Exploring homologous recombination repair and base excision repair pathway genes for possible diagnostic markers in hematologic malignancies.

Hematologic malignancies (HMs) are a collection of malignant transformations, originating from the cells in the bone marrow and lymphoid organs. HMs comprise three main types; leukemia, lymphoma, and multiple myeloma. Globally, HMS accounts for approximately 10% of newly diagnosed cancer. DNA repair pathways defend the cells from recurrent DNA damage. Defective DNA repair mechanisms such as homologous recombination repair (HRR), nucleotide excision repair (NER), and base excision repair (BER) pathways may lead to genomic instability, which initiates HM progression and carcinogenesis. Expression deregulation of HRR, NER, and BER has been investigated in various malignancies. However, no studies have been reported to assess the differential expression of selected DNA repair genes combinedly in HMs. The present study was designed to assess the differential expression of HRR and BER pathway genes including RAD51, XRCC2, XRCC3, APEX1, FEN1, PARP1, and XRCC1 in blood cancer patients to highlight their significance as diagnostic/ prognostic marker in hematological malignancies. The study cohort comprised of 210 blood cancer patients along with an equal number of controls. For expression analysis, q-RT PCR was performed. DNA damage was measured in blood cancer patients and controls using the comet assay and LORD Q-assay. Data analysis showed significant downregulation of selected genes in blood cancer patients compared to healthy controls. To check the diagnostic value of selected genes, the Area under curve (AUC) was calculated and 0.879 AUC was observed for RAD51 (p < 0.0001) and 0.830 (p < 0.0001) for APEX1. Kaplan-Meier analysis showed that downregulation of RAD51 (p < 0.0001), XRCC3 (p < 0.02), and APEX1 (p < 0.0001) was found to be associated with a significant decrease in survival of blood cancer patients. Cox regression analysis showed that deregulation of RAD51 (p < 0.0001), XRCC2 (p < 0.02), XRCC3 (p < 0.003), and APEX1 (p < 0.00001) was found to be associated with the poor prognosis of blood cancer patients. Comet assay showed an increased number of comets in blood cancer patients compared to controls. These results are confirmed by performing the LORD q-assay and an increased frequency of lesions/Kb was observed in selected genes in cancer patients compared to controls. Our results showed significant downregulation of RAD51, XRCC2, XRCC3, APEX1, FEN1, PARP1, and XRCC1 genes with increased DNA damage in blood cancer patients. The findings of the current research suggested that deregulated expression of HRR and BER pathway genes can act as a diagnostic/prognostic marker in hematologic malignancies.

miRNA-767 and its binding site polymorphism in the mTOR gene act as potential biomarkers for female reproductive cancers.

Aims: The present study aimed to understand the relationship between the mTOR gene SNP (rs2536) and reproductive cancer risk. The expression level of miRNA-767 was also assessed. Methods: 700 tumor samples (300 breast, 200 ovarian and 200 cervical cancers), along with adjacent uninvolved control tissue, were used. rs2536 was screened using Tetra-ARMS PCR and expression level of miRNA-767 was assessed using quantitative PCR. Results: The frequency of the homozygous mutant genotype of rs2536 was observed significantly higher in breast (p < 0.04), ovarian (p < 0.005) and cervical (p < 0.003) cancers. Significant downregulation of miRNA-767 was observed in tumors compared with controls. Conclusion: The present study demonstrates that increased mutant frequency of rs2536 and deregulation of miRNA-767 are associated with increased reproductive cancer risk.

Role of Chk1 gene in molecular classification and prognosis of gastric cancer using immunohistochemistry and LORD-Q assay.

Purpose: The aim of the current study was to assess the prognostic value of the Chk1 gene in the DNA damage response pathway in gastric cancer (GC). Methods: Expression levels of the Chk1 were measured in 220 GC tumor tissues and adjacent healthy/noncancerous tissues using real-time PCR and immunohistochemical staining. Genomic instability in GC patients was measured using the long-run real-time PCR technique for DNA-damage quantification assay and comet assay. Results: Significantly downregulated expression of Chk1 was observed at the mRNA level (p < 0.0001) and protein level (p < 0.0001). Significantly increased frequency of lesions/10 kb and comets was observed in tumor tissues compared with control tissues. Conclusion: The data suggest that downregulated expression of Chk1 and positive Heliobacter pylori infection status may have prognostic significance in GC.

