Unveiling the significance of Gremlin-1 as a novel biomarker for enhanced severity prediction in COVID-19 patients.

Gremlin-1 is associated with lung disease and plays a role in the initiation and progression of pulmonary fibrosis. This suggests that Gremlin-1 may be associated with lung involvement in COVID-19 and poor clinical outcomes and warrants further investigation. This prospective, cross-sectional, single-blind study was the first to investigate Gremlin-1 levels in COVID-19 patients and whether Gremlin-1 levels could be used to predict and guide clinical follow-up in outpatients and inpatients. In this context, serum Gremlin-1 levels were measured and compared in 2 groups of patients who were diagnosed as positive for COVID-19 by RT-PCR and were followed up as outpatients (n = 28) or required hospitalization (n = 30). The median Gremlin-1 values were statistically significantly different between outpatients and intensive care unit patients (0.367 ng/mL [IQR = 0.377], 1.858 ng/mL [IQR = 2.245], respectively) (P < .0001). The area under the ROC curve value to determine the discriminative power of Gremlin-1 was found to be 0.772 (95% CI: 0.672-0.871; P < .0001), and the cutoff value of Gremlin-1 to discriminate between outpatients and hospitalized patients was found to be 1.242 ng/mL with 66.7% sensitivity and 67.2% specificity. Serum Gremlin-1 level is an important biomarker that can be used as a clinical decision-making tool for COVID-19 positive patients.

Gut microbiome dysbiosis is associated with lumbar degenerative spondylolisthesis in symptomatic patients.

Background: Lumbar degenerative spondylolisthesis (LDS), characterized as degeneration of the intervertebral disc and structural changes of the facet joints, is a condition with varying degrees of instability that may lead to pain, canal stenosis, and subsequent surgical intervention. However, the etiology of LDS remains inconclusive. Gut microbiome dysbiosis may stimulate systemic inflammation in various disorders. However, the role of such dysbiosis upon spine health remains under-studied. The current study assessed the association of gut microbiome dysbiosis in symptomatic patients with or without LDS. Methods: A cross-sectional analysis within the framework of a prospective study was performed. DNA was extracted from fecal samples collected from adult symptomatic patients with (n = 21) and without LDS (n = 12). Alpha and beta diversity assessed differences in fecal microbial community between groups. Taxon-by-taxon analysis identified microbial features with differential relative abundance between groups. Subject demographics and imaging parameters were also assessed. Results: There was no significant group differences in age, sex, race, body mass index, smoking/alcohol history, pain profiles, spinopelvic alignment, and Modic changes (p >0.05). LDS subjects had significantly higher disc degeneration severity (p = 0.018) and alpha diversity levels compared to non-LDS subjects (p = 0.002-0.003). Significant differences in gut microbial community structure were observed between groups (p = 0.046). Subjects with LDS exhibited distinct differences at the phylum level, with a significantly higher Firmicutes to Bacteroidota ratio compared to non-LDS (p = 0.003). Differential relative abundance analysis identified six taxa with significant differences between the two groups, with LDS demonstrating an increase in putative pro-inflammatory bacteria (Dialister, CAG-352) and a decrease in anti-inflammatory bacteria (Slackia, Escherichia-Shigella). Conclusion: This study is the first to report a significant association of gut microbiome dysbiosis and LDS in symptomatic patients, noting pro-inflammatory bacterial taxa. This work provides a foundation for future studies addressing the role of the gut microbiome in association with spine health and disease.

Geographical variations and predictors of coronary artery disease mortality in Turkiye: an environmental and behavioral analysis.

