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Bitter taste receptors (T2Rs) are G protein‑coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra‑oral cells eliciting non‑gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor‑derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated

Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body distribution in the skin would be lipedema stage-dependent, and could, thus, serve to objectively characterize neuropathic pain in lipedema. The pain was assessed by questionnaire and peripheral cutaneous mechanical sensitization (von-Frey) in lipedema (n = 27) and control (n = 23) consenting female volunteers. Dermal biopsies from (n = 11) Stages 1–3 lipedema and control (n = 10) participants were characterized for neuronal cell body and nociceptive neuropeptide calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) distribution. Stage 2 or 3 lipedema participants responded positively to von Frey sensitization in the calf and thigh, and Stage 3 participants also responded in the arm. Lipedema abdominal skin displayed reduced Tuj-1+ neuronal cell body density, compared to healthy controls, while CGRP and NGF was significantly elevated in Stage 3 lipedema tissues. Together, dermal neuronal cell body loss is consistent with hyper-sensitization in patients with lipedema. Further study of neuropathic pain in lipedema may elucidate underlying disease mechanisms and inform lipedema clinical management and treatment impact.

Sexual health concerns after cancer are common and distressing, and mindfulness-based interventions (MBIs) are effective in supporting women experiencing these concerns. The goals of this study were to: (i) systematically adapt and document modifications to a mindfulness-based sexual health intervention for cancer survivors in a community setting and (ii) assess feasibility, appropriateness, and acceptability, and to identify strategies to increase reach for future implementation and dissemination. Following the ADAPT-ITT model, we first conducted key informant interviews with 10 female cancer survivors and four healthcare providers to obtain feedback on perceived need and feasibility of the intervention approach, and preferences for content, structure, and delivery format. This feedback informed initial intervention adaptations, which we then pretested with five female cancer survivors. We tracked and coded intervention adaptations. Key informant cancer survivors and providers confirmed the lack of sexual health services, acceptability of a sexual health MBI, and identified initial adaptations including modifying the intervention for delivery in a community, rather than clinical, setting. Pretest participants (aged 48–57) were survivors of breast (n = 4) and cervical (n = 1) cancer. All participants completed the intervention attending an average of 7.2 of 8 weekly sessions. Qualitative and quantitative results suggest the intervention was feasible, appropriate and acceptable. Engaging stakeholders in the adaptation process is essential for creating a feasible, appropriate, and acceptable intervention. Tracking intervention modifications contributes to our overall understanding of how MBIs can be adapted for new populations and contexts.

Introduction Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has repeatedly been suggested to be associated with tumorigenesis. To evaluate the role of LPCAT1 in esophageal cancer, LPCAT1 immunostaining was analyzed on a tissue microarray containing samples from esophageal cancer patients. Results In benign esophageal tissue, LPCAT1 staining was detectable in low intensities. LPCAT1 staining was increased in malignant as compared to benign esophageal tissue and was found in high intensity in 26.4% of 288 interpretable esophageal adenocarcinomas (EACs) and in 23.2% of 211 squamous cell carcinomas (ESCCs). Increased LPCAT1 staining was linked to undifferentiated tumor grading in both subtypes of EACs and ESCCs (p = 0.0273 and p = 0.0085). Conclusion However, LPCAT1 was not associated with prognosis of EAC and ESCC patients (p = 0.6838 and p = 0.4695) and thus cannot be considered a prognostic biomarker in esophageal cancers.

IntroductionPulmonary arterial hypertension (PAH) is a rare, multifactorial, chronic condition that requires ongoing monitoring and assessment. PAHcare™ is a novel, patient-centered digital platform that provides software intended for use on patients' mobile phones (downloadable application) and web-based dashboards for use by physicians and health coaches (HC). We describe herein the protocol of a clinical study aimed at evaluating the clinical benefit and safety of PAHcare™ for the routine management of patients with PAH.Methods and analysisIn this prospective, single cohort, multicenter study, 50 patients with PAH will be recruited at six specialized PAH units from reference hospitals of the public Spanish healthcare system. The PAHcare™ digital health platform allows patients to log health and lifestyle information while also providing structured content for patient education, medication reminders, and behavioral and lifestyle coaching from a remote HC. Evaluation will be primarily focused on the impact of the platform use on the patient's health-related quality of life (HRQoL) via questionnaires completion through electronic patient-reported outcomes. Moreover, the analysis of the impact on the patient's functional status, signs and symptoms of PAH, patient costs and healthcare resource utilization, satisfaction, knowledge of the disease and its management, and adherence to and safety of the platform will be secondary outcomes. The clinical investigation started in July 2021 and is expected to end by September 2022.DiscussionThe PAHcare™ platform is anticipated to provide direct benefits to healthcare professionals, patients, and caregivers. These include the simplification of the multidisciplinary approach needed to tailor routine PAH management, enhancement of the patient/healthcare professional interaction, patient's empowerment to become more actively involved in the management and treatment of the disease, and increase of the patient's and caregiver's knowledge on PAH.

Objective Common to many countries in the Middle East, Lebanon has an increasing cancer burden; however, national screening programs are limited to breast cancer. The literature on cancer screening practices and beliefs is scarce. This cross-sectional study investigates the knowledge, beliefs, and practices related to the prevention and screening for breast, cervical, colon, lung, and skin cancers among Lebanese residents, recruited through social media advertisements and community outreach activities. Methods Participants filled an anonymous questionnaire either via a web-based interface or using tablets distributed at primary health clinics. The characteristics of the two cohorts were compared with chi-square and t-tests. We performed descriptive analysis, followed by multivariate logistic regression for predictors of cancer screening. Results A total of 407 participants completed the survey online, and 262 filled the study in tablets available at primary care clinics. The two samples were significantly different in terms of age, education, and perceived socioeconomic status. Online participants demonstrated higher knowledge and higher participation in screening practices than their counterparts recruited through community outreach. Mammography (44.7% online and 39.9% in-person), and cervical cancer screening (44.5% online and 36.7% community) had the highest participation rates. In both samples, participants who were older and more educated were more likely to report engagement with cancer screening practices. Conclusions Our study revealed significant knowledge gaps in cancer prevention and screening. Different sampling techniques accessed diverse populations, highlighting the need for educational messages and targeted screening programs to be inclusive of socio-economically disadvantaged communities with low education and health literacy.