Genetic interactions of mitochondrial sirtuins in brain tumorigenesis.

Purpose: The present study was designed to understand the role of expression variations of mitochondrial imported sirtuins in brain tumorigenesis. The expression levels of mitochondrial imported sirtuins were further analyzed for biomarker potential. Methods: Samples from 200 brain tumors and 200 healthy control tissues were used for expression analysis using quantitative PCR and for DNA damage using LORD-Q analysis. Results: Significant deregulation of SIRT3 (p = 0.002), SIRT4 (p = 0.03) and SIRT5 (p = 0.006) was observed in brain tumors versus controls. Co-expression analysis showed a significant correlation between the mitochondrial imported sirtuins versus apoptotic genes. LORD-Q analysis showed a significantly increased frequency of lesions/10 kb of mitochondrial imported sirtuins (p < 0.0001) in brain tumor tissue versus controls. Conclusion: The present study showed a correlation between variations of mitochondrial imported sirtuins and increased brain tumor risk.

Impact of COVID Pandemic and Hybrid teaching on Final year MBBS students' End of clerkship Exam performance.

BACKGROUND & OBJECTIVES: The novel coronavirus (SAR-CoV-2) pandemic has revolutionized medical education worldwide. Most medical schools have adopted the online teaching and assessments. Students attending modified clerkships and assessments under the stress of the pandemic, perform and score differently when compared to normal clerkships. We aimed to identify the impact of COVID-19 on final year MBBS students' EOC (End of Clerkship) examination by comparing them with their scores prior to the COVID and with scores of the previous final year. METHODS: This cross-sectional study was conducted at Shifa College of Medicine. Final year MBBS students' scores of years 2019 and 2020 were included. Students' EOC MCQ and OSCE scores were compared in pre-COVID and COVID affected rotations of the same year and with the previous year (2019). Data were analyzed in SPSS version 21, means scores were calculated, and one-way ANOVA was applied. Pearson correlation was calculated for correlation assessment of MCQ and OSCE scores. RESULTS: There were 118 students. The mean EOC, OSCE, and MCQ scores in rotations one to four were 72.8±6.4, 73.3± 8.1, 71.6± 7.4, 72.7± 6.7 and 44.4± 8, 47.2± 8.4, 46.1± 8.2, 48.8± 8.1, respectively. One-way ANOVA results before and after COVID lockdown were statistically insignificant (p=0.3) for OSCE and significant for MCQ in the final year class of 2020 (p=0.001). The Pearson correlation assessment between MCQ and OSCE scores (n=416) had a significant positive correlation (r=0.42, p=0.000). The overall comparison between scores of the final year class of 2019 and 2020 showed significant improvement in Surgery and Obstetrics/Gynae scores in 2020. CONCLUSION: During the COVID pandemic, the final year students' performance in EOC MCQ and OSCE over all remained unaffected.

Lessons from the COVID-19 pandemic: Perspectives of medical students.

OBJECTIVE: The objective of the study was to assess the impacts of the COVID-19 pandemic on the mental health and lifestyle of our medical students. METHODS: This observational study was conducted on medical students of Shifa College of Medicine, Islamabad from June to August 2020. The GAD-7 and PHQ-9 questionnaires were used for anxiety and depression assessment. Different aspects of changes in lifestyle were evaluated and students were inquired about their views regarding the COVID-19 pandemic. The chi-square test was applied to assess the associations between levels of anxiety and depression with student's responses to the concerns and lifestyle changes. The binomial logistic analysis was used to highlight important predictors of anxiety and depression. The Wilcoxon signed-rank test was used to compare the time spent on various activities before and during the pandemic. RESULTS: There were 234 participants in the study. The depression and anxiety were detected in 151 (64.5%) and 146 (66.7%) students. The college closure led to a significant increase in sleeping time, sedentary time, and time on gadgets (Z=-4.67, Z=-7.23, Z= -6.72, respectively) on the Wilcoxon signed-rank test. The binomial regression analysis identified study years be the significant predictors for the development of depression and anxiety (p<0.05). CONCLUSIONS: Our study emphasizes prioritizing both the physical and mental health of medical students is vital to avoid complications related to the pandemic.

