Mass online training of health care workers during COVID-19: approach, impact, and outcomes for over 10,000 health care providers.

OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.

Risk Factors Associated with Adverse Outcomes after Ablative Surgery for Lymphedema.

BACKGROUND: Postmastectomy breast cancer lymphedema poses an important health threat. Historically, physical therapy was the exclusive treatment option. More recently, lymphedema surgery has revolutionized care. As a first-in-kind, multicenter report, the postmastectomy breast cancer patients' risk factors associated with postlymphedema ablative surgical outcomes were documented. METHODS: Using the New York Statewide Planning and Research Cooperative System database from 2010 to 2018, multivariable models identified the postmastectomy breast cancer lymphedema surgical patients' characteristics associated with major adverse outcomes and mortality. RESULTS: Of 65,543 postmastectomy breast cancer patients, 1,052 lymphedema surgical procedures were performed including 393 (37.4%) direct excisions and 659 (63.6%) liposuctions. Direct excision and liposuction surgical patients had median ages of 58 and 52 years, respectfully (p < 0.001). Although a 30-day operative mortality was rare (0.3%, all direct excisions), major adverse outcomes occurred in 154 patients (28.5% direct excision; 6.4% liposuction; p < 0.0001). Multivariable clinical outcomes model identified that patients with higher Elixhauser's score, renal disease, emergent admissions, and direct excision surgery had higher incidences of adverse outcomes (all p < 0.01). For those patients with 30-day readmissions (n = 60), they were more likely to have undergone direct excision versus liposuction (12.5 vs. 1.7%; p < 0.0001). The important risk factors predictive of future cellulitis/lymphangitis development included diabetes mellitus, Medicaid insurance, renal disease, prior cellulitis/lymphangitis, chronic obstructive pulmonary disease (COPD), and chronic steroid use (all p < 0.01). CONCLUSION: Lymphedema surgery carries a favorable risk profile, but better understanding the "high-risk" patients is critical. As this new era of lymphedema surgery progresses, evaluating the characteristics for adverse postoperative outcomes is an important step in our evolution of knowledge.

Risk Factors Associated With Postmastectomy Breast Cancer Lymphedema: A Multicenter Retrospective Analysis.

BACKGROUND: Lymphedema is an edematous condition that afflicts the postmastectomy breast cancer population, with diminished quality of life with substantial financial costs. The factors predictive of postmastectomy lymphedema development in breast cancer patients are unknown. The objective was to evaluate the trends over time in lymphedema development and the risk factors predictive of lymphedema-related events within 2 years of mastectomy. METHODS: Using the New York Statewide Planning and Research Cooperative System multicenter deidentified database from 2010 to 2016, a total of 65,543 breast cancer postmastectomy female patients (mean age, 59 ± 20 years) were identified across 177 facilities. The breast cancer patients were followed for any 2-year postmastectomy lymphedema-related events. A multivariable model identified predictors of 2-year lymphedema using eligible variables involving demographics, comorbidities, and complications. Elixhauser score was defined as a comorbidity index based on International Classification of Diseases codes used in hospital settings. RESULTS: Overall, 5.2% (n = 3409) of the breast cancer postmastectomy patients experienced a lymphedema-related event within 2 years of initial surgery. Over time, 2-year postmastectomy lymphedema rates have more than doubled from 4.62% in 2010 to 9.75% in 2016 (P < 0.001). Two-year postmastectomy lymphedema rates varied significantly by mastectomy procedure type: 5.69% of the mastectomy-only procedures, 5.96% of the mastectomies with lymph node biopsies, and 7.83% of the mastectomies with lymph node dissections (P < 0.0001). Full mastectomies had a greater 2-year lymphedema rate of 7.31% when compared with partial mastectomies with 2.79% (P < 0.0001). The top predictive risk factors for a lymphedema-related event included higher Elixhauser score, prolonged hospitalization for mastectomy, more recent mastectomy procedure, obesity, younger age, non-Asian race, Medicaid insurance, and hypertension (all P's < 0.01). CONCLUSIONS: Although more recent postmastectomy lymphedema rates may not be as high as historical estimates, the 2-year postmastectomy lymphedema rates have more than doubled from 2010 to 2016 requiring further elucidation as well as continued focus on treatment. Furthermore, risk factors were identified that predispose postmastectomy breast cancer patients to developing lymphedema. Given these findings, perioperative screening seems warranted to proactively identify, educate, and monitor postmastectomy patients at greatest risk of future lymphedema development.

