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Ventricular septal defect (VSD) is common in pediatric patients. This study aimed to evaluate the safety and effectiveness of using fast-track anesthesia and comparing it to traditional anesthesia, among children undergoing a transthoracic device closure for VSD. A systematic review following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Relevant literature was identified through specific search terms in the Scopus, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (Embase), Web of Science, The Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. The inclusion criteria focused on observational studies that compared fast-track anesthesia with conventional anesthesia in pediatric VSD closure cases. Data extraction, quality assessment, and meta-analysis were performed using standard differences in means. Initially, 6,535 papers were identified, and subsequent screening of titles and abstracts led to the inclusion of four retrospective studies from a total of 51 studies. The analysis encompassed 477 patients, with 235 in the fast-track anesthesia group and 242 in the conventional anesthesia group. No statistically significant disparities were observed between the two groups concerning the operative duration and hemodynamic variations post-intubation or post-procedure (P >0.05). Nevertheless, the fast-track anesthesia group demonstrated significantly reduced healthcare expenses as well as shorter periods of mechanical ventilation, ICU stay, and overall hospitalization compared to conventional anesthesia (P <0.05). The use of fast-track anesthesia in combination with transthoracic device closure for VSD demonstrates a safe and effective approach for pediatric patients. This approach results in reduced healthcare costs (10,000 Renminbi (RMB)) and shorter durations of mechanical ventilation, ICU admission, and hospitalization compared to conventional anesthesia. Further clinical trials are necessary to confirm these results and assess long-term outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nasif et al.)

Cytokines, notably interleukin-6 (IL-6), increase considerably in patients with severe corona virus disease 2019 (COVID-19). This vigorous immune response may cause end-organ failure or death; hence, measuring IL-6 in the context of patient characteristics may help predict outcomes and encourage early comprehensive therapy. This study investigated the association between serum IL-6 levels, COVID-19 severity, and demographic, clinical, and biochemical characteristics. COVID-19 inpatients in NMC hospitals were investigated between November 2020 and November 2021. Several patient variables related to serum IL-6 and COVID-19 severity have been examined. The study included 374 COVID-19 inpatients, 235 of whom had severe disease with a median age of 51. The elderly had an increased risk of severe COVID-19 (73.8%) compared with young adults (71%), with higher white blood cells, D-dimer, Lactate dehydrogenase, creatinine, ferritin, prothrombin time, Procalcitonin, and fibrinogen levels (P < .001). C-reactive protein, troponin, intensive care unit admission, disease severity score, and mortality were significantly associated with higher serum IL-6 levels (P = .05) in the univariate analysis, but this significance disappeared in the multivariate analysis. IL-6, along with other demographic and clinical variables affected COVID-19 severity. These characteristics may predict patients at risk of severe disease and assist in establishing early comprehensive disease outcome strategies. Large-scale clinical research is needed to emphasize IL-6 and COVID-19., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Proton pump inhibitors (PPIs) are commonly used to treat acid-related disorders. Their appropriate use depends on the correct indications from the clinician. Owing to the high incidence of use and misuse, PPIs have been identified as an essential pharmacological class for developing deprescribing recommendations. Therefore, assessing physicians' knowledge and practice regarding PPI usage is critical for paving the way toward targeted recommendations and efforts. Objective: This study aimed to assess Syrian physicians' perceptions of proton pump inhibitors adverse effects, their benefit in upper gastrointestinal bleeding (UGIB) prophylaxis, and how these perceptions are related to PPI prescription practice. Methods: A cross-sectional study was performed using a web-based questionnaire distributed among Syrian physicians in internal medicine between 28 November and 23 December 2022. The questionnaire assessed perceptions and experiences of PPIs, concerns about specific adverse effects, and their effectiveness for UGIB prophylaxis, in addition to the different scenarios used to determine the best practice for appropriate treatment to manage minimal, mild, moderate, and high-risk UGIB patients. Results: A total of 473 participants completed the questionnaire, with median age ±SD was (28.46 ± 4.58), and most participants (83.3%) were residents. Approximately half of the participants (45.5%) agreed that discussion assistance was provided to continue or terminate PPIs properly. Only 8.9% were very familiar with published evidence of PPI adverse effects. Bone weakening and vitamin B12 deficiency were the most frequently reported side effects (81.8% and 79.7%, respectively). However, dementia (0.4%) and mortality (1.9%) were the least reported adverse effects. More than half of the participants (64%) perceived using PPIs to prevent upper GI bleeding. Non-trainee physicians were less knowledgeable about appropriate GERD management than resident physicians ( p < 0.001). Conclusion: The study showed a gap between Syrian physicians' perceptions and practices regarding PPI use, which necessitates spreading awareness of updated guidelines for PPI usage and their side effects., Competing Interests: Authors FM and BS were employed by Hamad Medical Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AG declared a shared parent affiliation with the authors FM and BS to the handling editor at the time of review., (Copyright © 2023 Swed, Alibrahim, Bohsas, Ibrahim, Siddiq, Jawish, Makhoul, Alrezej, Makhoul, Sawaf, Hafez, Makram Elsayed, Soliman and Wahsh.)

Background and Aims: We previously developed and validated a non-invasive diagnostic index based on routine laboratory parameters for predicting the stage of hepatic fibrosis in patients with chronic hepatitis C (CHC) called FIB-6 through machine learning with random forests algorithm using retrospective data of 7238 biopsy-proven CHC patients. Our aim is to validate this novel score in patients with metabolic dysfunction-associated fatty liver disease (MAFLD)., Method: Performance of the new score was externally validated in cohorts from one site in Egypt (n = 674) and in 5 different countries (n = 1798) in Iran, KSA, Greece, Turkey and Oman. Experienced pathologists using METAVIR scoring system scored the biopsy samples. Results were compared with FIB-4, APRI, and AAR., Results: A total of 2472 and their liver biopsy results were included, using the optimal cutoffs of FIB-6 indicated a reliable performance in diagnosing cirrhosis, severe fibrosis, and significant fibrosis with sensitivity = 70.5%, specificity = 62.9%. PPV = 15.0% and NPV = 95.8% for diagnosis of cirrhosis. For diagnosis of severe fibrosis (F3 and F4), the results were 86.5%, 24.0%, 15.1% and 91.9% respectively, while for diagnosis of significant fibrosis (F2, F3 and F4), the results were 87.0%, 16.4%, 24.8% and 80.0%). Comparing the results of FIB-6 rule-out cutoffs with those of FIB-4, APRI, and AAR, FIB-6 had the highest sensitivity and NPV (97.0% and 94.7%), as compared to FIB-4 (71.6% and 94.7%), APRI (36.4% and 90.7%), and AAR (61.2% and 90.9%)., Conclusion: FIB-6 score is an accurate, simple, NIT for ruling out advanced fibrosis and liver cirrhosis in patients with MAFLD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To assess annual change in prevalence of methicillin resistant Staphylococcus aureus (MRSA) from tissue and wound swab samples from foot ulcers (DFUs) in people with diabetes between 2005 and 2021., Methods: A retrospective analysis of everyone with MRSA positive wound or tissue swabs taken from our specialist multidisciplinary foot clinic between July 2005 and July 2021., Results: A total of 406 MRSA positive isolates from DFU swabs were identified from 185 individuals attending the foot clinic. There were 22 hospital-acquired infections (HAIs) and 159 community-acquired infections (CAIs). Fifty-two per cent (n = 37) of these individuals from 2010 to 2021 (n = 71) had presence of at least three risk factors for MRSA. The total number of swabs sent was 6312 from 1916 individuals living with diabetes. Annual MRSA DFU prevalence peaked in 2008 at 14.6% (n = 38), decreased in 2013 to 5.2% (n = 20) and did not exceed 4% (n = 6) from 2015 to 2021. Hospital MRSA was lowest in 2021 (n = 211), a 76% fall from 2007 (n = 880). Incidence of MRSA HAI from 2015 to 2021 ranged from 5.4% (n = 14) in 2020 to 11.5% (n = 41) in 2018., Conclusions: Prevalence of MRSA in DFU infections treated as outpatients is decreasing in line with falls in hospital acquired blood-borne infections and with overall hospital MRSA incidence. This is likely a reflection of the combination of interventions, including stringent antibiotic prescribing and decolonisation strategies. Reduction in prevalence should have positive impact on outcomes in people living with diabetes, reducing the complication of osteomyelitis and necessity for long-term antibiotic administration., (© 2023 Diabetes UK.)