OBJECTIVE: This study aims to analyze the geographical variations and identify key environmental and behavioral predictors of coronary artery disease (CAD) mortality in Turkiye. METHODS: A 10-year longitudinal province-level data was used to identify change trajectories of CAD mortality. Environmental determinants (such as air quality and climatic conditions) and behavioral factors of alcohol consumption and smoking were examined for their association with CAD mortality change trajectories using Ordinal Logistic Regression models. RESULTS: The study revealed significantly different trajectoriesof CAD mortality across Turkiye. Environmental factors, particularly air quality (Particulate Matter-10 variation) and climatic conditions (humidity and temperature variations), were heavily associated with the level of CAD mortality. Behavioral factors, notably alcohol consumption and smoking, also exhibited a significantly positive association. Humidity, sunlight, and temperature remained as key predictors of CAD after controlling for smoking and alcohol consumption. CONCLUSION: The study underscores the importance of addressing environmental and lifestyle factors in CAD management and prevention strategies. The findings suggest the necessity for region-specific interventions and public health policies tailored to the unique characteristics of each province in Turkiye. This research contributes to a deeper understanding of the multifactorial nature of CAD mortality, providing valuable insights for future research to investigate causal associations, healthcare planning, and policy-making. TRIAL REGISTRATION: Our study has been registered in ClinicalTrials.GOV system with a procotol ID of CAD001.

Vinpocetine Ameliorates Neuronal Injury After Cold-Induced Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI), also known as intracranial injury, is a common condition with the highest incidence rate among neurodegenerative disorders and poses a significant public health burden. Various methods are used in the treatment of TBI, but the effects of cold-induced traumatic brain injury have not been thoroughly studied. In this context, vinpocetine (VPN), derived from Vinca minor, exhibits notable anti-inflammatory and antioxidant properties. VPN is known for its neuroprotective role and is generally utilized for treating various neurodegenerative disorders. However, the function of VPN after cold-induced TBI needs to be studied in more detail. This study aims to investigate the neuroprotective effects of VPN at varying doses (5 mg/kg or 10 mg/kg) after cold-induced TBI. C57BL/6 mice were sacrificed 2 or 28 days after cold-induced TBI. Results indicate that VPN administration significantly reduces brain infarct volume, brain swelling, blood-brain barrier disruption, and DNA fragmentation in a dose-dependent manner. Additionally, VPN enhances neuronal survival in the ipsilesional cortex. In the long term, VPN treatment (5 mg/kg/day or 10 mg/kg/day, initiated 48 h post-TBI) improved locomotor activity, cell proliferation, neurogenesis, and decreased whole brain atrophy, specifically motor cortex atrophy. We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate the underlying mechanisms to profile proteins and signaling pathways influenced by prolonged VPN treatment post-TBI. Notably, we found that 192 different proteins were significantly altered by VPN treatment, which is a matter of further investigation for the development of therapeutic targets. Our study has shown that VPN may have a neuroprotective role in cold-induced TBI.

The impact of body mass index on the progression-free survival of CDK 4/6 inhibitors in metastatic breast cancer patients.

Aim: Endocrine therapy (ET) plus cyclin-dependent kinase (CDK) 4/6 inhibitors is a standard treatment for hormone receptor (HR) positive HER-2-negative metastatic breast cancer patients. In this study, we aimed to investigate the effect of body mass index (BMI) on progression-free survival (PFS) in patients receiving ET plus CDK 4/6 inhibitors.Materials & methods: Patients with metastatic HR-positive breast cancer receiving CDK 4/6 inhibitors were included in the study. A total of 116 patients were retrospectively evaluated. Patients were divided into three groups according to BMI level: normal weight (group 1) 18.5-24.9 kg/m2, overweight (group 2) 25-29.9 kg/m2 and obese (group 3): ≥30 kg/m2. Median follow-up was 10.83 months. Comparisons of PFS and BMI categories were performed by Kaplan-Meier curve and log-rank test.Results: PFS was 9.3 (5.3-13.4) months in normal weight patients and 11.1 (9.7-12.56) months in obese patients and was not reached in overweight patients. This difference was statistically significant (p = 0.02).Conclusion: Low BMI has been shown to have a negative prognostic effect on survival in patients with metastatic breast cancer and overweight patients had a longer PFS.

[Box: see text].

Association of environmental and behavioural factors with cardiovascular disease mortality.