Alpha-lipoic acid: An inimitable feed supplement for poultry nutrition.

Alpha-lipoic acid (ALA) is a multifunction antioxidant that is produced in small amount by cells as well as its dietary provision facilitates fatty acid mobilization, energy expenditure as well as can scavenge free radicals in poultry birds. It exists in oxidized as well as reduced form, characterized by growth promoting, anti-inflammatory, antioxidative, immunostimulatory, and hypocholesterolemic properties when fed as dietary supplement to farm animals particularly chicken birds. Recently, several studies reported that dietary supplementation of ALA can influence growth performance indicators, immunological, biochemical characteristics, lipid metabolism, and oxidative stress as well as increase antioxidant potential and storability of poultry meat and meat products. Accordingly, this paper adds the reviews and discusses the outcomes of studies documenting the effect of lipoic acid dietary fortification on growth performance, biochemical, and immunological characteristics as well as the effects on lipid peroxidation of fresh meat and meat-based products. Furthermore, this paper also describes the possibilities of utilization of ALA as a feed additive in poultry nutrition to improve the growth performance of poultry as well as meat quality of resultant chicken birds.

Tonsillar synovial sarcoma, unusual anatomical location: case report and literature review.

BACKGROUND: Synovial sarcoma is a rare soft tissue malignancy, occasionally found in the head and neck region. The diagnosis necessitates a multidisciplinary approach involving the clinical presentation, proper imaging studies and histological confirmation, with molecular testing for definitive identification. Treatment entails surgical resection with adjuvant therapies as needed. CASE PRESENTATION: A 33-year-old male patient presented with globus sensation concomitant with right-sided neck swelling. He was clinically found to have right tonsil enlargement with posterior extension. Therefore, he underwent right tonsillectomy with pharyngoplasty. Histopathological examination revealed a biphasic tumor consistent with synovial sarcoma, confirmed by immunohistochemistry and fluorescence in situ hybridization. CONCLUSIONS: Tonsillar synovial sarcoma represents a diagnostic challenge, requiring a high index of suspicion and comprehensive evaluation. With only twenty previously published cases documented in the literature, awareness of this rare presentation is crucial for prompt diagnosis and appropriate management. Collaboration among multidisciplinary healthcare teams and ongoing research efforts are essential for optimizing diagnostic accuracy, treatment efficacy, and patient outcomes in this rare malignancy.

Comparison of High-Normal Versus Low-Normal Mean Arterial Pressure at Target on Outcomes in Sepsis or Shock Patients: A Meta-Analysis of Randomized Control Trials.

The objective of this meta-analysis was to compare the impact of a high-normal and a low-normal mean arterial pressure (MAP) target on outcomes in patients with sepsis or shock. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, two investigators conducted a thorough literature search across online databases, including PubMed, Cochrane Library, Web of Science, and EMBASE, spanning from inception to December 10, 2023. The assessed outcomes encompassed all-cause mortality, the need for renal replacement therapy, and the length of intensive care unit (ICU) stay. A total of four randomized controlled trials (RCTs) were included, involving 3507 participants with individual study participant counts ranging from 118 to 2463. The pooled analysis revealed no statistically significant difference in the risk of all-cause mortality between the two groups (Risk Ratio (RR): 0.94, 95% Confidence Interval (CI): 0.87 to 1.01). Furthermore, there was no disparity in the rates of renal replacement therapy and the duration of ICU stay between the high-normal and low-normal MAP groups. Our findings indicate no significant distinctions in mortality, rates of renal replacement therapy, or ICU stay duration between the two groups. However, future trials with larger sample sizes are warranted to comprehensively understand the nuanced effects of different MAP settings on outcomes in patients with sepsis and shock.

Comparing the Efficacy and Safety of Warfarin Monotherapy vs. Warfarin and Aspirin for Adult Patients With Left Ventricular Assist Devices: A Meta-Analysis.