Epilepsy is a chronic brain disorder characterized by unprovoked and recurrent seizures, of which 60% are of unknown etiology. Recent studies implicate microglia in the pathophysiology of epilepsy. However, their role in this process, in particular following early-life seizures, remains poorly understood due in part to the lack of suitable experimental models allowing the in vivo imaging of microglial activity. Given the advantage of zebrafish larvae for minimally-invasive imaging approaches, we sought for the first time to describe the microglial responses after acute seizures in two different zebrafish larval models: a chemically-induced epileptic model by the systemic injection of kainate at 3 days post-fertilization, and the didy s552 genetic epilepsy model, which carries a mutation in scn1lab that leads to spontaneous epileptiform discharges. Kainate-treated larvae exhibited transient brain damage as shown by increased numbers of apoptotic nuclei as early as one day post-injection, which was followed by an increase in the number of microglia in the brain. A similar microglial phenotype was also observed in didy s552-/- mutants, suggesting that microglia numbers change in response to seizure-like activity in the brain. Interestingly, kainate-treated larvae also displayed a decreased seizure threshold towards subsequent pentylenetetrazole-induced seizures, as shown by higher locomotor and encephalographic activity in comparison with vehicle-injected larvae. These results are comparable to kainate-induced rodent seizure models and suggest the suitability of these zebrafish seizure models for future studies, in particular to elucidate the links between epileptogenesis and microglial dynamic changes after seizure induction in the developing brain, and to understand how these modulate seizure susceptibility., Competing Interests: Declaration of Competing Interest A.D.C. is an executive and shareholder of Theracule AS. The remaining authors declare that the work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Chronic pelvic pain in women is a disorder brought on by pelvic vein incompetence (PVI). In this prospective, randomized study, the effects of percutaneous coil embolization and surgical ovarian vein ligation and division combined with retrograde sclerotherapy were compared with regard to ovarian vein occlusion, improvement of pelvic congestion symptoms, and their influence on estradiol level after intervention., Methods: A total of 50 patients with PVI were enrolled, with a mean age of 31.9 ± 4.7 years and a pain score of 9 (range, 0-10; from 0 [no pain] to 10 [the highest level of pain]). Both percutaneous coil embolization of ovarian veins (endovascular group) and surgical ovarian vein ablation with retrograde sclerotherapy were offered to the patients at random., Results: In the open group, the pain level decreased to 2, whereas in the endovascular group, it decreased to 1 (range, 0-10). Estradiol levels were 224 (range, 9-612) in the open group and 478 (range, 18-613) in the endovascular group before the intervention, with no significant change (P = .1120). After 1 week of intervention, estradiol levels in the open group were 89 (range, 18-243) and 124 (range, 22-298) in the endovascular group, respectively, with statistical insignificance (P = .225). After 1 month of intervention, the endovascular group's estradiol level was 101 (range, 20-196) and the open group's was 89 (range, 15-190) (P = .382). After 3 months of intervention, the open group's estradiol level was 78 (range, 12-132) and the endovascular group's was 65 (range, 18-110) (P = .045)., Conclusions: In addressing PVI, both methods seemed to have promising results. Nevertheless, endovascular management was more effective at decreasing estrogen levels and relieving discomfort. Three months should be the time at which estradiol levels are measured, because this is when they are at their lowest. In both the open and endovascular groups as well as in the pooled data, there was a significant association between estradiol level from before the intervention and improvement in pain scores (P = .005). Because it was linked to a lower pain score, the high preoperative estradiol level can be used to predict postintervention improvement., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Amyotrophic lateral sclerosis (ALS) is the most common, fatal adult neuromuscular disease. It is a multi-system disorder characterized primarily by motor manifestations, but there is established evidence for cognitive and behavioral impairment, which is associated with poor prognosis, hence, the importance of tools for its assessment. The Edinburgh Cognitive and Behavioral Assessment Screen (ECAS) is an invaluable assessment tool for cognition in ALS-front temporal spectrum dementia (FTSD), as it accommodates physical challenges that usually confound traditional neuropsychological testing in those patients., Objective and Methods: To validate the Egyptian Arabic version of ECAS (ECAS-EG) based on the original English scale. This is a prospective study. The ECAS was adapted and administered to 62 Egyptian ALS patients and 60 healthy controls. Patients were recruited from the Neuromuscular Unit, Ain Shams University Hospital. The ECAS was adapted to Egyptian Arabic after being translated using the back translation method. Internal consistency of the test, inter-rater reliability, and construct validity were assessed., Results: The Egyptian Arabic version of ECAS (ECAS-EG) showed good internal consistency using Cronbach's alpha of 0.84. Inter-rater reliability was tested, values for all variables were compared, and no statistically significant differences were found (ICC = .997). ECAS-EG discriminated significantly between the patients from the control subjects (p-value of 0.001). There was a strong positive correlation between the ECAS-EG total score and the MoCA total score with a p-value of 0.001, thus indicating convergent validity. The test showed that 63% of Egyptian ALS patients were cognitively affected; most affected domains were executive functions and verbal fluency., Conclusion: The current study proves that the Egyptian version of the ECAS (ECAS-EG) is valid and reliable among Egyptian ALS patients and it would be applicable to the general Arabic-speaking population., (© 2023. The Author(s).)

Purpose: Childhood cancer treatment is complex, resource-intensive, and expensive, and resource-limited settings would benefit from providing cost-effective treatment approaches on the basis of evidence. Effective implementation of cost-effective evidence-based treatment requires knowledge about factors influencing its use. In this study, we determined the clinicians' perceptions of the barriers and facilitators to implementing cost-effective evidence-based treatment for children with cancer in a resource-limited pediatric oncology setting in Egypt., Methods: We conducted a qualitative study on the basis of semistructured interviews with senior clinicians who make high-level decisions on treatment protocols and tailored decisions for the atypically complicated group of patients. Purposive sampling was used to recruit the participants. Thematic analysis was conducted semantically to develop themes of barriers and facilitators., Results: Fourteen participants agreed to participate in the study: nine pediatric oncologists; three surgeons; and two radiation oncologists. We identified four main themes of barriers and facilitators: awareness and orientation; knowledge, skills, and attitudes; system, resources, and context; and clinical practice. The main barriers included absence of easily available costs/cost-effectiveness data, limited resources and inability to pay for expensive novel (cost-effective) drugs, and gap between evidence and practice. The main facilitators included adopting standard treatment protocols on the basis of clinical effectiveness, leadership support, availability of patients' clinical and cost data from local context, and existing knowledge and skills in clinical research and health economic evaluation. The interview participants also provided suggestions to promote the implementation of cost-effective evidence-based treatment in priority areas., Conclusion: Our study findings provide an understanding of the barriers and facilitators affecting the implementation of cost-effective evidence-based treatment for childhood cancers in Egypt. We provide practical recommendations to address the implementation gaps with implications on practice, policy, and research.

