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The aim of this paper is to familiarize readers with several telematic systems that may be observed on the Czech railway network. In order to function correctly, they use special technical devices for detecting positions of trains and their tracking. In the introductory part, a brief overview of individual ways of train detecting and tracking in the Czech Republic is given, which is then followed by a detailed description of the related telematic systems, including the principles of their functioning and graphic presentation of their practical use. The paper also contains demonstrative photo documentation and schematic illustrations of principles of functioning of the discussed systems.

Genetic testing for breast cancer susceptibility genes (BRCA1/2) plays a pivotal role in risk assessment and preventive interventions. However, individuals' awareness, knowledge, and attitudes toward genetic testing can vary across different societies. This study focuses on understanding Turkish women's knowledge, perceptions, and attitudes toward BRCA1/2 testing, considering demographic factors and awareness. In this cross-sectional study, 301 Turkish participants, including breast/ovarian cancer patients and their first-degree relatives, were surveyed. Information on sociodemographics, cancer history, awareness, knowledge, and perceptions was collected. The study aimed to assess knowledge levels about breast cancer inheritance and BRCA1/2 testing, describe perspectives about testing in women with a family history of breast or ovarian cancer, and determine associations between knowledge, personal factors, anxiety, and genetic testing perspectives. Results showed a wide range in correct responses (31.6%-96.7%) for knowledge items. No significant relationship between knowledge levels and positive perception was observed. However, participants answering a specific question incorrectly showed higher negative perceptions. While most participants recognized the benefits of genetic testing, concerns centered around passing the genes to future generations. Participants who were younger, more educated, had higher income, were employed, at an earlier disease stage, and were social media users demonstrated more positive attitudes. Negative perceptions were higher among younger patients, physicians, and healthcare professionals. Interestingly, anxiety in cancer patients did not correlate with either positive or negative perceptions. In conclusion, this study identifies participant-related factors influencing perceptions of hereditary genetic tests. Understanding these factors and addressing associated issues can enhance the utilization of genetic testing and promote preventive oncology applications., (© 2024 National Society of Genetic Counselors.)

Objective: This study aimed to investigate the impact of analyzing somatic alterations using next-generation sequencing (NGS) on treatment management in patients with metastatic solid cancers and their ability to access NGS recommended treatments., Methods: This retrospective study included eligible patients who underwent NGS on somatic tumor tissue. We examined the clinical and pathological characteristics of these patients and the alterations in their treatment following NGS results., Results: A total of 101 patients who underwent NGS were included in the study. The most common cancers were non-small cell lung cancer (NSCLC), colorectal, and breast cancers, in that order. The median age was 58 (range 21-82) years, with 60 (59.4%) male participants. The median NGS turnaround time was 23 (range 17-29) days. NGS was performed on tissue from the primary lesion in 89(88%) patients. Predictive, prognostic, actionable, or variants of unknown significance were detected in 62(61.4%) patients. The most frequent variants identified were KRAS, EGFR, TP53, PIK3CA , and other rare mutations. Treatment was altered in 17(16.8%) patients based on NGS results. Of the 30 (29.7%) patients for whom NGS-informed treatment was recommended, only seven (6.9%) received the recommended therapy. There was no significant difference in overall survival (OS) between patients whose treatment was changed based on NGS results and those whose treatment remained unchanged (p = 0.897). There was no difference in OS between patients with and without variants (p = 0.384)., Conclusions: NGS analysis of somatic alterations in patients with metastatic cancer may reveal additional variants beyond those identified by baseline tests. However, based on the recommendations of the reimbursement institution in Turkey, only a limited number of patients are able to access treatments recommended by NGS results. Therefore, baseline tests established in Turkey need to be made available in more centers in an appropriate time., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for assessing axillary lymph node status in clinically node-negative breast cancer patients. However, the approach to axillary surgery after neoadjuvant treatment is still controversial. In the present study, our objective was to predict the pathological nodal stage based on SLNB results and the clinicopathological characteristics of patients who initially presented with clinical N1 positivity but whose disease status was converted to clinical N0 after neoadjuvant chemotherapy (NAC)., Materials and Methods: After NAC, 150 clinically node-negative patients were included. The relationships between clinicopathologic parameters and the number of positive lymph nodes in SLNBs and ALNDs were assessed through binary/multivariate logistic regression analysis., Results: Among 150 patients, 78 patients had negative SLNBs, and 72 patients had positive SLNBs. According to the ALND data of 21 patients with SLNB1+, there was no additional node involvement (80.8%), 1-2 lymph nodes were positive in 5 patients (19.2%), and no patient had ≥ 3 lymph nodes involved. Following the detection of SLNB1 + positivity, the rate of negative non-sentinel nodes were 75% in the luminal A/B subgroup, 100% in the HER-2-positive subgroup, and 100% in the triple-negative subgroup. Patients with a lower T stage (T1-3 vs. T4), fewer than 4 clinical nodes before NAC (< 4 vs. ≥4), and a decreased postoperative Ki-67 index (< 10% vs. stable/increase) were included. According to both univariate and multivariate analyses, being in the triple-negative or HER2-positive subgroup, compared to the luminal A/B subgroup (luminal A/B vs. HER2-positive/triple-negative), was found to be predictive of complete lymph node response., Conclusion: The number of SLNB-positive nodes, tumor-related parameters, and response to treatment may predict no additional nodes to be positive at ALND., (© 2024. The Author(s).)