The aim of this meta-analysis was to assess the safety and efficacy of warfarin plus aspirin versus warfarin monotherapy in patients with left ventricular assist devices (LVAD). The present meta-analysis was conducted using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two authors systematically searched online databases, including PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to December 31, 2023. Outcomes assessed in this meta-analysis included any thrombotic event, bleeding events, and all-cause mortality. A total of five articles were included in the meta-analysis, enrolling a pooled sample size of 876 patients, including 405 in the warfarin monotherapy group and 471 in the warfarin plus aspirin group. Pooled analysis showed that the risk of thrombotic events was not significantly different between the two groups (risk ratio (RR): 0.46, 95% confidence interval (CI): 0.15-1.37). The risk of bleeding events was significantly lower in patients receiving warfarin alone compared to patients receiving aspirin plus warfarin (RR: 0.67, 95% CI: 0.53-0.85). The risk of all-cause mortality was not significantly different between patients receiving warfarin alone and patients receiving aspirin plus warfarin (RR: 0.92, 95% CI: 0.65-1.30). Despite the potential benefits of discontinuing aspirin, the decision should be approached cautiously, considering the undefined risks of discontinuing anticoagulation in LVAD patients.

Analysis of IDH and EGFR as biomarkers in glioblastoma multiforme: A case-control study.

Background: Glioblastoma multiforme (GBM) is a very aggressive primary central nervous system (CNS) tumor with limited therapeutic options and poor prognosis. This study aimed to analyze the association between single nucleotide polymorphisms (SNPs), including IDH1 rs121913500C > T, IDH2 rs11540478G > A, and EGFR rs1468727C > T, and their association on the risk and overall survival of GBM patients in Jordan. Methods: Using a case-control study design involving 63 GBM patients and 226 healthy controls was conducted at King Abdullah University Hospital in Jordan. DNA extraction was performed using formalin-fixed and paraffin-embedded tissue for GBM samples and blood samples for controls. SNPs analysis was performed using the Sequenom iPLEX assay sequencing technique. Survival outcomes were assessed using Cox models and hazard ratios (HR), and single-cell RNA (scRNA) analysis was performed from GSE70630. Results: The study showed a significant association between genotype frequency in GBM cases and controls for specific SNPs, including IDH1 rs121913500C > T, and EGFR rs1468727C > T. The G/G genotype of rs11540478 (IDH2) was associated with better prognostic outcomes in GBM patients. The scRNA analysis demonstrated the differential expression of IDH1, IDH2, and EGFR in GBM, with enrichment in central carbon metabolism in cancer. Conclusion: Our findings suggest that SNPs, particularly in IDH1 and IDH2 genes and EGFR, may serve as diagnostic and prognostic biomarkers for GBM. While the study underscores the clinical relevance of these genetic variants, further investigations with larger and more diverse populations are essential to validate and extend these associations.

Exploring Genetic Determinants: A Comprehensive Analysis of Serpin B Family SNPs and Prognosis in Glioblastoma Multiforme Patients.

Serpins are serine proteinase inhibitors, with several serpins being overexpressed in cancer cells. Thus, we aim to analyze the single-nucleotide polymorphism (SNP) of Serpinb11 and its association with GBM survival. A cohort of 63 GBM patients recruited from King Abdullah University Hospital in Jordan underwent polymorphism analysis and overall survival (OS) assessments. The Cancer Genome Atlas (GBM) cohort was useful for validation. We constructed a risk score using the principal component analysis for the following Serpin genes: Serpinb3, Serpinb5, Serpinb6, Serpinb11, and Serpinb12, and patients were grouped into high- vs. low-risk groups based on the median cutoff. Univariable Cox models were used to study the survival outcomes. We identified a significant association between rs4940595 and survival. In the TCGA cohort, Serpinb3 alterations showed worse OS. Univariable Cox showed worse PFS outcomes with higher SERPINB5 and SERPINB6 expression. A Serpin B 5-gene risk score showed a trend towards worse PFS in the high-risk group. Upregulated DEGs showed GO enrichment in cytokine regulation and production, positive regulation of leukocyte activation, and the MAPK cascade. The high-risk group showed a significantly higher infiltration of M2 macrophages and activated mast cells. Our findings showed a significant role of the Serpin B family in GBM survival in the Jordanian population.

