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    Corona mortis: clinical evaluation of prevalence, anatomy, and relevance in anterior approaches to the pelvis and acetabulum.

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    PURPOSE To evaluate the clinical prevalence, characteristics, and relevance of the corona mortis (CM) in anterior approaches to the pelvis and acetabulum. METHODS Retrospective analysis of 185 theater reports from patients (73 females; mean age 62.8 ± 17.2 years) who underwent surgeries for pelvic ring injuries, acetabular fractures, or combined injuries using anterior approaches (Modified Stoppa or Pararectus) at our institution between 01/2008 to 12/2022. During procedures, the CM was routinely identified, evaluated, and occluded. Bilateral exposure of the superior pubic branch in 25 cases led to 210 hemipelvises analyzed. EXCLUSIONS CM not mentioned in report and revisions via the initial approach. RESULTS In the 210 hemipelvises examined, the prevalence of any CM vessel was 81% (170/210). Venous anastomoses were found in 76% of hemipelvises (159/210), arterial in 22% (47/210). Sole venous anastomoses appeared in 59% (123/210), sole arterial in 5% (11/210). Both types coexisted in 17% (36/210), while 19% (40/210) had none. A single incidental CM injury occurred without significant bleeding. In ten cases, trauma had preoperatively ruptured the CM, but bleeding was readily managed. Females had a significantly higher CM prevalence than males (p = 0.001). CONCLUSION Our findings show a CM prevalence aligning more with anatomical studies than prior intraoperative series. Although we observed one incidental and ten trauma-related CM injuries, we did not encounter uncontrollable bleeding. Our data suggest that in anterior pelvic approaches, when the CM is actively identified and occluded, it is not associated with bleeding events, despite its high prevalence

    Prevalence of Painful Lesions of the Digits and Risk Factors Associated with Digital Dermatitis, Ulcers and White Line Disease on Swiss Cattle Farms.

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    The first aim of this study was to calculate the prevalence of painful lesions of the digits ("alarm" lesions; ALs) in Swiss dairy herds and cow-calf operations over a three-year study period. The following ALs were included in the calculation: the M2 stage of digital dermatitis (DD M2), ulcers (U), white line fissures (WLF) of moderate and high severity, white line abscesses (WLA), interdigital phlegmon (IP) and swelling of the coronet and/or bulb (SW). Between February 2020 and February 2023, digit disorders were electronically recorded during routine trimmings by 40 specially trained hoof trimmers on Swiss cattle farms participating in the national claw health programme. The data set used consisted of over 35,000 observations from almost 25,000 cows from 702 herds. While at the herd-level, the predominant AL documented in 2022 was U with 50.3% followed by WLF with 38.1%, at the cow-level, in 2022, it was DD M2 with 5.4% followed by U with 3.7%. During the study period, within-herd prevalences of ALs ranged from 0.0% to a maximum of 66.1% in 2020. The second aim of this study was to determine herd- and cow-level risk factors associated with digital dermatitis (DD), U and white line disease (WL) in dairy cows using data from 2022. While for DD, analysed herd-level factors appeared to have a greater effect on the probability of its occurrence, the presence of U and WL was mainly associated with the analysed cow-level factors. The risk for DD increased with a higher herd trimming frequency. Herds kept in tie stalls had a lower risk for DD and WL and a higher risk for U compared to herds kept in loose housing systems. Herds with predominantly Holstein Friesian cows as well as Holstein Friesian cows had a higher risk for the occurrence of DD compared to herds and cows of other breeds. With increasing parity, cows had a higher risk of developing U and WL, whereas for DD, parity was negatively associated with prevalence. Cows trimmed during the grazing period had a higher risk of U and WL than cows trimmed during the housing period. These findings may contribute to improve management measures affecting the health of the digits in farms with structures similar to those evaluated in the current study, such as small herds with frequent access to pasture. Further research is warranted to demonstrate how measures addressing the current results combined with those of individual herd risk assessments might contribute to an improvement in the health of the digits in the respective dairy herds

    Treatment Patterns and Use of Immune Checkpoint Inhibitors Among Patients with Metastatic Bladder Cancer in a Dutch Nationwide Cohort.

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    Since 2017, two immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of metastatic urothelial carcinoma in Europe: pembrolizumab as second-line therapy and avelumab as maintenance therapy. Our aim was to describe the use of ICIs as first and later lines of treatment in patients with metastatic bladder cancer (mBC) in the Netherlands. We identified all patients diagnosed with primary mBC between 2018 and 2021 in the Netherlands from the Netherlands Cancer Registry (NCR). NCR data were supplemented with data from the Dutch nationwide Prospective Bladder Cancer Infrastructure (ProBCI) collected from medical files, with follow-up until death or end of data collection on January 1, 2023. A total of 1525 patients were diagnosed with primary mBC between 2018 and 2021 in the Netherlands. Of these, 34.7% received at least one line of systemic treatment with chemotherapy or ICI. After first-line platinum-based chemotherapy, 34.1% received second-line ICI and 3.9% received maintenance ICI. Among patients who completed or discontinued first-line cisplatin- or carboplatin-based chemotherapy after approval of maintenance ICI in the Netherlands, 40.7% and 19.7% received second-line ICI, and 9.3% and 14.1% received maintenance ICI, respectively. ICI use for mBC treatment has not increased considerably since their introduction in 2017. Future research should assess whether the introduction of maintenance avelumab (available since April 2021 in the Netherlands) has led to increases in the proportion of patients with mBC patients receiving systemic treatment and the proportion receiving ICI. PATIENT SUMMARY We assessed the rate of immunotherapy use for patients with metastatic bladder cancer in the Netherlands. Since its introduction, immunotherapy has been used in a minority of patients, mostly as second-line treatment after platinum-based chemotherapy

    Decreasing implant load indicates spinal fusion when measured continuously.

