Serum angiopoietin-2: a promising biomarker for early diabetic kidney disease in children and adolescents with type 1 diabetes.

Albuminuria has been considered the golden standard biomarker for diabetic kidney disease (DKD), but appears once significant kidney damage has already occurred. Angiopoietin-2 (Angpt-2) has been implicated in the development and progression of DKD in adults. We aimed to explore the association of serum Angpt-2 levels with DKD in children and adolescents with type 1 diabetes mellitus (T1DM) of short duration (3-5 years) and to evaluate the predictive power of serum Angpt-2 in the early detection of DKD prior to the microalbuminuric phase. The current cross-sectional study included 90 children divided into three age and sex-matched groups based on urinary albumin-to-creatinine ratio (UACR): microalbuminuric diabetic group (n = 30), non-albuminuric diabetic group (n = 30), and control group (n = 30). All participants were subjected to anthropometric measurements, serum Angpt-2 and fasting lipid profile (total cholesterol, triglycerides, LDL-C, HDL-C, and Non-HDL-C) assessment. Glomerular filtration rate was estimated based on serum creatinine (eGFR-Cr). Higher serum Angpt-2 levels were detected in both diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric diabetic group. There was no detected significant difference in eGFR-Cr values across the study groups. Serum Angpt-2 was positively correlated with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR, while UACR, HbA1c, and Non-HDL-C were independent predictors for serum Angpt-2. Serum Angpt-2 at level of 137.4 ng/L could discriminate between microalbuminuric and non-albuminuric diabetic groups with AUC = 0.960 and at level of 115.95 ng/L could discriminate between the non-albuminuric diabetic group and controls with AUC = 0.976.Conclusion: Serum Angpt-2 is a promising potent biomarker for the detection of early stage of DKD in childhood T1DM before albuminuria emerges. What is Known? • Urine albumin-to-creatinine ratio (UACR) and glomerular filtration rate (GFR) are the golden standard but late biomarkers for DKD. • Angiopoietin-2 has been implicated in the development and progression of DKD in adults with diabetes, but has not been explored in T1DM children with DKD. What is New? • Higher serum angiopoietin-2 was detected in diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric group. • Angiopoietin-2 correlated positively with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR. • Serum angiopoietin-2 is a promising early diagnostic biomarker for DKD in children with T1DM.

The effect of lacosamide on calcitonin gene-related peptide serum level in episodic migraine patients: a randomized, controlled trial.

BACKGROUND: Migraine affects 11-15% of people worldwide, and the calcitonin gene-related peptide (CGRP) is released during the migraine attack, producing pulsating pain of migraine. Also, lacosamide reacts with collapsin-response mediator protein 2, preventing its phosphorylation and leading to the inhibition of CGRP release in the trigeminal system. OBJECTIVE: The primary outcome was the difference in the serum level of CGRP-LI after three months of treatment with either lacosamide and ibuprofen or ibuprofen alone in episodic migraine patients. The secondary outcomes were assessing safety and efficacy of lacosamide in episodic migraine patients. METHODS: We conducted an open-label randomized controlled trial on episodic migraine patients aged 10-55 years diagnosed according to (ICHD-3) in Kafr El-Sheikh University Hospital, Egypt. We assessed serum levels of CGRP-LI before and three months after treatment in our two groups, the lacosamide, and the control groups. We also assessed the side effects of treatment in each group, the percentage of patients who achieved ≥ 50% reduction in the migraine monthly days (MMD) frequency and the percentage of patients who achieved pain freedom within 2 h in ≥ 4 of 5 attacks in each group. RESULTS: 200 episodic migraine patients completed the study. There was a statistically significantly higher reduction in the serum CGRP-LI level in the lacosamide group compared with the control group. In addition, lacosamide was well tolerated by patients. Also, the lacosamide group had statistically significant higher percentage of patients who achieved ≥ 50% reduction in the migraine monthly days (MMD) frequency and pain freedom within two hours in ≥ 4 of 5 attacks with P-values 0.002, 0.02 respectively. CONCLUSION: The daily use of lacosamide 50 mg Bid for three months in episodic migraine patients was associated with a significant reduction in serum CGRP-LI, better clinical outcomes regarding frequency and duration of migraine attacks, and was well tolerated by patients. These results were derived from an open-label pilot study that needed to be thoroughly investigated by a large-scale, randomized, double-blinded, placebo-controlled study. TRIAL REGISTRATION:  We registered our trial on ClinicalTrials.gov, named after "The Lacosamide's Effect on Calcitonin Gene-related Peptide in Migraine Patients," and with a clinical trial number (NCT05632133)-August 8, 2023.