Gene expression of thrombomodulin, TNF-α and NF-KB in coronary artery disease patients of Pakistan.

Thrombomodulin (THBD) is an endothelial surface glycoprotein receptor, having a pivotal role in maintaining laminar blood flow. It functions to protect endothelial integrity by exhibiting anti-coagulation and anti-inflammatory properties thereby playing a key role in cardiovascular disease (CVD) pathology. Cholesterol lowering drugs have shown to alter the anti-inflammatory effects of cytokines. Understanding the molecular aspects of THBD gene and its relation to inflammatory cytokines is important to identify new prognostic and therapeutic targets for the CVD treatments. The present study was conducted to measure the expression of THBD, TNF-α and NF-kB genes in coronary artery disease patients (CAD) in Pakistani population. Lipid profile and BMI was compared both on fifty CAD patients and fifty healthy individuals. Expression analysis for THBD, TNF-α and NF-kB was carried out using real time PCR. The effect of lipid lowering drugs on cardiometabolic risk variables especially gene expression was analyzed. Our results indicated that the difference in BMI was marginal; however LDL-cholesterol and triglycerides levels in CAD patients were significantly higher than healthy individuals. THBD gene was significantly up-regulated whereas TNF-α and NF-kB were significantly down regulated in CAD individuals. Further exploration revealed that these variations were accounted to the use of statins by the patients. The use of statins by CAD patients up-regulated the mRNA expression of THBD by down-regulation of inflammatory mediators. The enhanced expression of endothelial THBD in response to cholesterol lowering drugs establishes a novel pleiotropic target that can be of clinical significance in thromboembolic and inflammatory disorders.

Evaluating the combination of Metarhizium anisopliae and an enhanced form of diatomaceous earth (Grain-Guard) for the environmentally friendly control of stored grain pests.

Stored grain pests cause great damage to various grain products, and protection against these pests is currently based on synthetic insecticides and fumigants. As a result, these chemicals cause problems, including grain contamination with chemical residues and the development of resistance by insect pests to these chemicals. Therefore, to combat this issue, in the present study, an enhanced form of diatomaceous earth (DE), Grain-Guard, and Metarhizium anisopliae (Metschnikoff) Sorokin (Ascomycota: Sordariomycetes) were evaluated alone and in combination against adults of Liposcelis paeta (Pearman) (Psocoptera: Liposcelididae), Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae), Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae), and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). M. anisopliae was used at a rate of 1.7 × 104 conidia kg-1 grain alone as well as with two doses of DE (25 and 50 ppm) on wheat under different exposure time courses (4, 7, and 14 days). It is worth mentioning that the combination of M. anisopliae and DE was highly effective against the adults of L. paeta, C. ferrugineus, R. dominica, and T. castaneum after 14 days of exposure. When DE and M. anisopliae were applied alone, DE showed more effectiveness than fungal conidia. Progeny emergence was decreased when modified DE was applied at a high dose rate with the fungus and suppressed at a low dose. The cadavers of all species in the trials showed a maximum percentage of mycosis, and sporulation (conidia/ml) also showed the same result when the fungus was tested alone, while low mycosis and sporulation were achieved under the application of a mixture with a high dose of modified DE. Our findings indicate the best possible combination of DE (at low dose rates) along with a fungus that might contribute to lowering health and environmental risks.

Knowledge and perceptions about Pre-diabetes amongst doctors, medical students, and patients in a tertiary care hospital of Islamabad.

