Hesse (Germany)

ObjectiveStatus epilepticus (SE) represents one of the most common neurological emergencies. The International League Against Epilepsy (ILAE) redefined SE duration thresholds from 30 to 5 min for convulsive SE in 2015. We conducted a prospective population‐based study to determine SE incidence and outcomes under the revised criteria and compared findings with historical data using the 30‐min definition.MethodsA prospective, population‐based cohort study was conducted over a period of 18 months to determine the incidence of SE in Germany, replicating the methodology of a first study conducted in this region in 1999. The study included all adults residing within the 35‐postcode area, with participation from all regional hospitals and emergency departments. SE cases were prospectively identified and reported. To ensure comparability with the historical data, the analysis focused on the Primary Service Area (PS‐Area)—the direct catchment region of the University Hospital Marburg.ResultsA total of 180 adults with SE (96 men, mean age 66.47 years, SD ± 18.5 years, range: 20–94 years). The crude annual incidence in the PS‐Area increased from 15.8/100 000 (95% confidence interval [CI] 11.2–21.6) in 1999 to 29.4/100 000 adults (95% CI 20.5–40.0). It was higher in men than in women (30.9 vs 28.1/100 000, p = .11) and in patients ≥60 years (68.5 vs 13.5/100 000; p < .0001). The calculated age‐ and gender‐adjusted incidence was 32.5/100 000 in the PS‐Area. The case–fatality rate was 5.77% (95% CI 1.2%–12.7%) and the crude annual cause‐specific mortality rate per 100 000 is 1.70 (95% CI 0.21–4.73). In 53% SE was the first seizure episode; only 47% had a history of epilepsy. When extrapolating these findings to the entire German population, there were at least 20 000 cases of SE with 1000 associated deaths annually.SignificanceThese findings provide new epidemiologic evidence that the incidence of SE has increased by ~12% with the adoption of the ILAE 2015 definition, underscoring the impact of updated diagnostic criteria on epidemiological estimates.

Investigations into the maximum strength capacity of the plantarfl exors have gained interest. An excellent intraclass correlation coeffi &amp;nbsp;cient (ICC) for the standing calf raise-1RM has been reported. However, research has shown that ICC alone does not suffi &amp;nbsp;ciently refl ect measurement reliability. The aim of this study was to reassess the reliability of the standing calf raise-1RM. Fifty-six physical education students performed standing calf raises on two occasions. ICC, standard error of measurement (SEM), and minimal detectable change (MDC) were calculated, as well as mean absolute error, mean absolute percentage error, and typical error. A dependent t-test was performed to assess systematic error, and a Bland-Altman plot was created. Low levels of both absolute and relative error were observed. Comparing the diff erent measures, previous criticisms of the ICC and measures calculated from it, such as SEM and MDC, are highlighted. Researchers are advised to report various independent measures to illustrate the accuracy of their procedures.

Aneurysms and dissections represent some of the most serious cardiovascular diseases. The prevailing theory posits that mechanical overloading of the vessel wall is the underlying cause. Inspired by Barkhordarian et al, the authors present matrix metalloproteinases (MMPs) and their inhibitors in immunohistological analyses as contributing factors in the pathophysiology of aortic aneurysms (AA). Data analysis of MMP-1, MMP-9, tissue inhibitors of metalloproteinases (TIMPs), including TIMP-1 and TIMP-2 expression reveals a varied distribution between the adventitia and media and a non-uniform expression of the investigated markers. These elements, as key components of the extracellular matrix (ECM), indicate that the formation of AA is not solely driven by endoluminal pressure loading of the aortic wall. Instead, degenerative processes within ECM elements contribute significantly. Importantly, AA do not necessarily imply dissection. Tissue destruction, allowing blood flow entry, arises from reduced oxygen supply to the media, primarily due to incomplete capillarization or neocapillarization.

Tumor-associated antigen-based cancer vaccines suffer from limited clinical success compared to alternative immunotherapies in melanoma, an aggressive skin cancer with an immunosuppressive tumor microenvironment. The anti-tumor potential of a multivalent nanoconjugate cancer vaccine platform - a cross-linked star-shaped polyglutamate carrier (StCl) with marked lymphotropic character conjugated with melanoma-associated peptide antigens is evaluated through redox-responsive linkers. The co-delivery of melanoma-associated peptide antigens by the nanoconjugate platform induced significant effector immune responses in a mouse melanoma model. The nanoconjugate platform synergized with a PD-1 inhibitor to revert the immunosuppressive melanoma tumor microenvironment by improving cytotoxic T-cell infiltration, which prompted a superior anti-tumor effect with prolonged overall survival without acute organ toxicity. The antigen-specific anti-tumor immune response induced by the nanoconjugate platform is also validated in a melanoma patient-derived xenograft mouse model. A promising, versatile StCl-based platform is reported for generating off-the-shelf multivalent nanoconjugate cancer vaccines for the safe and efficient immunotherapeutic treatment of melanoma.