Accurate staging of invasive lobular carcinoma (ILC), a subtype of breast cancer, is vital for effective clinical management. Although 18 F-FDG PET/CT is a commonly used tool, its efficacy varies across different histologic subtypes. To mitigate this challenge, our investigation delves into the potential utility of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT as an alternative for staging ILC, aiming to address a significant research gap using a more expansive patient cohort than the smaller samples commonly found in the existing literature. Methods: In this retrospective analysis, women diagnosed with primary ILC of the breast underwent both 18 F-FDG PET/CT and 68 Ga-FAPI PET/CT. Both modalities were compared across all lesion locations with the used reference standard. The interval between scans was 1 wk, without any intervening treatments. Lesions were categorized visually, and tracer activity was analyzed using SUV max , tumor-to-background uptake ratio, and uptake ratios. Both modalities were compared across various parameters, and statistical analysis was performed using SPSS 22.0. A P value of less than 0.05 was chosen to determine statistical significance. Results: The study included 23 female ILC patients (mean age, 51 y) with hormone-positive, human epidermal growth factor receptor type 2-negative tumors. Most (65%) had the luminal A subtype. 68 Ga-FAPI PET/CT outperformed 18 F-FDG PET/CT, with higher tumoral activity and tumor-to-background uptake ratios ( P < 0.001). Primary tumors showed significantly increased uptake with 68 Ga-FAPI PET/CT ( P < 0.001), detecting additional foci, including multicentric cancer. Axillary lymph node metastases were more frequent and had higher uptake values with 68 Ga-FAPI PET/CT ( P = 0.012). Moreover, 68 Ga-FAPI PET/CT identified more lesions, including bone and liver metastases. Pathologic features did not significantly correlate with imaging modalities, but a positive correlation was observed between peritumoral lymphocyte ratio and 68 Ga-FAPI PET/CT-to- 18 F-FDG PET/CT uptake ratios ( P = 0.026). Conclusion: This study underscores 68 Ga-FAPI PET/CT's superiority over 18 F-FDG PET/CT for ILC. 68 Ga-FAPI PET/CT excels in detecting primary breast masses, axillary lymph nodes, and distant metastases; can complement 18 F-FDG PET/CT in ILC; and holds potential as an alternative imaging method in future studies., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

A consensus guideline, iRECIST, was developed by the Response Evaluation Criteria in Solid Tumours (RECIST) working group for the use of the modified RECIST version 1.1 in cancer immunotherapy trials. iRECIST was designed to separate pseudoprogression from real progression. However, this is not the only ambiguous situation. In clinical immunotherapy trials, stable disease may reflect three tumor responses, including real stable disease, progressive disease and responsive disease. The prediction of a " true complete/partial response" is also important. Much data has accumulated showing that ctDNA can guide decisions at this point; thus, integrating ctDNA into the RECIST 1.1 criteria may help to distinguish a true tumor response type earlier in patients treated with immunotherapy; however, prospectively designed validation studies are needed.

The incorporation of sex and gender variables in medical education can be made more intuitive and accurate with thoughtful intervention. The authors propose a flowchart to make medical education tools more precise and applicable to patients who would benefit from a nuanced approach to sex and gender. The Body Guidelines can empower educators to consider sex and gender in terms of the etiology and epidemiology of any given pathologic process or disease., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objective: We aimed to evaluate the efficacy oflutetium-177-prostate-specific membrane antigen-617 ( 177 Lu-PSMA-617) with the luteinizing hormone releasing hormone (LHRH) analogues in the first or in the second-line setting formetastatic castration sensitive patients and metastatic castration resistance after progression with LHRH analogues., Subjects and Methods: Sixteen consecutive patients with high volume metastatic prostate cancer undergone 177 Lu-PSMA-617 therapy who were refused chemotherapy and were unable to use new generation anti-androgen drugs because of unavailibility of reimbursement, were included in this retrospective study. Prostate specific antigen (PSA) response (>50% decrease), disease control rate (DCR: complete or partial response), progression-free survival (PFS) and overall survival (OS) were calculated to evaluate according to the clinicopathological features of the patients. Treatment response evaluated by 68 Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT)., Results: Mean age was 74,6 (SD±8,36). Among them, 7 (43,8%) patients has castration resistant disease, while the remaining has castration sensitive disease. Lutetium-177-PSMA-617 was administered to 10 (62,5%) patients as one of the first-line treatment and 6 patients received the treatment after progression on LHRH as a second-line treatment. Considering all patients, PSA response rate and DCR were 50% and 62% respectively. The median PFS and OS (with 95% CI) were 11,2 months (11-15) and 29 months (25,6-32,4), respectively in patients treated with 177 Lu-PSMA-617 and LHRH analogues. Clinicopathological features and basal PSA level did not have effect on PSA response rates, DCR, OS and PFS. On the other hand, increment in PFS and OS (with 95% CI) was observed in castration resistant disease and in the second-line therapy; for castration resistant disease 16,5 months (12.3-19.7); 30 months (25.3-32.7), for the second-line therapy 14.5 months (12-20.5); 29 months (NR), respectively but statistically not significant. Serious toxicity was observed in a limited number of patients (18,7%), treatment-related death was not observed., Conclusion: Favorable results can be achived with second-line 177 Lu-PSMA-617 treatment in terms of OS and PFS, especially in castration-resistant disease, when chemotherapy and new generation ADT's cannot be used.

