Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.

Aim: Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed. Methods & results: We introduce 5-hydroxybenzothiophene derivatives as effective multi-target kinase inhibitors, showing notable growth inhibitory activity across different cancer cell lines. Specifically, compound 16b, featuring a 5-hydroxybenzothiophene hydrazide scaffold, emerged as a potent inhibitor, displaying low IC50 values against key kinases and demonstrating significant anti-cancer effects, particularly against U87MG glioblastoma cells. It induced G2/M cell cycle arrest, apoptosis and inhibited cell migration by modulating apoptotic markers. Conclusion: 16b represents a promising lead for developing new anti-cancer agents targeting multiple kinases with affinity to the hydroxybenzothiophene core.

[Box: see text].

Chemoprotective effect of arbutin on azoxymethane-induced aberrant crypt foci in rat colon via modulation of PCNA/Bax protein.

Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.

Left versus right ventricular pacing during TAVR and balloon aortic valvuloplasty: A systematic review and meta-analysis.

INTRODUCTION: While right ventricular pacing (RVP) is the conventional temporary pacing modality used for transcatheter aortic valve replacement (TAVR), this approach possesses inherent risks and procedural challenges. We aim to assess and compare the safety and efficacy of left ventricular pacing (LVP) and RVP during TAVR and balloon aortic valvuloplasty (BAV). METHODS: Following PRISMA guidelines, a comprehensive literature search was conducted in four databases from inception to December 15th, 2023. We included observational studies and clinical trials comparing LVP with RVP during TAVR and BAV procedures. Primary outcomes included short-term mortality, mortality due to cardiac tamponade, and procedural complications including bleeding, vascular complications, and cardiac tamponade. Secondary outcomes comprised procedure duration and length of hospital stay. RESULTS: Five studies involving 830 patients with RVP and 1577 with LVP were included. Short-term mortality was significantly higher in the RVP group (RR 2.32, 95% CI: [1.37-3.93], P = .002), as was the incidence of cardiac tamponade (RR 2.19, 95% CI: [1.11-4.32], P = .02). LVP demonstrated shorter hospital stays (MD = 1.34 d, 95% CI: [0.90, 1.78], P < .001) and reduced procedure duration (MD = 7.75 min, 95% CI: [5.08, 10.41], P < .00001) compared to RVP. New pacemaker implantation was higher in the RVP group (RR 2.23, 95% CI: [1.14, 4.39], P = .02). CONCLUSION: LVP during TAVR and BAV emerges a safer alternative to RVP, offering reduced mortality, hospital stays, and procedure durations.

The impact of ethical implications intertwined with tuberculosis household contact investigation: a qualitative study.

Background: Household contact investigation (HCI) is an effective and widely used approach to identify persons with tuberculosis (TB) disease and infection, globally. Despite widespread recommendations for the use of HCI, there remains poor understanding of the impact on and value of contact investigation for participants. Further, how HCI as a practice impacts psychosocial factors, including stigma and possible unintended disclosure of illness among persons with TB, their families, and communities, is largely unknown. Methods: This exploratory qualitative study nested within a randomized trial (ClinicalTrials.gov: NCT04520113 , 17 August 2020) was conducted in South Africa to understand the impacts of HCI on index patients living with TB and their household contact persons in two rural districts in the Limpopo province (Vhembe and Capricorn) and Soshanguve, a peri-urban township in Gauteng province. People with TB and household members of people with TB were recruited to participate in in-depth interviews and focus group discussions using semi-structured guides. We explored individual, interpersonal, and community-level perceptions of potential impacts of household contact investigation to elucidate their perceptions of HCI. Thematic analysis identified key themes. Results: Twenty-four individual interviews and six focus group discussions (n=39 participants) were conducted. Participants viewed HCI as an effective approach to finding TB cases, helpful in educating households about TB symptoms and reducing barriers to health-related services. At the interpersonal level, HCI aided people with TB in safely disclosing their TB status to family members and facilitated family and social support for accountability. The introduction of HIV testing during HCI was reported by some participants as making household members slightly uncomfortable, decreasing interest in household members being tested for TB. HCI negatively impacted community-level TB and HIV-related stigma due to healthcare worker visibility at home. Conclusion: Our data suggests varying impacts of HCI on people with TB, their families and interpersonal relationships, and communities, highlighting the importance of considering approaches that address concerns about community stigma and HIV testing to enhance acceptance of HCI.