Background The diagnosis of major complications seems to be more challenging in obese patients. We aimed to show the relevance of routinely assessed clinical and paraclinical parameters as well as the relevance of CT scans in the diagnosis of major complications after bariatric procedures. Methods All patients who underwent operations (primary or revisional) in a 3-year period were retrospectively studied after bariatric surgery with a specific focus on the routinely assessed clinical parameters (tachycardia, temperature), paraclinical parameters on postoperative day (POD) 1 and 3 (C-reactive protein (CRP), leukocytes), and additional computed tomography (CT) scan results for the diagnosis of leakage, bleeding, intraabdominal abscess, superficial abscess, and other complications. Results A total of 587 patients were examined. In this cohort, 73 CT scans were performed due to suspected intraabdominal or pulmonary complication according to our hospital standard operating procedure. In total, 14 patients (2.4%) had a major complication (Clavien-Dindo grade IV/V). Of those, 10 patients (1.7%) had postoperative leakage. While the correct leakage diagnosis was only found in 33% of the patients by CT scan, the overall specificity of CT as a diagnostic tool for all kinds of complications remained high. Especially for abscess detection, CT scan showed a sensitivity and specificity of 100%. Multivariate analysis showed a significantly higher risk of leakage development characterized by a doubling of postoperative CRP level (odds ratio 4.84 (95% confidence interval 2.01–11.66, p < 0.001)). To simplify the use of CRP as a predictive factor for the diagnosis of leakage, a cut-off value of 2.4 was determined for the CRP quotient (POD3/POD1) with a sensitivity of 0.88 and a specificity of 0.89. Conclusion CT diagnostic after bariatric surgery has a high positive predictive value, especially for intraabdominal abscess formation. Nevertheless, CT scan for the diagnosis of leakage has a low sensitivity. Thus, a negative CT scan does not exclude the presence of a leakage. Using the described CRP quotient with a cut-off of 2.4, the risk of early leakage can be easily estimated. Furthermore, in any uncertain case of clinically suspected leakage, diagnostic laparoscopy should be performed.

Background The aim of this study is to evaluate whether adenocarcinomas of the esophagogastric junction (AEG) are better staged as cancers of the esophagus (TNM-EC) or stomach (TNM-GC) according to the 8th edition of the UICC classification. Methods A single-center cohort of 246 patients operated on for AEG type II was staged according to the 8th edition of the UICC classification for esophageal and stomach cancer. Kaplan-Meier and univariate Cox regression analyses were performed to investigate the impact on survival. Results For AEG type II TNM-EC classified most of the patients (n = 126; 51.2%) to UICC stage IIIC and IVA while TNM-GC more evenly distributed the patients over the stages. Hazard ratios increased in between all stages in a stepwise manner except between stage IA and IIA for TNM-EC and between stage IIB and IIIA for TNM-GC. Survival curves for TNM-GC demonstrated significant differences between all four major UICC stages, while in TNM-EC no significant difference between stage I and II was found. When comparing the area under the curves of both staging systems a marginal superiority for TNM-EC was found. Conclusion Neither the esophageal nor the stomach staging system is flawless in predicting survival in AEG type II. A marginal superiority of the TNM-EC was found in discriminating survival rates after three and five years. However, the advantage of the TNM-GC lies in the division of the N3 category into N3a and N3b. We therefor suggest a similar division in future TNM-EC classifications to improve its prognostic value.

Osteoarthritis (OA) is a degenerative joint disease resulting in limited mobility and severe disability. Type II diabetes mellitus (T2D) is a weight-independent risk factor for OA, but a link between the two diseases has not been elucidated. Adipose stem cells (ASCs) isolated from the infrapatellar fat pad (IPFP) may be a viable regenerative cell for OA treatment. This study analyzed the expression profiles of inflammatory and adipokine-related genes in IPFP-ASCs of non-diabetic (Non-T2D), pre-diabetic (Pre-T2D), and T2D donors. Pre-T2D ASCs exhibited a substantial decrease in levels of mesenchymal markers CD90 and CD105 with no change in adipogenic differentiation compared to Non-T2D and T2D IPFP-ASCs. In addition, Cyclooxygenase-2 (

Brain tumor heterogeneity and progression are subject to complex interactions between tumor cells and their microenvironment. Glioblastoma and brain metastasis can contain 30–40% of tumor-associated macrophages, microglia, and astrocytes, affecting migration, proliferation, and apoptosis. Here, we analyzed interactions between glial cells and LN229 glioblastoma or A375 melanoma cells in the context of motility and cell–cell interactions in a 3D model. Furthermore, the effects of phytocannabinoids, cannabidiol (CBD), tetrahydrocannabidiol (THC), or their co-application were analyzed. Co-culture of tumor cells with glial cells had little effect on 3D spheroid formation, while treatment with cannabinoids led to significantly larger spheroids. The addition of astrocytes blocked cannabinoid-induced effects. None of the interventions affected cell death. Furthermore, glial cell-conditioned media led to a significant slowdown in collective, but not single-cell migration speed. Taken together, glial cells in glioblastoma and brain metastasis micromilieu impact the tumor spheroid formation, cell spreading, and motility. Since the size of spheroid remained unaffected in glial cell tumor co-cultures, phytocannabinoids increased the size of spheroids without any effects on migration. This aspect might be of relevance since phytocannabinoids are frequently used in tumor therapy for side effects.

IntroductionThe role of CD147 as an important indicator of tumor prognosis remains controversially discussed in literature. We focused on the prognostic significance of CD147 expression in esophageal cancer patients. While some studies report that CD147 is an unfavorable prognostic factor in esophageal squamous cell carcinoma, others showed no significant correlation. However, only one study draws attention to the significance of CD147 in esophageal adenocarcinoma, which is one of the most rapidly increasing neoplasms in the western world.MethodsTo finally clarify the impact of CD147 as a prognostic factor, especially for esophageal adenocarcinomas, we analyzed CD147 expression in a tissue microarray of 359 esophageal adenocarcinomas and 254 esophageal squamous cell cancer specimens. For the immuno-histochemical analysis, we used a primary antibody specific for CD147. Staining intensity and proportion of positive tumor cells were scored (negative, weak, moderate, strong staining). These findings were compared to normal esophageal tissue and correlated to the histopathological tumor phenotype and survival data.ResultsCD147 expression was detectable in weak intensities in benign esophageal tissue (85.78%) and expressed in predominately moderate to strong intensities in esophageal cancer (88.34%). Strong CD147 immunostaining was linked to increased infiltration depth (p = 0.015) and differentiation (p = 0.016) in esophageal squamous cell cancer but revealed no significant correlation with histopathology of adenocarcinoma. Moreover, CD147 intensity was unrelated to overall survival in this collective for both subtypes of esophageal cancer.ConclusionThus, our data show that CD147 has no prognostic value, neither in esophageal adenocarcinoma nor squamous cell carcinoma.

