Nevin Manimala

SAR QSAR Environ Res. 2024 Apr 9:1-20. doi: 10.1080/1062936X.2024.2332203. Online ahead of print.

ABSTRACT

Eight QSAR models (M1-M8) were developed from a dataset of 118 benzo-fused heteronuclear derivatives targeting VEGFR-2 by Monte Carlo optimization method of CORALSEA 2023 software. Models were generated with hybrid optimal descriptors using both SMILES and Graphs with zero- and first-order Morgan extended connectivity index from a training set of 103 derivatives. All statistical parameters for model validation were within the prescribed limits, establishing the models to be robust and of excellent quality. Among all models, split-2 of M5 was the best-fit as reflected by rvalidation2, Qvalidation2 and MAE. Mechanistic interpretation of this model assisted the identification of structural descriptors as promoters and hinderers for VEGFR-2 inhibition. These descriptors were utilized to design novel VEGFR-2 inhibitors (YS01-YS07) by bringing modifications in compound MS90 in the dataset. Docking of all designed compounds, MS90 and sorafenib with VEGFR-2 binding site revealed favourable binding interactions. Docking score of YS07 was higher than that of MS90 and sorafenib. Molecular dynamics simulation study revealed sustained interactions of YS07 with key amino acids of VEGFR-2 at a run time of 100 ns. This study concludes the development of a best fit QSAR model which can assist the design of new anticancer agents targeting VEGFR-2.

PMID:38591137 | DOI:10.1080/1062936X.2024.2332203

ACR Open Rheumatol. 2024 Apr 9. doi: 10.1002/acr2.11666. Online ahead of print.

ABSTRACT

OBJECTIVE: Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life.

METHODS: People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.0^plus) at baseline and thereafter monthly for 12 months (3 months per quarter). Adherence to allopurinol was measured using medication event monitoring technology (Medication Event Monitoring System cap). Time spent below the target urate concentration (<0.36 mmol/L) was determined. Health-related quality of life was measured using a survey (EuroQoL EQ-5D-5L). Gout flares were recorded. Two-tailed Spearman correlation and the Wilcoxon matched-pairs signed-rank test (P < 0.05) were used for statistical comparisons.

RESULTS: Most participants were male (94%) and had urate concentrations below the target (74%) at baseline. Overall, seven participants demonstrated repeated periods of “missed doses” (two or fewer allopurinol doses missed consecutively) and “drug holidays” (three or more missed doses). Most participants (94%) persisted with allopurinol. Time spent within the target urate concentration increased 1.3-fold (from 79% to 100%; P = 0.346), and the incidence of gout flares decreased 1.6-fold (from 8 to 5; P = 0.25) in the final quarter compared to that in the first quarter of the study. Health-related quality of life was reduced for participants reporting at least one gout flare (median utility values 0.9309 vs 0.9563, P = 0.04).

CONCLUSION: Patient-led urate self-monitoring may support the maintenance of allopurinol adherence and improve urate control, thus reducing the incidence of gout flares. Further research on patient-led urate self-monitoring in a randomized controlled study is warranted.

PMID:38591107 | DOI:10.1002/acr2.11666

Eur Urol Open Sci. 2024 Apr 4;63:104-112. doi: 10.1016/j.euros.2024.03.013. eCollection 2024 May.

ABSTRACT

BACKGROUND AND OBJECTIVE: The Hugo RAS and DaVinci Xi systems are used for performing robot-assisted radical prostatectomy (RARP). This study aims to compare these two platforms providing granular and comprehensive data on their intraoperative performance.

METHODS: The Comparison of Outcomes of Multiple Platforms for Assisted Robotic surgery-Prostate (COMPAR-P) trial is a prospective post-market study (clinicaltrials.org NCT05766163). Enrollment began in March 2023, allocating patients to DaVinci or Hugo RAS for RARP, without selection criteria, for up to 50 consecutive cases. Two experienced console surgeons performed the procedures, following the same technique. Evaluation focused on timing, learning curves, malfunctioning events, complications, and users’ satisfaction, using standard statistical methods, including the cumulative summation analysis (CUSUM) for the learning curve assessment.

KEY FINDINGS AND LIMITATIONS: Fifty patients each were enrolled for DaVinci (DV-RARP) and Hugo RAS (H-RARP) RARP. Baseline features were balanced. DV-RARP showed significantly shorter “setup” and “console” phase durations than H-RARP (37 vs 55 min and 97 vs 126 min, respectively, p < 0.001). A longitudinal timing analysis revealed DV-RARP’s flat line, while H-RARP showed a modest decline with breakpoints at 22 and 17 procedures by CUSUM for the setup and console phases. The numbers of malfunctioning events were 4 (DV-RARP) and 20 (H-RARP). DV-RARP had high user satisfaction, while the user satisfaction of H-RARP varied. The comparison was between the first 50 H-RARP and the last 50 DV-RARP cases performed at our institution. This likely accounts for the observed differences in setup and console times between the cohorts. The specialized expertise of the surgeons involved could limit the generalizability of our findings.