Formic acid as an antibiotic alternative in broiler diets: effects on growth, carcass characteristics, blood chemistry, and intestinal microbial load.

This study explored the ability of formic acid (FA) to replace antibiotics in broiler chicken diets. It examined how FA affected the chickens' growth, carcass characteristics, blood chemistry, and gut bacteria. The experiment randomly assigned 300 one-day-old (Ross 308) broiler chicks to 5 groups, each divided into 6 replicates with 10 unsexed chicks. The following were the treatments: 1st group, negative control (NC): only received a basal diet; 2nd group, positive control (PC): received a basal diet supplemented with 0.5 grams of Colistin antibiotic per kilogram of diet; 3rd, 4th, and 5th groups (FA2, FA4, and FA6) these groups received a basal diet along with formic acid added at increasing levels: 2, 4, and 6 Cm3 per kilogram of diet, respectively. Results found no significant differences in live body weight (LBW) or body weight gain (BWG) between treatment groups, except for LBW at one week and BWG at 0 to 1 and 4 to 5 wk of age. No significant variations were found in feed intake (FI) and feed conversion ratio (FCR) among the treatment groups, excluding FI and FCR at 1 to 2 wk of age. The treatments significantly impacted carcass traits, dressing percentage, breast meat, thigh meat, spleen, giblets, blood levels of urea, creatinine, total protein, globulin, and albumin, as well as the activity of enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in chicks fed different diets compared to control groups. The addition of FA to the diet significantly impacted antioxidant levels. Also, the FA2 group had the highest total bacterial count (TBC). However, the FA6 group was the opposite; it had the lowest levels of harmful bacteria, such as E. coli and Coliform. Supplementing broiler diets with formic acid improves blood parameters, antioxidant activity, and gut bacteria counts, with 4.0 cm³ formic acid/kg diet supplementation promoting optimal broiler health and product quality.

Patient-specific Implants Improve Volumetric Surgical Accuracy Compared to Stock Reconstruction Plates in Modern Pardigm Virtual Surgical Planning of Fibular Free Flaps for Head and Neck Reconstruction.

BACKGROUND: Virtual surgical planning (VSP) for composite microvascular free flaps has become standard of care for oncologic head and neck reconstruction. Controversy remains as to the use of three-dimensional (3D)-printed titanium patient-specific implants (PSIs) versus hand-bent stock reconstruction plates. Proponents of PSIs cite improved surgical accuracy, reduced operative times, and improved clinical outcomes. Detractors purport increased cost associated with PSIs and presumed equivalent accuracy with less expensive stock plates. PURPOSE: The study purpose was to measure and compare the 3D-volumetric accuracy of PSI versus stock reconstruction plates among subjects undergoing VSP-guided mandibular fibular free flap reconstruction. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study of subjects undergoing VSP-guided fibular free flap reconstructions at Mayo Clinic between 2016 and 2023 was performed. Subjects were excluded for non-VSP guidance, midfacial reconstruction, nonfibular free flaps, and lack of requisite study variables. PREDICTOR VARIABLE: The primary predictor was the type of reconstruction plate utilized (PSI vs stock plate). MAIN OUTCOME VARIABLE: The main outcome was volumetric surgical accuracy of the final reconstruction compared to the preoperative surgical plan by root mean square error (RMSE) calculation. Lower RMSE values indicated a higher surgical accuracy. COVARIATES: Covariates included age, sex, race, smoking status, American Society of Anesthesiologists Physical Status Classification System, Charlson Comorbidity Index, preoperative diagnosis, and number of fibular segments. ANALYSES: Differences in surgical accuracy were assessed between preoperative and postoperative segmented scans using volumetric overlays from which RMSE values were calculated. Univariate and multivariate modeling of plate type to RMSE calculation was performed. Statistical significance set to P < .05. RESULTS: Total of 130 subjects were identified, 105 PSI and 25 stock plates. Calculated mean RMSE in millimeters (mm) for stock plates was 1.46 (standard deviation: 0.33) and 1.15 (standard deviation: 0.36) for PSIs. Univariate modeling demonstrated a statistically significant difference in RMSE of 0.31 (95% confidence interval: 0.16-0.47) (P < .001) equating to a 21.2% (P < .001) improved volumetric surgical accuracy for PSIs. The association of improved volumetric accuracy with PSIs has been maintained in all multivariate models controlling for confounding. CONCLUSION AND RELEVANCE: In modern era VSP-guided head and neck fibular free flap reconstruction, patient-specific 3D-printed titanium implants confer a statistically significant improvement in volumetric surgical accuracy over stock reconstruction plates.

