Biomarker for cardiorenal syndrome risk in patients with liver cirrhosis and type 2 diabetes in Saudi Arabia.

OBJECTIVES: To evaluate the correlation between different attributes, levels of biomarkers, and the probability of developing cardiorenal syndrome (CRS) in patients who have been diagnosed with type 2 diabetes mellitus (T2DM) and liver cirrhosis (LC). The hypothesis suggests that liver illness may be linked to renal impairment, cardiac dysfunction, and the development of cardiorenal syndrome METHODS: The current study retrospectively assessed the medical records of patients who had LC and T2DM diagnoses and were hospitalized at Al Madina Al Munwara hospitals in 2022 and 2023. RESULTS: This research investigated T2DM patients with physician-confirmed to have LC. Poor glycemic control is indicated by high blood glucose and glycated hemoglobin (HbA1c) readings in research participants. High blood pressure, atherogenic plasma indicator (AIP), and obesity plagued most of these individuals. High creatinine, moderate estimated Glomerular Filtration Rate (eGFR) decline, and a modest urinary albumin-to-creatinine (UACR) rise were the most prevalent variables in LC and T2DM patients. Cardiorenal syndrome risk factors, including elevated blood pressure, triglyceride levels, body mass index (BMI), and high-sensitivity C-reactive protein (hs-CRP) concentrations, were identified through logistic regression. It has been demonstrated that the prevalence of these risk factors increases with age; women may be at a greater risk for developing CRS. Specific biomarker evaluations classified 108 (22.6%) LC and T2DM patients at high risk for chronic kidney disease (CKD), 100 (20%) at risk for cardiovascular disease (CVD), and 91 (18.2%) at risk for CRS. CONCLUSION: The current assessment included 500 patients with T2DM and LC. The risk factors for CRS identified in this study included elevated cholesterol and triglyceride levels, high BMI, and elevated blood pressure, with age being a significant factor, particularly in female patients. Early identification of these characteristics in patients with LC and T2DM could aid in mitigating the progression of chronic illnesses and their associated complications.

Autoimmune diseases and their prevalence in Saudi Arabian patients with type 1 diabetes mellitus.

OBJECTIVES: To evaluate the prevalence of autoimmune disorders among young and adult populations diagnosed with type 1 diabetes mellitus (T1DM) in Al-Madinah Al-Munawarah, Saudi Arabia, and assess the potential impact of these conditions on other comorbidities. METHODS: A retrospective, descriptive study examined autoimmune disorders in T1DM youth and adults. A total of 2258 verified T1DMs were tested. Analyzed hospital and laboratory data. Autoimmune T1DM was investigated clinically and laboratory. RESULTS: A total of 2258 T1DM adults, adolescents, and children were investigated; 500 (22.2%) were under 12, 540 (23.9%) were 13-17, and 1218 (53.9%) were 18 plus. Autoimmune with T1DM was 67.4%. Gender and age affect prevalence. 25.7% of adult females had autoimmune thyroiditis. Children and adolescents have greater rates of celiac disease than adults of both genders. Adrenal insufficiency was more frequent in adults. Adult males had 28.5% polyglandular autoimmune diseases, and women had 19.7%. Type 1 DM and other autoimmune illnesses increase the risk of nephropathy, CVD, and hypoglycemia. Bloodstream biomarkers linked to these disorders corroborate this. CONCLUSION: Autoimmune diseases in Saudi patients with T1DM exhibited specificity with respect to gender and age. Al-Madinah Al-Munawwarah have a heightened prevalence of autoimmune diseases among young individuals diagnosed with T1DM, such as celiac disease and autoimmune thyroiditis. Conversely, older individuals in the region have been observed to exhibit a greater incidence of adrenal failure and polyglandular autoimmune disorders. Autoimmune diseases that result in nephropathy, CVD, and hypoglycemia are highly prevalent based on biomarker levels.

The Association Between Physical Activity and Peripheral Neuropathy in Diabetic Patients: A Cross-Sectional Multicenter Study From Saudi Arabia.

