation due to challenges in locating mitosis hotspots and accurately detecting mitotic figures. To address this issue, we leverage digital pathology and propose a computational strategy to enhance pathologists' mitosis assessment. The strategy has two components: (1) A depth-first search algorithm that quantifies the mathematically maximum mitotic count in 10 consecutive high-power fields, which can enhance the preciseness, especially in cases with borderline mitotic count. (2) Implementing a collaborative sphere to group a set of pathologists to detect mitoses under each high-power field, which can mitigate subjective random errors in mitosis detection originating from individual detection errors. By depth-first search algorithm (1) , we analyzed 19 meningioma slides and discovered that the proposed algorithm upgraded two borderline cases verified at consensus conferences. This improvement is attributed to the algorithm's ability to quantify the mitotic count more comprehensively compared to other conventional methods of counting mitoses. In implementing a collaborative sphere (2) , we evaluated the correctness of mitosis detection from grouped pathologists and/or pathology residents, where each member of the group annotated a set of 48 high-power field images for mitotic figures independently. We report that groups with sizes of three can achieve an average precision of 0.897 and sensitivity of 0.699 in mitosis detection, which is higher than an average pathologist in this study (precision: 0.750, sensitivity: 0.667). The proposed computational strategy can be integrated with artificial intelligence workflow, which envisions the future of achieving a rapid and robust mitosis assessment by interactive assisting algorithms that can ultimately benefit patient management.

Asthma Cases Treated With Inhaled Anesthetics or Extracorporeal Membrane Oxygenation: A Virtual Pediatric Systems Database Study of Outcomes.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) and/or inhaled anesthetics (IAs) are considered in the management of asthma when refractory to conventional therapy. We aimed to compare the outcomes of these two modalities in asthma PICU care and determine associated survival to hospital discharge among patients in a United States database. DESIGN: Retrospective analysis using the Virtual Pediatric Systems (VPS, LLC) database. SETTING: PICUs participating in the VPS database. PATIENTS: Patients less than 18 years old with diagnosis of asthma treated with IA and/or ECMO from January 2010 to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 221 patients were included; 149 (67%) received ECMO, 62 (28%) received IA, and 10 (5%) received both interventions. We failed to identify any difference between the ECMO and IA groups in demographics, Pediatric Index of Mortality 2 percentage, Pediatric Risk of Mortality 3 score, Pediatric Logistic Organ Dysfunction score, or pre-intervention pH and Pa co2 levels. Use of ECMO versus IA was associated with lower pre-intervention Pa o2 (60 torr [7.99 kPa] vs 78 torr [10.39 kPa]; p < 0.001) and higher utilization of high-frequency oscillatory ventilation. We failed to identify an association between type of intervention (IA vs ECMO) and greater odds of survival (57/62 [92%] vs 128/149 [86%]; odds ratio [OR], 1.87; 95% CI, 0.67-5.21; p = 0.23). However, these data do not exclude the possibility that IA use is associated with more than five-fold greater odds of survival. ECMO use was associated with longer duration of intervention (5 vs 1.3 d; p < 0.001) and PICU length of stay (LOS) (13 vs 7 d; p < 0.001). As expected, ECMO versus IA was also associated with greater odds of undergoing bronchoscopy (34% vs 11%; OR, 3.7; 95% CI, 1.5-9.4; p = 0.004). CONCLUSIONS: In the VPS database of asthma management cases, we failed to identify an association between ECMO versus IA use and survival to hospital discharge. However, ECMO was associated with longer duration of intervention and PICU LOS.

Inhalational Anesthesia for Near-fatal Pediatric Asthma Complicated by Malignant Hyperthermia.

Acute severe asthma is a commonly encountered condition in the pediatric emergency room and the pediatric intensive care unit (PICU). Its treatment involves the use of bronchodilatory agents acting on different receptors, steroids to reduce ongoing inflammation, and non-invasive or invasive mechanical ventilation to offload the increased work of breathing from the respiratory muscles. Patients refractory to these therapies may require the use of inhaled anesthetic agents and extracorporeal gas exchange (ECMO) for life-threatening asthma exacerbations. Depending on institutional protocols, the use of these therapies may vary. The use of inhaled anesthetic agents for asthma management in the PICU is infrequent and is limited to centers with specialized equipment. Commonly encountered side effects include hypotension, arrhythmias, and delirium. Malignant hyperthermia (MH) is a well-known but infrequent side effect of inhaled anesthetic use, depolarizing muscle agents, and has not been described in the PICU following the use of anesthetics for pediatric asthma.

