Whole-exome sequencing of a Saudi epilepsy cohort reveals association signals in known and potentially novel loci.

BACKGROUND: Epilepsy, a serious chronic neurological condition effecting up to 100 million people globally, has clear genetic underpinnings including common and rare variants. In Saudi Arabia, the prevalence of epilepsy is high and caused mainly by perinatal and genetic factors. No whole-exome sequencing (WES) studies have been performed to date in Saudi Arabian epilepsy cohorts. This offers a unique opportunity for the discovery of rare genetic variants impacting this disease as there is a high rate of consanguinity among large tribal pedigrees. RESULTS: We performed WES on 144 individuals diagnosed with epilepsy, to interrogate known epilepsy-related genes for known and functional novel variants. We also used an American College of Medical Genetics (ACMG) guideline-based variant prioritization approach in an attempt to discover putative causative variants. We identified 32 potentially causative pathogenic variants across 30 different genes in 44/144 (30%) of these Saudi epilepsy individuals. We also identified 232 variants of unknown significance (VUS) across 101 different genes in 133/144 (92%) subjects. Strong enrichment of variants of likely pathogenicity was observed in previously described epilepsy-associated loci, and a number of putative pathogenic variants in novel loci are also observed. CONCLUSION: Several putative pathogenic variants in known epilepsy-related loci were identified for the first time in our population, in addition to several potential new loci which may be prioritized for further investigation.

Predictors of myocardial functional recovery following successful reperfusion of acute ST elevation myocardial infarction.

BACKGROUND: Following acute ST elevation myocardial infarction (STEMI), restoration of large-vessel patency does not mean complete perfusion recovery. Little is known regarding the predictors of successful myocardial reperfusion for the STEMI patients undergoing pharmacologic and mechanical reperfusion strategies. AIM OF THE WORK: The aim of this clinical study was to find out the predictors of myocardial functional recovery following reperfusion of acute STEMI, represented by 3-month global longitudinal strain (GLS) value assessed by speckle tracking echocardiography. MATERIAL/METHODS: The study population included 400 patients presented with first acute STEMI with successful reperfusion by thrombolysis (group I) or primary percutaneous coronary intervention (PPCI) (group II). Electrocardiography (ECG) at baseline and 90 minutes after coronary reperfusion was performed with assessment of ST resolution. Basal and 3-month follow-up echocardiography was performed with assessment of ejection fraction (EF), myocardial performance index (MPI), systolic myocardial excursion (S'), and GLS. RESULTS: There was nonsignificant difference between patients of both groups regarding age (P = 0.422) and gender (P = 0.272). Also, there was a nonsignificant difference between both groups regarding the risk factors of coronary artery disease like hypertension (P = 0.511), diabetes mellitus (P = 0.332), and smoking (P = 0.381). But there was significant statistical difference between both groups regarding dyslipidemia (P = 0.012). Ninety-minute ST resolution was significantly higher in PPCI group (P = 0.042). Moreover, PPCI group had significant improvement of EF (P = 0.013) during follow-up, and highly significant improvement of MPI, S' and GLS (P Ë‚ 0.001) compared to the basal echocardiographic study. The percentage of change (∆) of each of the echocardiographic parameter was compared between both groups and revealed statistically significant improvement regarding EF, highly significant improvement of MPI, S' and GLS in favor of PPCI arm (group II). Multivariate regression analysis demonstrated that pain to reperfusion time, MI territory, ST resolution, and basal GLS value are the most important predictors for LV functional recovery. CONCLUSION: The study found pain to reperfusion time, MI territory, ST resolution, basal GLS value are the most important predictors of myocardial functional recovery. Regular follow-up with echocardiography for STEMI patients with different reperfusion strategies has informative impact on long-term clinical outcome. Also the study confirmed that PPCI is better than thrombolysis not only in restoring epicardial coronary flow but also in restoring microvascular and tissue perfusion assuring better myocardial functional recovery and better long-term clinical outcomes.