Purpose: In this study, we aimed to investigate the utilization of 68 Ga-FAPI PET/CT in comparison to 18 FDG PET/CT to evaluate the peritoneal involvement of the gastrointestinal malignancies alongside primary lesions and other metastatic foci., Procedures: A total of 37 patients with various gastrointestinal malignancies with accompanying peritoneal involvement who underwent 68 Ga-FAPI PET/CT and 18 FDG PET/CT imaging between September 2020 and June 2021 were included in this retrospective study. SUV max values of 68 Ga-FAPI and 18 FDG were compared according to lesion locations. Also, the lesion localization ability of both imaging was compared in patient basis., Results: Of the 37 patients with peritoneal involvement (23 males and 14 females; median age, 62.8 ± 12.7 years), 35.1% (n = 13) had colorectal cancer, 37.8% (n = 14) gastric cancer, and 27.0% (n = 10) pancreaticobiliary cancer. While 45.9% of them were operated, the remaining did not have surgery. The mean time interval between two studies was 3.2 days (range: 2-6 days). The mean SUV max value of peritoneal metastases (p < 0.001) was significantly higher with 68 Ga-FAPI PET/CT compared to that with 18 FDG PET/CT, as in primary lesions (p < 0.001), lymph node metastases (p = 0.006), liver metastases (p = 0.002), and bone metastases (p = 0.018). A total of 185 lesions was detected in the initial assessment with 18 FDG PET/CT. Of the total lesions detected with 18 FDG PET/CT, 5 of them were evaluated as benign lesions with 68 Ga-FAPI PET/CT also in accordance with the reference standard. In addition to 180 lesions detected with 18 FDG PET/CT, a total of 37 additional malignant lesions, 12 of which were peritoneal metastases, were detected with 68 Ga-FAPI PET/CT., Conclusion: 68 Ga-FAPI PET/CT was determined to be superior to 18 FDG PET/CT in terms of detection of peritoneal involvement with high image quality as well as primary tumor and other metastatic foci. Consequently, 68 Ga-FAPI PET/CT can be used as a complementary imaging modality especially for inconclusive 18 FDG findings due to the lack of accuracy of 18 FDG PET/CT in some of the metastatic regions, especially in the liver., (© 2022. World Molecular Imaging Society.)

Aim: Vitamin D has a role in carcinogenesis and may have effect on recurrence. Thus, we aim to analyze the prognostic effect of vitamin D levels at beginning and follow-up together with the contribution of vitamin D supplementation on patients with colorectal cancer (CRC). Materials & methods: CRC patients who underwent curative surgery were included. Patients' vitamin D values were assessed under four groups according to baseline and follow-up vitamin D values, and whether vitamin D supplementation was used. Survival distributions were compared for vitamin D groups. Results: Patients with a high follow-up vitamin D level and a high vitamin D level after supplementation presented with better disease-free survival and overall survival than patients with low vitamin D and low vitamin D levels after supplementation. Conclusion: Follow-up vitamin D values seems to be a good predictive biomarker and vitamin D supplementation may have a positive effect on survival.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3-5% of non-small-cell lung cancer (NSCLC), while it was 0.2% in NSCLC tumors. Due to its low frequency, it is extremely challenging to conduct randomized clinical trials of ALK-targeted therapies in NSCLC tumors. In the present case, we describe the first reported case of triple-negative breast cancer (TNBC) harboring the ALK fusion mutation that responded to ALK-targeted therapy after progression with two lines of chemotherapy. Searching for ALK gene rearrangement or other fusion, especially in patients with chemotherapy-resistant TNBC, opens the door to new treatment strategies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: In this study, we aimed to compare [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging to detect lesions in multiple myeloma., Methods: A total of 14 patients with multiple myeloma who underwent [68Ga]FAPI PET/CT and [18F]FDG PET/CT imaging were included in this retrospective study. SUV max values of [68Ga]FAPI and [18F]FDG were compared according to lesion locations. Also, lesion localization ability of both imaging methods was compared on the patient basis., Results: In 4 of 14 patients, [68Ga]FAPI PET/CT and [18F]FDG PET/CT have not detected any bone lesions. In 8 of the remaining 10 patients [18F]FDG PET/CT detected bone lesions but in this group, 6 patients showed more higher SUV max values than [18F]FDG PET/CT in [68Ga]FAPI PET/CT.In contrast, 2 of 8 patients showed more higher SUV max values than [68Ga]FAPI PET/CT in [18F]FDG PET/CT. Moreover, [68Ga]FAPI PET/CT detected bone lesions in two patients, which werenot detected by [18F]FDG PET/CT. Also, in five patients, [68Ga]FAPI PET/CT showed more bone lesions in comparison with[18F]FDG PET/CT. Only one patient, [18F]FDG PET/CT showed more bone lesions. Three extramedullary involvements were observed in the following locations: lung, presacral lymph node, and soft tissue mass lateral to the right maxillary sinus. Among these involvements, higher SUV max values were observed in the lung and presacral lymph node with [68Ga]FAPI compared to [18F]FDG. However, the soft tissue mass showed a higher SUV max value in [18F]FDG than [68Ga]FAPI., Conclusions: No significant superiority was observed in [68Ga]FAPI PET/CT over [18F]FDG PET/CT in patients with MM. However, [68Ga]FAPI PET/CT can be utilized as a complementary imaging method to [18F]FDG PET/CT in some settings, especially in low-[18F]FDG affinity and inconclusive cases. Considering the favorable aspects of [68Ga]FAPI PET/CT in MM, such as low background activity, absence of non-specific bone marrow, and physiological brain involvement, further studies with a larger sample size should be conducted.