AIMS: Recognizing the rising concern of environmental impacts on health, the study aims to explore how specific environmental factors such as air pollution, humidity, and temperature variations contribute to the prevalence of cardiovascular disease (CVD) mortality, emphasizing the role of air quality, climate variables, and lifestyle factors in the disease mortality specifically. METHODS AND RESULTS: Analysis of province-level data on CVD mortality in Turkey from 2010 to 2019, assessing the correlations with environmental and lifestyle factors like particulate matter, sulfur dioxide, meteorological variables, and smoking and alcohol consumption. The study employs the SAS TRAJ procedure and Ordinal Logistic Regression for statistical analysis. The multiplicity correction was done through Benjamini-Hoechberg false discovery rate (FDR) approach. As expected, both smoking and alcohol consumption were found to be significantly associated with CVD mortality (odds ratio (OR): 1.10, 95% CI: 1.08, 1.11, P-value < 0.0001). While median Air Pressure and Humidity were among the most significant markers with OR of 1.10 indicating an increasing CVD mortality, their variability metrics such as coefficient of variation (CV) showed significant protective effects with OR of 0.37 and 0.89, respectively. Temperature and its variability seemed to be protective overall. CONCLUSIONS: Our research highlights the significant influence of environmental factors on cardiovascular health, especially air pressure and humidity, beyond the known factors such as smoking and alcohol consumption. These findings suggest the need for comprehensive public health strategies that address both environmental and lifestyle risk factors to effectively reduce the burden of cardiovascular diseases.

Comparison of granisetron and palonosetron in triplet anti-emetic prophylaxis in non-small cell lung cancer patients receiving cisplatin-based highly emetogenic chemotherapy.

INTRODUCTION: We compared the efficacy of first-generation granisetron and second-generation palonosetron in triplet anti-emetic prophylaxis in patients with non-small cell lung cancer (NSCLC) receiving cisplatin-based high emetogenic chemotherapy (HEC). METHODS: This prospective, multicenter, non-randomized, observational study was conducted between June 2018 and December 2021. Patients diagnosed with NSCLC who received triplet anti-emetic prophylactic treatment with aprepitant and dexamethasone plus granisetron or palonosetron before the first cycle of chemotherapy were included in the study. At the end of the first week after chemotherapy, the emesis scale was applied to the patients during the outpatient control. The primary endpoint was complete response (CR) and total control (TC). RESULTS: One hundred twenty-one patients were included in the study. Sixty-one patients were in the granisetron group and 60 patients were in the palonosetron group. CR was higher with granisetron in the acute phase (70.5% vs. 58.3%, p = 0.16; respectively) and higher with palonosetron in the delayed phase (61.7% vs. 55.7%, p = 0.5; respectively), although not statistically significant. The TC rates were also not significantly different between the groups (54.1% vs.57.6%, p = 0.69). CONCLUSIONS: There was no significant difference between granisetron and palonosetron in both acute and delayed control of emesis in NSCLC patients receiving cisplatin-based HEC.

Volumetric Analysis of Carpal Bones by Sex with 3D Slicer Software Program / Análisis Volumétrico de los Huesos del Carpo por Sexo con el Programa de Software 3D Slicer

SUMMARY: In this study, we aim to share the volumes of the carpal bone and the ratio of these volumes to the total volume of wrist bones from Computed Tomography (CT) images obtained from individuals of different ages and sex using 3D Slicer. Right wrist CT images of 0.625 mm slice thickness of 42 healthy individuals (21 female, 21 male) of both sexes were included in our study. Volume calculations were made by loading the images into 3D Slicer, an open-source software package. In this study, mean capitate volume was the largest in both sexes (male 3479.9±679.2; female 2207.1±272.1 mm3), while pisiform had the smallest mean volume (male 810.0±141.2; female 566.6±97.7 mm3). This order was ordered from largest to smallest as hamate, scaphoid, trapezium, lunate, triquetrum, trapezoid, and pisiform. According to this study, carpal bone volumes were larger in males than in females (p0.05). In this study, it was seen that carpal bone volume differed according to sex. However, it was observed that the bone volumes of both sexes took up the same amount in the total bone volume. This information will be very useful in sex determination, 3D anatomical material creation, implant applications and reconstructive surgery.