Determination of dosage compensation of the mammalian X chromosome by RNA-seq is dependent on analytical approach.

BACKGROUND: An enduring question surrounding sex chromosome evolution is whether effective hemizygosity in the heterogametic sex leads inevitably to dosage compensation of sex-linked genes, and whether this compensation has been observed in a variety of organisms. Incongruence in the conclusions reached in some recent reports has been attributed to different high-throughput approaches to transcriptome analysis. However, recent reports each utilizing RNA-seq to gauge X-linked gene expression relative to autosomal gene expression also arrived at diametrically opposed conclusions regarding X chromosome dosage compensation in mammals. RESULTS: Here we analyze RNA-seq data from X-monosomic female human and mouse tissues, which are uncomplicated by genes that escape X-inactivation, as well as published RNA-seq data to describe relative X expression (RXE). We find that the determination of RXE is highly dependent upon a variety of computational, statistical and biological assumptions underlying RNA-seq analysis. Parameters implemented in short-read mapping programs, choice of reference genome annotation, expression data distribution, tissue source for RNA and RNA-seq library construction method have profound effects on comparing expression levels across chromosomes. CONCLUSIONS: Our analysis shows that the high number of paralogous gene families on the mammalian X chromosome relative to autosomes contributes to the ambiguity in RXE calculations, RNA-seq analysis that takes into account that single- and multi-copy genes are compensated differently supports the conclusion that, in many somatic tissues, the mammalian X is up-regulated compared to the autosomes.

The impact of IDH and NAT2 gene polymorphisms in acute myeloid leukemia risk and overall survival in an Arab population: A case-control study.

Acute myeloid leukemia (AML) is a malignancy of the myeloid cells due to the clonal and malignant proliferation of blast cells. The etiology of AML is complex and involves environmental and genetic factors. Such genetic aberrations include FLT3, DNMT3, IDH1, IDH2, NAT2, and WT. In this study, we analyzed the relationship between five, not previously studied in any Arab population, single nucleotide polymorphisms (SNPs) and the risk and overall survival of AML in Jordanian patients. The SNPs are NAT2 (rs1799930 and rs1799931), IDH1 (rs121913500), and IDH2 (rs121913502 and rs1057519736). A total number of 30 AML patients and 225 healthy controls were included in this study. Females comprised 50% (n = 15) and 65.3% (n = 147) of patients and controls, respectively. For AML patients (case group) Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues and from peripheral blood samples for the control subjects group. Genotyping of the genetic polymorphisms was conducted using a sequencing protocol. Our study indicates that NAT2 rs1799930 SNP had a statistically significant difference in genotype frequency between cases and controls (p = 0.023) while IDH mutations did not correlate with the risk and survival of AML in the Jordanian population. These results were also similar in the TCGA-LAML cohorts with the notable exception of the rare NAT2 mutation. A larger cohort study is needed to further investigate our results.

Subcutaneous panniculitis-like T-cell lymphoma: an unusual cause of right thigh hypertrophy.

A man in his mid-20s presented with a painless swelling over his right thigh, which had been progressively increasing over 3 years. He underwent an excisional biopsy for the same, which showed reactive lymphadenopathy. Since the last year and a half, he developed a lower abdominal wall swelling with mild redness over it. In addition, over the last few months before presentation to haematology outpatient clinic, he experienced bouts of fever, night sweats, anorexia, weight loss and right inguinal lymphadenopathy. On examination, splenomegaly was identified. In view of the patients' symptoms, he underwent a positron emission tomography scan, which showed hypermetabolic activity in the subcutaneous tissue sparing the lymph nodes and spleen. A deep skin punch biopsy taken from his right thigh was consistent with the diagnosis of subcutaneous panniculitis-like T-cell lymphoma αß T-cell phenotype. The patient was treated successfully with oral steroids and on routine follow-up, he is in remission for 5 years.

Nutritional assessment of servicemen in relation to area of duty and feeding habits: a Pakistani prospective.

