Risk factors for chronic kidney disease in middle eastern patients with type 2 diabetes mellitus: A cross-sectional study using the KDIGO classification.

AIMS: Chronic kidney disease (CKD) is prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate risk factors for CKD progression across the kidney disease-Improving Global Outcomes (KDIGO)categories in a Middle Eastern population beyond hyperglycemia as emphasized by KDIGO guidelines which classifying CKD by cause and severity. METHODS: This cross-sectional study targeted 1603 patients with T2DM. Risk factors for CKD progression were determined using odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: Overall, 35.5 %, 31.7 %, and 32.8 % of patients were classified as low-risk, moderate-risk, and high-/very high-/highest-risk, respectively. Several factors were associated with high/very high/highest risk categorization, including being aged >45 years (OR: 1.85, 95 % CI: 1.36-2.49; P < 0.001), male gender (OR: 1.87, 95 % CI: 1.38-2.54; P < 0.001), hypertension (OR: 3.66, 95 % CI: 2.32-5.78; P < 0.001), and T2DM duration of ≥15 years (OR: 3.2, 95 % CI: 2.27-4.5; P < 0.001). Patients with more concurrent risk factors were notably represented in the high/very high/highest risk category. CONCLUSIONS: Male patients, older patients, and those with comorbid hypertension, longstanding T2DM, and additional concurrent risk factors have a significantly higher risk of advanced CKD. Such findings should be considered when planning management approaches for patients with CKD.

From Diabetes to Oncology: Glucagon-like Peptide-1 (GLP-1) Receptor Agonist's Dual Role in Prostate Cancer.

Glucagon-like peptide-1 (GLP-1), an incretin hormone renowned for its role in post-meal blood sugar regulation and glucose-dependent insulin secretion, has gained attention as a novel treatment for diabetes through GLP-1 receptor agonists (GLP-1-RA). Despite their efficacy, concerns have been raised regarding the potential associations between GLP-1-RA and certain malignancies, including medullary thyroid cancer. However, evidence of its association with prostate cancer (PCa) remains inconclusive. This review delves into the intricate relationship between GLP-1-RA and PCa, exploring the mechanisms through which GLP-1-Rs may impact PCa cells. We discuss the potential pathways involving cAMP, ERK, AMPK, mTOR, and P27. Furthermore, we underscore the imperative for additional research to elucidate the impact of GLP-1-RA treatment on PCa progression, patient outcomes, and potential interactions with existing therapies. Translational studies and clinical trials are crucial for a comprehensive understanding of the role of GLP-1-RA in PCa management.

Gender inequality in genitourinary malignancies clinical trials leadership.

BACKGROUND: Over the past 2 decades, there has been a growing interest in the significance of gender roles in healthcare and several efforts and initiatives have focused on increasing female representation in the medical field. Clinical trials play a very important role in shaping medical practice; moreover, the leaders of clinical trials often represent the upper echelon of researchers in any designated field. Presently, there is no data regarding women's representation in urological oncology clinical trials leadership. Therefore, the aim of this study is to examine the extent of female representation in leading urological clinical trials. METHODOLOGY: To thoroughly examine the representation of females as principal investigators (PIs) in urological cancer clinical trials between 2000 and 2020, we conducted a comprehensive search of completed trials focused on kidney, prostate, and bladder cancer on ClinicalTrials.gov. We extracted relevant information regarding the PIs and analyzed the data using univariate analyses to identify any significant differences between male and female PIs. RESULTS: A total of 9145 cancer clinical trials were conducted over the last 2 decades, and 11.3% (n = 1033) of them were urological cancer clinical trials. We were able to obtain detailed information about the principal investigators (PI) in 79.0% (n = 816) of the clinical trials, and we found that 16.8% (n = 137) of them were led by female investigators. Upon evaluating the characteristics of the PIs, female PIs had a significantly lower median age and median total citations as compared to male PIs (55.0 vs 59.0 and 5333 vs 7902; p-value < 0.001 and 0.006, respectively). However, there was no statistically significant difference between the termination rate, publication rate, funding source, cancer type, and the subject of conducting the clinical trials between male and female PIs. CONCLUSION: Between 2000 and 2020, only 16.8% of urological cancer clinical trials were led by a female PI, perhaps reflective of a low percentage of senior female researchers in the fields of urology, oncology and radiation oncology. Universities, research institutes and funding agencies should work to improve mentorship, representation and opportunities for female investigators to encourage more involvement for female researchers in these clinical trials.

