Exploring the Interactions between Obesity and Diabetes: Implications for Understanding Metabolic Dysregulation in a Saudi Arabian Adult Population.

The rising prevalence of obesity in Saudi Arabia is a major contributor to the nation's high levels of cardiometabolic diseases such as type 2 diabetes. To assess the impact of obesity on the diabetic metabolic phenotype presented in young Saudi Arabian adults, participants (n = 289, aged 18-40 years) were recruited and stratified into four groups: healthy weight (BMI 18.5-24.99 kg/m2) with (n = 57) and without diabetes (n = 58) or overweight/obese (BMI > 24.99 kg/m2) with (n = 102) and without diabetes (n = 72). Distinct plasma metabolic phenotypes associated with high BMI and diabetes were identified using nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography mass spectrometry. Increased plasma glucose and dysregulated lipoproteins were characteristics of obesity in individuals with and without diabetes, but the obesity-associated lipoprotein phenotype was partially masked in individuals with diabetes. Although there was little difference between diabetics and nondiabetics in the global plasma LDL cholesterol and phospholipid concentration, the distribution of lipoprotein particles was altered in diabetics with a shift toward denser and more atherogenic LDL5 and LDL6 particles, which was amplified in the presence of obesity. Further investigation is warranted in larger Middle Eastern populations to explore the dysregulation of metabolism driven by interactions between obesity and diabetes in young adults.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Dose-Escalated Radiation Therapy as Primary Treatment for Residual Bladder Cancer After Transurethral Resection.

Purpose: The aim of this study was to determine whether escalating the local radiation dose can improve the outcome of residual bladder cancer after transurethral resection of bladder tumor without increasing treatment-related toxicity. Methods and Materials: The treatment plans and medical records of patients with bladder cancer treated with curative-intent radiation therapy between 2008 and 2020 were reviewed. Those who had residual tumors in the computed tomography simulation images were included. A cumulative radiation dose higher than 6600 cGy was defined as dose escalation. The effect of dose escalation on 3-year locoregional control, progression-free survival, and overall survival was evaluated. Results: A total of 149 patients with residual tumors were identified. The median follow-up period was 27.5 months. Among them, 51 patients received an escalated radiation dose, and 98 received a standard dose in the residual tumor area. Patients in the dose-escalation group had higher 3-year locoregional control (65.6% vs 27.8%; P < .001) and progression-free survival (42.6% vs 18.2%; P < .001) than the standard-dose group. Overall survival also showed a trend favoring the dose-escalation group (54.9% vs 36.2%; P = .059). In the multivariate analyses, the differences between the dose-escalation and standard-dose groups were significant in terms of locoregional control (hazard ratio, 0.32; CI, 0.18-0.59; P = <.001) and progression-free survival (hazard ratio, 0.51; CI, 0.32-0.82; P = .005). There was no statistical difference in acute and chronic treatment-related toxicities between the 2 groups. Conclusions: The outcome of residual bladder cancer after transurethral resection of bladder tumor could be improved by dose-escalated radiation therapy.

The Role of Mass Spectrometry in Hepatocellular Carcinoma Biomarker Discovery.

Hepatocellular carcinoma (HCC) is the main liver malignancy and has a high mortality rate. The discovery of novel biomarkers for early diagnosis, prognosis, and stratification purposes has the potential to alleviate its disease burden. Mass spectrometry (MS) is one of the principal technologies used in metabolomics, with different experimental methods and machine types for different phases of the biomarker discovery process. Here, we review why MS applications are useful for liver cancer, explain the MS technique, and briefly summarise recent findings from metabolomic MS studies on HCC. We also discuss the current challenges and the direction for future research.

MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2-GPX2 Molecular Axis in Head-Neck Cancer.

Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads to local recurrence, becoming a substantial factor in treatment failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs to inhibit protein translation. Although several studies have indicated that the dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family's role in radioresistance remains limited. This study determined the role of miR-630 in regulating radiosensitivity in HNC. We discovered that miR-630 functions as an oncomiR, marked by its overexpression in HNC patients, correlating with a poorer prognosis. We further delineated the malignant function of miR-630 in HNC cells. While it had a minimal impact on cell growth, the miR-630 contributed to radioresistance in HNC cells. This result was supported by decreased cellular apoptosis and caspase enzyme activities. Moreover, miR-630 overexpression mitigated irradiation-induced DNA damage, evidenced by the reduced levels of the γ-H2AX histone protein, a marker for double-strand DNA breaks. Mechanistically, the overexpression of miR-630 decreased the cellular ROS levels and initiated Nrf2 transcriptional activity, resulting in the upregulation of the antioxidant enzyme GPX2. Thus, this study elucidates that miR-630 augments radioresistance by inducing an anti-apoptotic effect via the Nrf2-GPX2 molecular axis in HNC. The modulation of miR-630 may serve as a novel radiosensitizing target for HNC.

