sIL-2R and sIL-2R/lymphocyte ratio as indicators of severity in COVID-19 pediatric patients

Objectives: To determine the role of sIL-2R and sIL-2R/lymphocyte ratio as indicators of COVID-19 severity and predictors of clinical progression among children and adolescents. Patients and Methods: This observational cross-sectional study enrolled 76 pediatric patients [40 (52.6%) males and 36 (47.4%) females] with confirmed COVID-19. Patients were classified into two groups; mild to moderate and severe to critical according to WHO classification of severity and were assessed using COVID‑19 severity assessment score and COVID-19 severity index. Soluble IL-2R (sIL-2R) concentrations were measured using a commercial enzyme-linked immunosorbent assay and sIL-2R/lymphocyte ratio was calculated for each patient. Results: Receiver-operating characteristic (ROC) curve analysis showed that sIL-2R has a significantly higher discriminative power between patients in both groups (AUC=0.955) as compared to sIL-2R/lymphocyte ratio (AUC=0.711) (p < /em> value<0.0001). At an associated criterion of >140 ng/l, the sensitivity and specificity of sIL-2R were 81.4.% and 100%, respectively.  Soluble IL-2R also showed better performance in predicting the need for supplemental oxygen [threshold>140 ng/l, AUC=0.904 (0.814 to 0.960)], ICU admission [threshold>140 ng/l, AUC=0. 935 (0.854 to 0.979)], and mechanical ventilation [threshold>180 ng/l, AUC=0. 892 (0.799 to 0.951)]. Conclusion:  Soluble IL-2R can play a potential role as a feasible indicator of COVID-19 severity in children and adolescents, thus informing healthcare providers to direct care to patients who may require intensive or critical care

Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Clinical significance of Galectin-1 and Galectin-4 in rheumatoid arthritis patients and their potential role as diagnostic markers

Aim of the work: To investigate the utility of serum Galectin-1 (Gal-1) and Galectin-4 (Gal-4) as potential markers for diagnosis of rheumatoid arthritis (RA) and to explore their relationship with disease activity. Patients and methods: Serum Gal-1 and Gal-4 of 60 RA patients were compared to 30 age and sex-matched controls. Potential relationship of both markers with disease activity assessed using Disease activity score-28 joints (DAS-28), seropositivity (Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA)), functional classification assessed using modified health assessment questionnaire (MHAQ), radiographic progression assessed using Larsen score and treatment was investigated. Results: The study included 60 patients; 54 (90 %) females and 6 (10 %) males with a mean age of 42.6 ± 10.1 years and disease duration of 7.5 ± 6.4 years. Their mean DAS-28 was 4.6 ± 1.0, their MHAQ was 1 ± 0.5 and their Larsen score was 41.3 ± 9.9. The mean of Gal-1 and Gal-4 were both significantly lower in RA patients in comparison to control group (4.4 ± 1.5 ng/ml vs 38.1 ± 25.5 ng/ml and 1.2 ± 0.7 ng/ml; p < 0.001vs 8.1 ± 7.0 ng/ml; p < 0.001 respectively. At a cut off value ≤7.7 for Gal-1 and ≤2.3 for Gal-4 was successfully able to differentiate between RA patients and control group. There was no correlation between both Gal-1 &amp; Gal-4 and DAS-28, MHAQ, Larsen score, RF or ACPA titres. Conclusion: Gal-1 &amp; 4 serum levels have a potential role as diagnostic markers in patients with RA. Both markers however cannot be regarded as disease activity or severity markers

Antigastric parietal cell antibody as a screening test for Autoimmune gastritis in Egyptian children and adolescents with juvenile autoimmune thyroid disease and those with type 1 diabetes, single center experience

Purpose: The diagnosis of pediatric autoimmune gastritis (AIG) is critical due to the poor outcome and risk of malignancy. Therefore, we evaluated the prevalence of autoimmune gastritis in children with autoimmune thyroid disease (ATD) and type 1 diabetes mellitus (T1D), using parietal cell antibody (PCA) to identify its use as a screening test. Methods: PCA was measured in 90 patients; 45 patients with ATD (Hashimoto Thyroiditis and Graves' Disease) and 45 patients with T1D. Their ages ranged from 5 to 18 years. Hemoglobin, ferritin, and HbA1c (in diabetic patients) were measured. &nbsp;Results: PCA demonstrated a statistically significant difference between the two groups of patients with a p-value (0.024). The mean value of&nbsp; PCA&nbsp; in patients with T1D&nbsp; was 196.45, while it reached 148.58 in patients with ATD, with a p-value (0.003). Thirty-one (68.9%) and twelve (26.7%) of patients with T1D had high (30-200) and extremely high (&gt; 200) values of PCA, respectively, compared to twenty-six (57.8%) and eight (17.8%) of patients with ATD who had high (30-200) and extremely high (&gt; 200) values of PCA, respectively. Seven (87.5%) of patients with ATD with extremely high PCA( above 200) also had normocytic anemia.&nbsp