Background Peripheral diabetic neuropathy (PDN) is a serious consequence of diabetes mellitus (DM) that can impair quality of life and result in physical disability. This study aimed to investigate the relationship between physical activity and the severity of PDN among a sample of Saudi diabetic patients in Medina city, Saudi Arabia. Methodology A total of 204 diabetic patients participated in this multicenter, cross-sectional study. A validated self-administered questionnaire was distributed electronically to patients on-site during follow-up. Physical activity and diabetic neuropathy (DN) were assessed using the validated International Physical Activity Questionnaire (IPAQ) and the validated Diabetic Neuropathy Score (DNS), respectively. Results The mean (SD) age of the participants was 56.9 (14.8) years. The majority of the participants reported low physical activity (65.7%). The prevalence of PDN was 37.2%. There was a significant correlation between the severity of DN and the duration of the disease (p = 0.047). Higher neuropathy score was noticed in those with hemoglobin A1C (HbA1c) level ≥7 compared to those with lower HBA1c (p = 0.045). Overweight and obese participants had higher scores compared to normal-weight participants (p = 0.041). The severity of neuropathy decreased significantly when the level of physical activity increased (p = 0.039). Conclusions There is a significant association between neuropathy and physical activity, body mass index, duration of diabetes mellitus, and HbA1c level.

Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series.

BACKGROUND: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. METHODS: This is a single-centre retrospective case series study. RESULTS: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. CONCLUSIONS: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.

Brentuximab vedotin does not cause clinically relevant QTc interval prolongation in patients with CD30-positive hematologic malignancies.

PURPOSE: Brentuximab vedotin (ADCETRIS®), an antibody-drug conjugate, comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In vitro studies showed that MMAE does not interfere with hERG K+ channels at clinically relevant concentrations. In pivotal phase 2 clinical trials in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin has shown substantial efficacy and an acceptable safety profile. This phase 1 open-label study was designed to evaluate the effect of brentuximab vedotin on the duration of cardiac ventricular repolarization. METHODS: Patients with CD30-positive hematologic malignancies were treated with 1.8 mg/kg brentuximab vedotin by intravenous infusion every 3 weeks for up to 16 cycles. The primary endpoint was the change from baseline to Cycle 1 Days 2, 3, and 4 in the duration of ventricular repolarization using Fridericia's corrected QT interval (QTcF). RESULTS: There was no clinically meaningful change from baseline in the duration of ventricular repolarization as measured by QTcF in the 46 evaluable patients out of 52 total patients treated with brentuximab vedotin. There was no evidence of treatment-emergent cardiac safety abnormalities. Brentuximab vedotin was generally well tolerated with a response rate and an adverse event profile consistent with prior studies. CONCLUSION: There is no significant prolongation of the QT/QTc interval with brentuximab vedotin in patients with CD30-positive hematologic malignancies.

Reduced-intensity allogeneic hematopoietic cell transplantation using fludarabine-melphalan conditioning for treatment of mature T-cell lymphomas.

Among non-Hodgkin's lymphoma subtypes, T-cell phenotype confers a poor clinical prognosis. For more aggressive histologies, patients frequently present with advanced disease that is inherently chemoresistant. For cutaneous histologies, disease progresses less rapidly, but is debilitating and often incurable in the long term. Here we report the retrospective analysis of data from 27 patients with mature T-cell lymphoma treated with salvage allogeneic haematopoietic cell transplantation at the City of Hope, Duarte, CA, USA, using a reduced-intensity fludarabine/melphalan conditioning regimen between the years 2001 and 2008. Eleven of the twenty-seven patients had cutaneous T-cell lymphoma (CTCL). The majority of patients had advanced disease at the time of transplant (17/27 or 63%). Median follow-up was 36 months. We observed a 2-year OS of 55%, a PFS of 47% and a cumulative incidence of relapse/progression and non-relapse mortality (NRM) of 30 and 22%, respectively. For CTCL, patients had a 2-year PFS of 45% and NRM of 27% compared with patients with other histologies, who had a PFS of 62% and NRM of 19%. Overall, our results suggest that meaningful long-term survival rates and disease control can be achieved with acceptable non-relapse mortality in patients with mature T-cell lymphomas, including CTCL using reduced-intensity conditioning with melphalan and fludarabine.

A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia.