The Unmet Needs of Hepatitis E Virus Diagnosis in Suspected Drug-Induced Liver Injury in Limited Resource Setting.

Background: Currently, there are no specific biomarkers for drug-induced liver injury (DILI), and the diagnosis of DILI is based mainly on the exclusion of other causes of liver dysfunction and the recognition of potential causative drugs. Hepatitis E virus (HEV) diagnosis is not routinely enrolled in many countries, and HEV infection could be misdiagnosed as DILI. Methodology: We retrospectively analyzed plasma samples (n = 80) collected from suspected DILI for HEV markers such as anti-HEV IgM, anti-HEV IgG, and HEV RNA. Anti-HEV antibodies were assessed using commercial ELISA kits. HEV RNA was tested by RT-qPCR targeting HEV ORF2/3, the receiver operating characteristic (ROC) curve was plotted, and a putative threshold for liver function parameters was determined. Results: Out of 80 samples, 12 samples were positive for anti-HEV IgM and anti-HEV IgG, and HEV RNA was detected in seven samples. The median viral load was 3.46 × 103 IU/ml, and the isolated viruses belonged to HEV genotype 1. The level of liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST), but not alkaline phosphatase (ALP), was significantly higher in HEV confirmed cases than in non-HEV confirmed cases. We identified a plasma ALT level of at least 415.5 U/L and AST level of at least 332 U/L; ALT/ALP ratio of at least 5.08 could be used as a guide for the patients diagnosed as DILI to be tested for HEV infection. The previous liver function parameters showed high sensitivity and good specificity. Conclusion: Hepatitis E virus was detected in suspected DILI cases. The diagnosis of DILI is not secure until HEV testing is done. Liver function parameters can be used as a guide for HEV testing in suspected DILI cases in countries with limited resources.

Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study.

BACKGROUND: To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported. OBJECTIVES: We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1ß, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia. METHODS: Ninety-two symptomatic patients aged less than 18 years with confirmed COVID-19 pneumonia and 100 well-matched healthy controls were included in this multi-center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory fluid specimens was detected by real-time reverse-transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry. RESULTS: Patients with COVID-19 had significantly higher median IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 serum levels than did control children (all p < 0.01). Patients with severe COVID-19 pneumonia had significantly higher median IL-1ß, IL-6, and IP-10 serum levels as compared with those with moderate COVID-19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL-6, IL-1ß, and IP-10) could predict severe COVID-19 pneumonia cases with the largest AUC for IL-6 of 0.893 (95% confidence interval: 0.84-0.98; p < 0.01). CONCLUSION: Our study shows that pediatric patients with COVID-19 pneumonia have markedly elevated serum IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 levels at the initial phase of the illness indicating a cytokine storm following SARS-CoV-2 infection. Moreover, serum IL-6, IL-1ß, and IP-10 concentrations were independent predictors for severe COVID-19 pneumonia.

A Rare Presentation of Multi-System Inflammatory Disease in Children Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Management of multi-system inflammatory disease in children (MIS-C) remains a challenge due to the evolving nature of the coronavirus disease 2019 (COVID-19) pandemic. This article reports a rare presentation of multi-system inflammatory disease in a previously healthy 16-month-old male who fully recovered with minimal residual cardiac insufficiency upon discharge. Our case is unique due to patient's young age, cardiac findings, and his response to our treatment protocol. A multi-disciplinary team in a tertiary center was involved with care.

Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study.