Purpose: We compared the ability of 68 Ga-FAPI PET//CT with 18 FDG PET/CT imaging techniques to detect additional lesions in breast cancer patients that may affect further chemotherapy options., Methods: A total of 48 patients with breast cancer underwent concurrent 68 Ga-FAPI-04 and 18 FDG PET/CT regardless of whether they had received chemotherapy or not in the last month before imaging. Both modalities were compared according to various parameters: clinical/pathological features, number of lesions detected, activity uptake (SUV max ), and the effect on the evaluation of response to treatment in the post-chemotherapy group., Results: This retrospective study included 48 patients with breast cancer (mean age 53.3 ± 11.7 years; IDC 89.6%; ILC 10.4%). In the comparison of both modalities, no statistical significance was obtained in terms of the pathological characteristics of the patients. More lesions were demonstrated in all categorized regions in 68 Ga-FAPI PET/CT imaging with higher uptake values compared to 18 FDG PET/CT in this study. In the treatment response evaluation of the post-chemotherapy group, 12 cases (12/24) who were evaluated as PMR, CMR, or SD according to 18 FDG PET/CT results were later accepted as PD due to newly detected lesions in complementary 68 Ga-FAPI PET/CT imaging and treatment of patients was managed accordingly by clinicians., Conclusion: It was determined that 68 Ga-FAPI PET/CT was superior to 18 FDG PET/CT in terms of accuracy and it was thought that 68 Ga-FAPI PET/CT could be utilized as an additional complementary imaging to 18 FDG PET/CT. Moreover, 68 Ga-FAPI PET/CT, with its significant theranostic potential, could become a key element in predicting the pathological response of breast cancer patients in further researches., (© 2021. The Japanese Society of Nuclear Medicine.)

Background: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope., Objective: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions., Design: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481)., Setting: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom., Patients: Patients with recurrent vasovagal syncope and no serious comorbid conditions., Intervention: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months., Measurements: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up., Results: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups., Limitation: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center., Conclusion: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden., Primary Funding Source: The Canadian Institutes of Health Research.

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.

Purpose: The peritoneum is the common recurrence site of gastric cancer (GC) presenting with worse survival. Although some predictive clinicopathological factors have been identified, there is no comprehensive assessment of peritoneal recurrence risk prediction for patients treated with adjuvant chemotherapy (CR) or chemoradiotherapy (CRT) after surgery. We aimed to predict peritoneal recurrence and develop a new scoring model in GC., Methods: This retrospective study included 274 GC patients who presented with recurrence after curative gastrectomy followed by adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). Risk factors for peritoneal recurrence were analyzed using the following parameters: age, gender, tumor location and characteristics, and differences between treatment modalities. All parameters were assessed by binary logistic regression analysis to compare the patients with and without peritoneal recurrence. Then, a new risk scoring model was developed., Results: Peritoneal recurrence was observed in 115 (44.1%) patients. Peritoneal recurrence was higher in female gender (odds ratio (OR), 1.93; 1.07-3.49, P = 0.030, 1 point), T4a-b stage (OR, 2.47; 1.14-5.36, P = 0.022, 1 point), poor/undifferentiated (OR, 2.04; 1.31-4.06, P = 0.004, 1 point), and signet cell carcinoma (OR, 2.04; 1.04-4.02, P = 0.038, 1 point) after adjusted for resection and dissection types. The risk scoring model was developed using the related parameters: Peritoneal recurrence rates were 24.6%, 42.6%, and 71.4% for group 1 (0 point), group 2 (1-2 points), and group 3 (3-4 points), respectively., Conclusion: Female gender, T4 tumor stage, undifferentiated histopathology, and signet cell type had a tendency to peritoneal recurrence after adjusted for treatment modalities. Patients with 3 or 4 risk factors had an 8.8-fold increased risk for the development of peritoneal recurrence.

Chemotherapy-induced nausea and vomiting (CINV) may be linked to the psychological status of cancer patients. Therefore, the authors aimed to better understand the underlying risk factors for CINV using the Brief Illness Perception Questionnaire. A total of 238 patients were recruited during three cycles of chemotherapy. Patient, disease and treatment characteristics were noted at the onset of chemotherapy. The Brief Illness Perception Questionnaire was administered face-to-face prior to chemotherapy. The relationship between illness perceptions and CINV was analyzed using Spearman's rank correlation. Positive illness perception parameters, including personal and treatment control, were negatively correlated, whereas negative illness perception parameters, including consequences, timeline, identity, concern and emotions, were positively correlated with CINV after adjusting for age, sex and emetogenic potential of chemotherapy (p < 0.001). Illness perception may be an underlying risk factor for CINV.