The present study was carried out to determine incidence of overweight and obesity in Pakistani servicemen with reference to their area of duty, feeding habits and also to identify risk factors. Accordingly, 2,501 servicemen selected from all over Pakistan using multiple stage stratified sampling protocol. Nutrition assessment performed using body mass index (BMI), waist to hip ratio (WHR) and dietary assessment using food frequency questionnaire. Collected data was analyzed using the SPSS version 25. Regression was used to find risk factors of obesity and WHR. Results indicated that about 1/4th of servicemen were smokers. Approximately, 1/5th of them were overweight and about one quarter were eating fruits and vegetables for <3 days/ week and <4 days/week, respectively. Only 1/3rd of them were physically active for at least <40 minutes per day. Age and fruits intake were significantly predicting BMI with a direct relation and vegetable intake was negatively correlated to BMI of the servicemen. Age and rank were significant predictors of WHR while, physical activity was negatively correlated to WHR. It is concluded and suggested from our study that there is a need to modify eating patterns and habits as well as improving physical activity on daily basis for healthy and long life of the servicemen.

Association of CYP2C19, TNF-α, NOD1, NOD2, and PPARγ polymorphisms with peptic ulcer disease enhanced by Helicobacter pylori infection.

OBJECTIVES: To assess the correlation between a number of genetic variations of CYP2C19, TNF-α, NOD1, NOD2, and PPARγ genes with the severity of Helicobacter pylori (H. pylori) infections and peptic ulcers (PU). METHODS: A retrospective cross-sectional design was used in this study. Formalin-fixed paraffin-embedded (FFPE) tissue was used to extract genomic DNA that was collected from Jordanian patients who visited endoscopy clinics between 2014 to 2018 at the King Abdullah University Hospital (KAUH), Irbid, Jordan. Genotyping of the studied single nucleotide polymorphisms (SNPs) were applied using the sequencing protocol. Results:  A total of 251 patients (mean age: 42.12 ± 16.09 years) and healthy controls (mean age: 52.76 ± 19.45 years) were enrolled in this study. This study showed no significant association between patients and the studied polymorphisms except for rs2075820 of the NOD1 (p=0.0046). It is hypothesized that the heterozygous genotype (TC); 44.8% in patients versus 61.3% in controls has a decreased risk of peptic ulcers (OR:  0.49). The alleles frequency association was insignificant in all studied SNPs with a p-value more than 0.05. CONCLUSION: This study provided evidence regarding the association of the rs2075820 with H. pylori infections. The other studied SNPs were not statistically significant.

Viral Clearance Course of COVID-19 Outbreaks.

BACKGROUND: Coronavirus disease 2019 (COVID-19) viral course and behavior remain unpredictable. This study describes incubation time and viral clearance of COVID-19 hospitalized cases in Northern Jordan. METHODS: All COVID-19 confirmed cases hospitalized from March 15 to June 09, 2020, were included. Nasopharyngeal swabs were collected, and COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) was performed every two days in all cases. The viral cure was defined when two negative RT-PCR tests were obtained ≥ 24 hours apart. Viral clearance time (VCT) reflects the time from the first positive nasopharyngeal swab to the first of two consecutive negative tests. RESULTS: In this cohort, a total of 157 patients were included. Most cases resulted from two major outbreaks. The median incubation period was 6 days (IQR, 3-10) and ranged from 1 to 17 days. The median VCT was 13 days (IQR, 7-2) and ranged from 1 to 40 days. Symptomatic presentation and abnormal chest radiograph were predictors for a prolonged VCT (p=0.015 and p=0.014, respectively). The median time of resolution of symptoms was 7 days (IQR, 3-10 days). Most symptomatic cases (91.7%) remained RT-PCR positive for up to 20 days after symptoms resolution, with a median of 13.5 days. VCT significantly correlated with the incubation period (p=0.013). CONCLUSION: Viral cure lagged for as long as 20 days after resolution of symptoms. Continuing with social-distancing, frequent hand hygiene, and wearing facial mask remains essential and is recommended even after clinical resolution of symptoms.

The epidemiology of lymphoma in Jordan: A nationwide population study of 4189 cases according to World Health Organization classification system.