Understanding the Termination of Urologic Cancer Clinical Trials: Insights and Challenges.

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of <50 were significant predictors of clinical trial termination OR of 5.26 (95% CI, 3.85 to 7.69); all P values are <.001. CONCLUSION: The termination rate of urologic cancer clinical trials was 25%, with low accrual being the most frequently reported reason. Trials funded by a university, single-center trials, and small trials (sample size <50) were associated with early termination. A better understanding of these factors might help researchers, funding agencies, and other stakeholders prioritize resource allocations for multicenter trials that aim to recruit a sufficient number of patients.

Comparison and evaluation of the 2009 and 2021 chronic kidney disease-epidemiological collaboration equations among Jordanian patients with type 2 diabetes mellitus.

AIMS: This study compared the 2009 versus 2021 chronic kidney disease (CKD) Epidemiological Collaboration (CKD-EPI) equations to calculate estimated glomerular filtration rate (eGFR) among Jordanian patients with T2DM to assess their agreement and impact on CKD staging. METHODS: This cross-sectional study included 2382 adult Jordanian patients with T2DM. The 2009 and 2021 CKD-EPI equations were used to calculate eGFR. Patients were reclassified according to kidney disease-Improving Global Outcomes (KDIGO) categories. Agreement between the equations was assessed using Bland-Altman plots and Lin's concordance correlation. RESULTS: The 2021 equation significantly increased eGFR by a median of 2.1 mL/min/1.73 m2 (interquartile range: 0.6-3.6 mL/min/1.73 m2). However, there was significant agreement between equations (Kappa: 0.99; 95% confidence interval: 0.95-1.00), independent of age, sex, and the presence of hypertension. In total, 202 patients (8.5%) were reclassified to higher KDIGO categories using the 2021 equation, with category G3 being most affected. The overall prevalence of patients in the high to highest risk categories decreased (28.0% vs. 26.5%). CONCLUSIONS: Although there was significant agreement with the 2009 equation, the 2021 equation increased eGFR and resulted in the reclassification of a subset of subjects according to KDIGO criteria. The uncertain impact of reducing high-risk category patients raises concerns about potential delays in referral and intervention, while holding the potential to enhance high-risk patient categorization, thus alleviating healthcare burden.

Unlocking the Potential of Artificial Intelligence in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

PURPOSE OF THE REVIEW: This review aims to elucidate the transformative impact and potential of machine learning (ML) in the diagnosis, prognosis, and clinical management of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). It further aims to bridge the gap between current advances of ML and their practical application in these diseases. RECENT FINDINGS: Recent advances in ML have revolutionized prognostication, diagnosis, and treatment of MDS and AML. ML algorithms have proven effective in predicting disease progression, optimizing treatment responses, and in the stratification of patient groups. Particularly, the use of ML in genomic and epigenomic data analysis has unveiled novel insights into the molecular heterogeneity of MDS and AML, leading to better-informed therapeutic strategies. Furthermore, deep learning techniques have shown promise in analyzing complex patterns in bone marrow biopsy images, providing a potential pathway towards early and accurate diagnosis. While still in the nascent stages, ML applications in MDS and AML signify a paradigm shift towards precision medicine. The integration of ML with traditional clinical practices could potentially enhance diagnostic accuracy, refine risk stratification, and improve therapeutic approaches. However, challenges related to data privacy, standardization, and algorithm interpretability must be addressed to realize the full potential of ML in this field. Future research should focus on the development of robust, transparent ML models and their ethical implementation in clinical settings.

Pathogenic germline variants in patients with breast cancer: conversations across generations, practices and patients' attitude.