Introduction: Mobile Stroke Units (MSUs) deliver acute stroke treatment on-scene in coordination with Emergency Medical Services (EMS). One criticism of the MSU approach is the limited range of a single MSU. The Houston MSU is evaluating MSU implementation, and we developed a rendezvous approach as an innovative solution to expand the range and number of patients treated., Methods: In addition to direct 911 dispatch of our MSU to the scene within our 7-mile catchment area, we empowered more distant EMS units to activate the MSU. We also monitored EMS radio communications to identify possible patients. For these distant patients, the MSU met the EMS unit en route to the stroke center and treated the patient at that intermediate location. The distribution of the distance from MSU base station to site of stroke and time from 911 alert to tissue plasminogen activator (tPA) bolus were compared between patients treated on-scene and by rendezvous using Wilcoxon rank sum test., Results: Over 4 years, 338 acute ischemic stroke patients were treated with tPA on our MSU. Of these, 169 (50%) were treated on-scene after MSU dispatch at a median of 6.4 miles (IQR 6.4 miles) from MSU base station. 169 (50%) were treated by 'rendezvous' pathway with assessment and treatment of stroke a median of 12.4 miles from base (IQR 5.5 miles) (p< 0.0001). Time (min) from MSU alert to tPA bolus did not differ: 36.0 ± 10.0 for on-scene vs 37.0 ± 10.0 with rendezvous (p=0.65). 13% of patients alerted via direct 911 dispatch were treated vs 44% of rendezvous patients., Conclusion: Adding a rendezvous approach to an MSU dispatch pathway doubles the range of operations and the number of patients treated by an MSU in an urban area, without incurring delay., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Grotta and Ms Parker receiving consulting fees from Frazer Ltd, a manufacturer or Mobile Stroke Units. Dr Grotta receives research support from the Patient Centered Outcomes Research Institute, Genentech, and CSL Behring, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Nivolumab is a human IgG4 programmed death-1 immune checkpoint inhibitor antibody. Immune-related toxicity may be associated with higher response even after interruption of nivolumab., Case Report: We reported a case diagnosed with metastatic clear cell renal cell carcinoma and treated with nivolumab as fourth-line therapy. Although nivolumab treatment was stopped after two cycles due to grade 3 renal toxicity, progression-free survival rates of 11 months, that is quite a long time for fourth-line treatment of renal cell carcinoma was observed., Management and Outcome: Therefore, we speculate that when renal toxicity develops, response may continue even after interruption of nivolumab in renal cell carcinoma., Discussion: Nivolumab was approved to be used for second-line treatment of renal cell carcinoma with 4.6 months of median progression-free survival benefit. Higher immune-related toxicity can produce higher efficacy for some instances such as malignant melanoma, lung cancer, and renal cell carcinoma. Renal disturbance during nivolumab treatment is extremely rare, and there are no data on survival after interruption due to renal toxicity of nivolumab without further treatment in renal cell carcinoma. In the present case, we obtained long duration of stable disease, with two cycles of nivolumab after the development of nephrotoxicity. Close follow-up without any treatment until progression may be a treatment choice, because nephrotoxicity can be a sign of benefit and durable response to nivolumab.

Aim: We aimed to investigate the impact of hepatosteatosis (HS) severity on the recurrence pattern of breast cancer and to clarify whether HS causes affinity to recurrence with liver metastasis. Materials & methods: The median follow-up was 80.0 (4-217) months and the mean age was 47.9 ± 11.3 years. Among all, 181 (39.9%) patients were diagnosed with grades 2 and 3 HS. Of total, 158 (34.8%) patients have experienced recurrence. Results: While higher degree of HS was more common in patients presented with liver recurrence (odds ratio; 95% CI: 2.50; 1.27-4.92; p = 0.007), it was lesser in those with other metastatic sites (all were >0.05). Liver-recurrence-free survival was significantly worse in the group with higher degree of HS (hazard ratio; 95% CI: 2.46; 1.4-4.3; p = 0.002) together with younger age (hazard ratio; 95% CI: 2.44; 1.4-4.3; p = 0.002) in multivariate analysis. Conclusion: HS might have produced an affinity for liver metastasis in common types of breast cancer patients in remission independent from metabolic disorders or clinicopathologic features.

Aim: The positive energy balance and insulin resistance caused by weight gain, physical inactivity, poor dietary quality are linked to a decreased breast cancer (BC)-specific survival. The aim of the present study was to assess whether or not hepatosteatosis, which reflect underlying insulin resistance, has a predictive value on recurrence in patients with nonmetastatic BC., Material Method: All diagnosed nonmetastatic BC patients between 2005 and 2016 were included in this retrospective analysis. Patients' medical characteristics included for analysis were age, menopausal status, presence of obesity, diabetes, dyslipidemia, and tumor features. Liver parenchyma was evaluated by ultrasonography, and then patients divided into 2 groups according to final follow-up findings; group 1: without hepatosteatosis or presence of grade 1 steatosis; group 2: presence of grades 2 and 3 hepatosteatosis. Survival distributions were estimated with the Kaplan-Meier method and compared between groups with the log-rank statistic., Results: Four hundred twenty-four patients included in this study. The median follow-up period of all patients was 6.7 years (range, 0.6-13 years). The mean age was 48.2 ± 0.5 years. Of total, 154 (36.3%) patients experienced recurrence. In total, 171 (40.6%) patients had grades 2 and 3 hepatosteatosis, and the remaining had no, or grade 1 hepatosteatosis during last follow-up or at recurrence. The clinicopathologic characteristics of the participants were well balanced between the 2 groups. Younger age (odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.3-3.8, P = 0.005), and higher tumor stage (OR: 7.52; 95% CI: 1.2-48.5, P = 0.035 for stage Ia vs stage IIIC) were associated with recurrence of BC during the entire follow-up in multivariate analysis. Hepatosteatosis predicted late recurrence after 5 years in nonmetastatic BC after adjusted for age, diabetes, tumor stage, grade, and luminal type (OR: 2.45; 95% CI: 1.1-5.6, P = 0.034) and the hazard ratio was 0.40 (95% CI: 0.18-0.88, P = 0.023 adjusted value) for relapse-free survival after 5 years., Conclusion: Higher degree of hepatosteatosis may predict recurrence after 5 years in BC survivors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope., Methods and Results: Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72)., Conclusion: Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: Mobile stroke units offer improved time to administration of thrombolytics for ischemic stroke patients. Acquisition of intravenous (IV) access, however, can be challenging in the prehospital environment leading to treatment delays. Intraosseous (IO) access is commonly used in the prehospital setting for a variety of conditions and may serve as a viable means for tPA (tissue plasminogen activator) administration. Methods/Results: We describe 3 cases in which tPA was administered via IO access on a mobile stroke unit as part of the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services (BEST-MSU) trial. Conclusion: No adverse events were observed in the process of obtaining IO access or administering tPA.

