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Background Vascular (VC) and cardiac structural complications (CSC) are frequent complications following transcatheter aortic valve implantation (TAVI). Aim of this single-center retrospective study was to evaluate strategies for minimizing periprocedural access complications as part of an interdisciplinary structural heart program. Methods Included were all patients who underwent TAVI between 09/2022 and 08/2023 at our institution. All procedures were performed by a heart team, consisting of a cardiovascular surgeon with peripheral vascular and interventional experience and an interventional cardiologist on site. Valvular type and size, access route and backup strategies were assessed by the heart team according to the preoperative CT-imaging. Baseline characteristics, periprocedural data, complications and 30-day outcomes were analyzed concerning the access route using Mann-Whitney-U-test or Fisher´s exact test. Results Analyzed were 167 consecutive patients (81 (76–85) years; 53.3% male). 48 (28.7%) of these had severe peripheral artery disease. 130 (77.8%) procedures were performed via a percutaneous transfemoral approach, 13 (7.8%) via a femoral cut-down and 4 (2.4%) via a transaxillary access. For 20 procedures (11.9%) a transapical access was used. 106 patients (72%) with transvascular and all patients with transapical access received a balloon-expanding valve, whereas 41 (28%) patients with transvascular access received a self-expanding prosthesis. No coronary occlusion was seen. Annular rupture occurred in one patient (0.6%), valve displacement in two patients (1.2%). Totally 5 (3%) access femoral arteries were stented and 8 (4.8%) needed a surgical reconstruction. 30-day mortality was 2.99%. Conclusions On site interventional and cardiovascular surgical expertise may minimize VC and CSC following TAVI.

Adverse outcomes associated with prescription drug use are common and costly. Many adverse outcomes can be avoided through pharmacogenomics: choosing and dosing of existing drugs according to a person's genomic variants. Finding and validating associations between outcomes and genomic variants and developing guidelines for avoiding drug-related adverse outcomes will require further research; however, no data-driven estimates yet exist for the time or money required for completing this research. We identified examples of associations between adverse outcomes and genomic variants. We used these examples to estimate the time and money required to identify and confirm other associations, including the cost of failures, and to develop and validate pharmacogenomic dosing guidelines for them. We built a Monte Carlo model to estimate the time and financial costs required to cut the overall rate of drug-related adverse outcomes by meaningful amounts. We analyzed the model's predictions for a broad range of assumptions. Our model projected that the development of guidelines capable of cutting overall drug-related adverse outcomes by 25%-50% with current approaches will require investment of single-digit billions of dollars and take 20 years. The model forecasts a pump-priming phase of 5-7 years, which would require expenditures of hundreds of millions of dollars, with little apparent return on investment. The single most important parameter was the extent to which genomic variants cause adverse outcomes. The size of the labor force was not a limiting factor. A \"50 000 Pharmacogenomes Project\" could speed progress. Our approach provides a template for other areas of genomic research.

The western painted turtle (Chrysemys picta bellii) can survive extended periods of anoxia via a series of mechanisms that serve to reduce its energetic needs. Central to these mechanisms is the response of mitochondria, which depolarize in response to anoxia in turtle pyramidal neurons due to an influx of K+. It is currently unknown how mitochondrial matrix pH is affected by this response and we hypothesized that matrix pH acidifies during anoxia due to increased K+/H+ exchanger activity. Inhibition of K+/H+ exchange via quinine led to a collapse of mitochondrial membrane potential (Ψm) during oxygenated conditions in turtle cortical neurons, as indicated by rhodamine‐123 fluorescence, and this occurred twice as quickly during anoxia which indicates an elevation in K+ conductance. Mitochondrial matrix pH acidified during anoxia, as indicated by SNARF‐1 fluorescence imaged via confocal microscopy, and further acidification occurred during anoxia when the F1Fo‐ATPase was inhibited with oligomycin‐A, indicating that ΔpH collapse is prevented during anoxic conditions. Collectively, these results indicate that the mitochondrial proton electrochemical gradient is actively preserved during anoxia to prevent a collapse of Ψm and ΔpH. The proton gradient is an essential component of adenosine triphosphate (ATP) production via the electron transport chain and oxidative phosphorylation. When oxygen availability is compromised (hypoxia/anoxia), mitochondrial electron transport ceases and the proton gradient is no longer maintained, which leads to mitochondrial dysfunction. We demonstrate here that the western painted turtle (Chrysemys picta bellii) defends mitochondrial membrane potential (Ψm) and the transmembrane pH gradient (ΔpH) during anoxia via a mitochondrial ATP‐sensitive potassium channel and potassium/proton exchanger circuit that is coupled to reversed ATP synthase activity, which hydrolyzes ATP to pump protons out of the mitochondrial matrix and preserve the proton gradient.