CONCLUSIONS AND CLINICAL IMPLICATIONS: This prospective study compared unselected patients who underwent DV-RARP and H-RARP. More malfunctioning events occurred in case of Hugo RAS, but surgical outcomes were similar. Longer operative times for Hugo RAS were attributed to meticulous care with the novel platform. Improvement potential was evident within a few procedures, providing valuable insights for adopting this new platform.

PATIENT SUMMARY: This study compared two advanced robotic systems, DaVinci and Hugo RAS, used to remove the prostate in patients diagnosed with prostate cancer. While both systems showed similar surgical outcomes, the newer Hugo RAS system required more meticulous movements, leading to slightly longer operation times. The findings suggest that, with further experience, both systems can provide effective treatment options for patients undergoing prostate surgery.

PMID:38591096 | PMC:PMC11000201 | DOI:10.1016/j.euros.2024.03.013

World J Diabetes. 2024 Mar 15;15(3):463-474. doi: 10.4239/wjd.v15.i3.463.

ABSTRACT

BACKGROUND: Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a class of drugs with modest antidiabetic efficacy, weight loss effect, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). However, real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.

AIM: To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.

METHODS: We evaluated the comparative efficacy data of 3 SGLT-2i drugs (dapagliflozin, canagliflozin, and empagliflozin) used for treating patients with type 2 diabetes mellitus. Data on the reduction of glycated hemoglobin (HbA1c), body weight, blood pressure (BP), urine albumin creatinine ratio (ACR), and adverse effects were recorded retrospectively.

RESULTS: Data from 467 patients with a median age of 64 (14.8) years, 294 (62.96%) males and 375 (80.5%) Caucasians were analysed. Median diabetes duration was 16.0 (9.0) years, and the duration of SGLT-2i use was 3.6 (2.1) years. SGLT-2i molecules used were dapagliflozin 10 mg (n = 227; 48.6%), canagliflozin 300 mg (n = 160; 34.3%), and empagliflozin 25 mg (n = 80; 17.1). Baseline median (interquartile range) HbA1c in mmol/mol were: dapagliflozin – 78.0 (25.3), canagliflozin – 80.0 (25.5), and empagliflozin – 75.0 (23.5) respectively. The respective median HbA1c reduction at 12 months and the latest review (just prior to the study) were: 66.5 (22.8) & 69.0 (24.0), 67.0 (16.3) & 66.0 (28.0), and 67.0 (22.5) & 66.5 (25.8) respectively (P < 0.001 for all comparisons from baseline). Significant improvements in body weight (in kilograms) from baseline to study end were noticed with dapagliflozin – 101 (29.5) to 92.2 (25.6), and canagliflozin 100 (28.3) to 95.3 (27.5) only. Significant reductions in median systolic and diastolic BP, from 144 (21) mmHg to 139 (23) mmHg; (P = 0.015), and from 82 (16) mmHg to 78 (19) mmHg; (P < 0.001) respectively were also observed. A significant reduction of microalbuminuria was observed with canagliflozin only [ACR 14.6 (42.6) at baseline to 8.9 (23.7) at the study end; P = 0.043]. Adverse effects of SGLT-2i were as follows: genital thrush and urinary infection – 20 (8.8%) & 17 (7.5%) with dapagliflozin; 9 (5.6%) & 5 (3.13%) with canagliflozin; and 4 (5%) & 4 (5%) with empagliflozin. Diabetic ketoacidosis was observed in 4 (1.8%) with dapagliflozin and 1 (0.63%) with canagliflozin.

CONCLUSION: Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c, body weight, and better than those reported in RCTs, with low side effect profiles. A review of large-scale real-world data is needed to inform better clinical practice decision making.

PMID:38591092 | PMC:PMC10999032 | DOI:10.4239/wjd.v15.i3.463

World J Diabetes. 2024 Mar 15;15(3):475-487. doi: 10.4239/wjd.v15.i3.475.

ABSTRACT

BACKGROUND: Dietary fiber (DF) intake may have a protective effect against type 2 diabetes (T2D); however, its relationship with diabetic kidney disease (DKD) remains unclear.

AIM: To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D.

METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018. DF intake was assessed through 24-h dietary recall interviews, and DKD diagnosis in individuals with T2D was based on predefined criteria, including albuminuria, impaired glomerular filtration rate, or a combination of both. Logistic regression analysis was used to assess the association between DF intake and DKD, and comprehensive subgroup and sensitivity analyses were performed.

