Association between genetic mutations and risk of venous thromboembolism in patients with solid tumor malignancies: A systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in cancer patients and is associated with significant morbidity, mortality, and burden on the health care system [1]. Previous studies have suggested an association between genetic mutations in solid tumors and VTE risk. METHODS: MEDLINE and EMBASE databases were searched from inception to February 2021. We aimed to include studies presenting data on VTE and genetic mutations with >5% frequency in patients with melanoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), and colon, gastric and ovarian cancers. Meta-analyses of proportions and size effects were conducted if possible. RESULTS: Of 682 eligible articles, we included 33 articles, of which 26 papers reporting on a total of 13,844 patients were included in the meta-analysis. The estimated proportions of VTE in lung cancer patients with EGFR, KRAS, and ALK mutations were 7.3, 18.2, and 30.6%, respectively, whereas for colon cancer with KRAS mutations was 13%. In NSCLC patients with EGFR, KRAS and ALK mutations the relative risk (RR) of VTE was 0.98 (0.81-1.18, P = 0.818), 1.24 (0.78-1.97 P = 0.358) and 1.70 (1.46-1.97, P < 0.001), respectively using a fixed-effects model. In patients with colon cancer and KRAS mutation, no significant increase in the VTE risk was observed according to the random-effects model, RR 1.31 (0.79-2.19, P = 0.285). CONCLUSION: In patients with NSCLC, the presence of ALK mutations was associated with a high proportion and RR of developing VTE. There was no significant increase in the risk of VTE in patients with colon cancer and KRAS mutations.

Comparing the utility of 30- and 60-minute cortisol levels after the standard short synacthen test to determine adrenal insufficiency: A retrospective cross-sectional study.

Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250 µg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level.Patients >14 years who underwent SST from January 2010 to December 2017 were included. Pearson's chi-square cross-tabulation was used to identify individuals with inconsistent 30- and 60-minute serum cortisol test results. Logistic regression analysis was performed to predict normal responses based on the baseline cortisol value.Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394 ±â€Š286.58, 722 ±â€Š327.11, and 827 ±â€Š369.30 nmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (n = 72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550 nmol/L at 60 minutes. This particular subgroup's mean change (240 nmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152 nmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226 nmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST (P-value < .0001).Relying on a 60-minute cortisol level can identify all normal and abnormal responses, while relying on 30-minute cortisol level alone may produce false-positives. Additionally, a baseline cortisol level of ≥226 nmol/L is a reliable threshold for determining adequate adrenal function, particularly with a low pretest hypoadrenalism probability.

Rivaroxaban Experience at Tertiary Care Centre in Saudi Arabia:A Retrospective Observational Study.

BACKGROUND: Atrial fibrillation (AF) and Venous Thromboembolism (VTE) are significant causes of morbidity and mortality. Direct oral anticoagulants (DOACs) are as effective as vitamin K antagonists (VKAs) with a propensity to cause less major bleeding. This study aimed to assess the safety and effectiveness of rivaroxaban in routine clinical practice in a large tertiary referral center in Saudi Arabia. MATERIALS AND METHODS: In this study, patients who received rivaroxaban at a tertiary referral hospital were included in this study. All adverse events were recorded, including major bleeding, non-major bleeding events, symptomatic thromboembolic events (deep vein thrombosis, pulmonary embolism) and all-cause death. RESULTS: A total of 509 patients were prescribed rivaroxaban during the study period. The most common indication for rivaroxaban was non-valvular AF (65.3%) and VTE (34.7%). The mean age was 60.4 ± 16.4 years, and 50.8% were female. The median CHA2DS2-Vasc score was 2.1 in patients on rivaroxaban for non-valvular AF. Bleeding occurred in 72 (14.1%) patients, of which 20 (3.9%) had major bleeds. Thrombosis events occurred in 13 (2.5%) patients in the overall cohort. Fourteen (2.7%) patients died during the study, including a case of fatal bleeding secondary to rivaroxaban. CONCLUSION: This study describes the use of rivaroxaban in a broad patient population in clinical practice in the Middle East. The overall bleeding and thrombosis rates in this study were comparable to those seen in major clinical trials.

Effects of smoking on outcomes of hematopoietic cell transplantation: a systemic review and future directions.

Hematopoietic cell transplantation (HCT) survivors are at risk of increased mortality compared to the general population. Smoking by HCT survivors has been reported to impact a variety of health outcomes, resulting in an increased risk for infections, cardio-pulmonary diseases, and cancer. The purpose of our study was to conduct a systematic literature search to determine the relationship between tobacco smoking pre-HCT and post-HCT outcomes. We conducted an electronic literature search from all languages from multiple peer-reviewed databases of studies that evaluated the effects of tobacco smoking prior to HCT on clinical outcomes. Data were extracted from the studies according to a strict selection criterion. Due to differences in primary endpoint and different populations evaluated in different studies, a meta-analysis was not possible, and a descriptive quantitative analysis is provided. Out of the 447 publications fulfilling the selection criteria for the electronic search, 17 articles were included in the final sample. The studies varied in terms of study design, patient characteristics, and HCT type. Considerable variability in definition of smoking was observed. We found that smoking pre-HCT was associated with a higher incidence of cardiovascular diseases, new infections, pulmonary complications, and cancers in comparison to non-smokers. Moreover, smoking pre-HCT was significantly associated with increased risks of both relapse and non-relapse mortality, and inversely related to median overall survival. Smoking adversely affects mortality in all HCT survivors by increasing the risks of both malignant and non-malignant complications. Thus, guidelines are urgently needed to formulate lifestyle factor modifications for HCT survivors focusing on smoking cessation strategies and abstinence maintenance in former smokers. Given the strength of these findings, guidelines should include systematic definitions of smoking for use in clinical trials as well as in standardized data reporting.