Background: Stool color card (SCC) screenings for biliary atresia (BA) have shown to improve Kasai timing and outcome significantly. Both obligatory and non-obligatory screenings with passive distribution strategies have proven to be effective. Therefore, we have initiated a voluntary SCC program and aim to describe our experience. Methods: Since 2017 we supply all maternity wards in Lower-Saxony with SCC. Attending pediatricians and parents of BA infants were contacted via questionnaires and asked for their evaluation of the SCC screening. Results: 85.2% of attending pediatricians support the SCC screening, but only 78.1% considered the initiative useful. In their clinical routine, only 67% of visiting parents report to have received an SCC at the maternity hospital. In the group of parents of BA infants, only 54% (7/13) had received an SCC. Out of those seven parents, only one had referred their child to a children’s hospital based on pathological SCC results. The lack of SCC education in the maternity hospitals was made responsible by parents. Within three years, only one infant with BA was identified through the SCC. Conclusions: Our voluntary SCC screening shows serious limitations with inacceptable distribution of SCCs and low acceptance of attending pediatricians. SCC programs in decentralized health care systems without educational campaigns, standardized diagnostic and treatment algorithms and the definition of reference centers are additional burdens for local health care providers without the promised benefit.

Initial identification of chronic myelogenous leukemia is very important since targeted therapy leads to life-saving remission. Rarely, chronic myelogenous leukemia presents with an unusual picture, making the diagnosis challenging. We describe such a case of chronic myelogenous leukemia in blast crisis in a previously healthy 61-year-old woman. The patient presented with fever, myalgias, and night sweats and was first worked up for an infectious etiology. Because of persistent anemia, a bone marrow biopsy was performed that revealed fibrosis with increased megakaryoblasts. Even though initial cytogenetic studies could not be performed because of “dry tap” aspirate, persistent efforts for cytogenetic studies were made, including a “squeeze preparation” from the core biopsy, which revealed t(9;22)(q34;q11.2) and trisomy 19. The patient was treated with tyrosine kinase inhibitors, chemotherapy, and subsequently an allogeneic stem cell transplant. She is in persistent remission. This case illustrates a complex presentation of chronic myelogenous leukemia and provides an overview of morphologic cues and the importance of performing cytogenetic studies that led to the diagnosis.

Context.—Clinical pathology (CP) laboratories are used for millions of tests each year. These lead to thousands of calls to CP residents. However, although laboratory utilization is a frequent topic of study, clinical utilization—the content of the interactions between clinicians and CP residents—is not. Because it reflects questions about laboratory utilization, clinical utilization could suggest ways to improve both training and care by reducing diagnostic error. Objectives.—To build and implement a secure, scalable Web-based system to allow CP residents at any hospital to track the calls they receive, the interaction's context, and the action taken as a result, with evidence where applicable, and to use this system to report on clinical utilization at a major academic hospital. Design.—Entries were analyzed from a nearly year-long period to describe the clinical utilization of CP at a large academic teaching hospital. Results.—Sixteen residents logged 847 calls during 10 months, roughly evenly distributed among transfusion medicine, chemistry, microbiology, and hematopathology. Calls covered 94 different analytes in chemistry and 71 different organisms or tests in microbiology. Analysis revealed areas where CP can improve clinical care through educating the clinical services, for example, about ordering Rh immune globulin, testosterone testing, and diagnosis of tick-borne diseases. Documenting calls also highlighted patterns among residents. Conclusions.—Clinical utilization is a potentially rich knowledge base for improving patient care and resident training. Our resident call-tracking system is a useful way for measuring clinical utilization and mining it for actionable information.