Infective endocarditis (IE) is associated with extremely high surgical mortality. During the SARS-CoV-2 pandemic, hospitals restructured their intensive care units and outpatient services to prioritize COVID-19 care, which may have affected the outcomes of patients requiring urgent procedures. This study aimed to evaluate the impact of the pandemic on surgical outcomes of IE patients in Southern Germany.This observational, community-based study compared two cohorts of surgical candidates: a pandemic cohort from March 2020 to November 2021 (n = 84) and a pre-pandemic cohort from August 2018 to March 2020 (before the lockdown, n = 94). Preoperative status and postoperative in-hospital complications were analyzed and compared between the groups.The pandemic cohort experienced longer symptom onset to diagnosis intervals (14.5 versus 8 days, p = 0.529). A higher incidence of definite IE was observed after the lockdown according to the modified Duke criteria (82.1% versus 68.1%, p = 0.035). Patients presented with more severe symptoms post-lockdown (NYHA Class III: 50% versus 33%; Class IV: 22.6% versus 11.7%, p = 0.001). Postoperative complications, such as re-thoracotomy due to bleeding and hemofiltration for acute renal failure, were significantly more frequent after the lockdown (p < 0.05). However, in-hospital survival rates did not differ significantly between the groups.The COVID-19 pandemic and related lockdown measures were associated with delayed diagnoses and worse perioperative outcomes for surgical IE patients, highlighting the need for improved management strategies during public health crises.

BackgroundResults from the CONVINCE clinical trial suggest a 23% mortality risk reduction among patients receiving high-volume (> 23 L) hemodiafiltration. We assessed the real-world effectiveness of blood-based kidney replacement therapy (KRT) with hemodiafiltration vs. hemodialysis in a large, unselected patient population treated prior to and during the COVID-19 pandemic.MethodsIn this retrospective cohort study, we analyzed pseudonymized data from 85,117 adults receiving in-center care across NephroCare clinics in Europe, the Middle East, and Africa during 2019–2022. Cox regression models with KRT modality and coronavirus disease 2019 (COVID-19) status as time-varying covariates, and adjusted for multiple confounders, were used to estimate all-cause (primary) and cardiovascular (secondary) mortality. Subgroup analyses were performed for age, dialysis vintage, COVID-19 status, diabetes, and cardiovascular disease.ResultsAt baseline, 55% of patients were receiving hemodialysis and 45% of patients were receiving hemodiafiltration. Baseline characteristics were similar between baseline modalities, except that hemodiafiltration patients were a median of 2 years younger, had higher percentage of fistula access (66% vs. 47%), and had longer mean dialysis vintages (4.4 years vs. 2.6 years). Compared with hemodialysis, hemodiafiltration was associated with an adjusted hazard ratio (HR) for all-cause mortality of 0.78 (95% confidence interval [Cl], 0.76–0.80), irrespective of COVID-19 infection. The pattern of a beneficial effect of hemodiafiltration was consistently observed among all analyzed subgroups. Among patients receiving high-volume hemodiafiltration (mean convection volume ≥ 23 L), the risk of death was reduced by 30% (HR, 0.70 [95% CI, 0.68–0.72]). Hemodiafiltration was also associated with a 31% reduced risk of cardiovascular death.ConclusionsOur results suggest that hemodiafiltration has a beneficial effect on all-cause and cardiovascular mortality in a large, unselected patient population and across patient subgroups in real-world settings. Our study complements evidence from the CONVINCE trial and adds to the growing body of real-world evidence on hemodiafiltration.

This study aims to evaluate the measurement accuracy of computed tomography (CT) systems, focusing on the necessity of using calibration phantoms for enhanced precision. Both clinical CT and micro-CT systems were evaluated using a specially designed two-ball phantom, which provides a reliable reference for spatial resolution and geometric accuracy. The study involved scanning the phantom with two micro-CT devices (the oversize micro-CT SkyScan 1173 and the high-resolution micro-CT SkyScan 1272) and a clinical CT device, a third-generation dual-source CT scanner (SOMATOM Force), measuring the distance between the centres of two ruby balls. The results showed significant differences in measurement accuracy between the devices. The high-resolution micro-CT provided the most consistent measurements with minimal variance, indicating its superiority in applications requiring high precision. In contrast, the oversize micro-CT exhibited larger errors, particularly at smaller voxel sizes, suggesting that internal calibration affected its accuracy. The dual source CT system had the smallest mean error but a larger standard deviation, indicating less consistency compared to micro-CT systems. Calibration with the two-ball phantom improved measurement accuracy across all devices. This improvement underscores the importance of using calibration phantoms to ensure accurate measurements, especially in fields that require high precision, such as clinical diagnostics and materials science. We concluded that routine calibration with phantoms is essential to achieve high measurement accuracy in CT imaging, thereby increasing the reliability of CT-based analyses in various disciplines.