Validity of the Triglyceride-Glucose Indices for Predicting the Severity of Coronary Artery Disease in Patients With Nondiabetic Chronic Coronary Syndrome.

BACKGROUND: The triglyceride-glucose (TyG) index was shown to be an independent predictor of coronary artery disease (CAD) progression and prognosis. However, whether the TyG index can predict the severity of CAD in nondiabetic patients with chronic coronary syndrome remains unclear. METHODS: A total of 118 individuals who underwent elective coronary angiography were classified into group A (59 with coronary lesions) and group B (59 with normal coronary arteries; as a control group) after coronary angiography and laboratory tests for fasting and the postprandial (PP) TyG index. The complexity of CAD was determined by the Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score >22 indicated moderate-high risk), and patients diagnosed with diabetes or prediabetes were excluded. RESULTS: The TyG index was not related to the SYNTAX score in groups A and B; however, in the CAD group with an low-density lipoprotein (LDL) concentration <70 mg/dL (group A1), a fasting TyG index ≥8.25 and a PP TyG index ≥11 could predict moderate-high SYNTAX risk score; in addition, the odds ratio (OR) was 4.3× higher and the relative risk (RR) was 1.8× greater (OR = 4.3, RR = 1.8, 95% confidence interval = 1.4-13.5, P < 0.05) for individuals with a higher fasting TyG index ≥8.25 to have a moderate-high SYNTAX risk score. Individuals with a higher PP TyG index ≥11 had OR of 2.6× higher and a RR of 1.4× greater to have moderate-high SYNTAX risk score. CONCLUSIONS: Both fasting and PP TyG levels were associated with greater coronary anatomical complexity (SYNTAX score >22) in nondiabetic chronic coronary patients with LDL <70 mg/dL. Fasting and the PP TyG indices can serve as noninvasive predictors of CAD complexity in nondiabetic patients with LDL <70 mg/dL and could change the management and therapeutic approaches.

Rates of cerebrospinal fluid infection and the causative organisms following shunt procedures in Saudi Arabia. A retrospective study based on radiological findings.

OBJECTIVES: To assess the incidence of infection following various cerebrospinal fluid (CSF) shunt procedures among patients with hydrocephalus and related conditions, based on the age of the patient, and to determine the types of pathogens responsible for shunt infections. Methods: This retrospective single center study reviewed the records of patients with culture-confirmed CSF shunt infection diagnosed between January 2012 and December 2017. Cases without central nervous system imaging investigations were excluded. Results: The incidence rate of shunt-related infections was 32.2%. Among the 189 patients whose records were included, Staphylococcus epidermidis (47.5%) and Acinetobacter baumannii (18%) were the most common causative organisms. The incidence of postoperative infection was higher among those who underwent external ventricular drain procedures (65%) than among those who underwent ventriculoperitoneal shunt procedures (24%). There were no intraoperative deaths. However, the postoperative death rate was 12.2% during hospital stay (mean duration = 9 days); 2% of these deaths occurred after shunt removal. Conclusion: The incidence of infections after CSF shunt procedures was high in our tertiary academic hospital during the study period, compared to those reported in similar clinical settings and before developing a detailed standardized protocol for infection control. Although gram-negative organisms were the most prevalent cause of CSF infections, S. epidermidis (a gram-positive organism) was the most commonly encountered causative agent. Shunt protocols should be implemented to address perioperative shortcomings and to reduce overall mortality and morbidity.

Ethical clinical translation of stem cell interventions for neurologic disease.