Nuestro objetivo fue determinar los volúmenes de los huesos del carpo y la relación entre estos volúmenes y el volumen total de estos huesos a partir de imágenes de TC obtenidas de individuos de diferentes edades y sexos utilizando 3D Slicer. En el estudio se incluyeron imágenes de TC del carpo de la mano derecha de los participantes en el estudio, con un grosor de corte de 0,625 mm, en 42 individuos sanos (21 mujeres, 21 hombres) de ambos sexos. Los cálculos de volumen se realizaron cargando las imágenes en 3D Slicer, un paquete de software de código abierto. El volumen medio del hueso capitado fue el mayor en ambos sexos (hombre 3479,9 ± 679,2; mujer 2207,1 ± 272,1 mm3), mientras que el hueso pisiforme tuvo el volumen medio más pequeño (hombre 810,0 ± 141,2; mujer 566,6 ± 97,7 mm3). De mayor a menor el volumen de los otros huesos fue: hamato, escafoides, trapecio, lunato, piramidal, trapezoide y pisiforme. Según este estudio, los volúmenes óseos del carpo eran mayores en hombres que en mujeres (p0,05). En este estudio se observó que el volumen de los huesos del carpo difería según el sexo. Sin embargo, se observó que los volúmenes óseos de ambos sexos ocuparon la misma cantidad del volumen óseo total. Esta información será de gran utilidad en la determinación del sexo, creación de material anatómico 3D, aplicaciones de implantes y cirugía reconstructiva.

Epidermal growth factor receptor and programmed cell death-1 expression levels in peripheral T cell subsets of patients with non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non-small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min-max) = 64.03 (45-83); 20 stage I-III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD-1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD-1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC.

Remote Monitoring App for Endocrine Therapy Adherence Among Patients With Early-Stage Breast Cancer: A Randomized Clinical Trial.

Importance: Adjuvant endocrine therapy (AET) use among women with early-stage, hormone receptor-positive breast cancer reduces the risk of cancer recurrence, but its adverse symptoms contribute to lower adherence. Objective: To test whether remote monitoring of symptoms and treatment adherence with or without tailored text messages improves outcomes among women with breast cancer who are prescribed AET. Design, Setting, and Participants: This nonblinded, randomized clinical trial (RCT) following intention-to-treat principles included English-speaking women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across 3 states from November 15, 2018, to June 11, 2021. All participants had a mobile device with a data plan and an email address and were asked to use an electronic pillbox to monitor AET adherence and to complete surveys at enrollment and 1 year. Interventions: Participants were randomized into 3 groups: (1) an app group, in which participants received instructions for and access to the study adherence and symptom monitoring app for 6 months; (2) an app plus feedback group, in which participants received additional weekly text messages about managing symptoms, adherence, and communication; or (3) an enhanced usual care (EUC) group. App-reported missed doses, increases in symptoms, and occurrence of severe symptoms triggered follow-ups from the oncology team. Main Outcomes and Measures: The primary outcome was 1-year, electronic pillbox-captured AET adherence. Secondary outcomes included symptom management abstracted from the medical record, as well as patient-reported health care utilization, symptom burden, quality of life, physician communication, and self-efficacy for managing symptoms. Results: Among 304 female participants randomized (app group, 98; app plus feedback group, 102; EUC group, 104), the mean (SD) age was 58.6 (10.8) years (median, 60 years; range, 31-83 years), and 60 (19.7%) had an educational level of high school diploma or less. The study completion rate was 87.5% (266 participants). There were no statistically significant differences by treatment group in AET adherence (primary outcome): 76.6% for EUC, 73.4% for the app group (difference vs EUC, -3.3%; 95% CI, -11.4% to 4.9%; P = .43), and 70.9% for the app plus feedback group (difference vs EUC, -5.7%; 95% CI, -13.8% to 2.4%; P = .17). At the 1-year follow-up, app plus feedback participants had fewer total health care encounters (adjusted difference, -1.23; 95% CI, -2.03 to -0.43; P = .003), including high-cost encounters (adjusted difference, -0.40; 95% CI, -0.67 to -0.14; P = .003), and office visits (adjusted difference, -0.82; 95% CI, -1.54 to -0.09; P = .03) over the previous 6 months compared with EUC participants. Conclusions and Relevance: This RCT found that a remote monitoring app with alerts to the patient's care team and tailored text messages to patients did not improve AET adherence among women with early-stage breast cancer; however, it reduced overall and high-cost health care encounters and office visits without affecting quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT03592771.

