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.

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.

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.

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.

When Bladder and Brain Collide: Is There a Gender Difference in the Relationship between Urinary Incontinence, Chronic Depression, and Anxiety?

In longitudinal and cross-sectional studies, depression and anxiety have been associated with urinary incontinence (UI) in women. However, this association has not been studied in men. Utilizing data from the 2008 Turkish Health Studies Survey conducted by the Turkish Statistical Institute, we analyzed 13,830 participants aged 15 years and above. We investigated the association of UI with psychological discomfort in both sexes using multivariable logistic regression. High psychological discomfort significantly correlated with UI in males (OR 2.30, 95% CI 1.43-3.71) and females (OR 2.78, 95% CI 1.80-4.29). Anxiety increased UI likelihood in females (OR 2.36, 95% CI 1.61-3.46) and males (OR 2.37, 95% CI 1.10-5.13). Depression related significantly to UI in females (OR 2.54, 95% CI 1.81-3.58) but not males (OR 1.63, 95% CI 0.71-3.76). Antidepressant and anxiolytic use was not significantly related to UI in either gender. Anxiety and psychological discomfort contribute to UI in both genders. While depression significantly correlates with UI in females, it does not show the same magnitude and significance in males. Antidepressant and anxiolytic use did not significantly influence the association. These findings underscore the psychological distress-UI link, advocating a holistic approach for managing UI in individuals with mental health conditions.

Is the Prognostic Nutritional Index a Prognostic Marker for the Survival of Patients with Lymph-Node Positive Stage II-III Gastric Cancer Who Receive Adjuvant Chemotherapy?

PURPOSE: The prognostic nutritional index (PNI), like other systemic inflammatory markers, has been shown to be a prognostic factor in various cancer patients. In this study, we aimed to show whether PNI calculated before adjuvant chemotherapy is a prognostic factor for overall survival (OS) and disease-free survival (DFS) in patients with lymph node-positive stage II-III gastric cancer. METHODS: The PNI was calculated using the albumin and lymphocyte count. The PNI cut-off value was found to be 39.5. They were divided into two groups as being ≤ 39.5 (PNI low group) and > 39.5 (PNI high group). RESULTS: Our study included 168 patients with lymph node-positive stage II-III gastric cancer who received adjuvant chemotherapy. Of the patients, 116 (69.0%) were 65 years or younger, and 52 (31.0%) were over 65 years old. Of the patients, 117 (69.6%) were pT3, 51 (30.4%) were pT4. Seventy-three (43.4%) patients had pN1-2 disease and 95 (56.6%) patients had pN3 disease. The number of stage II patients was 73 (43.5%) and the number of stage III patients was 95 (56.5%). There were 73 patients with PNI ≤ 39.5 and 95 patients with PNI > 39.5. The mOS of the patients with low PNI group was 39.5 months, while the OS of the patients with high PNI group was 96.8 months (p = 0.002). In the group of patients with PNI low group, mDFS 24.4 months was significantly higher than those with PNI high group was 50.7 months (p = 0.021). The PNI score was statistically significant in univariate and multivariate analyzes for both DFS and OS. CONCLUSION: PNI can be used as an independent prognostic factor for both OS and DFS in patients lymph node-positive, stage II-III gastric cancer who will receive adjuvant chemotherapy.

Evaluation of the relationship among gene expressions and enzyme activities with antioxidant role and presenilin 1 expression in Alzheimer's disease.

It is known that oxidative stress originating from reactive oxygen species plays a role in the pathogenesis of Alzheimer's disease. In this study, the role of antioxidant status associated with oxidative stress in Alzheimer's disease was investigated. Peripheral blood samples were obtained from 28 healthy individuals (as control) and 28 Alzheimer's patients who met the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria. Catalase, glutathione S-transferase and paraoxonase 1 enzyme activities in blood plasma and glutathione S-transferase enzyme activities in erythrocytes were determined by spectrophotometer. Catalase, glutathione S-transferase and presenilin 1 gene expressions in leukocytes were determined using qRT-PCR. Data were analysed with SPSS one-way anova, a LSD post hoc test at p < 0.05. The activity of each enzyme was significantly reduced in Alzheimer's patients compared to control. The catalase gene expression level did not change compared to the control. Glutathione S-transferase and presenilin 1 gene expression levels were increased compared to the control.

PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study.