The Coronavirus disease (COVID-19) pandemic has brought about drastic measures that have significantly altered the norms of daily living. These measures have affected human behaviors in disparate ways. This study seeks to understand the impact of the pandemic on physical activity and dietary behavior among adults living in Kuwait. A cross-sectional survey was conducted between 18 June and 15 July 2020, using a questionnaire disseminated through social media, including WhatsApp and Facebook. The target population was individuals aged 21 years or older living in the State of Kuwait. The study included 679 respondents, 57.9% were females, and 67.7% were Kuwaiti nationals. Both genders reported an increased consumption of vegetables, fruits, and carbohydrates, and a decreased consumption of fish and sugary drinks. Compared to males, females reported eating more during the outbreak than their pre-pandemic eating behaviors (32.3% vs. 35.9%, p &lt, 0.05). Approximately one-third of respondents (33.1%) reported performing less than 30 min of physical activity or exercise in a week, and 36.4% of respondents rated their quality of sleep as ‘poor’ or ‘very poor’. The rate of smoking cigarettes among males was significantly higher than in females (40.6% vs. 5.3%, p &lt, 0.001). Physical activity was positively correlated with vegetable consumption and quality of sleep. Quality of sleep was negatively correlated with the consumption of sweets and snacks, just as the consumption of vegetables was negatively correlated with the consumption of sugary drinks. The overall negative impact of the COVID-19 pandemic in Kuwait necessitates the development of health promotion interventions to support positive physical activity and dietary behaviors using alternative coping strategies among the residents of Kuwait.

Diverting esophagectomies in cases of benign esophageal perforations remain rare but potentially life saving procedures. Usually, an esophagostoma and a feeding jejunostomy or gastrostomy are created, and patients are given time to recover from the emergency situation. However, little is known about morbidity and mortality as well as the optimal timing for a staged reconstruction. Patients with benign esophageal perforations were selected from our retrospective database. Perforations in esophageal malignancies were excluded to avoid bias on patients’ general outcome. Clinical parameters and especially, the influence of the nutritional status indicated by the BMI (Body Mass Index) as well as serum albumin levels (g/l) were analyzed. A total of 24 patients with diverting esophagectomies were identified. Of these, 13 (54.2%) patients received a staged reconstruction after a median of 143.0 days. Patients presenting for their staged reconstruction demonstrated a significantly decreased level of their BMI (p = 0.026) as compared to their prior hospitalization. Interestingly, the relative decrease of BMI (8.5 kg/m2 vs. 4.3 kg/m2) and albumin levels (6.5 g/l vs. 0.0 g/l) was significantly different in patients with or without anastomotic leaks between both surgeries (p = 0.021; p = 0.034, respectively). In addition, higher rates of overall complications were associated with an increased rate of malnutrition. The relative amount of malnutrition indicated by BMI or serum albumin levels influences the rate of anastomotic leaks and general complications in patients with staged reconstruction after diverting esophagectomy for non-malignant esophageal perforations. Hence, reconstruction should be done as fast as possible to reduce the amount of malnutrition and a frequent assessment of the nutritional status must be done during recovery from the emergency surgery.

Background Acute postoperative peritonitis resulting from previous abdominal surgery is still a severe and potentially fatal disease, which is associated with high morbidity and mortality. The aim of the present study was to evaluate patients’ outcome after postoperative peritonitis and identify the most effective empiric antibiotic regimes. Methods 422 patients with acute postoperative peritonitis as a result to earlier abdominal operation (e.g. anastomotic leakage) were analyzed retrospectively focusing on the origin of the peritonitis, microbial flora and resistance patterns. Furthermore, mortality was estimated according to sensitivity results of the tested antibiotics. Results In 50% of the patients, anastomotic leakage was located in the colon. The predominantly cultured microorganisms were Escherichia coli and Enterobacteriaceae. The combination of meropenem and vancomycin was effective in 96% of these microbes. The frequently used combinations of piperacillin/sulbactam and cefotaxime/metronidazole were effective in only 67% and 43%, respectively. Conclusions We were able to show that the currently used antibiotic regimes with piperacillin/sulbactam and cefotaxime/metronidazole are ineffective in a relevant number of patients with anastomotic leakage. Only meropenem or meropenem/vancomycin cover most of the microbes predominant in postoperative peritonitis.

The study sought to purify and characterize a novel bacteriocin from oral L. salivarius and studying the effect of L. salivarius and its bacteriocin against multidrug-resistant (MDR) P. aeruginosa in vivo and in vitro. Saliva Lactobacillus salivarius bacteriocin was prepared and purified. The molecular weight of purified L. salivarius bacteriocin was 13,500Da protein. The antibacterial activity of purified salivaricin LHM was higher than crude (P

Previous studies have reported that peak serum troponin I levels were disproportionately elevated in patients with acute anterior ST-segment elevation myocardial infarction (STEMI) and left ventricular (LV) hypertrophy (LVH) compared with those with normal LV mass. The purpose of this retrospective study was to assess the relation of peak serum troponin T levels in patients with normal LV mass and in subjects with mild, moderate, and severe LVH in patients with acute STEMI or non-ST segment elevation myocardial infarction (NSTEMI) when stratified on variables that might be expected to affect serum troponin T levels. The study population consisted of 262 patients; 91 with STEMI and 161 with NSTEMI. Serum troponin levels and 2-dimensional echocardiograms were obtained within the first 24 hours of hospitalization for STEMI or NSTEMI. There was no significant difference in serum troponin T levels in LV mass and/or LVH groups (p = 0.3210). There was no significant difference in serum troponin T levels in LV mass and/or LVH groups when these data were stratified on third variables including serum creatinine1.2 mg/dl (p = 0.3681), LV ejection fraction60% (p = 0.0978), STEMI (p = 0.2576), NSTEMI (p = 0.4994), and location of severe coronary stenosis (p = 0.1981). The results of this study suggest that there is no association between peak serum troponin T levels and LV mass and/or LVH groups when such groups are stratified on a third variable that may influence peak serum troponin T levels.

Background Chronic pancreatitis remains a challenging inflammatory disease, causing progressive, irreversible fibrosis of the pancreatic parenchyma. Several surgical options for treatment have been established, but duodenum-preserving pancreatic head resections seem to be the most favorable option other than pancreatoduodenectomy. The aim of this retrospective analysis is to evaluate the outcomes of the Hamburg modification of duodenum-preserving pancreatic head resections. Methods We retrospectively evaluated—for long-term outcomes concerning pain control, quality of life, and symptom control—500 consecutive patients suffering from painful chronic pancreatitis who had undergone the Hamburg modification of the duodenum-preserving pancreatic head resection. Additionally, the patients were compared with a database of 104 patients who underwent duodenum-preserving pancreatic head resections according to Beger or Frey. Results After a mean follow-up of 10 years, overall survival was 90% in those patients having undergone the Hamburg modification. Regarding analgetic medications, the median pain score for frequency of pain attacks, measured by a visual analog scale and inability to work, was 0 (0–100), and the global quality of life revealed a median of 92 (0–100). In addition, we found that a high rate of patients continued consuming alcohol after the operation (37.9%). The rate of redo surgery owing to the recurrence of chronic pancreatitis was 7.6% after this Hamburg modification. Conclusion Duodenum-preserving pancreatic head resections provide adequate outcomes in terms of pain control, quality of life, and symptom control. In this retrospective analysis, the Hamburg modification was found to be a good alternative to other forms of duodenum-preserving pancreatic head resections. The choice of a certain modification of the duodenum-preserving pancreatic head resection may depend on the surgeon's expertise and the individual needs of the patient.