This study aims to compare the efficacy and safety of 3 different hemostatic agents in vascular surgeries in humans. Twenty-four patients were enrolled in the present study with 40 vascular anastomoses including 16 aortic and 24 femoral. The patients were randomized (computer-based) to either BloodSTOP iX, Gelfoam, or Surgicel. The hemostatic agent was applied at the site of the vascular anastomosis before declamping. The site of anastomosis was then observed for bleeding from the suture line for 2 min. If any bleeding was detected, blood was then collected for 5 min, and the time needed to stop bleeding was measured. A suction drain was fixed in the surgical bed to collect serous fluid postoperatively more than 48 h afterward. The volume of blood collected in 5 min was significantly lower in the BloodSTOP group compared with the other 2 hemostatics. There was a significant reduction in the mean time needed to stop bleeding from the anastomotic surface in the BloodSTOP group compared with the Surgicel and Gelfoam groups. In addition, Surgicel showed the highest rate of complication (46.2%) compared with BloodSTOP (7%). BloodSTOP iX dramatically reduced bleeding volume and time compared with the other hemostatic agents. Furthermore, it showed a lower complication rate and did not interfere with the healing process at the application sites.

Introduction: Endoscopic ultrasound (EUS)-guided pancreatic cysto-gastrostomy/duodenostomy is the current accepted practice for management of symptomatic pancreatic pseudocysts with insertion of two or more double-pigtail (DP) stents. There is no much work on the efficacy of using a single wide-caliber DP stent, aiming to decrease the time, complications, and accessories used in the procedure., Aim of the Work: The aim of this study was to assess technical and clinical outcomes of using a single wide-caliber DP stent in EUSguided pancreatic pseudocyst drainage., Methodology: This multicenter prospective study included 57 patients, from which the 35 patients with symptomatic pancreatic pseudocysts enrolled. Patients with cysts with multiple septations (7 cases) or cyst with >30% necrosis (8 cases) of the cyst content and patients with generalized ascites (4 cases) or patients with major comorbidities (3 cases) were excluded. Patients were followed up within 1 month and 6 months after stent placement to assess complete resolution or a decrease in the sizes of cysts with clinical symptomatic improvement., Results: From 57 patients, 35 patients (19 females/16 males, median age 40 years) with a symptomatic pancreatic pseudocyst were referred for EUS-guided drainage. All used stents were 10 Fr DP plastic stents. The median duration of the whole procedure was 16 min. Technical success was achieved in all cases. Clinical success was encountered in 32 patients (91.4%) without re-accumulation on follow-up. Minor adverse events were encountered in 3 patients (8.6%) including post-procedure abdominal pain (1 case) and fever (2 cases)., Conclusion: We suggest that using a wide-caliber single-pigtail stent for EUS-guided cystogastrostomy is safe and effective with short procedure time, with reduced risks from the insertion of another stent(s)., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basell.)

Background: Childhood cancer in low-and middle-income countries is a global health priority, however, the perception that treatment is unaffordable has potentially led to scarce investment in resources, contributing to inferior survival. In this study, we analysed real-world data about the cost-effectiveness of treating 8886 children with cancer at a large resource-limited paediatric oncology setting in Egypt, between 2013 and 2017, stratified by cancer type, stage/risk, and disease status., Methods: Childhood cancer costs (USD 2019) were calculated from a health-system perspective, and 5-year overall survival was used to represent clinical effectiveness. We estimated cost-effectiveness as the cost per disability-adjusted life-year (cost/DALY) averted, adjusted for utility decrement for late-effect morbidity and mortality., Findings: For all cancers combined, cost/DALY averted was $1384 (0.5 × GDP/capita), which is very cost-effective according to WHO-CHOICE thresholds. Ratio of cost/DALY averted to GDP/capita varied by cancer type/sub-type and disease severity (range: 0.1-1.6), where it was lowest for Hodgkin lymphoma, and retinoblastoma, and highest for high-risk acute leukaemia, and high-risk neuroblastoma. Treatment was cost-effective (ratio <3 × GDP/capita) for all cancer types/subtypes and risk/stage groups, except for relapsed/refractory acute leukaemia, and relapsed/progressive patients with brain tumours, hepatoblastoma, Ewing sarcoma, and neuroblastoma. Treatment cost-effectiveness was affected by the high costs and inferior survival of advanced-stage/high-risk and relapsed/progressive cancers., Interpretation: Childhood cancer treatment is cost-effective in a resource-limited setting in Egypt, except for some relapsed/progressive cancer groups. We present evidence-based recommendations and lessons to promote high-value in care delivery, with implications on practice and policy., Funding: Egypt Cancer Network; NIHR School for Primary Care Research; ALSAC., Competing Interests: RS was funded by Egypt Cancer Network (ECN) for her research work on this study. CH is funded by the National Institute for Health Research (NIHR) School for Primary Care Research [Project Number 390] and NIHR Oxford BRC. CH also received expenses for his media work and the WHO. The views expressed are those of the author(s) and not necessarily those of the NIHR, the NHS or the Department of Health. NB and NSB are funded, in part, by ALSAC. All remaining authors declared no conflicts of interest. The authors were not paid to write this article by a pharmaceutical company or other agency. The funders had no role in the study design, data collection, data analysis, data interpretation, writing of the manuscript, or in the decision to submit the manuscript for publication. All authors had full access to the full data in the study and accept responsibility to submit for publication., (© 2022 The Authors.)

Internal jugular phlebectasia is a rare entity in which there is a fusiform dilatation of the internal jugular vein (IJV), usually presenting as a neck mass or tinnitus. The jugular bulb (JB) is an enlarged confluence connecting the sigmoid sinus and the IJV. It has been suggested that JB abnormality might also cause vertigo and pulsatile tinnitus. This prospective interventional study involved 15 patients with pulsatile tinnitus associated with internal jugular phlebectasia. Four patients presented with recurrent vertigo attacks. IJV diameter at rest ranged from 11 to 18 mm. Eight patients have had inner ear bone dehiscence, and 40% had high JB. All cases were treated by surgical fixation using a ringed polytetrafluoroethylene graft extending from the costoclavicular joint to the sigmoid sinus under fluoroscopic guidance. Tinnitus disappeared immediately postoperatively in all cases, followed by the disappearance of vertigo on the fourth day. Two cases reported thrombosis of the graft in the sixth and seventh months but maintained symptomatic improvement. Recurrence was reported in 2 cases while the grafts were patent. Surgical fixation by replacing the jugular vein and bulb with a synthetic graft may offer an excellent surgical option for relieving vascular tinnitus, especially in these young patients in whom endovascular therapy may not be a durable treatment.

Purpose: To assess the use of a 2-mm miniplate as a dorsal blocking plate to stabilize the central avulsion fragment in a proximal interphalangeal joint (PIP) volar fracture dislocation., Methods: This was a case series comprising 8 patients with volar fracture dislocation of the PIP joint. The average age of the patients was 36 years. The patients were managed by this technique within an average of 11 days following the injury. The clinical outcome measurements included the assessment of pain and range of motion of the PIP and distal interphalangeal joints., Results: The average follow-up duration was 20 months. The mean visual analog scale pain score was 1.9. The average range of motion of the PIP joint was 82°, whereas the average range of motion of the distal interphalangeal joint was 43°. Reduction of the subluxation was achieved in all cases, with no articular step remaining., Conclusions: A dorsal blocking plate is a simple technique, associated with a satisfactory outcome, for volar fracture dislocation injuries of the PIP joint., Type of Study/level of Evidence: Therapeutic V., (Copyright © 2022 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6-7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12,038 patients with chronic HCV were analyzed in this study, of whom 11,202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and log-rank tests. The performance of the GES score was evaluated using Harrell's C-index (HCI). The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (p < .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs., (© 2022 John Wiley & Sons Ltd.)