Inhibition of farnesyltransferase (FT) activity has been associated with in vitro and in vivo anti-leukemia activity. We report the results of a phase 1 dose-escalation study of tipifarnib, an oral FT inhibitor, in patients with relapsed, refractory or newly diagnosed (if over age 70) acute myelogenous leukemia (AML), on a week-on, week-off schedule. Forty-four patients were enrolled, two patients were newly diagnosed, and the rest were relapsed or refractory to previous treatment, with a median age of 61 (range 33-79). The maximum tolerated dose was determined to be 1200 mg given orally twice daily (b.i.d.) on this schedule. Cycle 1 dose-limiting toxicities were hepatic and renal. There were three complete remissions seen, two at the 1200 mg b.i.d. dose and one at the 1000 mg b.i.d. dose, with minor responses seen at the 1400 mg b.i.d. dose level. Pharmacokinetic studies performed at doses of 1400 mg b.i.d. showed linear behavior with minimal accumulation between days 1-5. Tipifarnib administered on a week-on, week-off schedule shows activity at higher doses, and represents an option for future clinical trials in AML.

Reversible Watermarking Surviving JPEG Compression.

This paper will discuss the properties of watermarking medical images. We will also discuss the possibility of such images being compressed by JPEG and give an overview of JPEG compression. We will then propose a watermarking scheme that is reversible and robust to JPEG compression. The purpose is to verify the integrity and authenticity of medical images. We used 800x600x8 bits ultrasound (US) images in our experiment. SHA-256 of the image is then embedded in the Least significant bits (LSB) of an 8x8 block in the Region of Non Interest (RONI). The image is then compressed using JPEG and decompressed using Photoshop 6.0. If the image has not been altered, the watermark extracted will match the hash (SHA256) of the original image. The result shown that the embedded watermark is robust to JPEG compression up to image quality 60 (~91% compressed).

Reversible watermarking for authentication of DICOM images.

We propose a watermarking scheme that can recover the original image from the watermarked one. The purpose is to verify the integrity and authenticity of DICOM images. We used 800x600x8 bits ultrasound (US) images in our experiment. SHA-256 of the whole image is embedded in the least significant bits of the RONI (Region of Non-Interest). If the image has not been altered, the watermark will be extracted and the original image will be recovered. SHA-256 of the recovered image will be compared with the extracted watermark for authentication.

Monocytic leukemia cutis diagnosed simultaneously with refractory anemia with monocytosis: a case report.

A case of leukemia cutis (LC) of monocytic lineage in a patient with myelodysplastic syndrome (MDS) is presented. Cutaneous infiltrates were recognized concurrent with diagnosis of refractory anemia (RA) with monocytosis. Skin infiltrates subsequently spontaneously regressed although MDS progressed with increasing monocytosis, anemia, and thrombocytopenia. Death occurred 6 months after diagnosis with evolution of acute monoblastic leukemia complicated by sepsis. This case supports previous observations of poor prognosis associated with leukemia cutis. LC associated with MDS is reviewed including the role of monocytes.

Concentration-dependent dual effect of thrombin on impaired growth/apoptosis or mitogenesis in tumor cells.

Because thrombin-treated tumor cell-induced metastasis increases tumor nodule volume(12) greater than nodule number, we studied the effect of thrombin on tumor cell growth in vitro and in vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145 prostate carcinoma). Tumor cell growth was measured after 3 to 7 days in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L) enhance tumor cell growth in vitro approximately 2- to 3-fold, higher concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth approximately 2- to 4-fold. Impaired cell growth was associated with cell cycle arrest at G(2)M and increased pre-G(o) DNA, as well as apoptosis, measured by tumor cell binding to Annexin V and propidium iodide. Apoptosis was reversed with the general caspase inhibitor, FK-011. The enhancing and inhibiting effects were specific for thrombin (reversed with inactive diisopropyl-fluorophosphate [DFP]-thrombin) and mediated via the protease-activated receptor 1 (PAR-1). PAR-1 activation was demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity of PAR-1 transfected B16F10 and HCT8 cells to impaired cell growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a bimodal effect on PAR-1 in tumor cells: enhanced growth at low concentration, impaired growth/apoptosis at higher concentration.