Establishing minimal clinically important differences and patient acceptable symptom state thresholds following birmingham hip resurfacing.

INTRODUCTION: Birmingham Hip Resurfacing (BHR) has emerged as a compelling and innovative alternative to total hip arthroplasty (THA), especially among young, active patients. However, the Minimal Clinically Important Difference (MCID) and the Patient Acceptable Symptom State (PASS) thresholds have not yet been determined for patients undergoing BHR. Therefore, the current study aimed to (1) determine the MCID and PASS thresholds for both the Hip disability and Osteoarthritis Outcome Score (HOOS)-Pain and HOOS physical function shortform (PS), for patients who underwent BHR; and (2) identify factors influencing the achievement of MCID and PASS for HOOS-Pain and HOOS-PS. METHODS: Prospectively collected data from patients undergoing BHR was analyzed. Patients with osteoarthritis and completed preoperative and 1-year postoperative PROMs were included. Distribution-based and anchored-based approaches were used to estimate MCID and PASS, respectively. The optimal cut-off point for PASS thresholds was calculated using the Youden index. RESULTS: MCID for HOOS-Pain and PS were calculated to be 9.2 and 9.3, respectively. The PASS threshold for HOOS-Pain and PS were ≥ 77.7 and ≥ 87.3, respectively. The current study identified several factors affecting postoperative achievement of thresholds. Baseline Mental Component Summary (MCS) scores were a predictor for achieving MCID for postoperative HOOS-Pain, achieving MCID for postoperative HOOS-PS, achieving PASS for postoperative HOOS-Pain, and achieving PASS for postoperative HOOS-PS. Furthermore, baseline HOOS-Pain was a significant predictor for achieving MCID for postoperative HOOS-PS, achieving PASS for postoperative HOOS-Pain, and achieving PASS for postoperative HOOS-PS. CONCLUSIONS: MCID and PASS thresholds were established for HOOS-Pain and PS domains following BHR with most patients achieving these clinically meaningful benchmarks. Additionally, several factors affecting achievement of MCID and PASS were identified, including modifiable risk factors that may allow clinicians to implement optimization strategies and further improve outcomes.

Lipoprotein(a) and Long-term In-stent Restenosis after Percutaneous Coronary Intervention.

AIM: Lipoprotein(a) [Lp(a)] has demonstrated its association with atherosclerosis and myocardial infarction. However, its role in the development of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is not clearly established. The aim of this study is to investigate the association between Lp(a) and ISR. METHODS: A retrospective study of adult patients who underwent successful PCI between January 2006 and December 2017 at the three Mayo Clinic sites and had a preprocedural Lp(a) measurement was conducted. Patients were divided into two groups according to the serum Lp(a) concentration (high Lp(a) ≥50 mg/dl and low Lp(a) <50 mg/dl). Univariable and multivariable analyses were performed to compare risk of ISR between patients with high Lp(a) versus those with low Lp(a). RESULTS: A total of 1209 patients were included, with mean age 65.9 ±11.7 years and 71.8% were male. Median follow-up after baseline PCI was 8.8 (IQR 7.4) years. Restenosis was observed in 162 (13.4%) patients. Median serum levels of Lp(a) were significantly higher in patients affected by ISR versus non-affected cases: 27 (IQR 73.8) vs. 20 (IQR 57.5) mg/dL, p=0.008. The rate of ISR was significantly higher among patients with high Lp(a) versus patients with low Lp(a) values (17.0% vs 11.6%, p=0.010). High Lp(a) values were independently associated with ISR events (HR 1.67, 95%CI 1.18 to 2.37, p=0.004), and this association was more prominent after the first year following the PCI. CONCLUSION: Lipoprotein(a) is an independent predictor for long-term in-stent restenosis and should be considered in the evaluation of patients undergoing PCI.

