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BackgroundCOVID-19 vaccines are well tolerated and effective but may have adverse effects on the cardiovascular system. Vaccine-associated myocardial injury was analysed by measuring high-sensitive troponin T (hsTnT); mid-regional pro-adrenomedullin (MR-proADM) levels were evaluated to assess endothelial dysfunction.MethodsThis was a prospective study with a vulnerable population of healthcare workers (HCWs) and elderly patients (>70 years) who were vaccinated with either one dose of ChAdOx1 nCov-19 adenoviral vector vaccine (AZ) followed by one dose of the BNT162b2 messenger RNA vaccine (BNT), or with two doses of BNT (12th of January - 30th of November 2021). HsTnT and MR-proADM were measured in blood samples at three visits (V1: 1st immediately before vaccination; V2, 3: 3–4 weeks after 1st and 2nd vaccination). HsTnT of HCWs was compared to a healthy reference population.ResultsN = 162 volunteers were included (V1 = 161; V2, V3 = 162 each). N = 74 (45.7%) received AZ/BNT and n = 88 (54.3%) received BNT/BNT [elderly: n = 20 (12.3%), HCWs: n = 68 (42.0%)]. Median hsTnT levels were 4 ng/L, 5 ng/L and 4 ng/L (V1-V3) for AZ/BNT and at 5 ng/L, 6 ng/L and 6 ng/L (V1-V3) for BNT/BNT. Compared to the reference population (n = 300), hsTnT was significantly higher at all visits for both vaccination groups (p

Abstract Background In older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI. Methods We used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities. Results Out of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1–29.6); higher for men than women (33.9 (29.5–38.7) vs. 21.2 (18.1–24.6)). IR (CI) were lowest for persons aged 70–75 (13.1; 10.0-16.8) and highest for ≥ 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities. Conclusion AKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

Abstract Background Disruption of glucocorticoid (GC) signaling in osteoblasts results in a marked attenuation of acute antibody-induced arthritis. The role of endogenous GCs in chronic inflammatory arthritis is however not fully understood. Here, we investigated the impact of endogenous GC signaling in osteoblasts on inflammation and bone integrity under chronic inflammatory arthritis by inactivating osteoblastic GC signaling in a long-term K/BxN serum transfer-induced induced arthritis (STIA) model. Methods Intracellular GC signaling in osteoblasts was disrupted by transgenic (tg) overexpression of 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2). Inflammatory arthritis was induced in 5-week-old male tg mice and their wild type (WT) littermates by intraperitoneal (i.p.) injection of K/BxN serum while controls (CTRLs) received phosphate-buffered saline (PBS). In a first cohort, K/BxN STIA was allowed to abate until the endpoint of 42 days (STIA). To mimic rheumatic flares, a second cohort was additionally injected on days 14 and 28 with K/BxN serum (STIA boost). Arthritis severity was assessed daily by clinical scoring and ankle size measurements. Ankle joints were assessed histopathologically. Systemic effects of inflammation on long bone metabolism were analyzed in proximal tibiae by micro-computed tomography (μCT) and histomorphometry. Results Acute arthritis developed in both tg and WT mice (STIA and STIA boost) and peaked around day 8. While WT STIA and tg STIA mice showed a steady decline of inflammation until day 42, WT STIA boost and tg STIA boost mice exhibited an arthritic phenotype over a period of 42 days. Clinical arthritis severity did not differ significantly between WT and tg mice, neither in the STIA nor in the STIA boost cohorts. Correspondingly, histological indices of inflammation, cartilage damage, and bone erosion showed no significant difference between WT and tg mice on day 42. Histomorphometry revealed an increased bone turnover in tg CTRL and tg STIA boost compared to WT CTRL and WT STIA boost animals, respectively. Conclusions In contrast to the previously reported modulating effects of endogenous GC signaling in osteoblasts during acute K/BxN STIA, this effect seems to perish during the chronic inflammatory and resolution phase. These findings indicate that endogenous GC signaling in osteoblasts may mainly be relevant during acute and subacute inflammatory processes.

