Diagnostic Evaluation of Polycythemia Vera at High Altitude.

BACKGROUND: Polycythemia is a common medical problem, frequently acquired and reactive to secondary conditions. High-altitude-associated hypoxia contributes to the greater prevalence of polycythemia at altitude. Primary clonal polycythemia vera (PV), even though it is rare, requires a different therapeutic approach. Suspicion of PV usually drives the diagnostic workup of polycythemia. METHODS: In this retrospective lab record study, we collected all JAK2 tests requested over a three-year period. We analyzed requests that were made for the evaluation of polycythemia. Complete blood count (CBC) and imaging of the abdomen were collected. RESULTS: Out of 208 total requests, 136 were for the purpose of polycythemia evaluation. JAK2 mutation was positive (confirming the presence of PV) in 22 (16.7%) cases. PV patients have the usual demographics reported elsewhere. Additionally, PV patients exhibit distinct hemogram results featuring leukocytosis, thrombocytosis, and hypochromic microcytic red blood cells (RBCs) related to the associated iron deficiency. CONCLUSIONS: Many patients with polycythemia at altitude might be unnecessarily considered for an evaluation of PV, if hemoglobin/hematocrit is the sole deciding criterion. PV patients have a distinct CBC pattern that can be exploited to better select patients with polycythemia for further evaluation and thus reduce unnecessary workups.

Prediction of Diabetes and Prediabetes among the Saudi Population Using a Non-Invasive Tool (AUSDRISK).

Background and Objectives: Screening for type 2 diabetes mellitus (DM2) aims to identify asymptomatic individuals who may be at a higher risk, allowing proactive interventions. The objective of this study was to predict the incidence of DM2 and prediabetes in the Saudi population over the next five years. Materials and Methods: The study was conducted in the Aseer region through August 2023 using a cross-sectional survey for data collection. A multistage stratified random sampling technique was adopted, and data were collected through face-to-face interviews using the validated Arabic version of the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Results: In total, 652 individuals were included in the study. Their mean age was 32.0 ± 12.0 years; 53.8% were male, 89.6% were from urban areas, and 55.8% were single. There were statistically significant differences between males and females in AUSDRISK items, including age, history of high blood glucose, use of medications for high blood pressure, smoking, physical activity, and measurements of waist circumference (p < 0.05). Based on AUSDRISK scores, 46.2% of the included participants were predicted to develop impaired glucose tolerance within the coming five years (65.8% among females vs. 23.6%), and 21.9% were predicted to develop DM2 (35.6% among males vs. 6.0% among females); this difference was statistically significant (p = 0.0001). Conclusions: Urgent public health action is required to prevent the increasing epidemic of DM2 in Saudi Arabia.

Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness.

Background: Although estrogen (ERα/ERß), progesterone (PGR), and androgen (AR) receptors are pathologically altered in colorectal cancer (CRC), their simultaneous expression within the same cohort of patients was not previously measured. Methods: ERα/ERß/PGR/AR proteins were measured in archived paired normal and malignant colon specimens (n =120 patients) by immunohistochemistry, and results were analyzed by gender, age (≤50 vs. ≥60 years), clinical stages (early-stage I/II vs. late-stage III/IV), and anatomical location (right; RSCs vs. left; LSCs). Effects of 17ß-estradiol (E2), progesterone (P4), and testosterone alone or combined with the specific blockers of ERα (MPP dihydrochloride), ERß (PHTPP), PGR (mifepristone), and AR (bicalutamide) on cell cycle and apoptosis were also measured in the SW480 male and HT29 female CRC cell lines. Results: ERα and AR proteins increased, whilst ERß and PGR declined markedly in malignant specimens. Moreover, male neoplastic tissues showed highest AR expression, whilst ERß and PGR weakest alongside ERα strongest expression was seen in cancerous tissues from women aged ≥60 years. Late-stage neoplasms also revealed maximal alterations in the expression of sex steroid receptors. By tumor location, LSCs disclosed significant elevations in ERα with marked declines in PGR compared with RSCs, and ERα strongest alongside PGR weakest expression was detected in advanced LSCs from women aged ≥60 years. Late-stage LSCs from females aged ≥60 years also showed weakest ERß and strongest AR expression. In contrast, male RSC and LSC tissues exhibited equal ERß and AR expression in all clinical stages. ERα and AR proteins also correlated positively, whereas ERß and PGR inversely, with tumor characteristics. Concomitantly, E2 and P4 monotherapies triggered cell cycle arrest and apoptosis in the SW480 and HT29 cells, and while pre-treatment with ERα-blocker enhanced the effects of E2, ERß-blocker and PGR-blocker suppressed the E2 and P4 anti-cancer actions, respectively. In contrast, treatment with the AR-blocker induced apoptosis, whilst co-treatment with testosterone hindered the effects. Conclusions: This study advocates that protein expression of sex steroid receptors in malignant tissues could represent prognostic markers, as well as hormonal therapy could provide an alternative strategy against CRC, and their efficacies could be dependent on gender, clinical stage, and tumor location.

Predictors of Anti-TNF Therapy Failure among Inflammatory Bowel Disease (IBD) Patients in Saudi Arabia: A Single-Center Study.

BACKGROUND: The advent of monoclonal antibodies (mAbs) has revolutionized the management of many immune-mediated diseases such as inflammatory bowel disease (IBD). Infliximab and adalimumab were the first mAbs approved for the management of IBD, and are still commonly prescribed for the treatment of both Crohn's disease (CD) and ulcerative colitis (UC). Although mAbs have demonstrated high effectiveness rates in the management of IBD, some patients fail to respond adequately to mAbs, resulting in disease progression and the flare-up of symptoms. OBJECTIVE: The objective was to explore the predictors of treatment failure among IBD patients on infliximab (INF) and adalimumab (ADA)-as demonstrated via colonoscopy with a simple endoscopic score (SES-CD) of ≥1 for CD and a Mayo score of ≥2 for UC-and compare the rates of treatment failure among patients on those two mAbs. METHODS: This was a prospective cohort study among IBD patients aged 18 years and above who had not had any exposure to mAbs before. Those patients were followed after the initiation of biologic treatment with either INF or ADA until they were switched to another treatment due to failure of these mAbs in preventing the disease progression. Univariate and multiple logistic regressions were conducted to examine the predictors and rates of treatment failure. RESULTS: A total of 146 IBD patients (118 patients on INF and 28 on ADA) met the inclusion criteria and were included in the analysis. The mean age of the patients was 31 years, and most of them were males (59%) with CD (75%). About 27% and 26% of the patients had penetrating and non-stricturing-non-penetrating CD behavior, respectively. Patients with UC had significantly higher odds of treatment failure compared to their counterparts with CD (OR = 2.58, 95% CI [1.06-6.26], p = 0.035). Those with left-sided disease had significantly higher odds of treatment failure (OR = 4.28, 95% CI [1.42-12.81], p = 0.0094). Patients on ADA had higher odds of treatment failure in comparison to those on INF (OR = 26.91, 95% CI [7.75-93.39], p = 0.0001). CONCLUSION: Infliximab was shown to be more effective in the management of IBD, with lower incidence rates of treatment failure in comparison to adalimumab.