In the presented study, we developed a nanogold lateral glow immunoassay-based technique (LFI-COVID-19 antigen test) for the detection of SARS-CoV-2 nucleocapsid proteins; the developed LFI-COVID-19 Ag test has been tested for limit of detection (LOD), cross-reactivity and interfering substances, and performance. It was found that the performance of the developed LFI-COVID-19 antigen test when it was evaluated by RT-qPCR indicated 95, 98, and 97% for sensitivity, specificity and accuracy, respectively. This complies with the WHO guidelines. It was concluded that the developed LFI-COVID-19 antigen test is a point of care and an alternative approach to current laboratory methods, especially RT-qPCR. It provides an easy, rapid (within 20 min), and on-site diagnostic tool for COVID-19 infection, and it is a cheap test if it is manufactured on a large scale for commercial use.

Background: There is little evidence about childhood cancer burden in the WHO Eastern Mediterranean region (EMR). We aimed to provide an estimate of childhood cancer burden in the EMR, examine the connection between age-standardised mortality rate and level of income (gross domestic product [GDP] per capita), and reflect on the current status of childhood cancer registration in the EMR., Methods: Using the GLOBOCAN 2020 data from the Cancer Surveillance Unit of the International Agency for Research on Cancer, we extracted data for childhood cancer (at ages 0-14 years) incidence, prevalence, and mortality for 22 countries in the EMR, the EMR as a whole, and other WHO regions, and categorised by main cancer types. Childhood cancers were classified according to the 10th revision of the International Classification of Diseases. We also searched MEDLINE, Google Scholar, and the grey literature between May 17 and Aug 2, 2021, for English-language articles and reports about the status of childhood cancer registration in the EMR. We further examined the connection between age-standardised mortality rate and GDP per capita for the 22 countries in the EMR., Findings: The total estimated number of incident childhood cancer cases in the EMR was 23 847 in 2020, with an age-standardised incidence rate of 10·1 per 100 000 children at risk, ranging from 7·3 per 100 000 children at risk in Pakistan to 13·8 per 100 000 children at risk in Iran. The estimated number of incident cases was 7451 (age-standardised incidence rate 3·10 per 100 000 children at risk) for leukaemia, 3006 (1·30 per 100 000 children at risk) for brain and CNS tumours, 2222 (0·92 per 100 000 children at risk) for non-Hodgkin lymphoma, 1569 (0·67 per 100 000 children at risk) for kidney cancers, and 1420 (0·58 per 100 000 children at risk) for Hodgkin lymphoma. In 2020, the number of total estimated childhood cancer deaths in the EMR was 10 535, with an age-standardised mortality rate of 4·4 (per 100 000 children at risk, ranging from 0·8 per 100 000 children at risk in Qatar to 7·2 per 100 000 children at risk in Somalia. A negative correlation was found between countries' GDP per capita (income level) and mortality rates (r=-0·77, p<0·0001). The scarcity of data and quality of cancer registries in EMR countries prevented further analysis., Interpretation: Given the variable quality and coverage of cancer registries in EMR countries, these findings are likely to be underestimates. Nevertheless, these data, especially the high mortality rates, reflect a need for effective national childhood cancer plans in line with the WHO Global Initiative for Childhood Cancer to improve survival., Funding: Friends of Cancer Patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Survival outcomes of children with relapsed/refractory (r/r) acute leukemia remain poor. Novel expensive treatments have been developed to improve their outcomes, yet, limited evidence exists about cost-effectiveness of alternative treatment strategies., Areas Covered: A systematic review was conducted to summarize health-economic evidence about costs/cost-effectiveness of treating r/r acute leukemia in children/young adults. We searched Medline, Embase, and Cochrane databases until August 13th, 2021. Eligible articles included peer-reviewed original studies addressing r/r pediatric/young-adult acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Quality assessment was conducted using Consolidated Health Economics Evaluation Reporting Standards (CHEERS) checklist., Expert Opinion: The majority of papers focused on CAR-T cell therapy, which is still a novel treatment for r/r ALL, and was found to be cost-effective, yet, there remain concerns over its long-term effectiveness, affordability, and equity in access. The next best treatment option is Blinatumomab, followed by Clofarabine therapy, whereas FLA-IDA salvage chemotherapy provides least value for money. The quality of evidence is moderate to high, with limited generalizability of findings due to high variability in outcomes obtained from modeling studies. Limited studies evaluated r/r AML. We provide recommendations to deliver cost-effective treatments in real-world contexts, with implications for healthcare policy and practice.

Objective: The study aimed to evaluate the effect of mild and moderate hemodilution during CPB on the neurocognitive dysfunction in patients undergoing coronary artery bypass grafting., Design: A randomized clinical study., Setting: Cardiac center., Patients: 186 patients scheduled for cardiac surgery with cardiopulmonary bypass., Intervention: The patients were classified into 2 groups (each = 93), Mild hemodilution group: The hematocrit value was maintained >25% by transfusion of packed-red blood cells plus hemofiltration during CPB. Moderate hemodilution group: the hematocrit value was maintained within the range of 21-25%., Measurements: The monitors included the hemofiltrated volume, number of transfused packed red blood cells, and the incidence of postoperative cognitive dysfunction., Main Results: The hemofiltrated volume during CPB was too much higher with mild hemodilution compared to the moderate hemodilution (p = 0.001). The number of the transfused packed red blood cells during CPB was higher with mild hemodilution compared to the moderate hemodilution (p = 0.001), but after CPB, the number of the transfused packed red blood cells was lower with the mild hemodilution group than the moderate hemodilution (p = 0.001). The incidence of total postoperative neurological complications was significantly lower with the mild hemodilution group than moderate hemodilution (p = 0.033). The incidence of neurocognitive dysfunction was significantly lower with mild hemodilution group than moderate hemodilution (p = 0.042)., Conclusions: The mild hemodilution was associated with a significant decrease in the incidence of neurocognitive dysfunction compared to moderate hemodilution in patients undergoing coronary artery bypass grafting. Also, the transfused packed red blood cells increased during CPB and decreased after CPB with the mild hemodilution than moderate hemodilution., Competing Interests: None

Background: Non-invasive tests (NITs), such as Fibrosis-4 index (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI), developed using classical statistical methods, are increasingly used for determining liver fibrosis stages and recommended in treatment guidelines replacing the liver biopsy. Application of conventional cutoffs of FIB-4 and APRI resulted in high rates of misclassification of fibrosis stages., Aim: There is an unmet need for more accurate NITs that can overcome the limitations of FIB-4 and APRI., Patients and Methods: Machine learning with the random forest algorithm was used to develop a non-invasive index using retrospective data of 7238 patients with biopsy-proven chronic hepatitis C from two centers in Egypt; derivation dataset (n = 1821) and validation set in the second center (n = 5417). Receiver operator curve analysis was used to define cutoffs for different stages of fibrosis. Performance of the new score was externally validated in cohorts from two other sites in Egypt (n = 560) and seven different countries (n = 1317). Fibrosis stages were determined using the METAVIR score. Results were also compared with three established tools (FIB-4, APRI, and the aspartate aminotransferase-to-alanine aminotransferase ratio [AAR])., Results: Age in addition to readily available laboratory parameters such as aspartate, and alanine aminotransferases, alkaline phosphatase, albumin (g/dl), and platelet count (/cm 3 ) correlated with the biopsy-derived stage of liver fibrosis in the derivation cohort and were used to construct the model for predicting the fibrosis stage by applying the random forest algorithm, resulting in an FIB-6 index, which can be calculated easily at http://fib6.elriah.info. Application of the cutoff values derived from the derivation group on the validation groups yielded very good performance in ruling out cirrhosis (negative predictive value [NPV] = 97.7%), compensated advance liver disease (NPV = 90.2%), and significant fibrosis (NPV = 65.7%). In the external validation groups from different countries, FIB-6 demonstrated higher sensitivity and NPV than FIB-4, APRI, and AAR., Conclusion: FIB-6 score is a non-invasive, simple, and accurate test for ruling out liver cirrhosis and compensated advance liver disease in patients with chronic hepatitis C and performs better than APRI, FIB-4, and AAR., (© 2021 Japan Society of Hepatology.)