INTRODUCTION: In this study, the toxicities and management of palbociclib and ribociclib in older patients (≥65 years) with metastatic breast cancer patients were investigated. MATERIALS AND METHODS: Among older patients receiving palbociclib and ribociclib, Geriatric 8 (G8) and Groningen Frailty Index were used to evaluate frailty status. Dose modifications, drug withdrawal and other serious adverse events (SAEs) were recorded and analyzed according to baseline patient characteristics. RESULTS: A total of 160 patients from 28 centers in Turkey were included (palbociclib = 76, ribociclib = 84). Forty-three patients were ≥ 75 years of age. The most common cause of first dose modification was neutropenia for both drugs (97% palbociclib, 69% ribociclib). Liver function tests elevation (10%) and renal function impairment (6%) were also causes for ribociclib dose modification. Drug withdrawal rate was 3.9% for palbociclib and 6% for ribociclib. SAEs were seen in 11.8% of those taking palbociclib and 15.5% of those on riboclib. An ECOG performance status of ≥2 and being older than 75 years were associated with dose reductions. Severe neutropenia was more common in patients with non-bone-only metastatic disease, those receiving treatment third-line therapy or higher, coexistance of non-neutropenic hematological side effects (for ribociclib). Neutropenia was less common among patients with obesity. DISCUSSION: Our results show that it can be reasonable to start palbociclib and ribociclib at reduced dose in patients aged ≥75 years and/or with an ECOG performance status ≥2.

Active shrinkage protects neurons following axonal transection.

Trauma, vascular events, or neurodegenerative processes can lead to axonal injury and eventual transection (axotomy). Neurons can survive axotomy, yet the underlying mechanisms are not fully understood. Excessive water entry into injured neurons poses a particular risk due to swelling and subsequent death. Using in vitro and in vivo neurotrauma model systems based on laser transection and surgical nerve cut, we demonstrated that axotomy triggers actomyosin contraction coupled with calpain activity. As a consequence, neurons shrink acutely to force water out through aquaporin channels preventing swelling and bursting. Inhibiting shrinkage increased the probability of neuronal cell death by about 3-fold. These studies reveal a previously unrecognized cytoprotective response mechanism to neurotrauma and offer a fresh perspective on pathophysiological processes in the nervous system.

Nationwide analysis of unplanned conversion during minimally invasive distal pancreatectomy for pancreatic adenocarcinoma.

BACKGROUND: Utilization of minimally-invasive distal pancreatectomy (MIDP) for pancreatic adenocarcinoma has increased. While unplanned conversion to an open procedure during MIDP is associated with inferior short-term outcomes, the long-term consequences of conversion have not been adequately examined. METHODS: Patients with pancreatic adenocarcinoma undergoing MIDP were selected from the National Cancer Database (2010-2015) and subdivided based on the occurrence of unplanned conversion. Post-operative outcomes and overall survival (OS) were examined. Conversion was additionally compared to a matched group of planned open resections. RESULTS: Among 592 patients undergoing attempted MIDP, unplanned conversion occurred in 23.1%. Despite increased 90-day mortality among patients experiencing conversion, there was no difference in median OS between groups (25.0 vs 27.8 months, p = 0.095). For patients undergoing conversion, post-operative outcomes and long-term survival were similar when compared to a propensity-matched group of patients undergoing planned open resection. On multivariable analysis, treatment at an academic facility (OR 0.63) and a robotic approach (OR 0.50) were both significantly associated with completed MIDP. CONCLUSION: Despite inferior post-operative outcomes compared to successful MIDP, unplanned conversion did not result in significantly reduced long term survival. MIDP can be attempted selectively but treatment at experienced centers via a robotic approach should be considered.

Automatic Ventriculomegaly Detection in Fetal Brain MRI: A Step-by-Step Deep Learning Model for Novel 2D-3D Linear Measurements.

In this study, we developed an automated workflow using a deep learning model (DL) to measure the lateral ventricle linearly in fetal brain MRI, which are subsequently classified into normal or ventriculomegaly, defined as a diameter wider than 10 mm at the level of the thalamus and choroid plexus. To accomplish this, we first trained a UNet-based deep learning model to segment the brain of a fetus into seven different tissue categories using a public dataset (FeTA 2022) consisting of fetal T2-weighted images. Then, an automatic workflow was developed to perform lateral ventricle measurement at the level of the thalamus and choroid plexus. The test dataset included 22 cases of normal and abnormal T2-weighted fetal brain MRIs. Measurements performed by our AI model were compared with manual measurements performed by a general radiologist and a neuroradiologist. The AI model correctly classified 95% of fetal brain MRI cases into normal or ventriculomegaly. It could measure the lateral ventricle diameter in 95% of cases with less than a 1.7 mm error. The average difference between measurements was 0.90 mm in AI vs. general radiologists and 0.82 mm in AI vs. neuroradiologists, which are comparable to the difference between the two radiologists, 0.51 mm. In addition, the AI model also enabled the researchers to create 3D-reconstructed images, which better represent real anatomy than 2D images. When a manual measurement is performed, it could also provide both the right and left ventricles in just one cut, instead of two. The measurement difference between the general radiologist and the algorithm (p = 0.9827), and between the neuroradiologist and the algorithm (p = 0.2378), was not statistically significant. In contrast, the difference between general radiologists vs. neuroradiologists was statistically significant (p = 0.0043). To the best of our knowledge, this is the first study that performs 2D linear measurement of ventriculomegaly with a 3D model based on an artificial intelligence approach. The paper presents a step-by-step approach for designing an AI model based on several radiological criteria. Overall, this study showed that AI can automatically calculate the lateral ventricle in fetal brain MRIs and accurately classify them as abnormal or normal.