The role of Lp(a) in the development of in-stent restenosis is not clearly established. In this study including 1209 patients who underwent successful percutaneous coronary intervention and had a preprocedural Lp(a) measurement between 2006 and 2017, the rates of restenosis were significantly higher among patients with high Lp(a) versus patients with low Lp(a) values and high Lp(a) concentrations were independently associated with restenosis events. Lp(a) should be considered as a risk factor for long term in-stent restenosis in the evaluation of patients undergoing percutaneous coronary intervention and assessed as a potential therapeutic target for reducing residual cardiovascular risk in this population.

Identifying miRNA Signatures Associated with Pancreatic Islet Dysfunction in a FOXA2-Deficient iPSC Model.

The pathogenesis of diabetes involves complex changes in the expression profiles of mRNA and non-coding RNAs within pancreatic islet cells. Recent progress in induced pluripotent stem cell (iPSC) technology have allowed the modeling of diabetes-associated genes. Our recent study using FOXA2-deficient human iPSC models has highlighted an essential role for FOXA2 in the development of human pancreas. Here, we aimed to provide further insights on the role of microRNAs (miRNAs) by studying the miRNA-mRNA regulatory networks in iPSC-derived islets lacking the FOXA2 gene. Consistent with our previous findings, the absence of FOXA2 significantly downregulated the expression of islet hormones, INS, and GCG, alongside other key developmental genes in pancreatic islets. Concordantly, RNA-Seq analysis showed significant downregulation of genes related to pancreatic development and upregulation of genes associated with nervous system development and lipid metabolic pathways. Furthermore, the absence of FOXA2 in iPSC-derived pancreatic islets resulted in significant alterations in miRNA expression, with 61 miRNAs upregulated and 99 downregulated. The upregulated miRNAs targeted crucial genes involved in diabetes and pancreatic islet cell development. In contrary, the absence of FOXA2 in islets showed a network of downregulated miRNAs targeting genes related to nervous system development and lipid metabolism. These findings highlight the impact of FOXA2 absence on pancreatic islet development and suggesting intricate miRNA-mRNA regulatory networks affecting pancreatic islet cell development.

Generation of nine induced pluripotent stem cell lines from six young children with autism spectrum disorder and three matched control subjects from the Qatari population.

Autism spectrum disorder (ASD) is a complex developmental disorder characterized by challenges with social interactions and restricted/repetitive behaviors. Here, we recruited nine Qatari children of Arab ethnicity (males, aged 2-4 years), including six ASD subjects (n = 3 mild-to-moderate ASD and n = 3 severe ASD) and three control subjects. We generated induced pluripotent stem cell (iPSC) lines from PBMC samples of these subjects using non-integrating Sendai viral vectors. These iPSC lines were fully characterized and exhibited pluripotency characteristics, normal karyotypes, and trilineage differentiation potential. These iPSC lines provide valuable cell models for understanding ASD pathophysiology and developing new therapeutics for ASD.

Exploring the Interplay of Food Security, Safety, and Psychological Wellness in the COVID-19 Era: Managing Strategies for Resilience and Adaptation.

The global population surge presents a dual challenge and opportunity in the realms of food consumption, safety, and mental well-being. This necessitates a projected 70% increase in food production to meet growing demands. Amid this backdrop, the ongoing COVID-19 pandemic exacerbates these issues, underscoring the need for a deeper understanding of the intricate interplay between food consumption patterns and mental health dynamics during this crisis. Mitigating the spread of COVID-19 hinges upon rigorous adherence to personal hygiene practices and heightened disease awareness. Furthermore, maintaining stringent food quality and safety standards across both public and private sectors is imperative for safeguarding public health and containing viral transmission. Drawing upon existing research, this study delves into the pandemic's impact on mental health, food consumption habits, and food safety protocols. Through a comprehensive analysis, it aims to elucidate the nuanced relationship among food, food safety, and mental well-being amid the COVID-19 pandemic, highlighting synergistic effects and dynamics that underpin holistic human welfare. Our study offers a novel approach by integrating psychological wellness with food security and safety. In conceiving this review, we aimed to comprehensively explore the intricate interplay among food security, safety, and psychological wellness amid the backdrop of the COVID-19 pandemic. Our review is structured to encompass a thorough examination of existing research, synthesizing insights into the multifaceted relationships among food consumption patterns, mental health dynamics, and food safety protocols during the crisis. Our findings provide valuable insights and practical recommendations for enhancing food security and psychological well-being, thus supporting both academic research and real-world applications in crisis management and policy development.