Extrahepatic cholangiocarcinoma (ECC) is an aggressive malignancy causing a lot of fatalities and comorbidities. Endoscopic biliary stenting (EBS) is mostly needed for ECC. In this study, we aimed to investigate the prognostic factors for the overall survival (OS) and the factors predicting the patients eligible for chemotherapy after EBS in ECC.We retrospectively screened 153 advanced ECC patients who underwent EBS for jaundice to make the patients eligible for chemotherapy. Patient's clinical and laboratory parameters were recorded. OS was estimated by the Kaplan-Meier method. All parameters were assessed by binary logistic regression analysis to predict which patients are eligible for chemotherapy.The median OS of all patients was 12.0 months (10.1-13.8). The median OS of the patients treated with chemotherapy was 13.0 months (12.0-14.0), while it was 4.0 months (2.3-5.7) for patients unable for chemotherapy after EBS. Albumin, aspartate aminotransferase (ALT) and carbohydrate antigen 19-9 (CA 19-9) values were independent prognostic factors for OS. Higher albumin and lower prothrombin time (PT) levels were independent parameters to predict the patients eligible for chemotherapy after EBS.Being suitable for chemotherapy was the main determinant for prolonged survival and albumin and PT levels were independent predictors for chemotherapy eligibility after EBS. Albumin, ALT, and CA 19-9 values were independent prognostic factors for OS in ECC.

Background: Many diagnostic criteria for the differential diagnosis of wide complex tachycardia (WCT) are complex and not completely accurate. Incorrect diagnosis is also related to error in applying criteria., Objectives: To propose a novel reliable criterion for wide QRS complexes' differential diagnosis., Material and Methods: One hundred Electrocardiograms (ECGs) with wide QRS complexes were analyzed using the ECG software. Five variables were measured during the first 20 ms of QRS in leads V1 and V2 and compared between premature ventricular contraction (PVC) and conducted supraventricular impulse with bundle branch block (BBB) groups. The best discriminant variable was identified. The validity of this variable was tested on a group of 20 patients who had WCT during an electrophysiology study., Results: Almost all variables were statistically different between PVC and BBB groups. The sum of voltages in absolute value of vectors during the initial 20 ms of the QRS in leads V1 and V2 (ΣV1 + V2) was the most discriminant between the two groups (131 ± 85 microvolt [μV] vs. 498 ± 392 μV, p < 0.01). A ΣV1 + V2 < 258 μV (rounded to <0.25 millivolt [mV]) diagnosed PVCs with good sensitivity and specificity (90% and 85% respectively). The ΣV1 + V2 in WCT group had lower values in VT versus supra-ventricular tachycardia (SVT) group (0.53 ± 0.35 mV vs. 1.79 ± 1.04 mV, p = 0.004)., Conclusions: The ΣV1 + V2 < 258 μV is a reliable criterion for PVC diagnosis. It could be measured accurately using ECG Software, which could be programmed to calculate it automatically, limiting the risk of human error. The ΣV1 + V2 also seems capable of discriminating between VT and SVT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neurohumoral antagonists are the foundation of heart failure therapy in patients with reduced left ventricular ejection fraction. Cardiac resynchronization therapy (CRT) has also been associated with improved outcomes in these patients. We aimed to evaluate the use of neurohumoral antagonists in patients ≥75 years compared with <75 years of age receiving CRT. We searched electronic databases, up to December 20, 2016 for all studies reporting medication use in patients ≥75 years and <75 years of age who received CRT. We used random-effects meta-analysis models to summarize the studies. We retained 12 studies (1 randomized trial and 11 observational studies) enrolling 5,728 ≥75 years old and 9,549 patients of <75 years old. There were lower use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients ≥75 years compared with patients <75 years (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.47 to 0.74, p < 0.0001). In addition, there were lower use of mineralocorticoid receptor antagonists in patients ≥75 years compared with patients <75 years (OR 0.48, 95% CI 0.40 to 0.57, p < 0.0001). The use of β blockers was nonsignificantly lower in patients ≥75 years compared with patients <75 years (OR 0.70, 95% CI 0.47 to 1.03, p = 0.07). In conclusion, neurohumoral antagonists appeared to be underused in patients ≥75 years compared with patients <75 years receiving CRT. Consideration should be given to increase neurohumoral antagonism in patients ≥75 years referred for CRT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Illness perception has been suggested to have a significant effect on anxiety and depression in cancer patients. In this cross-sectional study, we aimed to evaluate this on Turkish breast cancer patients with follow-up periods up to 12 years., Patients and Methods: A total of 225 patients (with 6 months to 12 years follow-up) were recruited in this cross-sectional study. The patients were divided into three groups of follow-up: 6 months-2 years, 2-5 years, and >5 years. Beck Depression Inventory, Beck Anxiety Inventory, Duke-University of North Carolina Functional Social Support Questionnaire, and Brief Illness Perception Questionnaire were used to assess the depression, anxiety, functional social support (FSS), and illness perception, respectively. Statistical significance of the associations was analyzed using Spearman correlation, Student's t, Mann-Whitney U, and ANOVA tests., Results: Rates of moderate-severe anxiety and depression scores were not correlated with follow-up period and disease stage, whereas all these parameters were associated significantly with FSS and age. Parameters of illness perception were also not correlated with follow-up period and stage of disease. However, illness perception scores were noticeably better with increments in FSS. Also, the parameters of illness perception were strongly associated with the depression/anxiety score., Conclusion: Illness perception is an important determinant of the depression/anxiety score in Turkish breast cancer patients.