Background and Aim. Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women. Methods. Forty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to 2) and Obese (BMI 30 to 2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF. Results. Non-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p<0.005) and Obese (p<0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p<0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p<0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls. Conclusion. Hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.

BACKGROUND Despite advances in perioperative management, the 5-year survival rate of patients with esophageal adenocarcinoma (Barrett's cancer) is poor. Adjuvant immunotherapies are currently the subject of clinical trials. The prognostic role of tumor-infiltrating T-lymphocytes (TILs) expressing CD45 has only been investigated in primary tumors. The significance of TILs in the target organs of distant metastases, in particular the liver, is unclear. This study examined the influence of CD45-positive cells in liver parenchyma and primary tumors on cumulative survival. MATERIALS AND METHODS The density of CD45-positive cells was analyzed immunohistochemically using tissue microarrays. Sixty-five patients for whom a liver biopsy was available in addition to the primary tumor were included in the study. Liver metastases were found in 21 patients. The results of the immunohistochemical analysis were correlated with patient's outcomes. The Cox proportional hazard model was used to compute mortality hazard ratio in consideration of clinical variables. RESULTS Elevated density of CD45-positive cells in the liver biopsy corresponded with a better cumulative survival rate (p

In this study, we aimed to evaluate the psychological impact of the COVID-19 pandemic on healthcare workers to determine the prevalence of symptoms of depression, anxiety, and well-being, and to identify the factors associated with adverse psychological effects. This study was conducted 5 months into the COVID-19 pandemic. We used an online questionnaire to collect data from 378 healthcare workers. To examine the psychological impact, three standardized questionnaires were utilized. This includes the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Scale (GAD-7), and the WHO Well-Being Scale (WHO-5) to measure depression, anxiety, and quality of life, respectively. More than half of the participants (52.9%) exhibited moderate or high levels of depression, and 40.5% reported moderate or high levels of anxiety. Unmarried HCWs reported more severe levels of depression; moderately severe depression (24.0% vs. 16.1%) and severe depression (12.4% vs. 6.8%). Unmarried HCWs also reported more severity of anxiety as well as lower overall wellbeing. Understanding how personal factors such as marital status can influence the degree of psychological distress can allow us to make better investments in supporting the mental health needs of HCWs in Kuwait. Governments and organizations must establish protective measures, such as continually assessing the mental health status of HCWs throughout the pandemic and providing support services for HCWs in need to minimize adverse consequences and ensure optimal health system operation.

Background Oncological esophageal surgery has evolved significantly in the last decades. From open esophagectomy over (hybrid) minimally invasive surgery, nowadays, robot-assisted minimally invasive esophagectomy (RAMIE) approaches are applied. Current techniques require an analysis of possible advantages and disadvantages indicating the direction towards a novel gold standard. Methods Robot-assisted Ivor Lewis esophagectomies, performed in the period from April 2017 to June 2019 in five German centers (Berlin, Cologne, Hamburg, Kiel, Mainz), were included in this study. Pre-, intra-, and postoperative parameters were assessed. Cases were grouped for hybrid (H-RAMIE) versus totally robot-assisted (T-RAMIE) approaches. Postoperative parameters and complications were compared using risk ratios. Results A total of 175 operations were performed as T-RAMIE and 67 as H-RAMIE. Patient age (median age 62 years) and sex (83.1% male) were similarly distributed in both groups. Median duration of esophagectomy was significantly lower in the T-RAMIE group (385 versus 427 min, p < 0.001). The risks of “overall morbidity” (32.0 versus 47.8%; risk ratio [RR], 95% confidence interval (CI): 1.5, 1.1–2.1; p = 0.026), “anastomotic leak” (10.3 versus 22.4%; RR, CI: 2.2, 1.2–4.1; p = 0.020), and “respiratory failure” (1.1 versus 7.5%; RR, CI: 6.5, 1.3–32.9; p = 0.019) were significantly higher in case of H-RAMIE. Conclusions In the five participating German centers, T-RAMIE was the preferred procedure (72.3% of operations). In comparison to H-RAMIE, T-RAMIE was associated with a significantly reduced risk of postoperative morbidity, anastomotic leak, and respiratory failure as well as a significantly reduced time necessary for esophagectomy.

Human adipose-derived stem cells (hASCs) are potent modulators of inflammation and promising candidates for the treatment of inflammatory and autoimmune diseases. Strategies to improve hASC survival and immunoregulation are active areas of investigation. Autophagy, a homeostatic and stress-induced degradative pathway, plays a crucial role in hASC paracrine signaling—a primary mechanism of therapeutic action. Therefore, induction of autophagy with rapamycin (Rapa), or inhibition with 3-methyladenine (3-MA), was examined as a preconditioning strategy to enhance therapeutic efficacy. Following preconditioning, both Rapa and 3-MA-treated hASCs demonstrated preservation of stemness, as well as upregulated transcription of cyclooxygenase-2 (COX2) and interleukin-6 (IL-6). Rapa-ASCs further upregulated TNFα-stimulated gene-6 (TSG-6) and interleukin-1 beta (IL-1β), indicating additional enhancement of immunomodulatory potential. Preconditioned cells were then stimulated with the inflammatory cytokine interferon-gamma (IFNγ) and assessed for immunomodulatory factor production. Rapa-pretreated cells, but not 3-MA-pretreated cells, further amplified COX2 and IL-6 transcripts following IFNγ exposure, and both groups upregulated secretion of prostaglandin-E2 (PGE2), the enzymatic product of COX2. These findings suggest that a 4-h Rapa preconditioning strategy may bestow the greatest improvement to hASC expression of cytokines known to promote tissue repair and regeneration and may hold promise for augmenting the therapeutic potential of hASCs for inflammation-driven pathological conditions.

Despite improvements in diagnosis, intensive-care medicine and surgical technique, the mortality of patients with secondary peritonitis is still high. Early and aggressive empiric antibiotic treatment has strong impact on the outcome. This retrospective study investigates bacterial and fungal pathogens and their antibiotic sensitivity in patients with secondary peritonitis. All patients that underwent emergency laparotomy due to secondary peritonitis at the Department of Surgery, University Medical Center Hamburg-Eppendorf between 2005 and 2015 were reviewed and overall 414 patients were included. We correlated the intra-abdominal localization of the organ perforation with intraoperative microbiological findings and corresponding sensitivities to relevant antibiotics. Overall, the most common findings were Escherichia coli (39%) and other Enterobacterica (24%). Depending on the location of the perforation, Cefuroxime/Metronidazole and Cefutaxime/Metronidazole were effective (based on in vitro susceptibility testing) in only 55–73% of the patients, while Meropenem/Vancomycin was able to control the peritonitis in more than 98% of the patients; independent of the location. Besides early source control, appropriate empiric treatment plays a pivotal role in treatment of secondary peritonitis. We are able to show that the frequently used combinations of second or third generation Cephalosporins with Metronidazole are not always sufficient, which is due to the biological resistance of the bacteria. Further clinical studies are needed to determine whether calculated use of broad-spectrum antibiotics with a sensitivity rate > 99%, such as Carbapenem plus Vancomycin, can improve overall survival rates in critically ill patients with secondary peritonitis.

Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4+ T helper (Th) and T regulatory (Treg) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less Th and Treg cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.

Colorectal carcinoma (CRC) is one of the most common carcinomas worldwide. Early detection is crucial for reducing morbidity and mortality. Several promising studies described the use of midkine (MK) as a tumor marker. This study aimed to investigate a larger collective to ascertain if the preoperative serum midkine level (S‐MK) is suitable as a marker for screening and if S‐MK correlates with tumor progression and localization. It was also investigated for the first time whether patients with high S‐MK show poor survival. This prospective single‐center study included 299 patients with CRC. The preoperative serum midkine level (S‐MK) was determined using ELISA. Established tumor markers Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19‐9 (CA 19‐9) were collected for comparison. The median follow‐up period was 65 months. S‐MK was significantly elevated in patients with CRC (P, This study shows that preoperative serum midkine level (S‐MK) is suitable as marker for screening of patients with colorectal carcinoma. Moreover S‐MK correlates with poor survival.

Osteoarthritis (OA) is a common joint disorder with a significant economic and healthcare impact. The knee joint is composed of cartilage and the adjoining bone, a synovial capsule, the infrapatellar fat pad (IPFP), and other connective tissues such as tendons and ligaments. Adipose tissue has recently been highlighted as a major contributor to OA through strong inflammation mediating effects. In this study, methacrylated gelatin (GelMA) constructs seeded with adipose tissue-derived mesenchymal stem cells (ASCs) and cultured in a 3D printed bioreactor were investigated for use in microphysiological systems to model adipose tissue in the knee joint. Four patient-derived ASC populations were seeded at a density of 20 million cells/mL in GelMA. Live/Dead and boron-dipyrromethene/4&prime, 6-diamidino-2-phenylindole (BODIPY/DAPI) staining of cells within the constructs demonstrated robust cell viability after 28 days in a growth (control) medium, and robust cell viability and lipid accumulation in adipogenic differentiation medium. qPCR gene expression analysis and protein analysis demonstrated an upregulated expression of key adipogenesis-associated genes. Overall, these data indicate that ASCs retain their adipogenic potential when seeded within GelMA hydrogels and cultured within perfusion bioreactors, and thus can be used in a 3D organ-on-a-chip system to study the role of the IPFP in the pathobiology of the knee OA.

Studies comparing manual catheter navigation (MCN) to remote magnetic navigation (RMN) for atrial fibrillation (AF) ablation showed variable results. The aim of this meta-analysis is to compare the safety and clinical outcomes of AF radiofrequency (RF) ablation using MCN versus RMN with irrigated tip catheters. Medline and the Cochrane Central Register of Controlled Trials (CENTRAL) were queried from inception through January 2019. Studies comparing safety and clinical outcomes of AF ablation with RF using MCN versus RMN with irrigated tip catheters were included. Random effects meta-analysis was used to pool outcomes across studies. Study endpoints included freedom of AF at the end of the study, procedure total time, fluoroscopy time, and complications. A total of 14 studies (3 controlled non-randomized trials, 1 prospective observational, and 10 retrospective observational studies) involving 3375 patients (1871 in MCN and 1504 in RMN) were included in this meta-analysis. There was no significant difference between the two groups in terms of freedom of AF (OR 1.08, 95% CI 0.82–1.42, p = 0.52). The MCN group was associated with shorter procedure time (mean difference in minutes − 50.39, 95% CI − 67.99 to − 32.79, p

Skin cancer remains a major cause of mortality worldwide. It can be divided into melanoma and non-melanoma cancer, which comprise mainly squamous cell carcinoma and basal cell carcinoma. Although conventional therapies have ameliorated the management of skin cancer, the search for chemopreventive compounds is still the most effective and safer strategy to treat cancer. Nowadays, chemoprevention is recognized as a novel approach to prevent or inhibit carcinogenesis steps with the use of natural products. Crude extracts of plants and isolated phytocompounds are considered chemopreventive agents since they harbor anti-inflammatory, antioxidant and anti-oncogenic properties against many types of diseases and cancers. In this review, we will discuss the therapeutic effect and preventive potential of selected medicinal plants used as crude extracts or as phytocompounds against melanoma and non-melanoma cutaneous cancers.

Introduction/Objective: Acute mesenteric ischemia (AMI) is difficult to diagnose. Since the established parameters have low sensitivity and specificity, the aim of this study is to analyze the diagnostic quality of the established parameters of AMI. Methods: All patients that underwent emergency surgery due to suspected diagnosis of mesenteric ischemia at the University Medical Center Hamburg-Eppendorf between 2008 and 2014 were evaluated. Overall, 275 patients were enrolled and pre-, intra- and postoperative data were evaluated. Results: In 200 patients, a mesenteric ischemia was confirmed intraoperatively, and 75 patients had no ischemia. Comparing these groups, the rate of patients with pH < 7.2 (25 vs. 12%; p = 0.021) and elevated mean CRP level (175 ± 117 mg/L vs. 139 ± 104 mg/L; p = 0.019) was significantly higher in ischemic patients. There was no significant difference in the level of preoperative lactate. Concerning abdominal CT scan, a sensitivity and specificity of 61 and 68%, respectively, was found. Conclusion: New diagnostic parameters are needed. So far, explorative laparotomy is the only reliable diagnostic method to detect mesenteric infarction.

Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability to regulate the immune system by secreting anti-inflammatory cytokines and growth factors that play a crucial role in the pathology of many diseases, including multiple sclerosis, diabetes mellitus, Crohn’s, SLE, and graft-versus-host disease. The immunomodulatory effects and mechanisms of action of ASCs on pathological conditions are reviewed here.

BACKGROUND/AIM The clinical significance of circulating tumor cells (CTC) in non-metastatic esophageal cancer (EC) remains controversial and the cellular and molecular characteristics of CTCs are poorly understood. Especially the frequency and oncological impact of HER2 expression in CTCs in patients with EC have not been evaluated until now. MATERIALS AND METHODS In this single-center, prospective study, peripheral blood samples were obtained preoperatively from 45 patients who were diagnosed with resectable EC. CTC detection and HER2 expression were performed using the CellSearch System. Data were correlated with clinicopathological parameters and patient outcomes. RESULTS The study included 13 patients with squamous cell carcinomas (SCC) and 32 patients with adenocarcinomas (AC). HER2 gene amplification in the primary tumor was detected in 9.1% of patients. One or more CTCs were detected in 15.6% (SCC 1/13; AC 6/32) of the patients. None of the detected CTCs showed HER2 expression. Patients with CTCs showed significantly shorter relapse-free (p