Background: Breast cancer susceptibility genes such as BRCA1, BRCA2, PALB2, CHEK2 and many others are increasingly recognized among our patient population. In addition to their impact on treatment decisions of tested patients themselves, identifying at-risk family members offer opportunities for cancer preventive measures. Methods: This is an observational cross-sectional study of adult breast cancer patients with positive breast-cancer-susceptibility germline variants who received treatment at our institution. Patients with variants of uncertain significance (VUS), or who refused to give consent, were excluded. The data was collected from an eligible sample of breast cancer patients using a structured questionnaire developed by the study team and tested for validity and reliability, as well as a clinical chart review form. Patients were invited to participate in the study during their scheduled oncology clinics visit. Results: 169 patients were enrolled, including 42 (24.9%) with pathogenic/likely pathogenic (P/LP) BRCA1 variants, 84 (49.7%) with BRCA2 and 43 (25.4%) with non-BRCA variants. All patients were female and the mean age was 45 ± 9.9 years. Among 140 eligible patients, 104 (74.3%) underwent prophylactic mastectomy, while 79 (59.0%) of 134 eligible patients had prophylactic bilateral salpingo-oophorectomy (BSO). Results were communicated with family members by majority (n = 160, 94.7%), including 642 first degree female relatives, and 286 (44.5%) of them have taken no action. Fear of positive test results, cost of testing, unwillingness to undergo preventive measures, and social stigma were cited as barriers to genetic testing in 54%, 50%, 34% and 15%, respectively. Conclusion: Risk-reducing interventions including mastectomy and BSO were carried by majority of patients with P/LP variants. However, though the rate of communication of genetic testing results with family members was high, proper preventive measures were relatively low. Cost and fear of cancer diagnosis, were the leading causes that prevented cascade testing in our cohort.

The Risk of Developing Osteosarcoma After Teriparatide Use: A Systematic Review.

Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical efficacy. Its use is significantly hindered due to label warnings resulting from pre-clinical rat studies demonstrating an increased risk of osteosarcoma. However, clinical trials and post-marketing surveillance studies did not demonstrate any increased risk of osteosarcoma, even after prolonged periods of surveillance reaching up to 15 years, with most of the identified cases of osteosarcomas being solitary and predominantly attributed to other factors. This systematic review provides a comprehensive overview of the currently available literature and provides the highest level of clinical evidence towards demonstrating the lack of any substantial evidence towards osteosarcoma development in patients utilizing TPTD.

Differences in Treatment Outcomes Between Patients with HER2-Low versus HER2-Zero, Hormone Receptor-Positive Advanced-Stage Breast Cancer Treated with Ribociclib.

Background: Metastatic breast cancers (MBC) with no expression of human epidermal growth factor receptor-2 (HER2) are recently classified into two groups; HER2-zero [HER2-immunohistochemistry (IHC) score of 0 (IHC-0)] and HER2-low, defined as those with IHC score of 1+ or 2+ with negative in situ hybridization (ISH) assay. We investigate differences in treatment outcomes between both groups treated with endocrine therapy (ET) and the CDK4/6 inhibitor ribociclib. Methods: Data were retrospectively collected for patients with HR-positive+/HER2-negative MBC who received ribociclib with an aromatase inhibitor (AI) or fulvestrant and were divided into two groups: HER2-zero and HER2-low. Results: A total of 257 patients, median age 48 (22-87) years, all with MBC who were treated with ET and ribociclib were enrolled. One hundred and thirty-seven (53.3%) patients had de novo MBC, and majority (n = 162, 63.0%) received ribociclib as a first-line therapy. In total, 114 (44.4%) patients had HER2-zero (IHC-0), while 143 (55.6%) others had HER2-low disease. The overall response rate (ORR) was 52.0% for the HER2-zero group compared to 39.4% for the HER2-low group, p = 0.005. The median PFS was 22.2 (95% confidence interval [CI], 19.4-NR) months for HER2-zero versus 17.3 (95% CI, 14.1-20.6) months for HER2-low, P = 0.0039. In multivariable analysis, HER2-low expression remained significant determinant of inferior PFS after adjusting for other factors, including the site of metastasis, prior chemotherapy, and the line of treatment. Conclusion: In patients with MBC treated with ET and ribociclib, level of HER2 negativity may affect treatment outcomes; patients with HER2-zero had better response rate and PFS compared to those with HER2-low disease. These findings, if confirmed in larger studies, may help oncologists select patients with HER2-low for better treatment options.