OBJECTIVE: To explore the knowledge and perceptions about pre-diabetes screening and management amongst physicians, final year medical students, and patients. METHODS: The cross-sectional observational study was conducted at Shifa International Hospital, Shifa Foundation Clinic and Shifa College of Medicine, Islamabad, Pakistan, from November 2017 to February 2018. A structured questionnaire was used to assess doctors' and final year medical students' knowledge about screening and management of pre-diabetes. A group of patients were also interviewed about pre-diabetes awareness and their primary resources for health-related information. Data was analysed using SPSS 23. RESULTS: Of the 267 participants, there were 85(32%) doctors, 82(31%) medical students and 100(37%) patients. Only 61(71.8%), 44(51.7%) and 34(39.8%) physicians and 53(64.6%), 30(36.5%) and 26(31.6%) students could accurately identify impaired fasting blood glucose, glycated haemoglobin and impaired glucose tolerance criteria for pre-diabetes, respectively. Regarding risk factors for pre-diabetes screening, ethnicity, cardiovascular diseases and gestational diabetes were identified by 8(9.4%), 6(7.1%) and 9(10.6%) physicians and 10(12.2%), 6(7.3%) and 15(18.3%) students, respectively. There was no statistically significant relation of correct identification of pre-diabetes criteria with specialties, designations and years of experience post-qualification (p>0.5). Only 3(3%) patients were aware of pre-diabetes or borderline diabetes. CONCLUSIONS: Knowledge and perception of doctors, medical students and patients about pre-diabetes was found to be deficient. Efforts are required to reinforce its identification and management at all levels..

Effect of body mass index on operative outcome after robotic-assisted Ivor-Lewis esophagectomy: retrospective analysis of 129 cases at a single high-volume tertiary care center.

The impact of body weight on outcomes after robotic-assisted esophageal surgery for cancer has not been studied. We examined the short-term operative outcomes in patients according to their body mass index following robotic-assisted Ivor-Lewis esophagectomy at a high-volume tertiary-care referral cancer center and evaluated the safety of robotic surgery in patients with an elevated body mass index. A retrospective review of all patients who underwent robotic-assisted Ivor-Lewis esophagectomy between April 2010 and June 2013 for pathologically confirmed distal esophageal cancer was conducted. Patient demographics, clinicopathologic data, and operative outcomes were collected. We stratified body mass index at admission for surgery according to World Health Organization criteria; normal range is defined as a body mass index range of 18.5-24.9 kg/m2. Overweight is defined as a body mass index range of 25.0-29.9 kg/m2 and obesity is defined as a body mass index of 30 kg/m2 and above. Statistics were calculated using Pearson's Chi-square and Pearson's correlation coefficient tests with a P-value of 0.05 or less for significance. One hundred and twenty-nine patients (103 men, 26 women) with median age of 67 (30-84) years were included. The majority of patients, 76% (N = 98) received neoadjuvant therapy. When stratified by body mass index, 28 (22%) were normal weight, 56 (43%) were overweight, and 45 (35%) were obese. All patients had R0 resection. Median operating room time was 407 (239-694) minutes. When stratified by body mass index, medians of operating room time across the normal weight, overweight and obese groups were 387 (254-660) minutes, 395 (310-645) minutes and 445 (239-694), respectively. Median estimated blood loss (EBL) was 150 (25-600) cc. When stratified by body mass index, medians of EBL across the normal weight, overweight and obese groups were 100 (50-500) cc, 150 (25-600) cc and 150 (25-600), respectively. Obesity significantly correlated with longer operating room time (P = 0.05) but without significant increased EBL (P = 0.348). Among the three body mass index groups there was no difference in postoperative complications including thrombotic events (pulmonary embolism and deep venous thrombosis) (P = 0.266), pneumonia (P = 0.189), anastomotic leak (P = 0.090), wound infection (P = 0.390), any cardiac events (P = 0.793) or 30 days mortality (P = 0.414). Our data study demonstrates that patients with esophageal cancer and an elevated body mass index undergoing robotic-assisted Ivor-Lewis esophagectomy have increased operative times but no significantly increased EBL during the procedure. Other potential morbidities did not differ with the robotic approach.

The prognostic value of residual nodal disease following neoadjuvant chemoradiation for esophageal cancer in patients with complete primary tumor response.