Background and Aim: Many HCC risk prediction scores were developed to guide HCC risk stratification and identify CHC patients who either need intensified surveillance or may not require screening. There is a need to compare different scores and their predictive performance in clinical practice. We aim to compare the newest HCC risk scores evaluating their discriminative ability, and clinical utility in a large cohort of CHC patients., Patients and Methods: The performance of the scores was evaluated in 3075 CHC patients who achieved SVR following DAAs using Log rank, Harrell's c statistic, also tested for HCC-risk stratification and negative predictive values., Results: HCC developed in 212 patients within 5 years follow-up. Twelve HCC risk scores were identified and displayed significant Log rank (p ≤ 0.05) except Alonso-Lopez TE-HCC, and Chun scores (p = 0.374, p = 0.053, respectively). Analysis of the remaining ten scores revealed that ADRES, GES pre-post treatment, GES algorithm and Watanabe (post-treatment) scores including dynamics of AFP, were clinically applicable and demonstrated good statistical performance; Log rank analysis < 0.001, Harrell's C statistic (0.66-0.83) and high negative predictive values (94.38-97.65%). In these three scores, the 5 years cumulative IR in low risk groups be very low (0.54-1.6), so screening could be avoided safely in these patients., Conclusion: ADRES, GES (pre- and post-treatment), GES algorithm and Watanabe (post-treatment) scores seem to offer acceptable HCC-risk predictability and clinical utility in CHC patients. The dynamics of AFP as a component of these scores may explain their high performance when compared to other scores., (© 2022. Asian Pacific Association for the Study of the Liver.)

Importance: Rates of opioid overdose deaths are increasing for older adults. Less is known about these deaths compared with those of younger adults., Objective: To analyze rate variation among opioid overdose deaths in older adults by sex and by race and ethnicity over time., Design, Setting, and Participants: This 21-year longitudinal cross-sectional study of adults who died due to opioid overdose at 55 years or older stratified by sex and by race and ethnicity used data from the Multiple Cause of Death database from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. The data include all opioid overdose deaths among this age group that occurred between January 1, 1999, and December 31, 2019 (N = 79 893)., Exposures: Sex and racial and ethnic groups., Main Outcomes and Measures: Rates of opioid overdose deaths per 100 000 population by sex and by race and ethnicity for persons 55 years or older., Results: During the period 1999 to 2019, 79 893 US residents 55 years or older died due to an opioid overdose. Among these individuals, 79.97% were aged 55 to 64 years, and 58.98% were men. Annual numbers of deaths increased over time from 518 in 1999 to 10 292 in 2019. Annual rates of opioid overdose deaths per 100 000 persons 55 years or older increased over time and ranged from 0.90 in 1999 to 10.70 in 2019. Substantial variation by sex and by race and ethnicity was found. In 2013, rates among non-Hispanic Black men began to diverge from those of other demographic subgroups. By 2019, the opioid overdose fatality rate among non-Hispanic Black men 55 years or older was 40.03 per 100 000 population, 4 times greater than the overall opioid overdose fatality rate of 10.70 per 100 000 for persons of the same age., Conclusions and Relevance: In this longitudinal cross-sectional study of US adults who died due to opioid overdose, the burden of opioid overdose deaths among older adults since 2013 was most concentrated among non-Hispanic Black men. Deaths among non-Hispanic Black men were disproportionality represented in the overall increase in the rate of opioid overdose deaths among older adults. Further research is needed to inform policy and practice.

The epidemiology of HDV infection worldwide is obscure. Mapping the epidemiology of the infection is highly required, so, we aimed to estimate the prevalence of hepatitis D virus infection among chronic hepatitis B patients and the epidemiological characteristics in the Nile delta in Egypt. This was a prospective observational cross-sectional study including consecutive chronic hepatitis B patients in the out-patient clinics at the Egyptian Liver Research Institute and Hospital (ELRIAH) and its satellites in the Nile Delta from January 2016 until August 2018. They were recruited from patients enrolled in Educate, Test and Treat program, which was implemented in 73 Egyptian Villages. Subjects were tested by using HBsAg serological rapid diagnostic tests (RDTs), and then HBV DNA by PCR was done in HBsAg-positive cases. HDV IgG antibody testing and confirmatory HDV RNA PCR were done. Complete liver functions, abdominal ultrasonography and FibroScan were also performed. The prevalence of HDV was 3.4% using anti-delta antibody (22/631), and only 8 were positive for HDV RNA (8/22, 36.4%). Overall HDV prevalence using PCR was 8/631(1.27%). HDV-positive cases were mainly males (68.2%). Eight cases were cirrhotic (36.4%), 3 (13.6%) had HCC and 7 (31.8%) were HBeAg positive. HDV prevalence is low among chronic hepatitis B patients in the Nile delta, Egypt. Screening for HDV IgG is recommended in CHB patients who had cirrhosis, HCC or HBeAg positive., (© 2021 John Wiley & Sons Ltd.)

Much concern was directed towards the crucial role of recombinant tissue plasminogen activator (rt-PA) in improving neuroplasticity in patients with acute ischemic stroke. The aim of the work to investigate the effect of treating patients with acute ischemic stroke with rt-PA, on the level of brain derived neurotrophic factor (BDNF) as a marker of neuroplasticity. This study was conducted on 47 patients presenting with acute ischemic stroke (during the first 4.5 h from stroke onset); 26 patients of them eligible for receiving rt-PA (patient group) and 21 patients having contraindications for treatment with rt-PA (control group). Neurological, radiological and laboratory assessment (including BDNF serum level) were done for both groups at stroke onset (before receiving rt-PA) and at day 7. There was a statistically significant increase in BDNF serum level from day 1 to day 7 in rt-PA treated patients in comparison to control group (P-value˂ 0.001). Serum level of BDNF is significantly higher at the onset of stroke in female patients and non-smokers than males or smokers (P-value = 0.011, 0.01 respectively). There was no effect of either age, body mass index, hypertension, diabetes, drug abuse, past or family history of stroke, valvular heart diseases, atrial fibrillation, cardiomyopathy, ejection fraction, carotid atherosclerotic changes, lipid profile or uric acid, on BDNF serum level measured at the onset of stroke. Treatment of patients with acute ischemic stroke with rt-PA causes significant improvement in neuroplasticity through increasing BDNF serum level., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: There is a lack ofevidence about resource use and costs of childhood cancer care in Egypt. Knowledge about resource use/costs can help in better resource planning to improve care and outcomes efficiently. In this study, we estimated patterns and trends of hospital resource use and costs for children with cancer (n = 8886, aged 0-18 years) treated at Children's Cancer Hospital, Egypt (CCHE), between 2013 and 2017, by ICCC-3 groups, at one and three years post-diagnosis., Methods: We estimated costs from the healthcare provider perspective, expressed in USD 2019. We also studied resource use/cost trends, and factors associated with inpatient days and costs., Results: For all cancers combined, median costs were $14,774 (IQR: $6,559-$23,738) at one year and $19,799 (IQR: $8,921-$34,204) at three years post-diagnosis. Median inpatient days were 38 days (IQR: 17-60) at one year, and 43 days (IQR: 20-74) at three years post-diagnosis. Patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and neuroblastoma imposed the greatest financial burden on CCHE, representing 53.1% of total costs. AML patients had the highest costs/resource use of all childhood cancers. Cost trends decreased by 2.9% (P < 0.001) for all cancers combined, due to economic instability in Egypt between 2013 and 2017. The use of IV supportive drugs increased by 24.3% (P < 0.001) over time for children with solid tumors., Conclusion: These findings will inform hospital resource planning and budgeting to promote value in care delivery, with implications for pediatric oncology practice and policy in Egypt/CCHE. Estimated costs provide the foundation for cost-effectiveness analysis., (© 2021 Wiley Periodicals LLC.)