Preoperative and intraoperative risk factors for acute kidney injury after hip fracture surgery: a cohort retrospective study.

INTRODUCTION: Hip fractures have several adverse effects on patients' morbidity and mortality. Postoperative Acute kidney injury (AKI) is one of the complications that have a significant impact on the patient's overall prognosis. We aimed to identify AKI risk after hip fracture surgery and the preoperative and intraoperative risk factors. METHODOLOGY: We conducted a retrospective cohort study in a tertiary care hospital on adult patients who underwent surgery for hip fractures between January 2015 and August 2021. All clinical data were reviewed. RESULT: A total of 611 patients were included (age = 76.44 ± 9.69 years). 126 (20.6%) of them developed AKI postoperatively. In multilinear logistic regression analysis, factors associated with postoperative AKI included eGFR [odds ratio (OR): 0.98; 95% confidence interval (CI): 0.97-0.99 with a p value .01], spinal anesthesia [OR: 1.78; 95% CI: 1.1-2.9 with a p value .01], and partial hip replacement (PHR) type of surgery [OR: 0.56; 95% CI: 0.32-0.96 with a p value .036]. The development of postoperative AKI was the strongest factor that increase mortality of the patients as the (HR = 2.42, CI 95% [1.57-3.74]; p value <.001). CONCLUSION: In this study, we highlight that lower eGFR, and spinal anesthesia were associated with a higher risk of AKI, and PHR surgery has lower odds to develop AKI. Postoperative AKI is associated with a higher mortality rate after hip fracture surgery.

Clinical outcomes in patients with type 2 diabetes mellitus-related kidney disease: A Jordanian population cohort study.

BACKGROUND: Diabetic kidney disease (DKD) increases the risk of cardiovascular (CV) complications, kidney disease progression, and mortality. We aimed to determine the incidence and risk of these outcomes according to DKD phenotype among the Jordanian population. METHODS: A total of 1172 type 2 diabetes mellitus patients with estimated glomerular filtration rates (eGFRs) of >30 ml/min/1.73 m2 were followed-up from 2019 to 2022. At baseline, patients were classified according to the presence of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 ml/min/1.73 m2) into four phenotypes: non-DKD (reference category), albuminuric DKD without decreased eGFR, non-albuminuric DKD with decreased eGFR, and albuminuric DKD with decreased eGFR. RESULTS: Mean follow-up was 2.9 ± 0.4 years. Overall, 147 patients (12.5 %) experienced CV events, while 61 (5.2 %) demonstrated kidney disease progression (eGFR: <30 ml/min/1.73 m2). The mortality rate was 4.0 %. Multivariable-adjusted risk for CV events and mortality was greatest for the albuminuric DKD with decreased eGFR group (hazard ratio [HR]: 1.45, 95 % confidence interval [CI]: 1.02-2.33 and HR: 6.36, 95 % CI: 2.98-13.59, respectively), with the risk increasing when adjusted for prior CV history (HR: 1.47, 95 % CI: 1.06-3.42 and HR: 6.70, 95 % CI: 2.70-16.60, respectively). Risk of a ≥40 % decline in eGFR was greatest for the albuminuric DKD with decreased eGFR group (HR: 3.45, 95 % CI: 1.74-6.85), followed by the albuminuric DKD without decreased eGFR group (HR: 1.6, 95 % CI: 1.06-2.75). CONCLUSION: Thus, patients with albuminuric DKD and decreased eGFR were at greater risk for poor CV, renal, and mortality outcomes compared to other phenotypes.