The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory.

Background: The dysregulation of Isocitrate dehydrogenase (IDH) and the subsequent production of 2-Hydroxyglutrate (2HG) may alter the expression of epigenetic proteins in Grade 4 astrocytoma. The interplay mechanism between IDH, O-6-methylguanine-DNA methyltransferase (MGMT)-promoter methylation, and protein methyltransferase proteins-5 (PRMT5) activity, with tumor progression has never been described. Methods: A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors. Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis. Inter-cohort statistical significance was evaluated. Results: Both IDH-mutant WHO grade 4 astrocytomas (n = 22, 64.7%) and IDH-wildtype glioblastomas (n = 12, 35.3%) had upregulated PRMT5 gene expression except in one case. Out of the 22 IDH-mutant tumors, 10 (45.5%) tumors showed MGMT-promoter methylation and 12 (54.5%) tumors had unmethylated MGMT. All IDH-wildtype tumors had unmethylated MGMT. There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma (p-value = 0.006). Statistically significant differences in progression-free survival (PFS) were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide (TMZ) or TMZ plus other chemotherapies, regardless of their IDH or MGMT-methylation status (p-value=0.0014). Specifically, IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation, who received only TMZ, have exhibited longer PFS. Conclusions: The relationship between PRMT5, MGMT-promoter, and IDH is not tri-directional. However, accumulation of D2-hydroxyglutarate (2-HG), which partially activates 2-OG-dependent deoxygenase, may not affect their activities. In IDH-wildtype glioblastomas, the 2HG-2OG pathway is typically inactive, leading to PRMT5 upregulation. TMZ alone, compared to TMZ-plus, can increase PFS in upregulated PRMT5 tumors. Thus, using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.

Rapidly Progressive Apical Hypertrophic Cardiomyopathy: Not Everything is What It Seems.

Apical hypertrophic cardiomyopathy (HCM) is a rare variant of HCM. A 43-year-old female with a past medical history significant for hypertension and kidney transplantation presented with recurrent syncopal episodes and dyspnea on exertion. Electrocardiogram showed characteristic diffuse giant T-waves inversion, and cardiac magnetic resonance showed HCM with circumferential apical thickening. This case highlights the rapid development of apical HCM and its challenging diagnostic characteristics.

Association between echocardiographic velocity time integral ratio of mitral valve and left ventricular outflow tract and clinical outcomes post transcatheter edge-to-edge mitral valve repair.

Background: Residual mitral regurgitation (MR) is frequent after transcatheter edge-to-edge repair (TEER). There is controversy regarding the clinical impact of residual MR and its quantitative assessment by transthoracic echocardiography (TTE), which is often challenging with multiple eccentric jets and artifact from the clip. The utility of the velocity time integral (VTI) ratio between the mitral valve (MV) and left ventricular outflow tract (LVOT), (VTIMV/LVOT), a simple Doppler measurement that increases with MR, has not been assessed post TEER. Methods: Baseline characteristics, clinical outcomes, and TTE data from patients who underwent TEER between 2014 and 2021 across three academic centers were retrospectively analyzed. Post-procedure TTEs were evaluated for VTIMV/LVOT in the first three months after TEER. One-year outcomes including all-cause and cardiac mortality, major adverse cardiac events, and MV reintervention were compared between patients with high VTIMV/LVOT (≥2.5) and low (<2.5). Results: In total, 372 patients were included (mean age 78.7 ± 8.8 years, 68 % male, mean pre-TEER ejection fraction of 50.5 ± 14.7 %). Follow up TTEs were performed at a median of 37.5 (IQR 30-48) days post-procedure. Patients with high VTIMV/LVOT had significantly higher all-cause mortality (HR 2.10, p = 0.003), cardiac mortality (HR 3.03, p = 0.004) and heart failure admissions (HR 2.28, p < 0.001) at one-year post-procedure. There was no association between raised VTIMV/LVOT and subsequent MV reintervention. Conclusion: High VTIMV/LVOT has clinically significant prognostic value at one year post TEER. This tool could be used to select patients for consideration of repeat intervention.