Background and Aims: With the growing number of treated hepatitis C patients, the current 'one-size-fits-all' hepatocellular carcinoma (HCC) surveillance strategies for patients with advanced fibrosis represents a great burden on healthcare systems. An individualized HCC risk strategy incorporates the dynamic changes of HCC risk are lacking., Methods: This single-centre observational study included 3075 patients, with advanced fibrosis (≥F3) who achieved SVR following DAAs at Egyptian Liver research institute and hospital (ELRIAH) with follow-up period (range 6-72 months). The performance of a recently developed General Evaluation Score (GES) HCC risk stratification score was calculated pre- and post-treatment using Harrell's c statistic. Times to HCC and cumulative incidences were calculated with Kaplan-Meier method and compared using log-rank (Mantel-Cox) test., Results: Pre-treatment GES score stratified patients into low (60.4%), intermediate (23.4%), and (16.2%) high-risk score where 5-year cumulative incidences of HCC were 1.66%, 4.45% and 7.64%, respectively. Harrell's c statistic was 0.801. Post-treatment GES score stratified patients into low (57.4%), intermediate (30.7%) and (11.9%) high-risk score where 5-year cumulative incidences of HCC were 1.35%, 3.49% and 11.09% respectively. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.818. Using pre- and post-treatment GES score, GES algorithm was developed with higher predictive value. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.832., Conclusion: A dynamic algorithm incorporating both pre- and post-GES scores have better performance and predictive value compared with only pre-treatment assessments. The proposed algorithm would help to stratify those who need intensive or being excluded from screening., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Numerous studies have been carried out to identify the role of microRNA (miRNA) as potential biomarkers for many diseases including amyotrophic lateral sclerosis (ALS). The aim of this study was to explore the circulating levels of some miRNAs in cohort of Egyptian ALS patients in an attempt to correlate the selected miRNA profiles with disease progression., Methods: Thirty ALS patients and 20 age and sex matched healthy controls were enrolled. Circulating miRNA levels were determined in venous blood samples, collected on EDTA, from all the study subjects. The selection of miRNA species (miR-206, miR-142-3p, miR-143-3p, miR-181a-5p, miR-106b-3p, miR-4516 and Let7f-5p) was based on their involvement in the pathophysiology of ALS and was further confirmed by data mining of specific miRNA databases (miRBase and miRDB)., Results: As compared to the control group, significant consistent upregulation was found in the levels of miR-206, miR-143-3p and to a lesser extent in miR-142-3p. An elevation trend, although not significant, was also found in the levels of miR-181a-5p, miR-106b-3p, and miR-4516. Interestingly, we found that the levels of miR-142-3p were elevated in familial cases, while that of miR-4516 were significantly increased in sporadic cases. Furthermore, the levels of Let7f-5p, although were generally lowered in ALS patients but were also decreased in familial cases as well as in spinal onset ALS as compared to bulbar onset., Conclusion: This is the first study investigating miRNA profiles in Egyptian ALS patients. We found that some miRNAs are significantly altered in ALS patients, and some may be used to distinguish familial and sporadic cases and bulbar and spinal onset. Larger study is needed, in which we will conduct a correlation of miRNA levels against variations in disease onset, progression as well as systemic inflammatory responses and the extent of neuromuscular involvement in Egyptian ALS patients in an attempt to identify environmental/occupational risk factors., (Copyright © 2021. Published by Elsevier B.V.)

Background: The choice of ring type for mitral valve (MV) repair is still debatable and usually is left to the surgeon's discretion., Aim: The aim of this study was to compare the early and mid-term results after repair of ischaemic mitral regurgitation (MR) with complete and incomplete annuloplasty rings., Methods: Collected data included preoperative assessment (age, sex, comorbidities, clinical status, NYHA grade, and the EURO score); intraoperative details (echocardiography, degree of MR, and cross-clamp time); and results (the length of ICU and hospital stay, duration and need for inotropes, duration of mechanical ventilation, and postoperative adverse events). Follow up after discharge included assessment of dyspnea status, the degree and progression of MR, and left ventricular function and dimensions., Results: The present study included 133 patients: 61 with incomplete rings and 72 with complete rings inserted. There was no significant difference in the rate of postoperative complications between the two groups, apart from a significantly higher percentage of patients with incomplete ring who required prolonged ventilation >24 hours (P = 0.002). There were no significant differences between the two groups, regarding the grade of residual MR (P = 0.464), postoperative dyspnea status (P = 0.723), 30-day mortality rate (P = 0.687), and mean duration of survival (P = 0.276)., Conclusion: The choice of incomplete or complete annuloplasty ring was not associated with a marked difference in the early and midterm results of ischaemic MV repair.

Autoimmune hepatitis is a chronic inflammatory hepatic disorder which may cause liver fibrosis. Appropriate treatment of autoimmune hepatitis is therefore important. Adult stem cells have been investigated as therapies for a variety of disorders in latest years. Hematopoietic stem cells (HSCs) were the first known adult stem cells (ASCs) and can give rise to all of the cell types in the blood and immune system. Originally, HSC transplantation was served as a therapy for hematological malignancies, but more recently researchers have found the treatment to have positive effects in autoimmune diseases such as multiple sclerosis. Mesenchymal stem cells (MSCs) are ASCs which can be extracted from different tissues, such as bone marrow, adipose tissue, umbilical cord, and dental pulp. MSCs interact with several immune response pathways either by direct cell-to-cell interactions or by the secretion of soluble factors. These characteristics make MSCs potentially valuable as a therapy for autoimmune diseases. Both ASC and ASC-derived exosomes have been investigated as a therapy for autoimmune hepatitis. This review aims to summarize studies focused on the effects of ASCs and their products on autoimmune hepatitis.

Background: Self-testing for hepatitis C virus antibodies (HCVST) may be an additional strategy to expand access to hepatitis C virus (HCV) testing and support elimination efforts. We conducted a study to assess the usability and acceptability of HCVST among the general population in a semi-rural, high-HCV prevalence region in Egypt., Methods: An observational study was conducted in two hospitals in the Nile Delta region. A trained provider gave an in-person demonstration on how to use the oral fluid HCVST followed by observation of the participant performing the test. Usability was assessed by observing errors made and difficulties faced by participants. Acceptability of HCV self-testing was assessed using an interviewer-administered semi-structured questionnaire., Results: Of 116 participants enrolled, 17 (14.6%) had received no formal education. The majority (72%) of participants completed all testing steps without any assistance and interpreted the test results correctly. Agreement between participant-reported HCVST results and interpretation by a trained user was 86%, with a Cohen's kappa of 0.6. Agreement between participant-reported HCVST results and provider-administered oral fluid HCV rapid test results was 97.2%, with a Cohen's kappa of 0.75. The majority of participants rated the HCVST process as easy (53%) or very easy (44%), and 96% indicated they would be willing to use HCVST again and recommend it to their family and friends., Conclusion: Our study demonstrates the high usability and acceptability of oral fluid HCVST in a general population. Further studies are needed to establish the optimal positioning of self-testing alongside facility-based testing to expand access to HCV diagnosis in both general and high-risk populations.