ObjectiveCold-inducible RNA binding Protein (CIRBP) has been shown to be a potent inflammatory mediator and could serve as a novel biomarker for inflammation. Systemic inflammatory response syndrome (SIRS) and capillary leak syndrome (CLS) are frequent complications after pediatric cardiac surgery increasing morbidity, therefore early diagnosis and therapy is crucial. As CIRBP serum levels have not been analyzed in a pediatric population, we conducted a clinical feasibility establishing a customized magnetic bead panel analyzing CIRBP in pediatric patients undergoing cardiac surgery.MethodsA prospective hypothesis generating observational clinical study was conducted at the German Heart Center Berlin during a period of 9 months starting in May 2020 (DRKS00020885, https://drks.de/search/de/trial/DRKS00020885). Serum samples were obtained before the cardiac operation, upon arrival at the pediatric intensive care unit, 6 and 24 h after the operation in patients up to 18 years of age with congenital heart disease (CHD). Customized multiplex magnetic bead-based immunoassay panels were developed to analyze CIRBP, Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Monocyte chemotactic protein 1 (MCP-1), Syndecan-1 (SDC-1), Thrombomodulin (TM), Vascular endothelial growth factor (VEGF-A), Angiopoietin-2 (Ang-2), and Fibroblast growth factor 23 (FGF-23) in 25 µl serum using the Luminex MagPix® system.Results19 patients representing a broad range of CHD (10 male patients, median age 2 years, 9 female patients, median age 3 years) were included in the feasibility study. CIRBP was detectable in the whole patient cohort. Relative to individual baseline values, CIRBP concentrations increased 6 h after operation and returned to baseline levels over time. IL-6, IL-8, IL-10, and MCP-1 concentrations were significantly increased after operation and except for MCP-1 concentrations stayed upregulated over time. SDC-1, TM, Ang-2, as well as FGF-23 concentrations were also significantly increased, whereas VEGF-A concentration was significantly decreased after surgery.DiscussionUsing customized magnetic bead panels, we were able to detect CIRBP in a minimal serum volume (25 µl) in all enrolled patients. To our knowledge this is the first clinical study to assess CIRBP serum concentrations in a pediatric population.

How do galaxies of different luminosities contribute to the metal absorber populations of varying species and strength? We present our analysis of the predicted metal contributions from galaxies as observed in quasar absorption line spectra during the end of the epoch of reionization (10 ≥ z ≥ 5.5). This was done by implementing on-the-fly particle tracking into the latest Technicolor Dawn simulation and then linking C ii , C iv , Si ii , Si iv , O i , and Mg ii absorbers to host galaxies in postprocessing. We define the host galaxy luminosity distribution (HGLD) as the rest-frame ultraviolet luminosity distribution of galaxies contributing ions to an absorber, weighted by the fractional contribution, and compute its dependence on ion and absorber strength. The HGLD shape is predicted to be indistinguishable from the field luminosity function, indicating that there is no relationship between the absorber strength or ion and the luminosity of the dominant contributing galaxy. Switching from galaxy luminosity to stellar mass, the predicted host galaxy mass distributions (HGMDs) indicate that more-massive galaxies contribute a higher fraction of metal ions to absorbers of each species, with the HGMDs of stronger absorbers extending out to higher masses. We conclude that the fraction of absorbing metal ions contributed by galaxies increases weakly with stellar mass, but the scatter in luminosity at fixed stellar mass obscures this relationship. For the same reason, we predict that observational analyses of the absorber–galaxy relationship will uncover stronger trends with stellar mass than with luminosity.

We implement a treatment of helium ii absorption and reemission into the Technicolor Dawn cosmological simulations to study its impact on the metagalactic ultraviolet background (UVB) in three dimensions. By comparing simulations with and without He ii reprocessing, we show that it weakens the mean UVB by ∼3 dex from z = 10–5 between 3.5 and 4 Ryd, where the He ii Lyman series resonance occurs. In overdense regions, the overall UVB amplitude is higher, and the impact of He ii reprocessing is weaker, qualitatively indicating an early start to He ii reionization near galaxies. Comparing our simulations to two popular one-dimensional UV models, we find good agreement up to 3 Ryd at z = 5. At higher energies, our simulation shows significantly greater He ii absorption because it accounts for He ii arising both in diffuse regions and in Lyman limit systems. By contrast, the comparison models account only for He ii in Lyman limit systems, which are subdominant prior to the completion of He ii reionization. The H i and He ii reionization histories are nearly unaffected by He ii reprocessing, although the cosmic star formation rate density is altered by up to 4%. The cosmic mass density of C iv is reduced by ∼2 dex when He ii is accounted for, while Si iv , C ii , Mg ii , Si ii , and O i are unaffected.