Association of IL-17F Gene Polymorphism and Its Serum Level with SARS-CoV-2 Infection.

OBJECTIVE: Although multiple studies have addressed the clinical outcomes of coronavirus disease, little data exist regarding the defi- nition of immune and inflammatory profiles associated with this infection. Its clinical manifestations often worsen in association with hypercytokinemia (elevated interleukin 8 and interleukin 17). We conducted this research to elucidate the effect of interleukin 17 levels and interleukin 17F gene polymorphism on the severity and outcomes of coronavirus disease. MATERIAL AND METHODS: Ninety patients with confirmed coronavirus disease and 30 healthy controls were enrolled. Coronavirus disease cases were classified into nonsevere, severe, and critical according to the World Health Organization definition. Approximately 10 mL peripheral blood sample was collected from all patients and controls by venipuncture in-plane and ethylenediaminetetraacetic acid tube. Enzyme-linked immunosorbent assay kits were used for calculating serum interleukin 17 levels, whereas real-time polymerase chain reaction was used for genotyping using the 5'-nuclease allelic discrimination assay for single nucleotide polymorphisms genotyping. RESULTS: As regards interleukin 17 levels, there was a significant elevation of interleukin 17 in coronavirus disease cases compared to control healthy persons (P < .001). Moreover, serum interleukin 17 levels tended to be significantly higher with increased disease sever- ity (P = .004). Patients with critical diseases expressed a significant rise of interleukin 17 compared to severe (P = .03) and nonsevere cases (P = .02). We noted no significant difference between the critical, severe, and nonsevere cases regarding different interleukin 17F genotypes. CONCLUSION: Coronavirus disease is associated with elevated levels of interleukin 17, which tended to be considerably higher with disease severity. However, different interleukin 17F genotypes do not affect either the predisposition or the severity of coronavirus disease.

Serum Cytokeratin 18 as a Potential Early Marker for Chemotherapy Response in Breast Cancer Patients: A Prospective Study.

BACKGROUND: Currently, it is well recognized that response to neoadjuvant chemotherapy is an important predictive factor for survival in breast cancer patients. However, it is still an area of research about which patient would respond to the neoadjuvant chemotherapy. METHODS: Serum CK18 levels were measured using ELISA from 52 newly diagnosed breast cancer patients, at presentation and after first cycle of neo-adjuvant chemotherapy. Pre- and post-treatment CK-18 levels were correlated with several clinical and pathological parameters. At the end of neoadjuvant treatment, changes in serum CK18 levels were correlated with tumors' response to therapy. RESULTS: Significant elevation of pre-chemotherapy CK18 level was observed in patients who had progressive disease compared to those who had complete or partial response to therapy (P=0.006 and P<0.001, respectively). Significantly higher CK18 levels were observed post-chemotherapy in complete and partial responders, in contrast to patients with stable or progressive disease (P=0.012% and P=0.001%, respectively). The percent of change was significantly higher in complete responders compared to patients who had stable or progressive disease (P=0.043% and P=0.045%, respectively). CONCLUSION: Our results suggest that patients with increasing CK18 level following chemotherapy are potential responders to their neoadjuvant protocol. Thus, the measurement of serum CK18 early in the treatment course could be a simple, noninvasive way to predict tumor response to neoadjuvant chemotherapy.

Seroprevalence of Toxoplasma gondii among hemodialysis patients: A possible link to main T-lymphocyte subsets levels and dialysis adequacy.

