Impact of residual coronary lesions on outcomes of myocardial infarction patients with multi-vessel disease.

BACKGROUND: The residual burden of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) drew a growing interest. The residual SYNTAX Score (rSS) was a strong prognostic factor of adverse events and all-cause mortality in patients who underwent PCI. In addition, the SYNTAX Revascularization Index (SRI), a derivative of rSS, was used to figure out the treated proportion of CAD and could be used as a prognostic utility in PCI for patients with multi-vessel disease (MVD). PURPOSE: We aimed at the assessment of the use of rSS and the SRI as predictors of in-hospital outcomes and up to two-year cumulative follow-up outcomes in patients with MVD who had PCI for the treatment of ST-Elevation Myocardial Infarction (STEMI) or Non-STEMI (NSTEMI). METHODS: We recruited 149 patients who had either STEMI or NSTEMI while having MVD and received treatment with PCI. We divided them into tertiles based on their rSS and SRI values. We calculated baseline SYNTAX Score (bSS) and rSS using the latest version of the calculator on the internet, and we used both scores to calculate SRI. The study end-points were In-hospital composite Major Adverse Cardiovascular Events (MACE) and its components, in-hospital death, and follow-up cumulative MACE up to 2 years. RESULTS: Neither rSS nor SRI were significant predictors of in-hospital adverse events, while female sex, hypertension, and left ventricular ejection fraction were independent predictors of in-hospital MACE. At the two-year follow-up, Kaplan-Meyer analysis showed a significantly increased incidence of MACE within the third rSS tertile (rSS > 12) compared to other tertiles (log rank p = 0.03). At the same time, there was no significant difference between the three SRI tertiles. Unlike SRI, rSS was a significant predictor of cumulative MACE on univariate Cox regression (HR = 1.037, p < 0.001). On multivariate Cox regression, rSS was a significant independent predictor of two-year cumulative MACE (HR = 1.038, p = 0.0025) along with female sex, hypertension, and left ventricular ejection fraction. We also noted that all patients with complete revascularization survived well throughout the entire follow-up period. CONCLUSIONS: Neither rSS nor SRI could be good predictors of in-hospital MACE, while the rSS was a good predictor of MACE at two-year follow-up. Patients with rSS values > 12 had a significantly higher incidence of cumulative MACE after 2 years. The best prognosis was achieved with complete revascularization.

Introduction of Spring-Assisted Cranioplasty for Sagittal Craniosynostosis in a Craniofacial Service: A Report of Early Experience.

Spring-assisted cranioplasty (SAC) for the treatment of craniosynostosis uses internal springs to produce dynamic changes in cranial shape over several months before its removal. The purpose of this study was to report the first Egyptian experiences with SAC in the treatment of children with sagittal synostosis and evaluate the preliminary outcome. A total of 17 consecutive patients with scaphocephaly underwent SAC with a midline osteotomy along the fused sagittal suture and insertion of 3 springs with bayonet-shaped ends across the opened suture. Operative time, blood transfusion requirements and length of ICU, total hospital stay, and complications graded according to Oxford protocol classification were recorded. Spring removal was performed once re-ossification of the cranial defect occurred. All patients successfully underwent SAC without significant complications. The mean age at surgery was 6.8 months. The mean time of the spring insertion surgery was 63 minutes (SD 9.7). Blood transfusion was needed in less than half of the patients (41.2%).The mean duration of hospital stay was 3.2 days. The mean timing of spring removal was 5.5 months (SD 0.4). The mean time of the second surgery (spring removal) was 22.8 minutes (SD 3.6). In conclusion, SAC can easily be incorporated into the treatment armamentarium of craniofacial surgeons. The technique offers a safe and minimally invasive option for the treatment of sagittal craniosynostosis with the benefit of limited dural undermining, minimal blood loss, operative time, anesthetic time, ICU stay, and hospital stay.