Low-dose (7.5 mg/kg) bevacizumab may be a viable option in recurrent ovarian cancer: A retrospective study.

Objective: Bevacizumab (BEV) is a humanized monoclonal antibody of vascular endothelial growth factor receptors and, as a result of clinical trials, was approved for the treatment of recurrent ovarian cancer (ROC). The aim of this study was to assess the clinical utility of BEV in patients with ROC in real-world practice beyond clinical trials. Materials and Methods: In this single-center retrospective cohort study, we evaluated the medical data of all patients with ROC who were treated with BEV between October 2013 and March 2020. Results: A total of 76 females were evaluated. Forty-nine (64.5%) patients were platinum sensitive and 27 (35.5%) patients were platinum resistant. BEV was used in combination with chemotherapy agents in all patients, and the most preferred combinations were gemcitabine/carboplatin (GC) (78.9%) and carboplatin/paclitaxel (14.5%). In all patients, the BEV dose was 7.5 mg/kg every 3 weeks. The median progression-free survival (PFS) was 11.1 months (95% confidence interval [CI]: 9.6-12.6), and the median overall survival (OS) was 22.3 months (95% CI: 17.5-27.2). In multivariate analysis, serous histological type (P = 0.01), maintenance BEV administration (P = 0.001), and combination of GC-BEV (P < 0.001) were associated with better PFS, while serous histological type (P = 0.016) and good performance status (P = 0.006) were associated with prolonged OS. Conclusions: Low-dose (7.5 mg/kg) BEV was found to be effective in the second-line treatment of patients with ROC in our real-life study. In addition, the combination of BEV with GC was shown to be a viable option, especially in the treatment selection of platinum-resistant patients.

Sunitinib-induced small bowel wall edema as a prognostic marker in metastatic renal cell carcinoma.

Aim: The aim of this study was to evaluate the presence of small bowel wall edema (SBWE) on computed tomography (CT) images in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib and to investigate the relationship between the presence of SBWE and survival. Materials and Methods: We retrospectively evaluated the presence of SBWE on CT images of 27 mRCC patients who received at least one cycle of sunitinib. Then, we analyzed the relationship between the presence of SBWE and progression-free survival (PFS) and overall survival (OS). RESULTS: All 27 patients had SBWE on at least one CT scan. The median value of SBWE thickness was 2.5 mm. SBWE thickness was ≤2.5 mm in 13 patients (group A) and >2.5 mm in 14 patients (group B). The median OS was significantly higher in group B (55 vs. 18 months, respectively, P = 0.02). Although it was not statistically significant (13 vs. 8 months, respectively, P = 0.69), the median PFS was longer in group B than in group A. CONCLUSIONS: This study showed that sunitinib treatment caused SBWE in all patients with mRCC who received the drug. Also, this study demonstrated an association between higher SBWE thickness and better survival outcomes.

Review of deep learning and artificial intelligence models in fetal brain magnetic resonance imaging.

Central nervous system abnormalities in fetuses are fairly common, happening in 0.1% to 0.2% of live births and in 3% to 6% of stillbirths. So initial detection and categorization of fetal Brain abnormalities are critical. Manually detecting and segmenting fetal brain magnetic resonance imaging (MRI) could be time-consuming, and susceptible to interpreter experience. Artificial intelligence (AI) algorithms and machine learning approaches have a high potential for assisting in the early detection of these problems, improving the diagnosis process and follow-up procedures. The use of AI and machine learning techniques in fetal brain MRI was the subject of this narrative review paper. Using AI, anatomic fetal brain MRI processing has investigated models to predict specific landmarks and segmentation automatically. All gestation age weeks (17-38 wk) and different AI models (mainly Convolutional Neural Network and U-Net) have been used. Some models' accuracy achieved 95% and more. AI could help preprocess and post-process fetal images and reconstruct images. Also, AI can be used for gestational age prediction (with one-week accuracy), fetal brain extraction, fetal brain segmentation, and placenta detection. Some fetal brain linear measurements, such as Cerebral and Bone Biparietal Diameter, have been suggested. Classification of brain pathology was studied using diagonal quadratic discriminates analysis, K-nearest neighbor, random forest, naive Bayes, and radial basis function neural network classifiers. Deep learning methods will become more powerful as more large-scale, labeled datasets become available. Having shared fetal brain MRI datasets is crucial because there aren not many fetal brain pictures available. Also, physicians should be aware of AI's function in fetal brain MRI, particularly neuroradiologists, general radiologists, and perinatologists.