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    Reliable and timely assessment of bone union between vertebrae is considered a key challenge after spinal fusion surgery. Recently, a novel sensor concept demonstrated the ability to objectively assess posterolateral fusion based on continuous implant load monitoring. The aim of this study was to investigate systematically the concept in a mono-segmental fusion model using an updated sensor setup. Three sheep underwent bilateral facetectomy at level L2-L3 and L4-L5. The segments were stabilized using two unconnected pedicle-screw-rod constructs per level. Sensing devices were attached to the rods between each pedicle screw pair and the loads were continuously monitored over 16 weeks. After euthanasia, the spines were biomechanically tested for their range of motion and high-resolution CT scans were performed to confirm the fusion success. After an initial increase in implant load until reaching a maximum (100 %) at approximately week 4, eleven out of twelve sensors measured a constant decrease in implant load to 52 ± 9 % at euthanasia. One sensor measurement was compromised by newly forming bone growing against the sensor clamp. Bridging bone at each facet and minor remnant segmental motion (<0.7°) confirmed the fusion of all motion segments. Data obtained by continuous measurement of implant loading of spinal screw-rod constructs enables objective monitoring of spinal fusion progression. The sensor concept provides valuable real-time information, offering quantifiable data as an alternative to traditional imaging techniques. However, the design of the current sensor concept needs to be matured, tailored to, and validated for the human spine

    Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

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    BACKGROUND Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (177Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. FINDINGS Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225Ac-PSMA RLT. All patients who received more than seven cycles of 225Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. INTERPRETATION 225Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. FUNDING None

    Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms.

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    Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPNs), most commonly JAK2V617F. While clinically-approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined, Dre-rox/Cre-lox dual recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic stem/progenitor cells, and extends overall survival to an extent not observed with pharmacologic JAK inhibition, including when co-occurring with somatic Tet2 loss. Our data suggest JAK2V617F represents the best therapeutic target in MPNs and demonstrate the therapeutic relevance of a dual-recombinase system to assess mutant-specific oncogenic dependencies in vivo

    Une lutte pour la mémoire : entretien avec Hèctor Parra à propos de son opéra Justice

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    Dans cet entretien, le compositeur Hèctor Parra échange avec Luis Velasco-Pufleau à propos de son opéra "Justice", coproduit par le Grand Théâtre de Genève et le Festival Tangente St. Pölten (Autriche). Basé sur le scénario du metteur en scène suisse Milo Rau et le livret de l’écrivain congolais Fiston Mwanza Mujila, la trame de "Justice" se déroule dans le Katanga, une région de la République démocratique du Congo (RDC) extrêmement riche en minerais et dont les ressources ont attiré la convoitise des entreprises minières étrangères depuis la brutale colonisation belge du Congo jusqu’à aujourd’hui. Parra parle des collaborations artistiques et du processus de création de cet opéra

    Airborne transmission risks of tuberculosis and COVID-19 in schools in South Africa, Switzerland, and Tanzania: Modeling of environmental data.

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    The COVID-19 pandemic renewed interest in airborne transmission of respiratory infections, particularly in congregate indoor settings, such as schools. We modeled transmission risks of tuberculosis (caused by Mycobacterium tuberculosis, Mtb) and COVID-19 (caused by SARS-CoV-2) in South African, Swiss and Tanzanian secondary schools. We estimated the risks of infection with the Wells-Riley equation, expressed as the median with 2.5% and 97.5% quantiles (credible interval [CrI]), based on the ventilation rate and the duration of exposure to infectious doses (so-called quanta). We computed the air change rate (ventilation) using carbon dioxide (CO2) as a tracer gas and modeled the quanta generation rate based on reported estimates from the literature. The share of infectious students in the classroom is determined by country-specific estimates of pulmonary TB. For SARS-CoV-2, the number of infectious students was estimated based on excess mortality to mitigate the bias from country-specific reporting and testing. Average CO2 concentration (parts per million [ppm]) was 1,610 ppm in South Africa, 1,757 ppm in Switzerland, and 648 ppm in Tanzania. The annual risk of infection for Mtb was 22.1% (interquartile range [IQR] 2.7%-89.5%) in South Africa, 0.7% (IQR 0.1%-6.4%) in Switzerland, and 0.5% (IQR 0.0%-3.9%) in Tanzania. For SARS-CoV-2, the monthly risk of infection was 6.8% (IQR 0.8%-43.8%) in South Africa, 1.2% (IQR 0.1%-8.8%) in Switzerland, and 0.9% (IQR 0.1%-6.6%) in Tanzania. The differences in transmission risks primarily reflect a higher incidence of SARS-CoV-2 and particularly prevalence of TB in South Africa, but also higher air change rates due to better natural ventilation of the classrooms in Tanzania. Global comparisons of the modeled risk of infectious disease transmission in classrooms can provide high-level information for policy-making regarding appropriate infection control strategies

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