Efficacy of Systemic Treatments in Patients With Metastatic Lung Invasive Mucinous Adenocarcinoma.

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is a rare histological subtype of lung invasive adenocarcinoma with unique clinical, radiological, histopathological, and genomic characteristics. There have been limited studies on the effectiveness of systemic therapy for lung IMA, with conflicting results reported. METHODS: We retrospectively investigated the medical records of patients diagnosed with lung IMA. Patients who were ≥ 18 years of age and received at least 1 course of treatment for metastatic or locally advanced inoperable disease were included in the study. Archive records of 113 patients diagnosed with IMA were screened for the study. RESULTS: A total of 41 patients with lung IMA were included. The targetable mutation rate was 20.6% (in 6 of 29 patients). Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. The objective response rate (ORR) was 25.7%, and median progression-free survival (PFS) and overall survival (OS) were 8.1 months (95% CI, 5.02-11.2) and 17.5 months (95% CI, 11.7-23.3 months), respectively, in the patients who received chemotherapy. The median PFS and ORR were 20.6 (95% CI, 18.9-66.5) and 66.6%, respectively, in epidermal growth factor receptor (EGFR) mutation-positive patients (n = 3) with relevant targeted therapy. Only 1 patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy in the second-line treatment and achieved a partial response (PR) at 7.2 months. CONCLUSION: Platinum-based chemotherapies moderately enhance IMA patients' survival rates. Anti-EGFR-targeted drugs are seen as potentially effective in patients with EGFR driver mutation positive. Large, prospective studies are needed to confirm our findings.

Reassessing Normal Voiding Standards: A Cross-Sectional Study Based on Medical Professionals' Evaluations with Portable Uroflowmetry and IPSS.

Background/Objectives: LUTS and voiding dysfunctions are prevalent in urology clinics, with uroflowmetry and IPSS as the prevailing diagnostic methods. Nevertheless, objective assessment can be constrained by age, gender, and variability in the test conditions. Portable (home) uroflowmetry addresses these limitations, allowing for more natural urinary flow recordings beyond clinic confines. This study aims to characterize spontaneous voiding patterns in healthcare professionals, exploring gender differences, variability in repeated measurements, and correlations among voiding parameters, IPSS, age, and BMI. Methods: This cross-sectional study was conducted during the SIU 43rd Congress in Istanbul using smart uroflow devices such as the Oruba Oruflow Uroflow Recorder, which were installed in public toilets. A total of 431 healthcare professionals participated by providing demographic information and completing the IPSS questionnaire. The data analysis included uroflowmetric parameters such as maximum flow rate (Qmax), average flow rate (Qave), and voided volume (VV), in addition to IPSS and demographic data to assess the possible associations with IPSS, age, BMI, and gender differences. Results: Of the participants, 76% were male and 24% female, with a higher prevalence of LUTS in women. Despite no significant gender difference in voided volume, men with lower volumes demonstrated more severe LUTS. Notably, women exhibited higher Qmax and Qave rates irrespective of their IPSS scores, contrasting with men whose flow rates declined with age and LUTS severity. In men, the total IPSS score was inversely associated with uroflowmetric performance, particularly impacting voiding symptoms over storage symptoms. Repeated measurements revealed noteworthy variability in Qmax and VV, without any influence from gender, BMI, age, or symptom severity. Conclusions: Our findings highlight the importance of gender-specific considerations in evaluating voiding complaints through uroflowmetry and IPSS. The significant variability observed in repeated uroflowmetry studies underlines the need for multiple measurements. Overall, this research emphasizes the significance of portable (home) uroflowmetry and calls for a reassessment of normal voiding standards in (non) clinical settings.

Inflammation in cerebral ischemia reperfusion improved by avanafil via nod-like receptor protein-3 inflammasome: an experimental study in rats.

