Ahmed Elgebaly

The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review

Background The genetic alterations of papillary thyroid carcinoma (PTC) have been reported to change over the past few decades. We performed this systematic review to further examine the trends and modifications of patient demographic, clinicopathological features and molecular profiles of PTC over time. Methods A literature search was performed within six electronic databases to identify relevant articles. The inclusion criteria were published studies investigating BRAF mutations, RET/PTC rearrangements or RAS mutations in PTCs or classical PTCs. Two teams of reviewers independently screened titles and abstracts of all articles. Full texts of potential articles were read and extracted data were listed and stratified into an excel file according to country, city, institution, and surgical time period. Student t test and Pearson Chi-square were used to analyze the trends of demographic and clinicopathological features of PTC patients and the prevalence of each genetic alteration in individual institutions. Results From 3139 articles, we included 16 articles for final analysis. Our results showed an increasing trend of BRAF and a decreasing trend of RET/PTC prevalence over time in PTCs and classical PTCs, accompanied by an older age of PTC patients, an increase in proportion of PTMC and less aggressive behaviours of tumours. Conclusions The demographic and clinicopathological characteristics and molecular profile of PTCs have been changing over the past few decades. These modifications suggest changes in etiologies and risk factors of thyroid cancer that influence the tumorigenesis of PTCs.

Tolerability and Efficacy of Eltrombopag in Chronic Immune Thrombocytopenia: Meta-Analysis of Randomized Controlled Trials.

Background: Eltrombopag is an oral thrombopoietin receptor agonist that stimulates the production of normally functioning platelets. The aim of this meta-analysis is to synthesize evidence about the safety and efficacy of eltrombopag for both adult and children with primary immune thrombocytopenia (ITP). Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager for Windows. Subgroup analysis and sensitivity analysis were conducted to investigate whether treatment effect varies significantly between adults and children. Results: Six randomized controlled trials (N = 611 patients) were included in the final analysis. The overall effect estimates favored eltrombopag group in terms of overall platelet response (relative risk [RR]: 3.42; 95% confidence interval [CI]: 2.51-4.65; P < .0001), incidence of significant bleeding (RR: 0.56; 95% CI: 0.41-0.77; P = .0004), and number of cases needed to rescue treatment (RR: 0.45; 95% CI: 0.32-0.65; P < .0001). The efficacy of eltrombopag did not differ significantly between children and adults except for incidence of any bleeding (RR: 0.83 vs 0.51; P = .008). Conclusion: Eltrombopag is a tolerable and effective drug for the management of chronic ITP in children and adults.

Risk of cataract among interventional cardiologists and catheterization lab staff: A systematic review and meta‐analysis

We performed a systematic review and meta‐analysis to assess the risk of developing a radiation‐induced cataract in interventional cardiologists (ICs).

Regional versus local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis:

There is a consensus in the literature that regional anesthesia (RA) improves local hemodynamic parameters in comparison to local anesthesia (LA) during arteriovenous fistula (AVF) surgical construction. However, the effects of both techniques on fistula patency and failure rates are still controversial. The aim of this meta-analysis is to synthesize evidence from published randomized trials and observational studies regarding the safety and efficacy of RA versus LA in AVF surgical construction. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central retrieved six randomized trials (462 patients) and one retrospective study (408 patients). Pooling data using RevMan software (version 5.3) showed that RA was superior to LA in terms of primary fistula patency rate (RR = 1.22, 95% CI [1.08, 1.37], p = 0.0010); however, both types were comparable in terms of primary fistula failure rate (RR = 0.81, 95% CI [0.47, 1.40], p = 0.46). In comparison to LA, RA was associated with improved hemodynamic parameters including fistula blood flow (MD = 25.08, 95% CI [19.40, 30.76], p<0.00001), brachial artery diameter (SMD = 2.63, 95% CI [2.17, 3.08], p<0.00001), and outflow venous diameter (SMD = 0.93, 95% CI [0.30, 1.75], p = 0.004). Postoperative complications were comparable between both groups (OR = 0.23, 95% CI [0.05, 0.97], p = 0.05). In conclusion, RA was associated with higher primary patency rates of AVF and improved local blood flow in comparison to LA; however, both procedures were comparable in terms of primary failure rates and postoperative complications. Larger well-designed trials with longer follow-up periods should compare both techniques in terms of long-term patency rates and safety outcomes.