Clinicoradiologic Correlation in 22 Egyptian Children With Megalencephalic Leukoencephalopathy With Subcortical Cysts.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic form of cerebral white matter disease whose clinicoradiologic correlation has not been completely understood. In this study, we investigated the association between clinical and brain magnetic resonance imaging (MRI) features in 22 Egyptian children (median age 7 years) with MLC. Gross motor function was assessed using the Gross Motor Function Classification System, and evaluation of brain MRI followed a consistent scoring system. Each parameter of extensive cerebral white matter T2 hyperintensity, moderate-to-severe wide ventricle/enlarged subarachnoid space, and greater than 2 temporal subcortical cysts was significantly associated (P < .05) with worse Gross Motor Function Classification System score, language abnormality, and ataxia. Having >2 parietal subcortical cysts was significantly related to a worse Gross Motor Function Classification System score (P = .04). The current study indicates that patients with MLC manifest signification association between certain brain MRI abnormalities and neurologic features, but this should be confirmed in larger studies.

A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture.

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies. SIGNIFICANCE: The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

Molecular Mechanisms and Treatment Options of Nephropathic Cystinosis.

Nephropathic cystinosis is a severe, monogenic systemic disorder that presents early in life and leads to progressive organ damage, particularly affecting the kidneys. It is caused by mutations in the CTNS gene, which encodes the lysosomal transporter cystinosin, resulting in intralysosomal accumulation of cystine. Recent studies demonstrated that the loss of cystinosin is associated with disrupted autophagy dynamics, accumulation of distorted mitochondria, and increased oxidative stress, leading to abnormal proliferation and dysfunction of kidney cells. We discuss these molecular mechanisms driving nephropathic cystinosis. Further, we consider how unravelling molecular mechanisms supports the identification and development of new strategies for cystinosis by the use of small molecules, biologicals, and genetic rescue of the disease in vitro and in vivo.

Clinico-Radiological Correlation in 26 Egyptian Children with Glutaric Acidemia Type 1.

BACKGROUND: Glutaric acidemia type 1 (GA1) is an inherited neurometabolic disease with significant morbidity. However, neuro-radiological correlation is not completely understood. OBJECTIVE: The study aimed to characterize the neuroimaging findings and their association with neurological phenotype in GA1 children. METHODS: Twenty-six Egyptian children (median age = 12 months) diagnosed with GA1 underwent clinical evaluation and brain magnetic resonance imaging (MRI). We objectively assessed the severity of neurological phenotype at the time of MRI using movement disorder (MD) and morbidity scores. Evaluation of brain MRI abnormalities followed a systematic and region-specific scoring approach. Brain MRI findings and scores were correlated with MD and morbidity scores, disease onset, and presence of seizures. RESULTS: Fifteen (57.7%) cases had insidious onset, eight (30.8%) manifested acute onset, whereas three (11.5%) were asymptomatic. Ten (38.5%) cases had seizures, five of which had no acute encephalopathic crisis. Putamen and caudate abnormalities (found in all acute onset, 93.3 and 73.3% of insidious onset, and one of three asymptomatic cases) were significantly related to MD (p = 0.007 and 0.013) and morbidity (p = 0.005 and 0.003) scores. Globus pallidus abnormalities (50% of acute onset, 46.7% of insidious onset, and one of three of asymptomatic cases) were significantly associated with morbidity score (p = 0.023). Other MRI brain abnormalities as well as gray and white matter score showed no significant association with neurological phenotype. Younger age at onset, acute onset, and seizures were significantly associated with worse neurological manifestations. CONCLUSION: Patients with GA1 manifest characteristic and region-specific brain MRI abnormalities, but only striatal affection appears to correlate with neurological phenotype.

Propionic and Methylmalonic Acidemias: Initial Clinical and Biochemical Presentation.