This retrospective study was performed to evaluate the safety and feasibility of the new Senhance robotic system (Transenterix) for robotic cholecystectomy. Our series is the first experience with cholecystectomies utilizing this new platform. From May 2017 to August 2017, 20 robotic cholecystectomies were performed using the Senhance robotic system. Patients were between 23 years and 78 years of age, eligible for a laparoscopic procedure with general anesthesia, with no life-threatening co-morbidities that limited the subjects’ life-expectancy to fewer than 12 months. A retrospective chart review was performed for a variety of pre-, peri- and postoperative data including, but not limited to patient demographics, intraoperative complications and postoperative complications. 9 male and 11 female patients were included in this study. Median age was 39.5 years (range 23–78); median BMI was 27.35 kg/m2 (range 22.8–48.3). Median docking time was 10 min (range 2–26), and median operative time was 71.5 min (range 34–197). Conversion to standard laparoscopy occurred in one case for lysis of extensive adhesions. There were no conversions to open technique. There were no intra- or post-operative complications noted. We report the first series of robotic cholecystectomies using the new Senhance system. Docking time and total operative time decreased significantly over the course of this series and did not plateau; console time did not change significantly. This study demonstrates the feasibility of utilizing this platform in performing minimally invasive cholecystectomies.

Introduction: Arab Americans are a growing population in the United States. In the 2011 American Community Survey, the U.S. Census Bureau reported there were close to 1.8 million Arab Americans living within the United States, a 47% increase in population size from 2000. According to the Arab American Institute, currently, that estimate has grown to approximately 3.7 million. They have high rates of smoking and low rates of smoking cessation. In this study, the researchers investigated factors influencing desire to quit smoking among Arab Americans, and their association with acculturation and health beliefs. Methodology: Cross-sectional descriptive study investigating smoking behaviors and factors influencing the desire to quit smoking among adult Arab American. Data were collected to measure tobacco use, nicotine dependence, desire to quit smoking, acculturation, and health beliefs. Results: The sample ( N = 96) was 55% female, mean age of 44 years (±14.79). The desire to quit smoking was positively associated with perceived severity (p < .05) and susceptibility to cancer (p < .05), perceived benefits of quitting smoking ( p < .01); and negatively associated with smoking barriers (addiction barriers p < .05, external barriers p = .27, internal barriers p < .05), and nicotine dependence (p < .05). Being female, having a lower level of nicotine dependence, and a higher perception of cancer severity predicted higher desire to quit smoking ( p < .01). Discussion: Smoking cessation intervention studies need to target appropriate health beliefs, especially the high risk of cancer caused by smoking among Arab Americans.

Background Outcomes for debulking by atherectomy (ATH) for adjunctive treatment of below the knee (BTK) symptomatic arterial disease compared to percutaneous transluminal angioplasty alone (PTA) are unclear. Methods MEDLINE, EMBASE, PubMed and the Cochrane Central Register of Controlled Trials were queried from between 2000 and 2017 including studies comparing PTA alone to PTA-ATH. Random effect meta-analysis model was used to pool the data across the studies. Study endpoints included: vessel dissection, residual stenosis ( 30%), mortality at 12 months and amputation rates at 1 and 12 months. Results A total of 2587 patients (72.9 years; 63% male) were included from 4 studies (2 prospective, one of which was randomized, and 2 retrospective) comparing PTA alone to ATH-PTA in patients with symptomatic infra-popliteal disease. There was no significant difference between the two approaches in terms of vessel dissection [OR 3.73 with 95% CI 0.83 to 16.64, p = 0.08] or residual stenosis [OR 0.41 with 95% CI 0.11 to 1.60, p = 0.18]. Clinical outcomes did not differ in terms of 12 month mortality [OR 3.47 with 95% CI 0.15 to 81.37, p = 0.44], or limb amputation at 1 month [OR 1.23 with 95% CI 0.91 to 1.67, p = 0.18] or 12 months [OR: 1.02 with 95% CI 0.83 to 1.26, p = 0.83]. Conclusion In patients undergoing (BTK) intervention, PTA alone and ATH-PTA was associated with similar outcomes in terms of vessel dissection and residual stenosis, mortality at 12 months, and limb amputation at 1 or 12 months.

Based on oxidized regenerated cellulose (ORC), several hemostyptic materials, such as Tabotamp®, Equicel® and Equitamp®, have been developed to approach challenging hemostasis in neurosurgery. The present study compares ORC that differ in terms of compositions and properties, regarding their structure, solubility, pH values and effects on neuronal tissue. Cytotoxicity was detected via DNA-binding fluorescence dye in Schwann cells, astrocytes, and neuronal cells. Additionally, organotypic hippocampal slice cultures (OHSC) were analyzed, using propidium iodide, hematoxylin-eosin, and isolectin B4 staining to investigate the cellular damage, cytoarchitecture, and microglia activation. Whereas Equicel® led to a neutral pH, Tabotamp® (pH 2.8) and Equitamp® (pH 4.8) caused a significant reduction of pH (p &lt, 0.001). Equicel® and Tabotamp® increased cytotoxicity significantly in several cell lines (p &lt, 0.01). On OHSC, Tabotamp® and Equicel® led to a stronger and deeper damage to the neuronal tissue than Equitamp® or gauze (p &lt, 0.01). Equicel® increased strongly the number of microglia cells after 24 h (p &lt, 0.001). Microglia cells were not detectable after Tabotamp® treatment, presumably due to an artifact caused by strong pH reduction. In summary, our data imply the use of Equicel®, Tabotamp® or Equitamp® for specific applications in distinct clinical settings depending on their localization or tissue properties.

Investigate the efficacy of intravitreal adalimumab in breakthrough panuveitis in patients on systemic adalimumab for more than 3 months.Retrospective study of patients on systemic adalimumab with breakthrough panuveitis requiring intravitreal adalimumab therapy.Seven eyes of four patients with Adamantiades-Behçet disease panuveitis were included and all were maintained on systemic adalimumab for 7.3 months (range 3-11) with inflammation controlled for 4.1 months (range 2-10) before breakthrough uveitis. The total number of attacks was 13 over 24.5 months (range 12-30). Resolution of attack was defined as return to baseline visual acuity with resolution of inflammatory markers. Three attacks resolved after only one injection and 10 attacks required an average of 2.4 injections (range 2-3). No systemic or ocular complications were noted.Intravitreal adalimumab warrants further investigation as a potentially effective, practical and safe adjunctive therapy for the control of breakthrough inflammation in select patients maintained on systemic adalimumab.