Purpose: The aim of this retrospective study was to compare the different treatment options of patients with advanced biliary tract carcinoma (BTC) who were treated with platinum-gemcitabine (CG) or platinum-5-fluorouracil (CF) or 5-Fluorouracil-oxaliplatin-irinotecan (FOLFIRINOX) chemotherapy., Methods: We included the patients with advanced BTC who were registered at the Department of Oncology in Gaziantep University between January 2008 and January 2016. The following data were analyzed: disease control rate (DCR), progression free survival (PFS) of first and second-line of chemotherapy, and overall survival (OS). Kaplan-Meier method and Log-rank test was used to compare two survival curves, and hazard regression model was used to evaluate risk factors for PFS., Result: Ninety-two patients were recruited. 53 (57.6 %), 27 (29.3 %), and 12 (13 %) patients received CG, CF, and FOLFIRINOX regimen as first-line chemotherapy, respectively. Median PFS and DCR of CG group were 22 weeks and 56.6 %, and these were 12 weeks and 44.4 % for CF group, and 9 weeks and 41.7 % for FOLFIRINOX group. Median OS of CG, CF, and FOLFIRINOX groups was 28, 21,and 23.5 weeks, respectively (p = 0.497). Second-line PFS of fluoropyrimidine-based chemotherapy group and gemcitabine-based chemotherapy group was 12 vs. 14 weeks (p = 0.988). Second-line PFS of FOLFIRINOX was 20 weeks, whereas it was 14 weeks for other fuoropyrimidine-based chemotherapies (p = 0.190)., Conclusions: This was the first study evaluating the FOLFIRINOX regimen in BTC. Cisplatin-gemcitabine therapy still provides better survival in BCT. However, FOLFIRINOX can be an option in the second-line treatment of BTC patients who are eligible for chemotherapy.

Purpose: Sorafenib, a multikinase inhibitor, is effective in patients with advanced hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is an important palliative treatment for unresectable HCC, but TACE-induced ischemic injury can upregulate angiogenic factors and it might be associated with poor prognosis. The purpose of this study was to evaluate the efficacy of conventional TACE with or without sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage A-B HCC., Methods: Thirty patients with BCLC stage A or B HCC who had undergone TACE were enrolled in this retrospective study. Child-Pugh score, BCLC staging classification, size and number of lesions were recorded. Sorafenib was given 1 month after TACE to some patients who responded to TACE. Repeated TACE was performed on demand. Tumor response was assessed every 12 weeks. The primary objective of this trial was the progression free survival (PFS). Secondary objectives were overall survival (OS), disease control rate (DCR) and total number of TACE interventions. Kaplan-Meier method was used for the estimation of survival and survival curves were compared with Log-rank test., Results: Twenty-five (83.3%) patients had Child-Pugh A and 5 (16.7%) Child-Pugh B, and 24 (80%) patients had BCLC stage B disease and remanining had stage A disease. Lesion size >10 cm was found in 6 patients and 16/7/7 patients had single/two/multiple lesions, respectively. Mean number of TACE was 2.10±1.369. Seventeen (56.7%) patients used sorafenib after TACE whereas 13 (43.3%) patients were followed without any treatment but received consequent TACEs if needed. PFS of all patients was 10 months (range 3-48); it was 13 months for TACE plus sorafenib group and 9 months for TACE group (p=0.081). In subgroup analysis, TACE plus sorafenib group had better PFS (36 vs 12 months) in patients with tumor size > 10 cm (p=0.025). In the analysis of Child- Pugh A cases, PFS of TACE plus sorafenib group was 23 months while it was 10 months in TACE group (p=0.007)., Conclusion: Concurrent treatment in Child-Pugh A group HCC with conventional TACE and sorafenib demonstrates a significant efficacy in patients having tumor size >10 cm. In Child-Pugh A group, PFS was superior in the sorafenib plus TACE group than in TACE alone group.

Purpose: The aim of this study is to describe a new simple score to predict the occurrence of severe adverse events in patients admitted for syncope to a tertiary cardiology referral center., Methods: Three hundred ninety-three subjects with emergency department visits for syncope were identified and followed prospectively. The primary endpoint was death or unplanned hospital admission after the syncopal episode. The score consisted of sum of the following: previous syncope (2 points), an abnormal electrocardiogram (3 points), and history of heart disease (4 points). The accuracy of our score was compared to other scores available in the literature., Results: Of the 393 subjects, 87 were diagnosed with syncope secondary to structural or electrical heart disease and 306 with noncardiac syncope. The primary endpoint occurred in 202 cases, including death occurring in 25 patients during the 12-month follow-up. The 30-day event rate for the primary endpoint was 26.5 %. The c-statistic for the new score was 0.76 (95 % CI 0.71-0.80) similar to other scores when applied to our sample. Patients with a score of 3 out of 9 had a hazard ratio of 3.46 (95 % CI 1.22-6.11) for death during the follow-up., Conclusions: In the study population, the new syncope score detected patients with an increased risk of death after discharge from a syncopal event. Our score predicted adverse events comparably to other scores reported in the literature. It has the advantage of being simple and easily obtained from the history and an inexpensive noninvasive test-the ECG.