Abstract Frailty is very common in old age and often associated with adverse events. Transitioning between frailty states is possible in both directions (improvement and worsening) offering targets for interventions. Frailty is more prevalent in women, but little is known about the impact of gender on frailty transition. The aim of this study is to identify gender differences for frailty transition in older adults and to develop gender-stratified prognostic prediction models for frailty transition. We performed a longitudinal analyses of the Berlin Initiative (cohort) Study with a frailty follow-up of 2.1 years. Description of frailty transition using the frailty phenotype and development of prognostic prediction models using multivariable logistic regressions for transition (improvement or worsening) stratified by gender following the TRIPOD statement were performed. In total, the study population consisted of 1158 community-dwelling adults with a mean age of 84.4 years and of whom 55% were women. Out of 1158 participants 225 (19%) were robust, 532 (46%) prefrail and 401 (35%) frail. After 2.1 (IQR 2.0–2.3) years, half of the participants had transitioned between frailty states. Men worsened more often and those who were already frail died more often than women. Gender-stratified prediction models for frailty transition demonstrated that some predictors (age, self-rated health, cognitive impairment, baseline frailty status) were included in all models. While stroke, diabetes mellitus, smoking and glomerular filtration rate were unique predictors in the models for females, osteoarthritis, hospitalization and education were predictors in the models for males. There are gender differences in frailty transition rates, patterns and prediction. This supports the importance of considering gender when addressing frailty and targeting interventions in old age.

Abstract Background Pancreatic cancer is one of the leading causes of cancer mortality and one of the most lethal malignant neoplasms worldwide. It is known for its local tumor extension to the liver; other common sites include the lung, distant lymph nodes, and bone. Brain metastases are extremely rare and represent less than 0.6% of all brain metastases. Case report We report the case of a 66-year-old Caucasian female known to have adenocarcinoma of the tail of the pancreas treated with chemotherapy. During follow-up, thoracoabdominal computed tomography scans did not reveal any residual tumor or any metastasis. Moreover, tumor markers were within normal limits. She presented to the emergency department of our institution following an episode of a generalized tonic–clonic seizure 5 years following the initial diagnosis. Brain magnetic resonance imaging revealed an expansive left frontal intraaxial lesion compatible with high-grade glioma. The patient underwent surgical treatment. Histological examination revealed pancreatic metastasis. Conclusions Thought to be rare, metachronous cerebral pancreatic metastasis should be kept in mind in patients with pancreatic cancer. Early diagnosis and complete surgical resection play a key role in the survival of these patients.