BACKGROUND: Recently, the interleukin-17A (IL-17A) gene has emerged as a potential candidate gene for autoimmune disorders, including systemic lupus erythematosus (SLE). OBJECTIVES: This study aimed to investigate whether IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T could be susceptibility markers for juvenile-onset SLE (JSLE) and lupus nephritis (LN) in Egyptian children and adolescents. METHODS: In this multi-centre study, we genotyped 320 patients diagnosed with JSLE and 320 matched control children for three IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T using TaqMan probe-based real-time polymerase chain reaction. Meanwhile, IL-17A serum levels were assessed using ELISA. RESULTS: The IL-17 rs2275913 A/A genotype and A allele were more represented in JSLE patients compared to the control group (21% vs. 7%, odds ratio (OR) = 3.8, 95% confidence interval (CI) 1.78-5.5, p = 0.001, pBonf = 0.003 for the A/A genotype; 37% vs. 29%, OR = 1.4, 95% CI 1.11-1.8, p = 0.003, pBonf = 0.009 for the A allele. No significant difference was found for IL-17 rs8193036 and rs3748067 single nucleotide polymorphisms (SNPs) in genotype distribution or allele frequencies (p>0.05). Patients carrying the IL-17 rs2275913 A/A genotype and A allele were more likely to develop LN (OR = 5.64, 95% CI 2.39-13.77, pBonf = 0.001 for the A/A genotype; OR = 2.73, 95% CI 1.84-4.07, pBonf = 0.02 for the A allele). CONCLUSION: The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE.

Endoscopic papillary large balloon dilatation for the extraction of common bile duct stones

Background and aim: endoscopic papillary large balloon dilatation (EPLBD) is increasingly accepted as an appropriate option for the management of difficult common bile duct stones (CBDS). This study aimed to evaluate the safety and efficacy of EPLBD with a relatively large balloon (15-20 mm) for the extraction of difficult CBDS. Patients and methods: a total of 40 patients were recruited with obstructive jaundice and dilated CBD (≥ 10 mm) subsequent to a single large CBDS of ≥ 10 mm or multiple stones (≥ 3). All patients underwent endoscopic retrograde cholangio-pancreatography (ERCP) with limited sphincterotomy and large balloon dilatation followed by stone extraction using an extraction balloon or dormia basket, without lithotripsy, stenting or further ERCP sessions. Results: successful stone extraction was achieved in 34 patients (85%) and stone extraction failure occurred in six patients (15%). Complications included minimal pancreatitis in four cases (10%), mild pancreatitis in two cases (5%), cholangitis in two cases (5%) and bleeding in two cases (5%). There were no recorded cases of perforation or mortality subsequent to the procedure. Conclusion: EPLBD is a safe and efficient procedure for the extraction of difficult CBDS and may be advisable in patients with a bleeding risk or abnormal papillary anatomy

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Endoscopic papillary large balloon dilatation for the extraction of common bile duct stones.

BACKGROUND AND AIM: endoscopic papillary large balloon dilatation (EPLBD) is increasingly accepted as an appropriate option for the management of difficult common bile duct stones (CBDS). This study aimed to evaluate the safety and efficacy of EPLBD with a relatively large balloon (15-20 mm) for the extraction of difficult CBDS. PATIENTS AND METHODS: a total of 40 patients were recruited with obstructive jaundice and dilated CBD (≥ 10 mm) subsequent to a single large CBDS of ≥ 10 mm or multiple stones (≥ 3). All patients underwent endoscopic retrograde cholangio-pancreatography (ERCP) with limited sphincterotomy and large balloon dilatation followed by stone extraction using an extraction balloon or dormia basket, without lithotripsy, stenting or further ERCP sessions. RESULTS: successful stone extraction was achieved in 34 patients (85%) and stone extraction failure occurred in six patients (15%). Complications included minimal pancreatitis in four cases (10%), mild pancreatitis in two cases (5%), cholangitis in two cases (5%) and bleeding in two cases (5%). There were no recorded cases of perforation or mortality subsequent to the procedure. CONCLUSION: EPLBD is a safe and efficient procedure for the extraction of difficult CBDS and may be advisable in patients with a bleeding risk or abnormal papillary anatomy.

Liver stiffness measurement and spleen diameter as predictors for the presence of esophageal varices in chronic hepatitis C patients.