Global 30-Day Morbidity and Mortality of Primary Bariatric Surgery Combined with Another Procedure: The BLEND Study.

BACKGROUND: No robust data are available on the safety of primary bariatric and metabolic surgery (BMS) alone compared to primary BMS combined with other procedures. OBJECTIVES: The objective of this study is to collect a 30-day mortality and morbidity of primary BMS combined with cholecystectomy, ventral hernia repair, or hiatal hernia repair. SETTING: This is as an international, multicenter, prospective, and observational audit of patients undergoing primary BMS combined with one or more additional procedures. METHODS: The audit took place from January 1 to June 30, 2022. A descriptive analysis was conducted. A propensity score matching analysis compared the BLEND study patients with those from the GENEVA cohort to obtain objective evaluation between combined procedures and primary BMS alone. RESULTS: A total of 75 centers submitted data on 1036 patients. Sleeve gastrectomy was the most commonly primary BMS (N = 653, 63%), and hiatal hernia repair was the most commonly concomitant procedure (N = 447, 43.1%). RYGB accounted for the highest percentage (20.6%) of a 30-day morbidity, followed by SG (10.5%). More than one combined procedures had the highest morbidities among all combinations (17.1%). Out of overall 134 complications, 129 (96.2%) were Clavien-Dindo I-III, and 4 were CD V. Patients who underwent a primary bariatric surgery combined with another procedure had a pronounced increase in a 30-day complication rate compared with patients who underwent only BMS (12.7% vs. 7.1%). CONCLUSION: Combining BMS with another procedure increases the risk of complications, but most are minor and require no further treatment. Combined procedures with primary BMS is a viable option to consider in selected patients following multi-disciplinary discussion.

Development of a Scoring Rubric Assessing Medical Students' Explanations of Pathology Reports.

CONTEXT.­: With increasing availability of immediate patient access to pathology reports, it is imperative that all physicians be equipped to discuss pathology reports with their patients. No validated measures exist to assess how pathology report findings are communicated during patient encounters. OBJECTIVE.­: To pilot a scoring rubric evaluating medical students' communication of pathology reports to standardized patients. DESIGN.­: The rubric was iteratively developed using the Pathology Competencies for Medical Education and Accreditation Council for Graduate Medical Education pathology residency milestones. After a brief training, third- and fourth-year medical students completed 2 standardized patient encounters, presenting simulated benign and malignant pathology reports. Encounters were video recorded and scored by 2 pathologists to calculate overall and item-specific interrater reliability. RESULTS.­: All students recognized the need for pathology report teaching, which was lacking in their medical curriculum. Interrater agreement was high for malignant report scores (intraclass correlation coefficient, 0.65) but negligible for benign reports (intraclass correlation coefficient, 0). On malignant reports, most items demonstrated good interrater agreement, except for discussing the block (cassette) summary, explaining the purpose of the pathology report, and acknowledging uncertainty. Participating students (N = 9) felt the training was valuable given their limited prior exposure to pathology reports. CONCLUSIONS.­: This pilot study demonstrates the feasibility of using a structured rubric to assess the communication of pathology reports to patients. Our findings also provide a scalable example of training on pathology report communication, which can be incorporated in the undergraduate medical curriculum to equip more physicians to facilitate patients' understanding of their pathology reports.

Ecological assessment and development of analytical methods for concurrent quantification of valsartan and sacubitril: whiteness comparative study based on relative scoring.