The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk. In some cases, patients undergoing such operations are not included in a clinical trial, and do not provide genuinely informed consent. For these reasons and others, some current stem cell interventions for neurologic diseases are ethically dubious and could jeopardize progress in the field. We provide discussion points for the evaluation of new stem cell interventions for neurologic disease, based primarily on the new Guidelines for Stem Cell Research and Clinical Translation released by the International Society for Stem Cell Research in May 2016. Important considerations in the ethical translation of stem cells to clinical practice include regulatory oversight, conflicts of interest, data sharing, the nature of investigation (e.g., within vs outside of a clinical trial), informed consent, risk-benefit ratios, the therapeutic misconception, and patient vulnerability. To help guide the translation of stem cells from the laboratory into the neurosurgical clinic in an ethically sound manner, we present an ethical discussion of these major issues at stake in the field of stem cell clinical research for neurologic disease.

Left atrial and left atrial appendage functional recovery after cardioversion in patients with recent atrial fibrillation: Serial echocardiographic study.

BACKGROUND: The aim of this study is to point out timing of left atrium and its appendage functional recovery after cardioversion (CV) in recent onset atrial fibrillation (AF). METHODS: Fifty patients; 27 within 48-h (group I) and 23 after 48-h (group II), of AF onset, who had successful CV underwent transthoracic echocardiography (TTE), before and immediately after CV, then 15, 30 and 90 days later. Transesophageal echocardiography (TEE) was performed for group II before and for all patients immediately after CV and 1 month later. Mitral peak A velocity and left atrial (LA) reversal (Ar) velocity, tissue Doppler imaging (TDI) of septal mitral annular velocity (A1) and LA free wall velocity (A3) were recorded. Absence or peak A velocity < 50 cm/s was taken as a cut off value for atrial stunning. Intra-atrial conduction time (IACT) was measured. LA appendage late emptying (LAALE) velocity was measured by TEE-pulsed TDI of LA appendage. RESULTS: Post CV, all group II and 34% of group I experienced stunning. In both groups, peak A, Ar, A1, A3 and LAALE velocities increased (p = 0.000), while IACT decreased (p = 0.000) progressively over time. Partial recovery occurred after 15 and 30 days, while full recovery occurred 30 and 90 days post CV in groups I and II, respectively. IACT1 and IACT2 correlated with LA diameter (r = 0.2778 and r = 0.227, respectively, p < 0.01). CONCLUSIONS: Stunning and functional recovery of the LA and its appendage are strongly determined by the duration being in AF. Serial IACT by TDI was a good new parameter for detection of functional recovery of LA and LA appendage.

Optical coherence tomography features of angiographic complex and smooth lesions in acute coronary syndromes.

Plaque rupture (PR) and superimposed thrombosis have been shown as the most frequent underlying substrate in acute coronary syndromes (ACS). Coronary angiography is a luminogram not able to define in vivo features of the culprit plaques. The aim of the study was to use optical coherence tomography (OCT) to investigate the pathology underlying complex (CL) and non-complex angiographic lesions (NCL). We retrospectively enrolled 107 ACS patients admitted to our institution; 83 with non-ST elevation ACS (NSTE-ACS) and 24 with ST-elevation myocardial infarction. Coronary angiography was performed and culprit lesions were classified according to Ambrose criteria into NCL (n = 47) and CL (n = 60). OCT imaging was then performed to better identify plaque morphology; either PR or intact fibrous cap, the presence of superimposed thrombosis, lipid rich plaque, and thin cap fibroatheroma (TCFA). OCT analysis showed that 58 lesions (54.2%) were classified as PR and 48 lesions (44.9%) were associated with thrombi. Lipid rich plaques were identified in 62 lesions (57.9%). PR, intracoronary thrombi, lipid rich plaques and TCFA were more frequent in CL compared with NCL (71.7 vs 31.9%, 63.3 vs 21.3%, 71.7 vs 40.4% and 46.7 vs 21.3% respectively), but PR with superimposed thrombus may be also detected in NCL. OCT demonstrates PR and thrombosis in the majority of ACS patients presenting with CL. However, one-third of NCL show PR by OCT, suggesting that additional intracoronary imaging by OCT may better identify the underlying mechanism of coronary instability than coronary angiography alone.