BACKGROUND: The prognostic significance of residual nodal disease in otherwise complete pathologic responders (ypT0N+) to neoadjuvant chemoradiation (nCRT) for esophageal cancer is unknown. METHODS: ypT0N+ responders were identified from a single institution database of esophageal cancer patients undergoing esophagectomy and were compared to patients without locoregional disease (ypT0N0) and to non-complete responders (ypT+). RESULTS: Out of 487 patients, 196 ypT0N0 and 14 ypT0N+ patients were identified. Pre-treatment stage was similar between ypT0N0 and ypT0N+ patients: 66% versus 73% of patients had uT3 disease (P = 0.50) and 76% versus 55% had nodal involvement (P = 0.49), respectively. Locoregional recurrence (43%) was more common in ypT0N+ patients. Median overall survival (OS) was worse in ypT0N+ patients (14.8 months) compared to ypT0N0 patients (92.2 months) and ypT+ patients (38.0 months, P < 0.001). Median OS of ypT0N+ patients was similar to ypT+ stage II (29.6 months, P = 0.84) and stage III (27.5 months, P = 0.95) disease. No difference in median OS existed in patients with residual nodal disease (n = 163) based on local response (14.8 months in ypT0N+ and 22.5 months in ypT+N+ patients, P = 0.55). CONCLUSIONS: Residual nodal disease in esophageal cancer patients with complete response in the primary tumor following nCRT portends a poor prognosis and behaves similar to pathologic stage II/III disease.

New extended exponentially weighted moving average control chart for monitoring process mean.

In this article, we develop a new control chart based on the Exponentially Weighted Moving Average (EWMA) statistic, termed the New Extended Exponentially Weighted Moving Average (NEEWMA) statistic, designed to recognize slight changes in the process mean. We derive expressions for the mean and variance of the NEEWMA statistic, ensuring an unbiased estimation of the mean, with simulation results showing lower variance compared to traditional EWMA charts. Evaluating its performance using Average Run Length (ARL), our analysis reveals that the NEEWMA control chart outperforms EWMA and Extended EWMA (EEWMA) charts in swiftly recognizing shifts in the process mean. Illustrating its operational methodology through Monte Carlo simulations, an illustrative example using practical data is also provided to showcase its effectiveness.

Dose-Volume Predictors of Radiation Pneumonitis After Thoracic Hypofractionated Radiation Therapy.

PURPOSE: Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis. METHODS AND MATERIALS: All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020. Tumors near critical structures (trachea, proximal tracheobronchial tree, esophagus, spinal cord, or heart) were considered central (within 2 cm), and those closer were classified as ultracentral (within 1 cm). The primary endpoint was grade ≥2 pneumonitis. Logistic regression analyses, adjusting for target size and dosimetric variables, were used to establish a dose threshold associated with <20% risk of grade ≥2 pneumonitis. RESULTS: During a median 24.3-month follow-up, 18 patients (16.8%) developed grade ≥2 radiation pneumonitis, with no significant difference between the 2 dose regimens (17.3% vs 16.3%, P = .88). Four patients (3.7%) experienced grade ≥3 pneumonitis, including 2 grade 5 cases. Patients with grade ≥2 pneumonitis had significantly higher lung V20 (mean 23.4% vs 14.5%, P < .001), MLD (mean 13.0 Gy vs 9.5 Gy, P < .001), and lung V5 (mean 49.6% vs 40.6%, P = .01). Dose thresholds for a 20% risk of grade ≥2 pneumonitis were lung V20 <17.7%, MLD <10.6 Gy, and V5 <41.3%. Multivariable analysis revealed a significant association between lung V20 and grade ≥2 pneumonitis (adjusted odds ratio, 1.48, P = .03). CONCLUSIONS: To minimize the risk of grade ≥2 radiation pneumonitis when delivering 4 Gy per fraction at either 60 Gy or 72 Gy, it is advisable to maintain lung V20<17.7%. MLD <10.6 Gy and V5<41.3% can also be considered as lower-priority constraints. However, additional validation is necessary before incorporating these constraints into clinical practice or trial planning guidelines.

Oncometabolic role of mitochondrial sirtuins in glioma patients.