Safety and efficacy of sofosbuvir plus ledipasvir with and without ribavirin for chronic HCV genotype-1 infection: a systematic review and meta-analysis.

BACKGROUND Ledipasvir and sofosbuvir are new direct-acting antiviral agents for patients with HCV infection. Ledipasvir inhibits the HCV non-structural 5A protein, while sofosbuvir is a nucleotide polymerase inhibitor. Many studies have evaluated the safety and efficacy of ledipasvir and sofosbuvir combination with and without ribavirin for patients with chronic HCV genotype-1. METHODS A computer literature search of PubMed, SCOPUS, Web of Knowledge and Cochrane CENTRAL has been conducted. Studies were screened for eligibility and data were extracted. Sustained virological response (SVR) rate and commonly reported adverse events were pooled as risk ratio (RR) using Review Manager version 5.3 for windows and OpenMeta (Analyst) software. RESULTS Eight randomized controlled trials (n=1,892) were pooled in the final analysis. A 12-week ledipasvir and sofosbuvir regimen achieved SVR in 97.5% and 89% of non-cirrhotic and cirrhotic patients, respectively. A 24-week ledipasvir and sofosbuvir regimen achieved SVR in 99.6% and 92.6% in non-cirrhotic and cirrhotic patients, respectively. When ribavirin was added to the treatment regiment, the SVR did not differ significantly in either of the treatment regimens (12-week SVR: 93.9% versus 96.7%, RR=0.97, P=0.19 and 24-week SVR: 94.8% versus 97.2%, RR=0.98, P=0.24). CONCLUSIONS The combination of sofosbuvir and ledipasvir achieved high SVR rates (>90%) in both cirrhotic and non-cirrhotic patients with HCV genotype-1. The addition of ribavirin to this regimen did not significantly increase the SVR rates.

Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

BACKGROUND Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinsons disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. METHODS A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). RESULTS Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). CONCLUSIONS There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

Impact of prior malignancy on outcomes of stage IV esophageal carcinoma: SEER based study

ABSTRACT Introduction: Usually, clinical trials on esophageal cancer exclude patients with a prior malignancy, assuming that this may influence survival outcomes. However, little is known about the impact of a prior malignancy on its prognosis. Methodology: The Surveillance, Epidemiology, and End Results database (SEER) was used to review patients with stage IV squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus during 1973–2014. We calculated overall and esophageal cancer-specific survival using unadjusted Kaplan-Meier and multivariable covariate-adjusted Cox models. Results: A total of 7,807 patients with stage IV SCC, and 11,238 patients with stage IV AC were reviewed, of which 652 and 840 patients, respectively, had a prior malignancy. Kaplan-Meier curves did not show difference in overall survival of SCC or AC in patients with prior malignancy. Stage IV AC patients with prior malignancy did not show different esophageal cancer-specific survival. However, esophageal cancer-specific survival was better among stage IV SCC patients with prior malignancy. Similar results were observed in Cox models after adjustment for: age, sex, race, marital status, grade, site in esophagus, and undergoing surgery. Conclusion: Prior malignancy does not adversely impact survival of stage IV esophageal cancer. These results should be taken into consideration when designing clinical trials.

Epstein-Barr virus and cytomegalovirus infections and their clinical relevance in Egyptian leukemic pediatric patients

BackgroundEpstein-Barr virus (EBV) and human cytomegalovirus (CMV) infections are environmental risk factors affecting the outcome of cancer due to an impairment in the cell-mediated immunity. Therefore, this study aimed to detect the frequency of EBV and CMV DNA and their association with clinical characteristics and outcome of pediatric leukemic patients.MethodsSamples of 50 immunocompromised pediatric leukemic patients and 30 apparently healthy children were subjected to the amplification of EBV DNA by one version of PCR targeting the Bam H1 W region of the genomic region of EBV, and the amplification of CMV DNA by targeting the CMV UL97 genomic region by a second round PCR. All investigations were performed on WBCs and sera. Results were correlated with the clinical and laboratory characteristics of the disease, and with overall survival.ResultsEBV and CMV DNA were detected in 20 and 54% of leukemic patients, respectively. Nine out of ten patients with EBV DNA (90%) were positive for CMV DNA in their sera. The presence of EBV DNA or CMV DNA was associated with neutropenia and a low total leukocyte count (TLC) (p = 0.02, 0.03, respectively). The presence of severe CMV disease, longer duration of febrile neutropenia, neutropenia, lymphopenia, thrombocytopenia and the presence of EBV DNA in patients’ sera were significantly associated with worse overall survival.ConclusionThe detection of CMV disease and EBV DNA is relatively common in leukemic children and is significantly associated with a decline in the overall survival.