BACKGROUND: A high prevalence of Toxoplasma gondii infection has been reported in patients with hemodialysis (HD). However, a lack of data exists on the relationship between T lymphocyte subsets and dialysis adequacy. This study aimed to investigate the seroprevalence of Toxoplasma gondii infection among HD patients and its relation to T lymphocyte cells subsets, CD3+, CD4+, CD8+, CD4+/CD8+ ratio, and HD adequacy. METHODS: This cross-sectional comparative study was conducted on 92 subjects. Of them, 42 HD patients and 50 were control participants. Anti-Toxoplasma gondii IgG, IgM antibodies, the T lymphocyte cells subset CD3+, CD4+, CD8+, CD4+/CD8+ ratio, and adequacy of dialysis via calculation of Kt/V were detected for all subjects. RESULTS: The seropositivity for anti-Toxoplasma gondii IgG antibodies was significantly higher in HD patients 66.7% (28/42) compared to 34% in controls (17/50), (p = 0.0003). The main T lymphocyte subsets was significantly lower in HD compared to controls (p < 0.05). Seropositive HD patients exhibited statistically significantly lower T lymphocyte cell subsets and CD4+/CD8+ ratio compared to seronegative patients (p < 0.05). There was a negative correlation between anti-Toxoplasma gondii IgG level and T lymphocyte subsets and the CD4/CD8+ ratio. Binary logistic regression showed that CD4+ T cell significantly predicts Toxoplasma gondii susceptibility among HD patients (p = 0.03). The mean Kt/V index is significantly lower among seropositive HD patients compared to seronegative HD patients (1.05 ± 0.46, 1.41 ± 0.53, respectively, p = 0.03) with a significant negative correlation with anti-Toxoplasma gondii IgG level (p < 0.05). ROC curve analysis showed the CD4+ T cell % had the highest AUC value among HD patients (AUC= 0.88, p < 0.001). The Kt/V value of ≤ 0.8 significantly predicted susceptibility to Toxoplasma gondii infection among HD patients (AUC = 0.68, p = 0.03). CONCLUSION: The current study reinforces previous reports of a high prevalence of Toxoplasma gondii infection among HD patients. CD4+ T cell and Kt/V showed a good diagnostic performance in predicting susceptibility for Toxoplasma gondii infection in HD patients. Considering the clinical consequences caused by Toxoplasma gondii infection in these patients, regular screening and adequate HD are recommended.

Influence of Micro-RNA-423 Gene Variation on Risk and Characteristics of Breast Cancer.

BACKGROUND: Micro-RNAs (miRNAs) are post-transcriptional regulators of gene expression that are abundantly expressed in a variety of cancers, including breast cancer. The mechanism of miRNAs in breast cancer oncogenesis is poorly understood. The goal of this study was to determine if there was a link between the miR-423 rs6505162 gene variation and breast cancer susceptibility among Egyptian patients. METHODS: This was a case control study that included 120 female patients with pathologically confirmed breast cancer and 120 healthy controls. The patients and controls were genotyped for miR-423 rs6505162 polymorphism by real time PCR. The association of breast cancer patients' genotypic variant and clinicopathological characteristics was analyzed. RESULTS: Breast cancer patients showed significantly higher AA and CA genotypes frequencies when compared to controls. This was translated as higher risk to develop breast cancer in patients harboring these genotypic variants (OR = 3.28, p= 0.002; OR = 2.11, p= 0.011, respectively). The frequencies of Her2 positive and advanced stage disease were significantly increased in the AA genotype variant (p<0.001). CONCLUSION: Our data suggest that miR-423 rs6505162 polymorphism could be a potential risk factor in the pathogenesis of breast cancer among Egyptian population.

Prevalence of pks genotoxin among hospital-acquired Klebsiella pneumoniae.

The pks genotoxic K. pneumoniae has recently triggered a widespread alarm. DNA damage and higher virulence have been linked to colibactin, a genotoxin expressed by the pks genomic island. Little is known about its molecular epidemiology in clinical isolates from Egypt. Therefore, this study was conducted to determine the prevalence and the microbiological and clinical features of pks harboring hospital-acquired K. pneumoniae isolates from Egypt. Eighty-seven hospital-acquired K. pneumoniae isolates from various specimen types were screened for pks colibactin island markers clbB, clbQ, clbA, and clbN by PCR. The pks-positive hvKp isolates were classified to one of the capsular types K1 and K2 using multiplex-PCR targeting K-serotype wzi and rmpA genes. The prevalence of pks+ strains was 27.6% (24/87). K1 capsular type, phenotypic, and genotypic hypervirulent isolates were significantly higher among pks+ strains than pks- strains (P < 0.001), while pks+ K. pneumoniae strains were found to be significantly less resistant to 8 of the antibiotic compounds tested than pks- strains. Carriage of K1 capsular type and mucoviscosity-associated rmp A gene and diabetes mellitus were identified to remain independent risk factors having a substantial association to pks-positivity by multivariate regression analysis. In conclusion, Hospital-acquired K. pneumoniae isolates in Egypt had an increased prevalence of the pks colibactin genotoxin. The significant occurrence of hypervirulent determinants in pks+ K. pneumoniae highlighted the genotoxin's possible pathogenicity combined with its distribution in several specimen types, which necessitates clinical attention and epidemic tracking.