OBJECTIVE/BACKGROUND: Lymphoma is a common human cancer that shows a variable geographic incidence worldwide. It is the fourth most common cancer in Jordan. Systemic reports of descriptive epidemiology on lymphoma from the Middle East are limited. METHODS: A nationwide multi-institutional retrospective study was conducted covering all major hospitals and laboratories that provide diagnostic services. We collected data on all cases diagnosed with lymphoma between 2014 and 2019. The included variables were patients' age, gender, anatomic site, and the histologic type according to the World Health Organization classification system. RESULTS: A total of 4189 cases were diagnosed with lymphoma. There was a statistically significant gender difference (p < .05), as 57.5% of patients were males. The peak incidence occurred at age 25-55 years. There were 1,652 (39%) cases of Hodgkin lymphoma (HL) and 2,537 (61%) of non-Hodgkin lymphoma (NHL), where nodular sclerosis (67%) and diffuse large B-cell lymphoma (53%) were the most common subtypes, respectively. The average age-adjusted incidence rates per 100,000 population were 8.01 for all lymphomas, 4.33 for NHL, and 3.16 for HL and all remained stable over the 6 years. CONCLUSION: HL is the most common lymphoma in Jordan, with a percentage higher than most of reported studies in Asian and Western countries. It also shows a unimodal distribution of age-specific incidence rates, with a single peak in young adults. The incidence rate of HL is higher than Eastern countries but comparable to the West. In contrast, NHL demonstrates a lower incidence rate than Western countries but a similar distribution of subtypes, as mature T/natural killer-cell lymphomas were rare.

Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: a retrospective analysis of 31 cases.

Primary central nervous system lymphomas are rare neoplasms characterized by a dismal prognosis relative to other extranodal lymphomas. Approximately 98% of primary central nervous system lymphomas are of B-cell origin, and most belong to the diffuse large B-cell type. Recently, diffuse large B-cell lymphomas have been subcategorized into germinal center and nongerminal center types based on gene expression profiles and immunohistochemical expression of CD10, Bcl-6, and MUM1. Studies have shown that the overall survival rate of the germinal center group is better than that of the nongerminal center lymphomas. In this study, 31 cases of primary central nervous system lymphomas of the diffuse large B-cell type were retrieved, reviewed, and immunostained for CD10, Bcl-6, MUM1, and Ki-67. Subclassification was carried out as described earlier, where CD10 and/or Bcl-6 positivity and negativity for MUM1 were considered characteristic of germinal center subtype and the opposite expression of nongerminal center subtype. Furthermore, the proliferative activity was semiquantitatively assessed using percent positive cells staining with Ki-67. Of the 31 cases examined, 26 (84%) were found to belong to the nongerminal center type. The Ki-67 index in these 26 cases ranged from 30 to 90% (mean, 69%). Five cases were categorized as the germinal center subtype. They had an Ki-67 index between 70 and 90% (mean, 78%). Interestingly, none of our patients were known to be HIV positive. One patient had a 10-year history of orthotopic liver transplant. We also performed fluorescence in situ hybridization analysis on formalin-fixed material and found that 38% of the cases where tissue was available had abnormalities of MYC/IGH and/or IGH/BCL2. We conclude that most primary central nervous system diffuse large B-cell lymphomas are of the nongerminal center origin. Regardless of the germinal center status, all cases showed a high proliferative rate. A statistically significant difference in the overall survival between the two groups was not seen.

Carbamazepine, a Histone Deacetylase Inhibitor Induces Apoptosis in Human Colon Adenocarcinoma Cell Line HT-29.