OBJECTIVE This study analyzes the clinicopathologic findings and their impact on outcome of patients so as to identify which patients benefit most from surgical treatment in chronic pancreatitis, especially in regard to pain relief. SUMMARY BACKGROUND DATA The predominant symptom of chronic pancreatitis is chronic pain resulting in reduced quality of life. It is well known that the main reason for development of the disease is abuse of alcohol and nicotine, but only little data on factors influencing outcome are available. METHODS One thousand one hundred forty-six consecutive patients who underwent surgery for chronic pancreatitis were included. Clinicopathologic data, including morphology of the pancreas in preoperative diagnostics and the histopathologic results, were evaluated. A long-term follow-up including Quality of Life and pain scores was performed. Additionally, we describe the novel Chronic Pancreatitis Pain Relief Score (CPPR-Score) as a tool for prediction of pain relief. RESULTS Overall the rate of pain relief was 79.8% after surgery. The presence of an inflammatory mass in the pancreatic head larger than 4 cm (P < 0.001), presence of a dilated main pancreatic duct of over 4 mm (P < 0.001), histopathologically detected severe calcifications (P = 0.001) and severe fibrosis (P < 0.001) as well as ethanol induced disease (P < 0.001) found to be strong independent prognostic factors for pain relief. The CPPR-Score (0-5 points) proved to be a very good predictive score for pain-relief (P < 0.001). CONCLUSIONS The rate of pain relief after surgical treatment in chronic pancreatitis is high and the commonly used procedures can be performed with acceptable morbidity and mortality. The Chronic Pancreatitis Pain Relief Score allows identifying patients who will benefit most from surgery.

Performing colorectal surgery with previous da Vinci system generations presented some limitations that caused uncertainty for surgeons as they began to apply robotic technologies. The da Vinci Xi system is designed to overcome these limitations and to enable multiquadrant colorectal surgery.The design concept of the da Vinci Xi system and the standardized access for colorectal surgery are explained.The da Vinci Xi system applies an overhead boom that maximizes the arm workspace, minimizes interference and makes the port placement universal for standardized access. Colorectal approaches have been validated in numerous cadaver models confirming the reproducibility of the standardized access.Standardized access with a straight-line port placement is possible in all colorectal applications. For right-sided hemicolectomy, a transverse abdominal approach as well as a suprapubic port placement are possible. Utilizing the same principles, left-sided colectomy, sigmoid colectomy and low anterior resections can be performed. Proctocolectomy is enabled through boom rotation and a second docking. Only minor arm-to-arm interferences occurred and were easily manageable by the bedside assistant. None of the approaches required rearrangement of the patient cart or swapping arms to different port locations.The da Vinci Xi system enables a standardized access for colorectal surgery through a universal straight-line port placement. Learning this standard principle once enables the surgeon to apply it to all colorectal surgeries and shorten the learning curve as well as minimizing stress for both novices and experienced robotic surgeons learning a new surgical robotic platform.

Purpose: Esophageal perforations are associated with high morbidity and mortality. Different nonoperative and operative treatment options have been proposed. This study focuses on the impact of different surgical treatments in nonmalignant esophageal perforations and tries to identify predictors of mortality in a single tertiary center over a 15-year period. Methods: From 2002 to 2017, patients with surgically managed esophageal perforation were identified from our database. Patients with esophageal malignancies were excluded. Etiology, clinical data, treatment, and outcome were analyzed. A multivariate logistic regression analysis was performed to investigate the impact on mortality. Results: A total of 72 patients were identified. The majority of perforations were iatrogenic (54.2%) followed by Boerhaave’s syndrome (23.6%). Most ruptures were found in the distal third of the esophagus (59.7%) measuring p < 0.0001) and mortality (p = 0.032). A correlation between an increasing perforation length with sepsis (p = 0.012) was observed. A higher Perforation Severity Score (PSS; OR 4.430; 95% CI 1.143–17.174; p = 0.031) and a higher American Society of Anesthesiologists (ASA) score (OR 2.923; 95% CI 1.011–8.448; p = 0.048) were associated with mortality in multivariate analysis. Conclusion: Esophageal perforations are associated with high mortality, and larger ruptures are associated with worse outcome. Rapid diagnosis and treatment are crucial for patient survival. Hence, PSS and ASA score help to identify high-risk patients. The advantage of surgical management lies in the rapid control of the septic focus in an already critically ill patient. Though, the kind of surgical technique needs to be adjusted to the individual situation.

Heparin dosing of patients anticoagulated with direct oral anticoagulants (DOACs) undergoing atrial fibrillation (AF) ablation can be challenging as they require more heparin than those on warfarin therapy. We sought to compare periprocedural activated clotting times (ACTs) of patients on warfarin vs. DOAC and determine an optimal weight-based heparin dosage strategy. Patients who underwent AF ablation over 28 months were reviewed for type of anticoagulation, intraprocedural heparin dosing, ACTs, and adverse outcomes. A heparin dosing strategy was then tested in a prospective validation cohort. There were 89 patients in the DOAC group and 43 in the warfarin group. Demographics, comorbidities, and complication rates were similar. Mean ACT and percentage of therapeutic ACTs were lower in the DOAC group, most significantly in those with a weight > 90 kg. In DOAC patients, a higher initial heparin bolus ≥ 150 units/kg yielded a higher percentage of therapeutic intraprocedural ACTs (49% ± 10 vs. 29% ± 7, p = 0.0008). In a prospective validation cohort of 25 patients administered an initial heparin bolus ≥ 150 units/kg, the mean ACT was 295 ± 33 and 49% of the ACTs collected were therapeutic, similar to findings of our high-dose retrospective subgroup. Patients on DOACs require more heparin during AF ablation to achieve therapeutic ACT. We suggest an initial heparin dose of at least 150 units/kg in this subset of patients, particularly in those with a weight > 90 kg.

The histological processing of musculoskeletal tissue might be challenging. The alteration of tissue composition e.g. by calcification of soft tissue in the elderly, after trauma or surgical interventions makes the histological processing of fixed tissue difficult. Additional steps of decalcification are then needed that probably affect the staining quality. In the present work, the effects of different decalcification agents and the intermedium methyl benzoate on histological staining methods and immunohistochemistry have been compared. Acetabular labra were fixed with 4% paraformaldehyde, left untreated or decalcified using 30% ethylenediaminetetraacetic acid (EDTA; Chelaplex®) or 6% trichloroacetic acid (TCA) for 1-4 days to investigate the effects of decalcification duration. Moreover, samples were pretreated with methyl benzoate or conventionally paraffin embedded independent of decalcification procedure and duration. The specimens were evaluated using hemalaun-eosin, Azur II- methylene blue staining or immunohistochemistry against ankyrin B to visualize nerve fibers. Decalcification with Chelaplex® or TCA reduced cutting artifacts without affecting the tissue morphology and proteoglycan staining but decreased antigenicity in immunohistochemistry. Interestingly, methyl benzoate further reduced cutting artifacts without altering tissue morphology and elevated antigenicity for Chelaplex® decalcified tissue samples in immunohistochemistry. The decalcification with Chelaplex® or 6% TCA preserves tissue morphology and proteoglycan staining similar to non- decalcified tissue but facilitates section processing. In immunohistochemistry both decalcification agents decreased antigenicity. Chelaplex® decalcified, methyl benzoate treated samples yielded an improved antigenicity.