Epicardial and Perihepatic Fat as Cardiometabolic Risk Predictors in Girls with Turner Syndrome: A Cardiac Magnetic Resonance Study

Objective: Turner syndrome (TS) patients are at high risk of cardiometabolic disorders. Cardiometabolic risk factors are more commonly related to visceral rather than total body adiposity. Adipocytokines have been explored as a potential link between obesity and obesity-related cardiometabolic dysfunction. This study explored the validity of epicardial fat-thickness (EFT) and perihepatic fat-thickness (PHFT) measurement as cardiometabolic-risk predictors in TS-girls in relation to standard obesity-indices and metabolic syndrome (MetS) components. Methods: Forty-six TS girls and twenty-five controls (10-16 years) were subdivided into two age-groups (10 to less than 13 and 13-16). Participants were assessed for body mass index (BMI) Z-scores, waist circumference (WC), total-fat mass (FM) and trunk-FM by bioimpedance-technique, EFT and PHFT by cardiovascular magnetic resonance, lipid-profile, homeostasis model assessment of insulin resistance (HOMA-IR), and serum chemerin. MetS was defined according to International Diabetes Federation criteria. Results: Overweight/obesity and MetS were detected in 45.7% and 37% of TS-girls respectively. BMI Z-score, WC, total-FM, trunk-FM, EFT and PHFT values were significantly higher in TS-age groups compared to age-matched control groups, being more pronounced in the older group when TS-girls had been exposed to estrogen. Dyslipidemia, higher HOMA-IR, chemerin, EFT and PHFT values were observed in lean-Turner compared to BMI-Z-matched controls. EFT and PHFT were significantly correlated with chemerin and several components of MetS. EFT at a cut-off-value of 6.20 mm (area under the curve=0.814) can predict MetS in TS-girls. Conclusion: TS-girls displayed an adverse cardiometabolic profile during late childhood and adolescence. EFT and PHFT are emerging cardiometabolic risk predictors in TS-patients. Excess EFT rather than total body adiposity may contribute to altered metabolic profile among lean-Turner patients.

Association between Toxoplasma gondii infection and metabolic syndrome in obese adolescents: A possible immune-metabolic link.

Background Toxoplasmosis as a global disease is considered as a triggering factor responsible for development of several clinical diseases. However, Toxoplasma gondii (T. gondii) is an understudied parasite of potential interest in obesity research. The current study aimed to explore the role of latent T. gondii infection in the pathogenesis of metabolic syndrome (MetS) in obese adolescents through studying the relationship between serum interferon-gamma [IFN-γ] and serum chemerin in context of MetS components. Methods Eighty-three obese adolescents were serologically screened for T. gondii-IgG antibodies and compared to 35 age-matched healthy T. gondii-seronegative controls. Participants were evaluated for anthropometric measurements, total-fat mass [FM], trunk-FM, serum lipid profile, IFN-γ, and chemerin levels. Homeostatic Model Assessment of insulin resistance (HOMA-IR) was calculated. Results The prevalence of MetS was significantly higher within obese T. gondii-seropositive group compared to obese T. gondii-seronegative group (P = 0.033). Seropositive obese MetS group displayed significantly higher trunk-FM, HOMA-IR, chemerin, and IFN-γ compared to seronegative obese MetS group. Serum chemerin and IFN-γ were strongly correlated (P < 0.001) and were positively correlated with BMI, WC, total-FM, trunk-FM, HOMA-IR, cholesterol, triglycerides and negatively correlated with HDLC. HOMA-IR was a common predictor for serum chemerin (P = 0.030) and IFN-γ (P < 0.001). Conclusions The study results suggest that T. gondii infection may exert an immune-metabolic effect that may have a potential role in the development of MetS among obese adolescents.