Fecal Calprotectin: A Screening Marker for the Early Detection of Necrotizing Enterocolitis among Children in Egypt

Background: Necrotizing enterocolitis (NEC) is a lethal disease affecting newborns with significant morbidity and mortality rates. Moreover, it is the most eminent gastrointestinal threat affecting premature newborns. Unfortunately, early symptoms and signs are usually vague; therefore, there is a special demand for sensitive biomarkers in this regard. This study aimed to investigate the role of fecal calprotectin in stage I NEC and identify specific cut off value at this stage to differentiate stage I NEC from other gastrointestinal disorders.Methods: This cross-sectional study was conducted at New Children Hospital, Cairo University, Egypt. In total, 100 newborns were included in this study who were assigned to the patient group with stage I NEC (n=60) and control group (n=40)with age and gender-matched newborns.Fecal calprotectin level was assessed using an enzyme-linked immunosorbent assay in both groups. Follow up of the patient group was performed for the development of stage II or III NEC.Results: The patient group obtained significantly elevated levels of fecal calprotectin, compared to the control group (P=0.000). Within the patient group, 43 (71.66%) newborns developed stage II or III NEC, whereas 17 (28.33%) cases developed no NEC. In addition, the level of fecal calprotectin was significantly higher in the group who developed stage II or III NEC (P=0.001). According to the receiver operating characteristic (ROC) curve, the cutoff value of 109.5 μg/g feces showed 100% sensitivity and specificity, and the area under the ROC curvewas equal to 1 in differentiating NEC from other conditions.Conclusion: The study showed that fecal calprotectin can be used as a sensitive and specific marker for the early detection of necrotizing enterocolitis

The Role of Prebiotics and Probiotics as an Adjuvant Therapy in Children with Idiopathic Relapsing Nephrotic Syndrome: A Prospective Open-label Clinical Trial

Idiopathic nephrotic syndrome (INS) is the most common cause of NS in children. It is characterized by the existence of edema, proteinuria, and hypoalbuminemia, as well as repeated relapses. The etiology remains unknown, but new evidence for its pathogenesis relates to the dysfunction of T-regulatory (T-reg) cells, which could be caused by dysbiosis of the gut microbiota. Our study aimed to investigate the effect of prebiotics and probiotics as adjuvant therapies for children with relapsing INS. The study was designed as a prospective open-label randomized clinical trial involving 30 children diagnosed with relapsing INS. The children were randomly divided into two groups. Group 1 was treated with prednisone only, and Group 2 was treated with prebiotics and probiotics in addition to prednisone. Fresh stool samples were collected from the children. Lactobacillus species were isolated and identified by conventional microbiological methods. The total number of Lactobacillus species was counted for each stool sample. The population of T-reg cells in the peripheral blood mononuclear cells was analyzed using flow cytometry. Children treated with prebiotics and probiotics in addition to steroids showed a significant increase in T-reg cells (CD4+/CD25+/FOXp3+) in the peripheral blood and a higher count of Lactobacillus species in their stool alongside a significant decrease in the rate of relapses in this group compared with Group 1. Treatment with prebiotics and probiotics signi-ficantly increased T-reg cells and decreased the rate of relapse in INS

Role of dexmedetomidine in modifying immune paralysis in patients with septic shock: randomized controlled trial