Objective: Modern coronary interventional practice can result in coronary vessels that are totally stented. The term "full metal jacket" has been coined to refer to vessels that have an overlapping stent in series along the whole length of the vessel. This poses a serious challenge to surgical revascularization, particularly when a left internal thoracic artery (LITA) to the left anterior descending (LAD) needs to be undertaken. We evaluated the early and midterm results of on-pump coronary artery bypass grafting (CABG) following "stent endarterectomy" for the LAD with LITA to LAD grafting., Methods: During October 2017 to September 2020, 21 patients presented with multi-vessel disease and a totally occluded LAD with a stent full metal jacket. No distal target for LITA grafting was available, despite a viable myocardial territory. The LAD was endarterectomised, removing the column of totally occluded stents with the medial wall of the vessel, leaving the proximal stent in place to avoid competitive flow. Long length anastomosis was then undertaken with the LITA graft. Postoperatively, patients were followed up clinically and by coronary computed tomography (CT) angiography at 6- and 18-month intervals. All patients were discharged on a combination of aspirin and warfarin for three months and then aspirin and clopidogrel for the rest of the first year and then aspirin alone for life., Results: Patients had a mean age of 58.07 ± 2.06 yr. Sixteen (76.2%) were males, 13 (61.9%) patients were diabetics, 18 (85.7%) were hypertensive, 15 (71.4%) were dyslipidemic, six (28.6%) were obese, 11 (52.4%) were smokers, and five (23.8%) had positive family history of ischemic heart disease (IHD). The number of grafts per patient ranged 3-5, with a mean cross-clamp time of 64.71± 8.84 min. There were no postoperative deaths nor MI clinically, by electrocardiogram (ECG) criteria nor by troponin or CK-MB. In-hospital complications included one (4.8%) patient who required re-exploration for bleeding, one (4.8%) developed a superficial wound, and three (14.3%) developed atrial fibrillation (AF), during their hospital stay. Mean hospital stay was 7.71±1.73 days. All patients completed the 6-month follow up showing patent LITA to LAD with coronary CT angiography. One patient was lost to follow up after six months; five patients are awaiting their 18-month CT angiography, while 15 (71.4%) patients have completed their 18-month CT angiography, and all have a patent LITA to LAD., Conclusions: Stent endarterectomy for a totally occluded LAD with a full metal jacket and viable myocardial territory is a safe procedure with good early and midterm results. This technique should be considered in these difficult cases presenting for revascularisation when no other option is available.

Introduction: ALSFRS-R is 12-item scale used to assess disability and to measure disease progression in ALS patients. The objective is to validate the Arabic version of ALSFRS-R based on the original English version. Methods and patients: This is a cross sectional study. ALSFRS-R was administered to 162 Egyptian patients with ALS after being translated in Arabic, and reapplied after 1 week. Patients were recruited from 2 centers: Neuromuscular unit, Ain Shams University hospitals and the specialized ALS clinic which is located at the international medical center (IMC). Results: No significant differences were found between the application and reapplication of the scale ( p  = 0.5). The linear regression and internal consistency that were measured by Pearson correlation and alpha Conbrach respectively were significant. Discussion: The Arabic version of the ALSFRS-R proposed by the current was proven to be reproducible and valid among Egyptian ALS patients. Thus, it will provide a useful tool for professionals to evaluate Arabic speaking patients in clinical practice and research.

Hepatic fibrosis is a progressive disease with serious clinical complications that arise from abnormal propagation and activation of multiple inflammatory pathways. Nilotinib is an oral tyrosine kinase inhibitor with antifibrotic activity. Mesenchymal stem cells (MSCs) are blank cells and can differentiate into specific cell types. They have the potential to repair and regenerate cells. MSCs have a special paracrine fashion where they produce special exosomes, microvesicles, and cytokines like IL-6, transforming growth factor-beta (TGF- β ), and HGF as well as hepatic stellate cell suppressors. This paracrine fashion can decrease collagen deposition, enhance antifibrotic, anti-inflammatory, and angiogenic activity in vitro and in vivo. In our study, the rat's hepatic stellate cells (HSCs) in addition to different normal cell lines were treated with Nilotinib alone and in combination with liver mesenchymal stem cells conditioned medium (LMSCs-CM) for 24 h. Mono and combined therapy antifibrotic and cytotoxicity effects were evaluated using different parameters including α -SMA, cytochrome c, P53 expression, collagen deposition, DNA content, oxidative stress parameters, cell viability, and apoptosis by flow cytometry analysis. Our results showed that Nilotinib and LMSCs-CM in combination had a significantly potent antifibrotic and anti-inflammatory effect on activated hepatic stellate cells than Nilotinib alone; otherwise, this combination showed the best safety with minimal cytotoxicity on different normal cell lines., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ahmed Nabil et al.)

The new anti-hepatitis C virus (HCV) molecules improve treatment regimens and outcomes, but there are drawbacks. New combinations should target the HCV infectious cycle and be effective against all HCV genotypes. We developed the novel formulation Catvira, composed of epigallocatechingallate (EGCG) + sofosbuvir + ribavirin. Here, we compared Catvira to sofosbuvir + ribavirin tablets in patients with CHC genotype 4 in a randomized open-label efficacy and safety study. Treatment-naïve and treatment-experienced patients (n = 80) were randomly assigned to receive a single daily fixed dose of Catvira or sofosbuvir + ribavirin for 12 or 24 weeks. Both Catvira and sofosbuvir + ribavirin yielded similar outcomes of viral load (p < 0.001). Patients receiving Catvira had a significantly more rapid rate of viral load decline with sustained virologic response (SVR12) achieved by 90% of patients receiving 12 weeks of treatment. Catvira did not impact hemoglobin levels while sofosbuvir + ribavirin showed significant decline in hemoglobin levels after 24 weeks (p < 0.05). In this clinical trial (ClinicalTrials.gov Identifier NCT02483156), we found that Catvira administered daily for 12 or 24 weeks is safe, effective, and well-tolerated in both naïve and treatment-experienced patients with HCV genotype 4.

Coronaviruses are positive-sense single-strand RNA viruses that infect amphibians, birds, and mammals. Coronavirus Disease 2019 (COVID-19) has become a major health problem caused by one of the coronaviruses called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread fast throughout the globe since its first identification in Wuhan, China, in December 2019. Although COVID-19 is principally defined by its respiratory symptoms, it is now clear that the virus can also affect the digestive system causing gastrointestinal (GI) symptoms like diarrhea, loss of appetite, nausea/vomiting, and abdominal pain as a major complaint. GI symptoms could be the initial signs of preceding respiratory signs, carrying a potential for slowed investigation and raised disease transmission opportunities. Various studies recognized the COVID-19 RNA in stool specimens of infected patients, and its viral receptor angiotensin-converting enzyme-2 (ACE-2) is highly expressed in GI epithelial cells. Many cases were reported negative using nasopharyngeal/oropharyngeal swabs and finally, SARS-CoV-2 RNA was detected in their anal/rectal swabs and stool specimens. These suggest that COVID-19 can actively infect and replicate in the GI tract. In this review, we elaborate on the close relationship between SARS-CoV-2 and the digestive system, focusing on the current status in the field of COVID-19 in gastroenterology, liver injury, endoscopy, inflammatory bowel disease, imaging, and the potential underlying mechanisms with illustrating the current epidemiological status regarding this pandemic., (Copyright © 2021 Nabil et al.)