Although it is an invasive and unpleasant procedure, esophagogastroduodenoscopy (EGD) is still the gold standard for esophageal varices (EV) detection. The aim of this study was to investigate liver stiffness measurement (LSM) and spleen diameter as simple noninvasive tools for EV prediction in chronic hepatitis C patients (CHC).A total of 123 Egyptian patients with CHC have been included and were classified based on screening EGD result into 2 groups; group A (without EV) and group B (with EV). Group (B) was subclassified according to EV grade into 4 subgroups: (B1, grade I), (B2, grade II), (B3, grade III), and (B4, grade IV). LSM was taken for each patient on the next day by an independent Fibroscan operator and correlated to the EGD result. Demographic, clinical, and biochemical data were recorded and analyzed using advanced data-mining computational technology.Mean LSM was 9.94 ±â€Š6 kPa for group A and 33.32 ±â€Š14 kPa for group B, whereas it was 21.22 ±â€Š3, 25.72 ±â€Š6, 33.82 ±â€Š8, and 46.1 ±â€Š15 kPa for subgroups B1, B2, B3, and B4, respectively. Mean spleen diameter was 11.09 ±â€Š1.7 cm for group A and 16.58 ±â€Š1.6 cm for group B. However, LSM ≥17 kPa was the only independent factor for EV prediction; splenic longitudinal span ≥15 cm was a complementary predictor when LSM was <17 kPa. The overall accuracy was 98.33 ±â€Š3.33, Mikro = 98.26%.LSM ≥17 kPa and spleen diameter ≥15 cm is a simple noninvasive algorithm that could be used for prediction of EV and discrimination among its different grades.

Ongoing Transmission of HCV: Should Cesarean Section be Justified? Data Mining Discovery.

BACKGROUND AND OBJECTIVES: Over the past few decades, cesarean section (CS) rates are steadily increasing in most of the middle- and high-income countries. However, most of the pregnant women (particularly undergoing CS) are not screened for hepatitis C virus (HCV); hence, neonates born to HCV-positive mother could be a source of future HCV infection. In this study, the role of the CS and other surgical interventions in HCV transmission in Egypt, the highest endemic country of HCV-4, was investigated. METHODS: From January to June 2016, a prospective cohort study was conducted among 3,836 pregnant women in both urban and rural areas across Egypt for HCV screening in both mothers and neonates born to HCV-positive mother. All pregnant women were screened during third trimester or just before delivery, neonates born to HCV-positive mothers were evaluated within 24-h postdelivery to record vertical transmission cases. Data mining (DM)-driven computational analysis was used to quantify the findings. RESULTS: Among 3,836 randomized pregnant women, HCV genotype 4 was identified in 80 women (2.08%). Out of 80 HCV-infected women, 18 have experienced surgical intervention (22.5%) and 62 CS (77.5%). HCV vertical transmission was identified in 10 neonates, 10/80 (12.5%). CONCLUSION: Screening women who had experienced surgical intervention or CS during child bearing period and before pregnancy might prevent HCV mother-to-child transmission (MTCT). CS should be ethically justified to decrease global HCV transmission.

Incidence of HCV induced-Esophageal varices in Egypt: Valuable knowledge using data mining analysis.

Esophageal varices is one of the most important comorbidity related liver cirrhosis, patients usually presented with hematemesis, melena, or both, ultimately 20% is the mortality during the first attack, hence we aimed to investigate the incidence of such esophageal varices related chronic Hepatitis C virus (HCV) in randomized Egyptian population.One thousand eighteen Egyptian patients, aged between 17 and 58 years, positive for Hepatitis C virus genotype 4 (HCV-4) by enzyme linked immunosorbent assay Ab and HCV RNA-polymerase chain reaction were screened for the presence of esophageal varices.Incidence of esophageal varices was 62.3%; 635 patients, those with large Esophageal varices (LEVs) was 47.4%; 301 patients. Model for end-stage liver disease (MELD) score has not been significantly improved post variceal band ligation (VBL). Using 2D U/S was useful for EVs prediction.Incidence of esophageal varices in HCV Egyptian patients still high, valuable knowledge would be helpful in clinical field have been discovered by data mining computational intelligent analysis using in practical medicine to improve overall health care.