Abstract Background Immune paralysis can be defined as a hypoinflammatory state associated with the incapacity of the immune system to release proinflammatory mediators despite the clearance of pathogens by antimicrobials. Persistent immune paralysis leads to failure to eradicate primary infections with a substantial increase in the risk of multiorgan dysfunction and mortality. The state of immune paralysis is caused mainly by the diminished ability of monocytes to release proinflammatory cytokines in response to endotoxin. This phenomenon is known as endotoxin tolerance. This study aimed to assess the role of dexmedetomidine in modifying immune paralysis in septic shock patients. Methods Twenty-four patients with septic shock were randomized into two groups of 12 patients. A continuous intravenous infusion of dexmedetomidine started at 0.15 µg kg−1 hr−1 and adjusted by 0.15 µg kg−1 h−1 to a maximum of 0.75 µg kg−1 h−1 (10 ml h−1), while midazolam was started at 1 mg h−1 (2 mL hr−1) and adjusted by 1 mg h−1 to a maximum of 5 mg h−1 (10 mL h−1). All infusions were adjusted by increments of 2 mL/hr−1 to maintain blinding. Serum levels of CD42a+/CD14+, HLADR+/CD14+, CRP, IL-6, IL-10 and TNF-α were measured at baseline (T1), 12 h (T2), and 24 h (T3). Results Treatment with dexmedetomidine yielded no significant difference in CD42a+/CD14+, HLADR+/CD14, CD24b-MFI, HLADR-MFI, IL6 and TREM1 at all time points when compared with midazolam treatment. There was no significant difference in TLR levels between the two groups. Cardiac output in the dexmedetomidine group showed a significant decrease at 6, 12 and 24 h (P = 0.033, 0.021, and 0.005, respectively) compared with that in the midazolam group. Conclusion Our results indicated that dexmedetomidine did not affect CD42a+/CD14+ and HLA-DR+/CD14+ expression in septic patients. Furthermore, cytokine production and inflammatory biomarkers did not change with dexmedetomidine infusion. Trial registration Clinical trial.gov registry (NCT03989609) on June 14, 2019, https://register.clinicaltrials.gov

Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity

The present experiment aimed to identify the potential protective role of empagliflozin (EMPA) on haloperidol (HAL)-induced ovarian damage in female rats because of its anti-inflammatory, antioxidant, and antiapoptotic effects. EMPA was administered in the presence and absence of HAL. Thirty-two adult female albino rats were divided into four groups. Control group, EMPA group: received EMPA (10 mg/kg/day) p.o., HAL group: received HAL (2 mg/kg/day) p.o., HAL + EMPA group: HAL (2 mg/kg/day) combined with EMPA for 28 days. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-mullerian hormone (AMH) levels were measured. Ovarian oxidative stress parameters, besides inflammatory and apoptotic biomarkers, and ovarian Sirtuin-1 (Sirt-1) were evaluated. Ovarian histopathological examination and heat shock protein 70 (Hsp70) immunohistochemical study were performed. HAL significantly increased serum levels of FSH, LH, and ovarian inflammatory, apoptotic, and oxidative stress biomarkers and decreased serum AMH levels and Sirt-1 expression. Histopathological findings of ovarian damage and high Hsp70 immunoexpression were detected. EMPA significantly normalized the distributed hormonal levels, oxidative stress, inflammatory, and apoptotic biomarkers with a prompt improvement in the histopathological picture and a decrease in Hsp70 immunoexpression. Accordingly, EMPA protected against HAL-induced ovarian toxicity by modulating the Sirt-1/Hsp70/TNF-&alpha;/caspase-3 signaling pathway

Health economics: direct cost of osteoporotic hip fracture in Egypt—an analysis for the Egyptian healthcare system by the Egyptian Academy of Bone Health

Abstract Mini abstract This work studies the direct cost of hip fractures in Egypt. The direct cost was calculated based on the incidence of hip fracture in Egypt retrieved from the national database. The result of this work raises red flags to the policy makers in Egypt that such fragility fractures are preventable, should appropriate approaches be implemented. Background This study provides an analysis for the healthcare system in Egypt. It was carried out to assess the direct annual cost incurred to the Egyptian healthcare system in 2023 as a result of fragility hip fractures in older adult Egyptians. Results The direct costs of hip fractures incurred during the first year after the injury were estimated at 1,969,385,000 Egyptian pounds (US $63,734,142.4). Time from fracture to surgery was 2.2 + 0.5 days. The average hospital stay after hip fracture surgery was 5.2 + 2.6 days. 4.5% of patients died after surgery, on average 2.3 + 0.4 months. After being discharged from the hospital, all patients needed home care. Conclusion Hip fractures have a significant clinical and financial impact on patients and the healthcare system. This study raises red flags for the healthcare policy makers in Egypt, as the financial burden due to the direct costs of hip fractures justifies extensive prevention programs for osteoporosis and fragility fractures. There is an urgent need to implement diagnostic approaches and validated management protocols for bone health disorders and its associated fractures in Egypt