Background: The Riata lead under advisory has posed a unique clinical scenario where inside-out abrasion results in externalization of conductor cables, with a higher risk of electrical failure. We developed a comprehensive registry to assist with clinical management of this lead., Methods and Results: This Canadian registry reports the findings of 3763 (74.2% of all Riata leads in Canada) Riata leads under advisory, with a mean follow-up time of 8.9±1.5 years. The overall electrical failure rate was 5.2% at 8 years, with no difference between 7-French and 8-French lead models. Cable externalization was found to be more common in the 8-French model (12.3% versus 5.2%, P<0.0001) and was associated with a higher risk of electrical failure. Predictors of electrical lead failure included cable externalization, higher left ventricular ejection fraction, younger age, higher body mass index, and a passive fixation lead. One patient died due to electrical failure, a further 2 patients survived an event where the device failed to deliver high-voltage therapy. Major complications because of lead extraction were higher when compared with lead abandonment, no difference among lead model observed. Two deaths occurred as a consequence of lead extraction, in the context of an underlying infection., Conclusions: The Riata lead under advisory has a steady electrical failure rate over time. There are identifiable predictors of lead failure that can assist with clinical decisions as to whether lead revision should be performed prophylactically., (© 2016 American Heart Association, Inc.)

Background: Oxaliplatin and taxane-induced neurosensory toxicity is dose-limiting and mostly presents with acute symptoms that affect the activities of daily living and overall quality of life. The objective of the present study is to assess the relief of acute neuropathy with venlafaxine treatment during the chemotherapy period., Patients and Methods: In this retrospective case-control study, from January 2010 to February 2015, patients who experienced treatment with oxaliplatin and taxane-induced acute neurotoxicity were evaluated according to the NCI-CTCAE v. 4.03 grading scale. Neurotoxicity was evaluated using a numeric rating scale (NRS) for pain intensity and experienced relief under the treatment of venlafaxine and using a neuropathic pain symptom inventory scale (NPSI) for the style of complaints. Patients who were diagnosed as mildly depressed according to the HOST anxiety and depression scale and who had grade 1 to 3 sensory neurotoxicity based on the NCI-CTCAE v. 4.03 grading scale, and who also reported ≥ 4/10 on a NRS were eligible. The primary end point was the rate of more than 75 % symptomatic relief under venlafaxine treatment., Results: Two hundred six patients were included (82 % female, median age: 52.7 years). Most patients had breast, gynecologic, and colon cancer (93.4 %). Ninety-one patients who received venlafaxine and 115 patients as the control group were assessed for neurotoxicity every 3 weeks. Based on the NRS, a rate of more than 75 % symptomatic relief was 53.5, 58.3, and 45.2 % in venlafaxine arm versus 0, 0, and 0 % in the control arm in the first, second, and third visits, respectively. Side-effects of venlafaxine (n = 7) were grade 1-2 nausea/vomiting (3.2 %) and asthenia/somnolence (3.2 %) without grade 3-4 events., Conclusion: Venlafaxine has a significant clinical activity against taxane-oxaliplatin-induced acute neurosensory toxicity.

The present study reports the case of a collision tumor consisting of follicular lymphoma (FL) and adenocarcinoma in the cecum of a 73-year-old man. To the best of our knowledge, the present study is the 11th case of a collision tumor consisting of colon adenocarcinoma and lymphoma to be reported in the literature, and the first case of cecum adenocarcinoma with low grade FL in the same segment of the cecum and the same regional lymph node to be reported. The present study reviewed the literature to determine treatment options for patients with collision tumors. The present patient was administered with adjuvant chemotherapy for T3N1M0 colon cancer following surgery, due to the dominance of colon adenocarcinoma in the collision tumor. Following the completion of treatment, progression of the untreated FL was observed. In the literature, patients with collision tumors are administered with chemotherapy for stage IV FL, and following the completion of treatment patients have presented with a recurrence of early stage colon adenocarcinoma. The recommended treatment for collision tumors is dependent on the dominant tumor; however, the treatment options for collision tumors in the literature appeared to exacerbate the other tumor. The characteristics of the tumors altered following chemotherapy, and immunological alterations in the tumors due to chemotherapy appear to have contributed to the exacerbation of the tumors. Therefore, patients with early-stage tumors should be considered at risk of recurrence of other malignancies, which are present in collision tumors.

Purpose: The purpose of this study was to determine whether the presence of diabetes mellitus (DM) influences the incidence and severity of peripheral sensory neuropathy (PSN) in patients using taxane therapy., Methods: A retrospective single-center analysis was conducted: Patients with PSN at baseline were excluded. The incidence of PSN was evaluated retrospectively in patient subgroups who received taxane arm and taxane-plus-platinum-agents combination arm with or without known DM at baseline., Results: Three hundred seventy-four patients were enrolled in this study, 81 (21.6%) of patients had DM at baseline. The incidence of grade 1 PSN (non-DM/DM) in patients receiving taxane-based chemotherapy was 33.4/25.9% and more than grade 2 PSN (non-DM/DM) was 15/34.6%. The rate of neuropathy of non-diabetic patients was 48.8%, while the rate of diabetic patients was 52.8 and 75% in DM duration below 5 years and above 5 years group, respectively., Conclusions: This retrospective analysis indicates that taxane-based therapy in DM patients whose disease duration is above 5 years appears to affect the incidence and severity of PSN without known baseline neuropathy. The probability of PSN with taxane-based therapy was similar in DM duration below 5 years and non-DM patients.