Does red blood cell distribution width predict prognosis in metastatic renal cell carcinoma patients using first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy?

Aim: It is red cell distribution width (RDW) that has been reported to show an inflammatory response which has been studied recently. The aim of this study is to investigate whether the pre-treatment RDW in patients using first-line vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI) with the diagnosis of metastatic renal cell carcinoma (mRCC) predicts treatment response and is a prognostic factor or not. Methods: About 92 patients diagnosed with mRCC who were being treated with sunitinib or pazopanib in the first line between January 2015 and June 2021 were included in the study. The patients were divided into 2 groups, as being ≤15.3 and >15.3, according to the RDW cut-off value calculated by ROC analysis. Results: The mOS of patients with a RDW of ≤15.3% was 45.0 (30.0-59.9) months, and of 21.3 (10.4-32.2) in those with a RDW of >15.3%. This difference was statistically significant (p < 0.001). In the group of patients with a RDW of ≤15.3, median progression free survival (mPFS) (38.04 [16.3-59.7] months) was found to be significantly higher than those with a RDW of >15.3 (17.1 [11.8-22.5] months) (p = 0.04). In multivariate analysis, RDW level (≤15.3, >15.3), was determined to be prognostic markers (p = 0.022). Conclusion: In mRCC patients, the RDW value measured before first-line VEGFR TKI therapy is an independent prognostic marker.

Thrombectomy with or without Bridging Thrombolysis for Anterior Circulation Stroke.

Background: Currently, there is still no clear consensus on bridging thrombolysis (BT) before mechanical thrombectomy (MT). In this study, we aimed to compare clinical and procedural outcomes and complication rates of BT versus direct mechanical thrombectomy (d-MT) in anterior circulation stroke. Methods: A total of 359 consecutive anterior circulation stroke patients who received d-MT or BT in our tertiary stroke center between January 2018 and December 2020 were retrospectively analyzed. The patients were divided into two groups as Group d-MT (n = 210) and Group BT (n = 149). The primary outcome was the impact of BT on clinical and procedural outcomes, whereas the secondary outcome was the safety of BT. Results: The incidence of atrial fibrillation was higher in the d-MT group (p = 0.010). The median duration of the procedure was significantly higher in Group d-MT than in Group BT (35 vs 27 min, respectively; P = 0.044). The number of patients achieving good and excellent outcomes was significantly higher in Group BT (p = 0.006 and P = 0.03). The edema/malign infarction rate was higher in the d-MT group (p = 0.003). Successful reperfusion, first-pass effects, symptomatic intra-cranial hemorrhage, and mortality rates were similar between the groups (p > 0.05). Conclusions: In this study, BT seems to yield better clinical and procedural outcomes with lower complication rates than d-MT. These findings may support the additional value of intravenous alteplase in anterior system strokes. Further large-scale, prospective, randomized-controlled studies will clarify the gray lines in this consensus, but this paper is important for reflecting the real-world data in developing countries.

The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers.

PURPOSE: It is known that the RAS and BRAF mutations are predictive for targeted therapies in treating metastatic colon cancer and negatively affect the prognosis of the disease. However, there are limited studies in early-stage colon cancer about the relationship of this mutational condition with the prognosis and relapse pattern of the disease. In this study, we evaluated the effects of mutational status on the clinical pattern of recurrence and survival in early-stage colon cancer in addition to classical risk factors. METHODS: Patients with early-stage colon cancer at the first time of diagnosis and developing recurrence or metastasis on following up were included in this study. Patients were divided into two groups according to the at the time of relapse RAS/BRAF mutation status: mutant or non-mutant/wild types. Then, mutation analysis was performed again from the early-stage tissue of the patients if available. The relationship between early-stage mutation status and progression-free survival (PFS), overall survival (OS), and relapse pattern was analyzed. RESULTS: The number of patients with mutant and non-mutations in the early stage was 39 and 40, respectively. Mutant and non-mutant patients with stage 3 disease were similar (69% and 70%, respectively). OS (47.27 months vs. 67.53 months; p = 0.02) and PFS (25.12 vs. 38.13 months; p = 0.049) were statistically significantly lower in mutant patients, respectively. Most patients had distant metastases on both sides at recurrence (61.5% vs. 62.5%, respectively). There was no significant difference between mutant and non-mutant patients regarding distant metastasis and local recurrence rates (p = 0.657). A discordance of 11.4% between early-stage and late-stage tissue mutation status. CONCLUSION: The presence of mutation in early-stage colon cancer is associated with shorter OS and PFS. The mutational status did not have a significant effect on the recurrence pattern. Because of the discordance of early-stage and late-stage mutational status, it is recommended to perform mutation analysis from tissue at relapse.