Background Between 3 and 15% of winter sports–related injuries are related to head injuries, which are the primary cause of mortality and disability among skiers. Despite the widespread adoption of helmets in winter sports, which has reduced the incidence of direct head injury, there is a paradoxical trend of an increasing number of individuals wearing helmets sustaining diffuse axonal injuries (DAI), which can result in severe neurologic sequelae. Methods We retrospectively reviewed 100 cases collected by the senior author of this work from 13 full winter seasons during the period from 1981 to 1993 and compared them with 17 patients admitted during the more shortened 2019 to 2020 ski season due to COVID-19. All data analyzed come from a single institution. Population characteristics, mechanism of injury, helmet use, need for surgical treatment, diagnosis, and outcome were collected. Descriptive statistics were used to compare the two databases. Results From February 1981 to January 2020, most skiers with head injuries were men (76% for the 1981–1993 and 85% for 2020). The proportion of patients aged over 50 increased from <20% in 1981 to 65% in 2020 (p < 0.01), with a median age of 60 years (range: 22–83 years). Low- to medium-velocity injuries were identified in 76% (13) of cases during the 2019 to 2020 season against 38% (28/74) during the 1981 to 1993 seasons (p < 0.01). All injured patients during the 2020 season wore a helmet, whereas none of the patients between 1981 and 1993 wore one (p < 0.01). DAI was observed in six cases (35%) for the 2019 to 2020 season against nine cases (9%) for the 1981 to 1993 season (p < 0.01). Thirty-four percent (34) of patients during the 1981 to 1993 seasons and 18% (3) of patients during the 2019 to 2020 season suffered skeletal fractures (p = 0.02). Among the 100 patients of the 1981 to 1993 seasons, 13 (13%) died against 1 (6%) from the recent season during care at the hospital (p = 0.15). Neurosurgical intervention was performed in 30 (30%) and 2 (12%) patients for the 1981 to 1993 and 2019 to 2020 seasons, respectively (p = 0.003). Neuropsychological sequelae were reported in 17% (7/42) of patients from the 1981 to 1993 seasons and cognitive evaluation before discharge detected significant impairments in 24% (4/17) of the patients from the 2019 to 2020 season (p = 0.29). Conclusion Helmet use among skiers sustaining head trauma has increased from none in the period from 1981 to 1993 to 100% during the 2019 to 2020 season, resulting in a reduction in the number of skull fractures and deaths. However, our observations suggest a marked shift in the type of intracranial injuries sustained, including a rise in the number of skiers experiencing DAI, sometimes with severe neurologic outcomes. The reasons for this paradoxical trend can only be speculated upon, leading to the question of whether the perceived benefits of helmet use in winter sports are actually misinterpreted. [ABSTRACT FROM AUTHOR]

Abstract Laparoscopic rectosigmoid resection for endometriosis is usually performed with the section of the inferior mesenteric artery (IMA) distal to the left colic artery (low-tie ligation). This study was to determine outcomes in IMA-sparing surgery in endometriosis cases. A single-center retrospective study based on the analysis of clinical notes of women who underwent laparoscopic rectosigmoid segmental resection and IMA-sparing surgery for deep infiltrating endometriosis with bowel involvement between March the 1st, 2018 and February the 29th, 2020 in a referral hospital. During the study period, 1497 patients had major gynecological surgery in our referral center, of whom 253 (17%) for endometriosis. Of the 100 patients (39%) who had bowel endometriosis, 56 underwent laparoscopic nerve-sparing rectosigmoid segmental resection and IMA-sparing surgery was performed in 53 cases (95%). Short-term complications occurred in 4 cases (7%) without any case of anastomotic leak. Preservation of the IMA in colorectal surgery for endometriosis is feasible, safe and enables a tension-free anastomosis without an increase of postoperative complication rates.

Purpose. In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction. Methods. We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention. Results. From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33–2.24; p

BackgroundSystemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease.MethodsSerum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT1R) and endothelin-1 type-A-receptors (ETAR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters.ResultsA total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT1R and anti-ETAR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events.ConclusionIn our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.

Abstract Zinc-alpha 2-glycoprotein (AZGP1) is a serum protein with postulated functions in metabolism, cancer and cardiovascular disease. We developed new prediction models for mortality or cardiovascular events investigating the predictive potential of serum AZGP1 in a community-based cohort of older adults. We measured AZGP1 (μg/ml) in stored serum samples of 930 individuals of the Berlin Initiative Study, a prospective, population-based cohort of adults aged ≥ 70. We determined the prognostic potential of 20 knowledge-based predictors including AZGP1 for the outcomes of mortality or the composite endpoint of death and cardiovascular events (stroke, myocardial infarction (MI)) using Cox models; their model fit was evaluated with calibration plots, goodness-of-fit tests and c-indices. During median follow-up of 48.3 months, 70 incident strokes, 38 incident MI and 234 deaths occurred. We found no associations or correlations between AZGP1 and other candidate variables. After multivariable Cox regression with backward-selection AZGP1 remained in both models for mortality (HR = 0.44, 95%CI: 0.24–0.80) and for the composite endpoint (HR = 0.43, 95%CI: 0.23–0.82). Within newly built prediction models, we found that increased AZGP1 levels were predictive for lower risk of mortality and the composite endpoint in older adults. AZGP1 as a predictor warrants further validation in older adults.