RESULTS: Among the 6032 participants, 38.4% had DKD. With lower DF intake-T1 (≤ 6.4 g/1000 kcal/day)-as a reference, the adjusted odds ratio for DF and DKD for levels T2 (6.5-10.0 g/1000 kcal/day) and T3 (≥ 10.1 g/1000 kcal/day) were 0.97 (95%CI: 0.84-1.12, P = 0.674) and 0.79 (95%CI: 0.68-0.92, P = 0.002), respectively. The subgroup analysis yielded consistent results across various demographic and health-related subgroups, with no statistically significant interactions (all P > 0.05).

CONCLUSION: In United States adults with T2D, increased DF intake may be related to reduced DKD incidence. Further research is required to confirm these findings.

PMID:38591085 | PMC:PMC10999041 | DOI:10.4239/wjd.v15.i3.475

Front Chem. 2024 Mar 25;12:1349531. doi: 10.3389/fchem.2024.1349531. eCollection 2024.

ABSTRACT

The immobilization of high-level nuclear waste (HLW) in glass waste matrices provides the key safety function of slowing down radionuclide emissions from an underground disposal site. This study examines the leaching behavior of two major elements, Na and Si, in HLW borosilicate glass simulated from waste of a 1000 MWe class pressurized water reactor (PWR) using response surface methodology and Box-Behnken Design. The design of the experiment was carried out considering three independent variables: the pH of the solution, the contact time, and the leaching temperature, leading to 17 leaching runs performed using the static product consistency test (PCT). The results of statistical analysis (ANOVA: analysis of variance) indicated that the effects of the individual variables and the interactions between them were statistically significant, and the relative consistency of the data further confirmed the model’s applicability. Data obtained from the PCT experiments revealed that the leaching behavior of Na and Si in the evaluated waste glass exhibited similar behavior to previously researched glasses for each condition tested.

PMID:38591058 | PMC:PMC11000124 | DOI:10.3389/fchem.2024.1349531

Ann Cardiothorac Surg. 2024 Mar 29;13(2):155-164. doi: 10.21037/acs-2023-afm-15. Epub 2023 Aug 29.

ABSTRACT

BACKGROUND: CONVERGE was a prospective, multicenter, randomized controlled trial that evaluated the safety of Hybrid Atrial Fibrillation Convergent (HC) and compared its effectiveness to endocardial catheter ablation (CA) for the treatment of persistent atrial fibrillation (PersAF) and longstanding PersAF (LSPAF). In 2020, we reported that CONVERGE met its primary safety and effectiveness endpoints. The primary objective of the present study is to report CONVERGE trial results for quality of life (QOL) and Class I/III anti-arrhythmic drug (AAD) utilization following HC.

METHODS: Eligible patients had drug-refractory symptomatic PersAF or LSPAF and a left atrium diameter ≤6.0 cm. Enrolled patients were randomized 2:1 to receive HC or CA. Atrial Fibrillation Severity Scale (AFSS) and the 36-Item Short Form Health Survey (SF-36) were assessed at baseline and 12 months; statistical comparison was performed using paired t-tests. AAD utilization at baseline through 12 and 18 months post-procedure was evaluated; statistical comparison was performed using McNemar’s tests.

RESULTS: A total of 153 patients were treated with either HC (n=102) or CA (n=51). Of the 102 HC patients, 38 had LSPAF. AFSS and SF-36 Mental and Physical Component scores were significantly improved at 12 months versus baseline with HC overall and for the subset of LSPAF patients treated with either HC or CA. The proportion of HC patients (n=102) who used Class I /III AADs at 12 and 18 months was significantly less (33.3% and 36.3%, respectively) than baseline (84.3%; P<0.001). In LSPAF patients who underwent HC (n=38), AADs use was 29.0% through 18 months follow-up versus 71.1% at baseline (P<0.001).

CONCLUSIONS: HC reduced AF symptoms, significantly improved QOL, and reduced AAD use in patients with PersAF and LSPAF.

CLINICALTRIALSGOV IDENTIFIER: NCT01984346.

PMID:38590997 | PMC:PMC10998972 | DOI:10.21037/acs-2023-afm-15

Cureus. 2024 Apr 8;16(4):e57814. doi: 10.7759/cureus.57814. eCollection 2024 Apr.