The mechanisms behind the anti-tumoral effects of cannabinoids by impacting the migratory activity of tumor cells are only partially understood. Previous studies demonstrated that cannabinoids altered the organization of the actin cytoskeleton in various cell types. As actin is one of the main contributors to cell motility and is postulated to be linked to tumor invasion, we tested the following hypothesizes: 1) Can cannabinoids alter cell motility in a cannabinoid receptor dependent manner? 2) Are these alterations associated with reorganizations in the actin cytoskeleton? 3) If so, what are the underlying molecular mechanisms? Three different glioblastoma cell lines were treated with specific cannabinoid receptor 1 and 2 agonists and antagonists. Afterwards, we measured changes in cell motility using live cell imaging and alterations of the actin structure in fixed cells. Additionally, the protein amount of phosphorylated p44/42 mitogen-activated protein kinase (MAPK), focal adhesion kinases (FAK) and phosphorylated FAK (pFAK) over time were measured. Cannabinoids induced changes in cell motility, morphology and actin organization in a receptor and cell line dependent manner. No significant changes were observed in the analyzed signaling molecules. Cannabinoids can principally induce changes in the actin cytoskeleton and motility of glioblastoma cell lines. Additionally, single cell motility of glioblastoma is independent of their morphology. Furthermore, the observed effects seem to be independent of p44/42 MAPK and pFAK pathways.

An experimental study was conducted to assess loss of

Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution. L3.6pl cell line served as a control. Anti-proliferative efficacy of three different HSP90 inhibitors (17-AAG, 17-DMAG and 17-AEPGA) was evaluated by the MTT assay. Alterations in signaling pathway effectors and apoptosis upon HSP90 inhibition were determined by western blot analysis and annexin V/PI staining. The cell lines 5061, 5072 and 5156 were resistant to gemcitabine and 5-FU. In contrast 17-AAG and the water-soluble derivates 17-DMAG and 17-AEPGA displayed high anti-proliferative activity in all tested cell lines. The calculated IC50 was below 1 µM. Highly significant down regulation of epidermal-growth-factor-receptor, insulin-like-growth-factor-receptor-1, AKT and MAPK reflected the intracellular molecular signaling-network disruption. Furthermore, besides HSP70 also HSP27 was upregulated in all cell lines. Apoptosis occurred early under HSP90 inhibition and was determined by annexin V/PI staining and CASPASE-3 and PARP assay. In contrast, gemcitabine treated cells did not show any apoptosis. HSP90 inhibition disrupts multiple signaling cascades in gemcitabine and 5-FU resistant PC simultaneously and promotes cancer cell apoptosis. Watersoluble 17-DMAG is equally effective as 17-AAG. HSP27, besides HSP70, may represent an effective response marker of successful HSP90 inhibition.

Esophageal resection for cancer (EC) is still associated with considerable mortality and morbidity rates. Allogenic blood transfusion (aBT) is associated with poor short-term and long-term outcome in surgical oncology. We aimed to evaluate the effect of aBT in a homogeneous population of EC patients undergoing esophagectomy without perioperative treatment. We analyzed 565 esophagectomies performed due to EC. Allogenic blood transfusion was correlated to clinicopathological parameters, perioperative mortality and morbidity as well as the long-term outcome. Results are presented as adjusted odds ratio (OR) or hazard ratio (HR) with 95 % confidence interval (95 % CI). Patients receiving aBT (aBT(+)) had no higher tumor stages or higher rates of lymph node metastasis (P = 0.65 and 0.17, respectively) compared to patients without aBT (aBT(−)). Allogenic blood transfusion was strongly associated with perioperative morbidity (OR 1.9, 95 % CI 1.1–3.5, P = 0.02) and mortality (OR 2.9, 95 % CI 1.0–8.6, P = 0.04). Tumor recurrence rate was significantly higher in aBT(+) patients (P = 0.001). The disease-free and overall survival were significantly longer in aBT(−) compared to aBT(+) patients (P = 0.016 and

Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue. We tested the hypothesis whether cannabinoids influence the tumor cell specific mechanical and migratory properties and if these factors are a prognostic marker for the invasiveness of tumor cells.3 different glioblastoma cell lines were treated with cannabinoids and changes of mechanical and migratory properties of single cells were measured using atomic force microscopy and time lapse imaging. The invasiveness of cell lines was determined using a co-culture model with organotypic hippocampal slice cultures.We found that cannabinoids are capable of influencing migratory and mechanical properties in a cell line specific manner. A network analysis revealed a correlation between a "generalized stiffness" and the invasiveness for all tumor cell lines after 3 and 4 d of invasion time: rHere we could show that a "generalized stiffness" is a profound marker for the invasiveness of a tumor cell population in our model and thus might be of high clinical relevance for drug testing. Additionally cannabinoids were shown to be of potential use for therapeutic approaches of glioblastoma.

Lipedema is a painful loose connective tissue disorder characterized by a bilaterally symmetrical fat deposition in the lower extremities. The goal of this study was to characterize the adipose-derived stem cells (ASCs) of healthy and lipedema patients by the expression of stemness markers and the adipogenic and osteogenic differentiation potential. Forty patients, 20 healthy and 20 with lipedema, participated in this study. The stromal vascular fraction (SVF) was obtained from subcutaneous thigh (SVF-T) and abdomen (SVF-A) fat and plated for ASCs characterization. The data show a similar expression of mesenchymal markers, a significant increase in colonies (p &lt, 0.05) and no change in the proliferation rate in ASCs isolated from the SVF-T or SVF-A of lipedema patients compared with healthy patients. The leptin gene expression was significantly increased in lipedema adipocytes differentiated from ASCs-T (p = 0.04) and the PPAR-&gamma, expression was significantly increased in lipedema adipocytes differentiated from ASCs-A (p = 0.03) compared to the corresponding cells from healthy patients. No significant changes in the expression of genes associated with inflammation were detected in lipedema ASCs or differentiated adipocytes. These results suggest that lipedema ASCs isolated from SVF-T and SVF-A have a higher adipogenic differentiation potential compared to healthy ASCs.

Minimally invasive surgery (MIS) has superior short-term outcomes than open surgery (OS) for colorectal cancer (CRC). However, a nationwide dataset has not been analysed to confirm these findings. We evaluated the distribution and outcomes of MIS for CRC from 2005 to 2015; all in-patients with CRC surgery procedure codes were identified from hospital data, which are entered into the nationwide diagnosis-related group database and forwarded anonymised to the Federal Bureau of Statistics. We determined absolute MIS, morbidity, and mortality rates for specific sub-categories, including procedure type. We identified 345,913 in-patient files. The MIS rate increased from 6.4% (n = 2366; 2005) to 28.5% (n = 8363; 2015), with the highest rates for sigmoid colon (38%) and rectal (39%) resections. The overall conversion rate was 14.4%, without noticeable improvement over time. International Classification of Disease codes related to postoperative complications were documented more frequently after OS than after MIS. OS was associated with a higher mortality rate (4.7%) than MIS (1.8%) (P