Treatment-related sequelae in Hodgkin's lymphoma after mediastinal irradiation.

BACKGROUND: Many studies have investigated treatment-related sequelae in Hodgkin's lymphoma (HL) in high-prevalence areas, but very few have been conducted in low-prevalence areas, including Taiwan and Japan. MATERIALS AND METHODS: We retrospectively reviewed 101 HL patients who had received mediastinal radiotherapy between January 1997 and April 2013. RESULTS: Nine patients had cardiac events and nine patients developed second malignancies. Univariate analysis showed that bulkiness of disease was significantly associated with higher incidence of cardiac events (HR 7.70, 95% CI 1.60-38.00, p = 0.012). Disease stage and cumulative dose of radiotherapy were significantly correlated with incidence of radiation pneumonitis (HR 1.40, 95% CI 1.00-2.10, p = 0.043 and HR 1.10, 95% CI 1.00-1.20, p = 0.009, respectively). All cases of grade III-IV radiation pneumonitis happened in patients receiving a radiation dose higher than 35 Gy and developed within 4 months after radiotherapy. CONCLUSIONS: Despite the similar incidence rates of treatment-related sequelae among HL survivors between areas with high and low prevalence of HL, cardiac events and second malignancies cannot be overlooked in HL survivors in low-prevalence areas.

Optimized Systematic Review Tool: Application to Candidate Biomarkers for the Diagnosis of Hepatocellular Carcinoma.

This review aims to develop an appropriate review tool for systematically collating metabolites that are dysregulated in disease and applies the method to identify novel diagnostic biomarkers for hepatocellular carcinoma (HCC). Studies that analyzed metabolites in blood or urine samples where HCC was compared with comparison groups (healthy, precirrhotic liver disease, cirrhosis) were eligible. Tumor tissue was included to help differentiate primary and secondary biomarkers. Searches were conducted on Medline and EMBASE. A bespoke "risk of bias" tool for metabolomic studies was developed adjusting for analytic quality. Discriminant metabolites for each sample type were ranked using a weighted score accounting for the direction and extent of change and the risk of bias of the reporting publication. A total of 84 eligible studies were included in the review (54 blood, 9 urine, and 15 tissue), with six studying multiple sample types. High-ranking metabolites, based on their weighted score, comprised energy metabolites, bile acids, acylcarnitines, and lysophosphocholines. This new review tool addresses an unmet need for incorporating quality of study design and analysis to overcome the gaps in standardization of reporting of metabolomic data. Validation studies, standardized study designs, and publications meeting minimal reporting standards are crucial for advancing the field beyond exploratory studies.

Utilization of the lymph node-to-primary tumor ratio of PET standardized uptake value and circulating Epstein-Barr virus DNA to predict distant metastasis in nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To determine the clinical impact of integrating Epstein-Barr virus (EBV) DNA and lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) in predicting distant metastasis, such as distant metastasis-free survival (DMFS), in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively reviewed patients diagnosed with non-disseminated NPC between 2010 and 2017. The optimal cut-off values of EBV DNA and SUV NTR were determined using receiver operating characteristic analysis. The prognostic values of SUV NTR and EBV DNA on DMFS and overall survival were evaluated using the Kaplan-Meier method. Univariate and multivariable analyses were performed using the Wald Chi-squared test and Cox proportional hazards regression, respectively. RESULTS: A total of 488 patients were included in the analysis. The median follow-up period was 61.6 months. The optimal cut-off values of EBV DNA and SUV NTR were 3377.5 copies per mL and 0.64, respectively. The five-year DMFS for patients with high vs low EBV DNA and SUV NTR levels were 64.9% vs 86.6% (p < 0.001) and 78.7% vs 87.4% (p = 0.021), respectively. In subgroup analysis, the high-risk group with high levels of pretreatment EBV DNA and SUV NTR had worse DMFS in either American Joint Committee on Cancer (AJCC) stage I-III or IVA-B (p = 0.001 and <0.001, respectively). Univariate and multivariable analyses showed the statistical significance of EBV DNA, SUV NTR, and their composite in DMFS (p < 0.001 for EBV DNA; p = 0.022 for SUV NTR; p < 0.001 for their composite). CONCLUSION: This study showed that EBV DNA and SUV NTR have independent and additive values as prognosticators for distant metastasis in patients with NPC, suggesting that these two individual factors, except the AJCC staging system, should be included in future studies.

Revisiting public health programming in Nigeria: challenges and solutions.

Public health programming has three main components - capacity development, service provision and documentation with monitoring. However, most funders and programmers now focus on just documentation and monitoring. In this communication, the authors extensively discuss the need for the full complement of public health programming and why it is important to restructure supportive site visits to make them both empowering and impactful to the health care workers resulting in higher quality of public health services and documentation with monitoring. The authors are of the view that following problem identification, comprehensive capacity development of field workers will engender quality service provision and appropriate documentation and monitoring.