Mitochondrial sirtuins have diverse role specifically in aging, metabolism and cancer. In cancer, these sirtuins play dichotomous role as tumor suppressor and promoter. Previous studies have reported the involvement of sirtuins in different cancers. However, till now no study has been published with respect to mitochondrial sirtuins and glioma risks. Present study was purposed to figure out the expression level of mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) and related genes (GDH, OGG1-2α, SOD1, SOD2, HIF1α and PARP1) in 153 glioma tissue samples and 200 brain tissue samples from epilepsy patients (taken as controls). To understand the role of selected situins in gliomagenesis, DNA damage was measured using the comet assay and oncometabolic role (oxidative stress level, ATP level and NAD level) was measured using the ELISA and quantitative PCR. Results analysis showed significant down-regulation of SIRT4 (p = 0.0337), SIRT5 (p<0.0001), GDH (p = 0.0305), OGG1-2α (p = 0.0001), SOD1 (p<0.0001) and SOD2 (p<0.0001) in glioma patients compared to controls. In case of SIRT3 (p = 0.0322), HIF1α (p = 0.0385) and PARP1 (p = 0.0203), significant up-regulation was observed. ROC curve analysis and cox regression analysis showed the good diagnostic and prognostic value of mitochondrial sirtuins in glioma patients. Oncometabolic rate assessment analysis showed significant increased ATP level (p<0.0001), NAD+ level [(NMNAT1 (p<0.0001), NMNAT3 (p<0.0001) and NAMPT (p<0.04)] and glutathione level (p<0.0001) in glioma patients compared to controls. Significant increased level of damage ((p<0.04) and decrease level of antioxidant enzymes include superoxide dismutase (SOD, p<0.0001), catalase (CAT, p<0.0001) and glutathione peroxidase (GPx, p<0.0001) was observed in patients compared to controls. Present study data suggest that variation in expression pattern of mitochondrial sirtuins and increased metabolic rate may have diagnostic and prognostic significance in glioma patients.

Utilization and Survival Impact of Hypofractionated Radiotherapy in Stage I Non-small Cell Lung Cancer.

OBJECTIVES: The optimal fractionation schedule in unresected stage I non-small cell lung cancer (NSCLC) unsuitable for stereotactic body radiation therapy is unclear. Given the lack of comparative data regarding nonstereotactic body radiation therapy schemas, we compared overall survival (OS) with hypofractionated radiotherapy (HFRT) versus conventionally fractionated radiotherapy (CFRT) and examined the OS impact of different HFRT doses. MATERIALS AND METHODS: This retrospective analysis included 2159 patients from the National Cancer Database diagnosed with stage I (cT1-2aN0M0) NSCLC between 2008 and 2016. Patients underwent CFRT (70≤BED10 [biologically effective dose] <100 Gy10 in ≥30 fractions), low-dose HFRT (LD-HFRT; 70≤BED10 [assuming α/ß=10] <100 Gy10 in 11 to 24 fractions), or high-dose HFRT (HD-HFRT; 100≤BED10 ≤120 Gy10 in 6 to 10 fractions). Patients who received surgery, chemotherapy, or immunotherapy were excluded. We compared CFRT versus all HFRT, and separately CFRT versus LD-HFRT and CFRT versus HD-HFRT. OS was evaluated with the Kaplan-Meier estimator, log-rank test, and Cox regression. RESULTS: A total of 63.2% of patients underwent CFRT, 23.5% LD-HFRT, and 13.3% HD-HFRT. OS was significantly longer with HFRT versus CFRT on univariable (28.2 mo [95% CI, 25.6-31.7] vs 26.4 mo [25.0-27.9]; log-rank=0.0025) but not multivariable analysis (MVA; hazard ratio [HR] 0.90; P=0.062). MVA yielded no significant difference in OS between CFRT and LD-HFRT (HR 0.96, P=0.53). OS was significantly longer with HD-HFRT versus CFRT on MVA (HR, 0.75; P=0.003). However, on sensitivity analysis using different multivariable modeling techniques, this did not retain statistical significance (HR, 0.83; P=0.12). CONCLUSIONS: For stage I NSCLC, HFRT does not show a robust OS benefit compared with CFRT but may be preferred given the convenience and lower costs.