OBJECTIVE: The aim of study was to investigate the effect of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on cerebral ischemia reperfusion (CI/R) model. METHODS: 32 male albino Wistar rats were used. Four groups were constituted, as I: the healthy (sham), II: the CI/R group, III: the CI/R +I 10 mg/kg avanafil group, and IV: the CI/R + 20 mg/kg avanafil group. Avanafil was administered twice via oral gavage, first shortly after ischemia reperfusion and once more after 12 h. The rats were euthanized after 24 h. Histopathological and Real Time PCR analyzes were performed on cerebral tissues. RESULTS: IL-1ß, NLRP3 and TNF-α mRNA expressions were statistically higher in the CI/R group when compared to healthy (sham) group. Conversely, the IL-1ß, NLRP3, and TNF-α mRNA expressions were significantly decreased in both of the avanafil-treated groups when compared to CI/R group. Histopathological results showed that both doses of avanafil also decreased cellular damage in cerebral tissue that occurred after CI/R. CONCLUSION: Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1ß, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil.

The Relationship between Urinary Incontinence, Osteoarthritis, and Musculoskeletal System Disorders.

Background/Objectives: Urinary incontinence diminishes quality of life, and its severity can be worsened by mobility impairments. This study explored the link between urinary incontinence, osteoarthritis, and back musculoskeletal system disorders, considering pain, mobility issues, and daily activity difficulties. Methods: This cross-sectional study included respondents aged ≥ 15 years from the 2008 Turkish Health Studies Survey (n = 13,976). We assessed self-reported urinary incontinence, daily activity, mobility impairment, pain, osteoarthritis, and musculoskeletal disorders to explore their association with urinary incontinence. Gender-specific logistic regression models included chronic conditions related to urinary incontinence. Results: The prevalence of urinary incontinence was higher in the participants with osteoarthritis and back musculoskeletal system problems. Among the patients with osteoarthritis, the prevalence was 25.84% in the mobility-impaired group and 10.03% in the non-impaired group. Similarly, 33.02% of those with activities of daily living (ADL) difficulties and 12.93% of those without difficulties had incontinence. The frequency of urinary incontinence increased with pain severity. According to the multivariable logistic regression analyses, the adjusted odds ratio (95% confidence interval) of urinary incontinence for osteoarthritis was 1.58 (95% CI 1.23-2.02, p < 0.01) for females and 2.38 (95% CI 1.62-3.49, p < 0.01) for males. Conclusions: Urinary incontinence was more common in females, increased with age, and was found to be associated with osteoarthritis and back musculoskeletal system disorders. Among the patients with osteoarthritis and back musculoskeletal system disorders, those with mobility impairment and daily activity difficulties had a higher prevalence of urinary incontinence. The patients with more severe pain had a higher frequency of urinary incontinence.

The effect of concomitant beta-blocker use on survival in patients with metastatic renal cell carcinoma treated with a vascular endothelial growth factor receptor inhibitors in the first line.

PURPOSE: Vascular endothelial growth factor (VEGF) inhibition is one of the cornerstones of treatment in the treatment of metastatic renal cell carcinoma (mRCC). Since RCC is a disease of advanced age and hypertension as a side effect of VEGF receptor inhibitors, beta-blocker use is common in these patients. We aimed to compare the treatment efficacy and survival results in case of concomitant use of these two drugs due to the inhibition of VEGF in beta-blockers. METHODS: A total of 121 patients with a diagnosis of mRCC who used sunitinib or pazopanib in first-line therapy were included in the study. These patients were divided into two groups as those using concomitant beta-blockers and those not using them. RESULT: The median overall survival (mOS) of the patient using sunitinib or pazopanib and concomitant beta-blocker was 47 (95% CI 29.0-65.0) months, and the mOS of those not using concomitant beta-blocker was 18 (95% CI 8.9-27.1) months (p < 0.001). The median progression-free survival (mPFS) of the patients using sunitinib or pazopanib and concomitant beta-blocker was 20.4 (95% CI 4.5-40.1) months, and the mPFS of those not using it was 11.4 (95% CI 5.9-16.9) months (p = 0.042). Concomitant beta-blocker use was found to be a good prognostic factor for OS in the multivariate analysis (p = 0.029). In the multivariate analysis, concomitant beta-blocker use had a trend towards statistical significance for PFS (p = 0.062). CONCLUSION: Concomitant use of betablockers with sunitinib or pazopanib is associated with longer overall survial and progression free survival.