Background & Aims: Egypt has a major HCV burden and a well established treatment programme, with an ambitious goal of HCV elimination. Our aim was to assess the impact of a comprehensive HCV prevention, test and treat programme on the incidence of new HCV infections in 9 villages in rural Egypt., Methods: An HCV "educate, test and treat" project was implemented in 73 villages across 7 governorates in Egypt between 06/2015 and 06/2018. In 2018, in 9 of the villages we re-tested individuals who originally tested HCV antibody (HCV-Ab) and HBsAg negative using rapid diagnostic tests (RDTs); confirmatory HCV RNA testing was performed for positive cases. The incidence rate per 1,000 person-years (py) was calculated, and risk factors for incident HCV infections assessed through an interviewer-administered questionnaire in 1:3 age- and gender-matched cases and controls., Results: Out of 20,490 individuals who originally tested HCV-Ab negative in the 9 villages during the 2015-2016 implementation of the "educate, test and treat" programme, 19,816 (96.7%) were re-tested in 2018. Over a median of 2.4 years (IQR 2.1-2.7), there were 19 new HCV infections all of which were HCV RNA positive (incidence rate 0.37/1,000 py) (95% CI 0.24-0.59). Compared to a previous estimate of incidence in the Nile Delta region (2.4/1,000 py) from 2006, there was a substantial reduction in overall incidence of new HCV infections. Exposures through surgery (odds ratio 51; 95% CI 3.5-740.1) and dental procedures (odds ratio 23.8; 95% CI 2.9-194.9) were significant independent predictors of incident infections., Conclusions: This is the first study to show a substantial reduction in incidence of new HCV infections in a sample of the general population in Egypt following attainment of high testing and treatment coverage. New infections were significantly associated with healthcare-associated exposures., Lay Summary: Egypt has a major national HCV testing and treatment programme with the goal of eliminating HCV infection. We assessed the impact of a comprehensive HCV prevention, test and treat programme in 73 villages that achieved high coverage of testing and treatment on the subsequent incidence of new HCV infections in nine of the villages. We re-tested people who were previously HCV antibody negative and found that the rate of new HCV infections was greatly reduced compared to previous estimates. We also found that exposure through surgery and dental procedures were associated with these new infections. This highlights the importance of continued strengthening of infection control and prevention measures, alongside treatment scale-up., Competing Interests: Conflicts of interest The authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 World Health Organization. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Myomectomy is associated with perioperative bleeding. The aim of the study is to evaluate the effect of intramyometrial vasopressin on blood loss and the associated cardiovascular complications during myomectomy., Methods: The study included 194 patients classified into two groups- 1) Vasopressin group: the vasopressin was diluted as 0.1 unit/ml and 15 ml was injected by the surgeon in the plane between the myometrium and the myoma. 2) Control group: The patients received an equal amount of normal saline. The monitored parameters included the amount of blood loss, required blood transfusion, heart rate, mean arterial blood pressure, the incidence of hypertension, hypotension, bradycardia, tachycardia, electrocardiogram (ECG) changes and the blood troponin I level., Results: The heart rate decreased significantly in both groups, but the decrease was lower with vasopressin than the control group through the time points T3 to T5 ( P < 0.05) The mean arterial blood pressure increased significantly in both groups, but the increase was higher with vasopressin than the control group through T3 to T5 ( P < 0.05). The amount of blood loss decreased significantly with vasopressin than the control groups ( P = 0.001). The number of transfused packed red blood cells was lower with vasopressin than the control group ( P = 0.001). The incidence of hypertension, bradycardia and atrial extrasystole was higher with vasopressin than the control group ( P = 0.005, P = 0.012, P = 0.033, respectively)., Conclusion: Intramyometrial vasopressin decreases blood loss and blood transfusion, but it is associated with cardiovascular complications that may be serious as reported in other studies. Therefore, anaesthesiologists and gynaecologists must follow the precautions to avoid and minimise the incidence of complications with intramyometrial vasopressin., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Anaesthesia.)

Isomerization of l-aspartyl and l-asparaginyl residues to l-isoaspartyl residues is one type of protein damage that can occur under physiological conditions and leads to conformational changes, loss of function, and enhanced protein degradation. Protein l-isoaspartyl methyltransferase (PCMT) is a repair enzyme whose action initiates the reconversion of abnormal l-isoaspartyl residues to normal l-aspartyl residues in proteins. Many lines of evidence support a crucial role for PCMT in the brain, but the mechanisms involved remain poorly understood. Here, we investigated PCMT activity and function in zebrafish, a vertebrate model that is particularly well-suited to analyze brain function using a variety of techniques. We characterized the expression products of the zebrafish PCMT homologous genes pcmt and pcmtl . Both zebrafish proteins showed a robust l-isoaspartyl methyltransferase activity and highest mRNA transcript levels were found in brain and testes. Zebrafish morphant larvae with a knockdown in both the pcmt and pcmtl genes showed pronounced morphological abnormalities, decreased survival, and increased isoaspartyl levels. Interestingly, we identified a profound perturbation of brain calcium homeostasis in these morphants. An abnormal calcium response upon ATP stimulation was also observed in mouse hippocampal HT22 cells knocked out for Pcmt1 . This work shows that zebrafish is a promising model to unravel further facets of PCMT function and demonstrates, for the first time in vivo , that PCMT plays a pivotal role in the regulation of calcium fluxes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Soliman, Cordero-Maldonado, Martins, Moein, Conrotte, Warmack, Skupin, Crawford, Clarke and Linster.)

With the increasing prevalence of obesity and type 2 diabetes, fatty liver disease associated with metabolic dysfunction is a global health problem, especially because it is one of the earliest consequences of obesity and it precedes diabetes development. Fatty liver disease associated with metabolic dysfunction is of particular concern in the Middle East and north Africa, where its prevalence is greater than that in the rest of the world. Despite the magnitude of the problem, no regional guidelines have been developed to address this disease. This Review describes suggestions of redefining fatty liver disease associated with metabolic dysfunction, including its terminology and criteria for diagnosis. Experts have raised serious concerns on the current nomenclature, which labels the disease as non-alcoholic fatty liver disease (NAFLD), and its diagnostic criteria. The panel reached a consensus that the disease should be renamed as metabolic-associated fatty liver disease (MAFLD) and that the disease should be diagnosed by positive criteria. The aim is now to work with authorities across the region to implement these proposed changes and reflect them in health-care policy and to improve health care for patients in this region., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite its increased recognition as a major health threat, fatty liver disease associated with metabolic dysfunction remains largely underdiagnosed and undertreated. An international consensus panel has called for the disease to be renamed from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) and has suggested how the disease should be diagnosed. This Viewpoint explores the call from the perspective of patient advocacy groups. Patients are well aware of the negative consequences of the NAFLD acronym. This advocacy group enthusiastically endorses the call to reframe the disease, which we believe will ultimately have a positive effect on patient care and quality of life and, through this effect, will reduce the burden on health-care systems. For patients, policy makers, health planners, donors, and non-hepatologists, the new acronym MAFLD is clear, squarely placing the disease as a manifestation of metabolic dysfunction and improving understanding at a public health and patient level. The authors from representative patient groups are supportive of this change, particularly as the new acronym is meaningful to all citizens as well as governments and policy makers, and, above all, is devoid of any stigma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background & Aims: Hepatocellular carcinoma (HCC) risk persists after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs), particularly in patients with cirrhosis. Identifying those who are likely to develop HCC is a critical unmet medical need. Our aim is to develop a score that offers individualized patient HCC risk prediction., Methods: This two-centre prospective study included 4400 patients, with cirrhosis and advanced fibrosis who achieved a sustained virologic response (SVR), including 2372 patients (derivation cohort). HCC-associated factors were identified by multivariable Cox regression analysis to develop a scoring model for prediction of HCC risk; and subsequently internally and externally validated in two independent cohorts of 687 and 1341 patients., Results: In the derivation cohort, the median follow-up was 23.51 ± 8.21 months, during which 109 patients (4.7%) developed HCC. Age, sex, serum albumin, α fetoprotein and pretreatment fibrosis stage were identified as risk factors for HCC. A simple predictive model (GES) score was constructed. The 2-year cumulative HCC incidence using Kaplan-Meier method was 1.2%, 3.3% and 7.1% in the low-risk, medium-risk and high-risk groups respectively. Internal and external validation showed highly significant difference among the three risk groups (P < .001) with regard to cumulative HCC risk. GES score has high predictive ability value (Harrell's C statistic 0.801), that remained robustly consistent across two independent validation cohorts (Harrell's C statistic 0.812 and 0.816)., Conclusion: GES score is simple with validated good predictive ability for the development of HCC after eradication of HCV and may be useful for HCC risk stratification in those patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)