Exploring the process of final year objective structured clinical examination for improving the quality of assessment.

OBJECTIVE: To explore the process of final year Objective Structured Clinical Examination (OSCE) for improving the quality of assessment. METHODS: The analytical cross-sectional study was conducted with purposive sampling on one-year Medicine Objective Structured Clinical Examination (OSCE) scores of Final Year batch of 2009 at the Shifa College of Medicine, Islamabad. The scores from December 2008 to December 2009 of 77 Final Year students were analysed. The process of examination and the interpretation of the scores was evaluated using the Standards for Educational and Psychological Testing as the conceptual framework for validity testing which identifies five sources of test validity evidence. Internal consistency reliability of the examination was determined by Cronbach's alpha. Comparison and Correlation between students' end-of-clerkship (EOC) and end-of-year (EOY) examination scores were analysed by paired sample t-test and Pearson's Correlation Coefficient respectively. RESULTS: There was no significant positive correlation between the scores of end-of-clerkship and end-of-year Medicine Objective Structured Clinical Examination. Overall, the students' performance in the former segment was better. Evaluation of exam stations showed that mean scores significantly decreased in almost all end-of-year stations. Reliability decreased from 0.53 in the former to 0.48 in the latter assessment. Validity evidence showed that content validity was established by blueprinting of the objective exam. Response process evidence revealed that checklists, response key and rating scale were discussed with the faculty observing the stations. However, lack of other important sources of validity like standard setting for pass/fail criteria and poor reliability are serious threats to the validity of such exam scores. CONCLUSIONS: Multiple sources of validity evidence are needed to make defensible assumptions from performance scores. Consideration of all sources and threats to validity evidence is important to improve the quality of assessment.

Choledochorraphy (primary repair) versus t-tube drainage after open choledochotomy.

BACKGROUND: T-tube drainage used to be standard practice after surgical choledochotomy, but there is now a tendency in some canters to close the common bile duct primarily. This study was designed to compare the clinical results of primary closure with T-tube drainage after open choledocotomy and assess the safety of primary closure for future application. METHODS: This study was conducted at surgical Unit-3, ward 26 Jinnah Postgraduate Medical Centre Karachi, from January 2007 to January 2008. Forty patients were included in this study out of which 20 underwent primary closure and 20 T-tube placements. It was Quasi-experimental, non-probability, purposive sampling. Main outcome measures were operating time, duration of hospital stay, and postoperative complications. SPSS-10 was used for data analysis. RESULTS: The age of patients in the study ranged from 29-83 years. There were 3 male while 37 female patients. Group-1 consisted of 20 patients underwent primary closure after choledocotomy, while Group-2 also consisted of 20 patients underwent T-tube drainage after duct exploration. Mean hospital stay in Group-1 patients was 7.63 days while in group 2 it was 13.6 days. Overall complication rate in group 1 was 15%, biliary leakage in 1 (5%), jaundice in 1 (5%), wound infection in 1 (5%). No re-exploration was required in Group-1. In Group-2 overall complication rate was 30%, biliary leakage in 2 (2%), jaundice in 1 (5%), dislodgement of T-tube in 1 (5%), wound infection in 1 (5%), and sepsis in 1 (5%) patients. Re-exploration was done in one patient. CONCLUSION: Primary closure of Common Bile Duct (CBD) is a safe and cost-effective alternative procedure to routine T-tube drainage after open choledocotomy.

Medical terminology-based computing system: a lightweight post-processing solution for out-of-vocabulary multi-word terms.