BACKGROUND AND AIM: Colon cancer ranks fourth and is responsible for causing 10% cancer-related mortality in western countries. Its incidence is rising in many countries due to widespread adoption of the Western diet and lifestyle. Carbamazepine (CBZ) is a FDA-approved antiepileptic drug and a histone deacetylase inhibitor. The aim of this study is to evaluate the cytotoxic potentials of CBZ in human colon cancer cells (HT-29 cells). METHODS: HT-29 cells were treated with 36 and 76 µg/ml of CBZ for 24 h. The cytotoxic effect was evaluated by MTT assay. The intracellular reactive oxygen species (ROS) expression was evaluated through dichloro-dihydro-fluorescein diacetate staining. Morphological changes related to apoptosis were evaluated by dual staining with acridine orange and ethidium bromide. Mitochondrial membrane potential was evaluated by rhodamine 123 staining. Immunofluorescence analysis of caspase 3 was done with confocal microscopy. RESULTS: CBZ caused significant cytotoxicity in HT-29 cells and the effect was concentration dependent. CBZ treatments also caused significant expression of ROS in HT-29 cells. Dual staining showed early and late apoptotic cells and morphological alterations induced by the CBZ. Confocal microscopic studies confirmed the increased caspase 3 expression in CBZ-treated cells. CONCLUSION: CBZ induced apoptosis in HT-29 cell through ROS generation and caspase 3 expression and these results pave the way for further in vivo studies.

LTA, LEP, and TNF-a Gene Polymorphisms are Associated with Susceptibility and Overall Survival of Diffuse Large B-Cell lymphoma in an Arab Population: A Case-Control Study.

OBJECTIVE: In this study, we aimed to explore the relationship between five selected proinflammatory and immune-mediated genes (TNF rs1800629G>A, rs361525G>A, rs1799964T>C, LTA rs1800683G>A, rs909253A>G, TNFAIP8 rs1042541C>T, LEPR rs1327118G>C, and LEP rs2167270G>A) and the risk and overall survival of DLBCL patients within the Jordanian Arab population. METHODS: One hundred twenty-five patients (125) diagnosed with DLBCL at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 238 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects and from peripheral blood samples of the controls. The Sequenom MassARRAY® sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival. RESULTS: Our study showed significant differences in the distribution of the studied polymorphisms of DLBCL between the patients and controls for TNF rs1800629G>A, LTA rs909253 G>A and LEP rs2167270 G>A. TNF rs1800629G>A (p = 0.01), in which the G allele harbors a higher risk of DLBCL (GG and GA genotypes when compared with AA genotype) (p = 0.044). The LTA rs909253 A>G polymorphism is associated with a higher risk of DLBCL in the allelic model (p = .004).  LEP rs2167270 G>A polymorphism is associated with a decreased risk of DLBCL in the recessive mode models (p = .03). Subjects with the dominant model for TNF-a rs1799964 (TT genotype in comparison with the combined TT/TC genotype) and patients with the homozygous genotype (GG) of rs361525 have better overall survival rates. CONCLUSION: Our results confirmed the diversity and the heterogeneity of the disease. Although the study has a limitation because of its relatively small size, it clearly emphasizes the significance of ancestry and genetic composition as the determinants of DLBCL risk and behavior.
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The Impact of IL-6 and IL-10 Gene Polymorphisms in Diffuse Large B-Cell Lymphoma Risk and Overall Survival in an Arab Population: A Case-Control Study.

B-cell lymphomas can be classified as Hodgkin and non-Hodgkin lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin Lymphoma (NHL). The incidence of NHL is variable and affected by age, gender, racial, and geographic factors. There is strong evidence that the immune-regulatory cytokines have a major role in hematologic malignancies. In this study, we analyzed the relationship between seven single nucleotide polymorphisms (SNPs) in two selected cytokines (IL-6 rs1800795G > C, rs1800796G > C, rs1800797G > A, IL-10 rs1800871G > A, rs1800872G > T, rs1800890A > T, rs1800896T > C) and the risk and overall survival of DLBCL patients in a Jordanian Arab population. One hundred and twenty-five DLBCL patients diagnosed at King Abdullah University Hospital (KAUH) from the period 2013-2018 and 238 matched healthy controls were included in the study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues. Genotyping of the genetic polymorphisms was conducted using a sequencing protocol. Our study showed no significant differences in the distribution of all studied polymorphisms of DLBCL between patients and controls. The IL-6 rs1800797 was the only SNP to show significant survival results, DLBCL subjects with the codominant model (GG/AG/AA) genotypes and recessive model (AA genotype in comparison with the combined GG/GA genotype) had worse overall survival (p = 0.028 and 0.016, respectively).