Guidelines for validating whole slide imaging (WSI) for primary diagnosis in surgical pathology have been recommended by an expert panel commissioned by the College of American Pathologists. The implementation of such a system using these validation guidelines has not been reported from the community hospital setting. The objective was to implement a WSI system, validate each pathologist using the system and run the system in parallel with routine glass slide interpretation. Six pathologists re-reviewed approximately 300 previously diagnosed specimens each, divided equally between glass slides and digital images (scanned at ×20). Baseline intraobserver discordance rates (glass to glass) were calculated and compared to discordance rates between the original glass slide interpretation and the reviewed digital slide interpretation. A minimum of 3 months was used as the washout period. After validation, a subset of daily cases was diagnosed in parallel using traditional microscopy (TM) and WSI over an 8-month period. The TM and WSI discordance rates ranged from 3.3% to 13.3% and 2.1% to 10.1%, respectively. There was no statistically significant difference among the pathologists. The parallel study yielded similar rates of discordances. In our laboratory, after appropriate implementation and training, there was no difference between the WSI and TM methods.

There has been a significant body of literature over the last decade that has focused on the growing prevalence of common mental disorders in elite athlete populations. This literature has provided the foundations for many other researchers to begin to develop focus on various concepts and phenomena associated with athlete mental health. However, within this body of literature there is a limited number of sources that have investigated the experiences of elite athlete mental health. The overall aim of this PhD was to explore experiences of athlete mental health and provide understanding of the potential antecedents associated with developing a common mental disorder in elite level sport, develop practical applications in treatment and referrals, contribute to future research, and reduce the stigma of mental health issues in elite level sport.Study OneThe aim of this research was to explore the mental health experiences of retired professional athletes. The study builds on existing sources that had developed the prevalence of common mental disorders in elite sport and sought to delve deeper into how elite athletes experience ‘mental health’. The study provided a novel insight of an often difficult to obtain participant sample and recruited four ex-professional athletes. Each participant was purposively recruited for the study and was selected based on the following inclusion criteria: 1) Participants must have been diagnosed with a common mental disorder during/post-career, 2) Participants must have competed to the highest possible level in their respective sport and achieved some success, e.g., won a major honour and represented their country. The four participants that were recruited were two retired English Premier League footballers, one retired rugby player, and one retired cricketer. Each participant had achieved the highest elite level in their sport, representing their country at a major tournament, as well as achieving domestic success with their club. Each participant took part in a semi-structured interview that ranged from 39-88 minutes. Once data was collected, interviews were transcribed verbatim and analysed using Braun and Clarke’s (2006, 2013) six phases of thematic analysis. Four main themes were found, (1) Injuries Affecting Mental Health, (2) Transitional Effects on Mental Health, (3) Identity Crisis Leading to Mental Health Issues, and (4) Coping Strategies to deal with Mental Health Issues. The findings indicated that athletes had suggested that retirement from sport, long-term or severe injuries, maladaptive coping mechanisms and identity crises either led to a common mental disorder or exacerbated a pre-existing common mental disorder. These findings outlined recommendations for enhancing mental health literacy in elite level sport, as well as also improving referral systems and the availability of professional support services to raise awareness and reduce the stigma of mental health in elite sport. This could improve the understanding of how mental health is perceived in elite level sport and how the stigma of this in professional sport has caused barriers to help-seeking in elite level athletes.Study TwoAs outlined in study one, several key themes were defined in accordance with retired athlete experiences in professional sport. As the study was exploratory in nature it was decided that the second study would seek to theorise and provide a greater sense of generalisability to the professional athlete population in the UK. To that end, the second study adopted a quantitative approach using a questionnaire specifically designed for the purposes of the study.