Efficacy of low-level laser therapy in carpal tunnel syndrome management: a systematic review and meta-analysis

We performed this meta-analysis to investigate the efficacy of low-level laser therapy (LLLT), a physiotherapy modality with anti-inflammatory and analgesic effects, in the management of mild-to-moderate carpal tunnel syndrome (CTS). We searched PubMed, Web of Knowledge, Scopus, Cochrane Central, and Virtual Health Library for randomized controlled trials (RCTs) that compared the effects of LLLT with or without splinting versus placebo on functional and electromyographic outcomes in CTS. All outcomes were pooled as mean differences (MD) under the inverse variance or random effects model, using the statistical add-in (MetaXL, version 5.0). Eight RCTs (473 patients/631 wrists) were eligible for the final analysis. The overall effect estimates did not favor LLLT therapy group over placebo in all primary outcomes: visual analogue scale (MD −1.11, 95% CI [−2.58, 0.35]), symptom severity scale score (MD −1.41, 95% CI [−5.12, 2.29]), and functional status scale score (MD −1.33, 95% CI [−3.27, 0.61]). However, LLLT was superior to placebo in terms of grip strength (MD 2.19, 95% CI [1.63, 2.76]) and inferior to placebo in terms of sensory nerve action potential (MD −2.74, 95% CI [−3.66, −1.82]). Laser therapy is superior to placebo in terms of improving the grip strength; however, no significant difference was found between both groups in terms of functional status improvement, pain reduction, or motor electrodiagnostic evaluations. Further high-quality trials with longer follow-up periods are required to establish the efficacy of LLLT for CTS treatment.

Sunitinib alone or in combination with chemotherapy for the treatment of advanced breast cancer: A systematic review and meta-analysis

INTRODUCTION Sunitinib is an orally delivered tyrosine kinase inhibitor that exhibits antiangiogenic effects. FDA has approved sunitinib for the treatment of metastatic renal cell carcinoma. However, its efficacy for the treatment of advanced breast cancer (ABC) remains controversial. Therefore, we performed this systematic review and meta-analysis to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of sunitinib alone and in combination with chemotherapy for the treatment of ABC. METHODS We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search of PubMed, SCOPUS, web of knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL) has been conducted using relevant keywords. Studies were screened for eligibility and data were extracted to an online data extraction form. Progression free survival (PFS) and overall survival (OS) were pooled as Hazard ratio (HR) in a meta-analysis model using generic inverse variance method. Objective response rate (ORR) and complications were pooled as relative risk (RR) in a random effect model meta-analysis using Mantel-Haenzel method. RESULTS Six RCTs, with a total sample size of 2273 patients, met our eligibility criteria and were included in this meta-analysis. Sunitinib monotherapy was not superior to chemotherapy in terms of PFS (HR = 1.00, 95% CI [0.86 to 1.16], P = 0.99), OS (HR = 1.07; 95% CI [0.87 to 1.32], P = 0.5), or ORR (RR = 0.70, 95% CI [0.74 to 1.03], P = 0.07). Sunitinib in combination with chemotherapy did not show superiority to chemotherapy in terms of PFS (HR = 0.99, 95% CI [0.86 to 1.14], P = 0.89) and OS (HR = 1.04, 95% CI [0.85 to 1.28], P = 0.69). However, the ORR favored sunitinib in combination with chemotherapy group (RR = 1.15, 95% CI [1.01 to 1.31]) with a statistically significant P value (P = 0.03). CONCLUSIONS Current evidence shows that sunitinib, either alone or in combination with chemotherapy, has no clinical benefit for patients with advanced breast cancer. However, previous studies did not considered patient stratification and outcome assessment based on molecular markers. In terms of safety, toxicity was common with sunitinib treatment.