PA and MAA have numerous nonspecific presentations, potentially leading to delayed diagnosis or misdiagnosis. In this paper, we present the clinical and biochemical characteristics of MMA and PA patients at initial presentation. Results. This is a retrospective review of 20 patients with PA (n = 10) and MMA (n = 10). The most observed symptoms were vomiting (85%) and refusing feeding (70%). Ammonia was 108.75 ± 9.3 µmol/l, showing a negative correlation with pH and bicarbonate and positive correlation with lactate and anion gap. Peak ammonia did not correlate with age of onset (r = 0.11 and p = 0.64) or age at diagnosis (r = 0.39 and p = 0.089), nor did pH (r = 0.01, p = 0.96; r = -0.25, p = 0.28) or bicarbonate (r = 0.07, p = 0.76; r = -0.22, p = 0.34). There was no correlation between ammonia and C3 : C2 (r = 0.1 and p = 0.96) or C3 (r = 0.23 and p = 0.32). The glycine was 386 ± 167.1 µmol/l, and it was higher in PA (p = 0.003). There was a positive correlation between glycine and both pH (r = 0.56 and p = 0.01) and HCO3 (r = 0.49 and p = 0.026). There was no correlation between glycine and ammonia (r = -0.435 and p = 0.055) or lactate (r = 0.32 and p = 0.160). Conclusion. Clinical presentation of PA and MMA is nonspecific, though vomiting and refusing feeding are potential markers of decompensation. Blood gas, lactate, and ammonia levels are also good predictors of decompensation, though increasing levels of glycine may not indicate metabolic instability.

Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion.

Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.

Pediatric self-inflicted eye trauma due to a major depressive disorder.

Self-inflicted eye trauma is a serious form of self-harm as it may lead to irreversible visual disability. Diagnosing self-inflicted ocular injuries, in all its forms, can be quite challenging. In this report, we are presenting a 5-year-old girl presented to Sohag University Outpatient Clinic with a history of repeated attacks of bilateral eye redness with blood-tinged strands removed from her eyes. After ocular examination, inferior bulbar conjunctival injection with blood-tinged strands were found. After careful examination of the strands, it was discovered that they were actual threads of cloth due to self-inflicted eye injury. Following psychiatric consultation, the patient was diagnosed as having a major depressive disorder. The case was subject to pharmacological and psychotherapeutic treatment, and showed significant improvement within two months of starting treatment as regard to depressive symptoms and self-injury behaviors. Although self-inflicted ocular injuries due to pediatric mood disorders are rare, it should be suspected in any case of unexplained chronic conjunctivitis.

Study of the C677T and 1298AC polymorphic genotypes of MTHFR Gene in autism spectrum disorder.

BACKGROUND: Autism is currently known as "a behaviorally defined syndrome" manifested as impairment in social communication, repetitive routines and restricted interests. There is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle. AIM: The aim of this study was to identify C677T and 1298AC polymorphic genotypes of MTHFR gene among a sample of Egyptian children with autism and to make a phenotype-genotype correlation for the autistic patients. METHODS: This case-control study was carried out from 2013 through 2015. The study included 31 children with autism and 39 children in a normal control group, the mean age of patients and control was comparable (4.5 years± 2) with males predominant in both groups. We used DSM-V-TR criteria, Stanford-Binet intelligence scale V and childhood autism rating scale (CARS) for assessments. Genotyping for MTHFR gene polymorphic loci C677T and 1298AC was performed on amplified DNA by PCR with subsequent reverse hybridization and restriction fragment length polymorphisms analysis. Data were analyzed by SPSS version 11, using Chi-Square, independent-samples t-test, and ANOVA. RESULTS: There was significant relationship between low birth weight and occurrence of autism (p<0.01), and between delayed motor and social milestones in cases of autism compared to controls (p<0.01). Heterozygosity for A1298C polymorphism was highest among patients (41.9%) followed by 35.5% mutant genotype CC and 22.6% normal AA (wild) type and Allele C was detected in patients more than in control (56.45% vs. 11.54%) (p<0.001). For C667T polymorphism, heterozygosity was also highest among patients (48.4%) followed by wild type genotypes C677 (38.7%) and 12.9% for mutant genotypes 667T. Allele T appeared more in patients than control (31.10 %vs. 5.13%) (p<0.00). Heterozygosity for CT and A-C genotypes were detected equally (46.2%) among patients with severe autism (according to CARS). CONCLUSION: There is a significant association between severity and occurrence of autism with MTHFR gene polymorphisms C677T and A1298C. Further studies are needed on a larger scale to explore other genes polymorphisms that may be associated with autism, to correlate the genetic basis of autism.

Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis.

BACKGROUND: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD. METHODS: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted. RESULTS: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous. CONCLUSION: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.