Sustainable analytical chemistry is gaining great interest in global environmental pollution control. In addition, valsartan (VAS) and sacubitril (SAB) have been recently approved by the FDA as a fixed-dose combination "LCZ696". It showed efficacy and safety enough to extend its application from heart failure to hypertension control. VAS/SAB dual therapy is considered expensive; however, its prescription has increased significantly worldwide. This prescription increased the demand for developing sustainable analytical methods that simultaneously analyze VAS and SAB. Highly sensitive and selective spectrofluorimetric methods have been developed for this purpose. A synchronous spectrofluorimetric technique was applied. In one method, it was followed by spectral derivatization at the first-order level. The signals were recorded at 230 and 211 nm for VAS and SAB, respectively. Synchronous spectrofluorimetry was coupled to a dual-wavelength mathematical approach in the second method. Signals were derived by subtracting synchronous responses at 241 nm, 226 nm, and 239 nm from the response at 208 nm for VAS and SAB, respectively. Method validation was carried out following ICH guidelines. VAS showed linear calibration curves spanning the range of 60-200 and 80-600 ng mL-1 for the derivative and dual wavelength-assisted approaches, respectively. SAB achieved linear responses in the range of 17-190 and 30-350 ng mL-1 for the first and second methods, respectively. The green profile of the proposed methods was confirmed using the analytical eco-scale (AES), green analytical procedure index (GAPI), and analytical greenness metric (AGREE) tools. The proposed hybrid methods proved highly sustainable through the whiteness RGB 12 algorithm evaluation approach. Whiteness was comparatively assessed for the proposed and reported methods based on relative scoring depending on the parameters of each method. Despite this scoring approach being accurate as a relative score for comparative purposes, it gave rise to underestimated absolute scores. Therefore, to obtain a proper conclusion from the comparative whiteness study, all the methods were ranked according to their whiteness score, illustrating the excellent whiteness ranks of the proposed methods. Upon complete comparison with the reported methods, the suggested ones showed several advantages concerning analytical performance and the greenness level. The proven affordability and simplicity encourage their wide industrial application in developing countries.

Intranodal Lymphangiography and Embolization for Management of Iatrogenic Chylous Ascites after Oncological Surgery.

PURPOSE: To investigate the safety and effectiveness of intranodal lymphangiography (INL) and lymphatic embolization (LE) in management of chylous ascites after oncologic surgery. MATERIALS AND METHODS: Retrospective review of records of patients who underwent INL with or without LE from January 2017 to June 2022 was performed. Adult patients with chylous ascites after oncologic surgery referred to interventional radiology after failure of conservative treatment were included. Thirty-nine patients who underwent 55 procedures were included (34 males and 5 females). Data on patient demographics, procedural technique, outcomes, and follow-up were collected. Descriptive statistics were used to illustrate technical success, clinical success, and adverse events. Univariate logistic regression analysis was performed to evaluate factors predicting clinical success. RESULTS: INL was technically successful in 54 of 55 procedures (98%; 95% confidence interval [CI], 90%-100%). A lymphatic leak was identified in 40 procedures, and LE was attempted in 36. LE was technically successful in 33 of the 36 procedures (92%; 95% CI, 78%-98%). Clinical success, defined as resolution of ascites with no need for peritoneovenous shunt placement or additional surgery, was achieved in 22 of 39 patients (56%; 95% CI, 40%-72%). Clinical success was achieved in 18 patients after 1 procedure, and patients who required repeat procedures were less likely to achieve clinical success (odds ratio, 0.16; 95% CI, 0.04-0.66; P = .012). Four grade 1 procedural adverse events were recorded. CONCLUSIONS: INL with or without LE is a safe minimally invasive tool that can help patients with chylous ascites after oncologic surgery who failed conservative treatment avoid more invasive interventions.

Specific discrimination of pathogenic bacteria causing septic arthritis using Raman spectroscopy: In-vitro study.

In this study we performed preliminary experiments using Raman spectroscopy as an evolving technology in biofluid and microbial characterization, to explore its potential for rapid diagnosis of pathogenic bacteria in an in-vitro synovial fluid infection model. Normal human synovial fluids samples were collected from patients undergoing knee surgery and the three most common pathogenic bacteria introduced in-vitro into the samples. The bacterial growth was systematically monitored using a Raman spectroscopy. Multivariate regression analysis of acquired spectra showed bacterial characteristic Raman bands related to bacterial cell membranes and DNA structures to increase continuously as the incubation period was increased. Spectra signature recorded from cultured synovial fluid samples showed a significant loss in synovial quality and protein morphology over time compared to control samples. In this study, Raman spectroscopy shows promise for rapid pathogenic bacteria identification in synovial fluid. Marker peaks distinguished inoculated bacteria, while chemical changes reveal infection dynamics.