Fetal MRI Analysis of Corpus Callosal Abnormalities: Classification, and Associated Anomalies.

BACKGROUND: Corpus callosal abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosal abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications for the postnatal outcome. METHODS: In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies. RESULTS: The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%), and hypoplasia with dysplasia (4.2%). Among them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both. CONCLUSION: The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a suspected diagnosis on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection.

Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants in-vitro, by utilizing Murine Leukemia Virus (MLV) based pseudovirus particles. We demonstrated that NP-101, TQ, and other individual ingredients, including oleic, linoleic, and palmitic acids inhibited SARS-CoV-2 infection in the MLV-based pseudovirus model. A large, randomized phase 2 study of NP-101 is planned in outpatient COVID-19 patients.

The effect of multiple triage points on the outcomes (time and accuracy) of hospital triage during mass casualty incidents.

INTRODUCTION: During mass casualty incidents (MCIs), the accuracy and timing of the triage of patients by the emergency department (ED) triage officers are essential. The primary triage is performed at the event's location by paramedics and intends a quick evaluation of the victims. Secondary triage may be used when the transfer of the victim is delayed. In this study, we aimed to investigate the effectiveness of two-point triage in a simulated environment of an MCI in the hospital setting. MATERIALS AND METHODS: In this case-control study, we used an online test module to assess single triage points (Group 1, n = 41) and two triage points (Group 2, n = 40). 60 vignettes for Group 1 and 55 vignettes (5 deceased cases removed) for Group 2 were used. The assessment utilized clinical MCI scenarios in a scheduled online meeting by using the Simple Triage and Rapid Treatment (START) system. Triage time and accuracy of the triage, along with the experience, and previous training of the participants, were assessed. RESULTS: A total of 81 triage officers participated in this study. The participants were divided into two independent groups homogenously according to their profession and experience. Groups were comparable primarily without any statistically significant difference in terms of the profession (p = 0.101), sex (p = 0.923), and MCI experience (p = 0.785). The difference between the two groups was not significant with regard to having received practical or theoretical triage training (p = 0.099). The mean time of a single vignette triage was 19.2 (SD 6.5) seconds and mean percentage of correct triage score was 65.0 (SD 12.6). The participants had a statistically significantly better performance in the single-point triage group regarding the median triage time (p < 0.001) and median percentages of under triage (p = 0.001), but a worse median percentage of over triage (p < 0.001). However, there was no significant difference between the two groups in terms of the percentage of accurate triage. Emergency residents performed better in accuracy and triage time than their non-physician colleagues (p = 0.019). CONCLUSIONS: Two-point triage does not demonstrate better outcomes in terms of accuracy and timing. Triage officers should be trained frequently with the preferred training methodology to prevent improper triage accuracy and timing. Well-defined medical disaster planning should include frequent training of the triage officers with case scenarios.

Use of bee venom in preventive medicine: An experimental hepatic encephalopathy study in rats.

OBJECTIVES: Bee venom is used for medicinal purposes, including the treatment of neurological and liver diseases, but its use as a primary health care approach for preventive purposes requires further exploration. The aim of this study was to provide the first investigation into the possible protective effects of bee venom against hepatic encephalopathy, a serious neurodegenerative disease. MATERIALS AND METHODS: An experimental animal study was conducted in which healthy albino Sprague-Dawley rats were randomized into three groups: healthy, control and bee venom groups. All rats were tested for locomotor activity at the beginning and end of the study. No intervention was made in the healthy group, whereas hepatic encephalopathy was induced in the control and bee venom groups by the administration of thioacetamide (TAA) (200 mg/kg/day). The bee venom group also received bee venom (5 mg/kg/day) subcutaneously every day for 14 days prior to the TAA administration. RESULTS: The results for the final locomotor activity tests were statistically better in the bee venom group than in the control group, supporting a beneficial effect of prophylactic bee venom application. Blood ammonia levels and liver weights, determined as indicators of inflammation, were lower in the bee venom group than in the control group and were close to levels in the healthy group, but not statistically significant. CONCLUSIONS: Bee venom administration has protective effects against the development of hepatic encephalopathy and offers a promising therapeutic opportunity in preventive medicine.