ABSTRACT

Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts the frequency of MSI in sporadic CRCs and its effect on prognosis. This study investigated the distribution of clinicopathologic features and the relationship between MSI and survival outcomes. Methodology This is a retrospective study of 101 consecutive cases of CRC and immunohistochemical studies. All cases were retrospectively reviewed and reevaluated by histological grade, lymphovascular invasion, perineural invasion, tumor borders, dirty necrosis, tumor-infiltrating lymphocytes (TILs), Crohn’s-like lymphoid reaction, mucinous and medullary differentiation, and tumoral budding from pathological slides. An immunohistochemical study was performed in appropriate blocks for using MLH-1, MSH-2, MSH-6, and PMS-2. We collected the clinical stage, pathological tumor stage, lymph node metastasis, age, sex, tumor diameter, distant metastasis, localization, and survival information from patients’ clinical data. Results There was no statistically significant difference between the two groups regarding age, gender, tumor diameter, histological grade, tumor border, dirty necrosis, TILs, N and M stage, perineural and lymphovascular invasion, mucinous differentiation, medullary differentiation, and tumor budding characteristics of the patients. The MSI-H group was more frequently located in the right colon and transverse colon (p < 0.001), and the T stage was higher among them than in the MSI-L group (p = 0.014). Upon multivariate regression analysis, MSI status had no significant effect on survival time. Age and stage N and M were independent prognostic factors for colon cancer prognosis. Conclusions Our study presented the distribution of clinicopathological features and their relationship with MSI for 101 regional CRC patients. MSI status was detected by immunohistochemistry. Identifying MSI in CRCs may help personalize therapy planning. As the distribution of the features may vary from population to population, further investigations are needed on this topic.

PMID:38590982 | PMC:PMC11000436 | DOI:10.7759/cureus.57814

Cureus. 2024 Apr 6;16(4):e57700. doi: 10.7759/cureus.57700. eCollection 2024 Apr.

ABSTRACT

Background The aim of this study is to emphasize the need to be careful in terms of internal organ injuries in patients with isolated transverse process fracture (ITPF), and to investigate the effectiveness of corset use in controlling acute pain. Methods This is a retrospective study including 72 patients with only transverse process fractures secondary to trauma, who were admitted to the Emergency Department of Sakarya University Research and Training Hospital between January 2020 and October 2022. The radiological diagnoses were collected from spinal vertebral computed tomography images. Twelve patients were excluded from the study due to exclusion criteria. Sixty patients with ITPF were included in the comparison group. All patients were divided into two groups. The group with no lumbar corset (LC) included those who were discharged with analgesic and muscle relaxant treatment without a brace (n = 33). The LC+ group (n = 27) included those who received rigid lumbosacral orthosis in addition to analgesic and muscle relaxant treatment. Pain levels of all cases in both groups were evaluated with Visual Analog Scale scores on the day of trauma, the first week, the first month, and the sixth month. Results A total of 25 cases had one ITPF, 25 had two, 17 had three, and five patients had four or more ITPFs. The hospitalization rate was the highest among patients with four or more ITPFs (40%). Although the hospitalization rates according to the number of ITPFs were not statistically significant (p = 0.528), there was a clinical significance regarding increasing hospitalization rates with the increasing number of ITPFs. The hospitalization rates were 12%, 16%, 17.6%, and 40% in patients with one, two, three, and four or more ITPFs, respectively. Conclusion ITPFs should be treated conservatively. Concomitant organ injuries must be ruled out before treatment. Medical treatment without a lumbar corset could be used as a cost-effective choice.

PMID:38590980 | PMC:PMC11000033 | DOI:10.7759/cureus.57700

Cureus. 2024 Apr 1;16(4):e57390. doi: 10.7759/cureus.57390. eCollection 2024 Apr.

ABSTRACT

Background Social media, notably YouTube (Google LLC, Mountain View, California, United States), has transformed global communication and access to information. In Saudi Arabia, with high internet usage, YouTube influencers play a significant role in shaping health attitudes and behaviors. This study investigates the impact of YouTube influencers on health behaviors among Saudi Arabian residents, considering the unique cultural and socio-demographic context. Methods We conducted a community-based cross-sectional study in Saudi Arabia. We surveyed a convenience sample of 703 young Saudi participants from September 2022 to March 2023. Data collection utilized an anonymous online questionnaire distributed via popular social media platforms. The questionnaire covered sociodemographic information, health habits, perceptions of influencers, and their impact on health attitudes. Descriptive statistics, including percentages, frequencies, means, and standard deviations, were employed to summarize participant characteristics and health-related variables. Pearson’s chi-square test was utilized to compare response variables among different groups. Results Findings show significant gender disparities in health habits, with males more likely to smoke but females less physically active (p<0.01). Influencers were perceived as encouraging healthy habits by 71.7% of participants, yet 55.6% also believed they promoted unhealthy habits. Positive outcomes included dietary improvements (62.6%) and smoking cessation (20.5%). People preferred healthcare influencers the most (66.8%), followed by sports and fashion influencers. Conclusions This study highlights YouTube influencers’ substantial influence on health behaviors in Saudi Arabia. It suggests the potential for influencers, especially in healthcare, to contribute positively to public health. Viewer discernment is essential due to varying influencer impacts. These findings underscore the complex role of YouTube influencers in shaping health behaviors and suggest avenues for targeted health interventions.

PMID:38590976 | PMC:PMC11000030 | DOI:10.7759/cureus.57390