The linguistic rules of medical terminology assist in gaining acquaintance with rare/complex clinical and biomedical terms. The medical language follows a Greek and Latin-inspired nomenclature. This nomenclature aids the stakeholders in simplifying the medical terms and gaining semantic familiarity. However, natural language processing models misrepresent rare and complex biomedical words. In this study, we present MedTCS-a lightweight, post-processing module-to simplify hybridized or compound terms into regular words using medical nomenclature. MedTCS enabled the word-based embedding models to achieve 100% coverage and enabled the BiowordVec model to achieve high correlation scores (0.641 and 0.603 in UMNSRS similarity and relatedness datasets, respectively) that significantly surpass the n-gram and sub-word approaches of FastText and BERT. In the downstream task of named entity recognition (NER), MedTCS enabled the latest clinical embedding model of FastText-OA-All-300d to improve the F1-score from 0.45 to 0.80 on the BC5CDR corpus and from 0.59 to 0.81 on the NCBI-Disease corpus, respectively. Similarly, in the drug indication classification task, our model was able to increase the coverage by 9% and the F1-score by 1%. Our results indicate that incorporating a medical terminology-based module provides distinctive contextual clues to enhance vocabulary as a post-processing step on pre-trained embeddings. We demonstrate that the proposed module enables the word embedding models to generate vectors of out-of-vocabulary words effectively. We expect that our study can be a stepping stone for the use of biomedical knowledge-driven resources in NLP.

Hazardous Attitudes: Physician Decision Making in Radiation Oncology.

Purpose: The Federal Aviation Administration quantifies hazardous attitudes (HAs) among pilots using a scale. HAs have been linked to aviation risk. We assessed the influence of HAs and other factors in treatment decision making in radiation oncology (RO). Methods and Materials: An anonymous survey was sent to 809 radiation oncologists in US cities housing the top 25 cancer centers. The survey included an HA scale adapted for RO and presented 9 cases assessing risk-tolerant radiation therapy prescribing habits and compliance with the American Society for Radiation Oncology's Choosing Wisely recommendations. Demographic and treatment decision data were dichotomized to identify factors associated with prescribing habits using univariable and multivariable (MVA) logistic regression analyses. Results: A total of 139 responses (17.1%) were received, and 103 were eligible for analysis. Among respondents, 40% were female, ages were evenly distributed, and 83% were in academics. Median scores for all attitudes (macho, anti-authority, worry, resignation, and impulsivity) were below the aviation thresholds for hazard and data from surgical specialties. On MVA, responders >50 years old with >5 years' experience were 4.45 times more likely to recommend risk-tolerant radiation (P = .016). Macho attitude was negatively associated with Choosing Wisely compliant treatments (odds ratio [OR], 0.12; P = .001). Physicians who reported having previously retreated the supraclavicular fossa without complication were more likely to recommend retreatment in medically unfit patients if they felt the complication was avoided owing to careful planning (OR, 5.2; P = .008). Conclusions: To our knowledge, this represents the first study analyzing physician attitudes in RO and their effect on self-reported treatment decisions. This work suggests that attitude may be among the factors that influence risk-tolerant prescribing practices and compliance with Choosing Wisely recommendations.

A Multicenter Study of Clinical Presentations and Outcomes of Multiple Myeloma in Pakistan: The Real-World Analysis in a Resource-Constrained Country.

This is the first multicenter study from Pakistan exploring the prevalence, clinical presentations and treatment outcomes of Multiple Myeloma patients. This retrospective study involved data collection from hospital record system of four tertiary care referral hospitals of Pakistan including all patients diagnosed as having Multiple Myeloma from January 2014 to December 2018. The demographic details, clinical presentations, laboratory findings, treatment responses, and mortalities were evaluated. The progression-free survival and overall survival were analyzed considering relapse and mortality as the end points, respectively. For the progression-free survival, the Kaplan-Meier survival analysis and the log rank test were used to compare the survival function for chemotherapy followed by autologous stem cell transplant (ASCT) as opposed to chemotherapy alone (non-ASCT). The overall survival analysis was assessed by Kaplan-Meier survival analysis. This study identified 403 Multiple Myeloma patients in five years. The median age at presentation was 55 years. Bortezomib based drug regimens were the most commonly used initial treatments (57.5%). Forty three patients received ASCT. The progression-free survival median for ASCT and non-ASCT patients were 50 months (95% CI, 42-57.9 months) and 26 months (95% CI, 21.5-30.5 months), respectively. The cumulative probability of survival rate at 60 months was 80%. This study identified 403 Multiple Myeloma patients over 5 years in four tertiary care hospitals of Pakistan. It underscores the importance of autologous stem cell transplant in Myeloma patients and advocates improving its facilities in Pakistan.