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Context Primary aldosteronism (PA) causes left ventricular hypertrophy (LVH) via hemodynamic factors and directly by aldosterone effects. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy (ADX) has been reported to improve LVH. However, the cardiovascular benefit could depend on plasma renin concentration (PRC) in patients on MRA. Patients and objective We analyzed data from 184 patients from the Munich center of the German Conn’s Registry, who underwent echocardiography at the time of diagnosis and 1 year after treatment. To assess the effect of PRC on cardiac recovery, we stratified patients on MRA according to suppression (n = 46) or non-suppression of PRC (n = 59) at follow-up and compared them to PA patients after ADX (n = 79). Results At baseline, patients treated by ADX or MRA had comparable left ventricular mass index (LVMI, 61.7 vs 58.9 g/m2.7, P = 0.591). Likewise, patients on MRA had similar LVMI at baseline, when stratified into treatment groups with suppressed and unsuppressed PRC during follow-up (60.0 vs 58.1 g/m2.7, P = 0.576). In all three groups, we observed a significant reduction in LVMI following treatment (P < 0.001). However, patients with suppressed PRC had no decrease in pro-BNP levels, and the reduction of LVMI was less intense than in patients with unsuppressed PRC (4.1 vs 8.2 g/m2.7, P = 0.033) or after ADX (9.3 g/m2.7, P = 0.019). Similarly, in multivariate analysis, higher PRC was correlated with the regression of LVH. Conclusion PA patients with suppressed PRC on MRA show impaired regression of LVH. Therefore, dosing of MRA according to PRC could improve their cardiovascular benefit.

BACKGROUND: Patients with kidney failure on dialysis or after renal transplantation have a high risk for severe COVID-19 infection, and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in patients with kidney failure, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in patients on dialysis and in kidney transplant recipients (KTRs) are still needed. METHODS: In this prospective, multicentric cohort study, antibody responses to COVID-19 mRNA vaccines (BNT162b2 [BioNTech/Pfizer] or mRNA-1273 [Moderna]) were measured in 32 patients on dialysis and in 28 KTRs. SARS-CoV-2–specific antibodies and neutralization capacity were evaluated and compared with controls (n=78) of a similar age range. RESULTS: After the first vaccination, SARS-CoV-2–specific antibodies were nearly undetectable in patients with kidney failure. After the second vaccination, 93% of the controls and 88% of patients on dialysis but only 37% of KTRs developed SARS-CoV-2–specific IgG above cutoff. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared with patients on dialysis (503±481 BAU/ml; P

Objectives Currently, there are no approved treatments for early disease stages of COVID-19 and few strategies to prevent disease progression after infection with SARS-CoV-2. The objective of this study is to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate administered within 72 h of diagnosis of SARS-CoV-2 infection in adult individuals with pre-existing risk factors at higher risk of getting seriously ill with COVID-19. Camostat mesylate acts as an inhibitor of the host cell serine protease TMPRSS2 and prevents the virus from entering the cell. CP represents another antiviral strategy in terms of passive immunization. The working hypothesis to be tested in the RES-Q-HR study is that the early use of CP or camostat mesylate reduces the likelihood of disease progression to (modified) WHO stages 4b-8 in SARS-CoV-2-positive adult patients at high risk of moderate or severe COVID-19 progression. Trial design This study is a 4-arm (parallel group), multicenter, randomized (2:2:1:1 ratio), partly double-blind, controlled trial to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 infection and high risk for progression to moderate/severe COVID-19. Superiority of the intervention arms will be tested. Participants The trial is conducted at 10–15 tertiary care centers in Germany. Individuals aged 18 years or above with ability to provide written informed consent with SARS-CoV-2 infection, confirmed by PCR within 3 days or less before enrolment and the presence of at least one SARS-CoV-2 symptom (such as fever, cough, shortness of breath, sore throat, headache, fatigue, smell/and or taste disorder, diarrhea, abdominal symptoms, exanthema) and symptom duration of not more than 3 days. Further inclusion criteria comprise: Presence of at least one of the following criteria indicating increased risk for severe COVID-19: Age > 75 years Chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis BMI > 40 kg/m2 Age > 65 years with at least one other risk factor (BMI > 35 kg/m2, coronary artery disease (CAD), chronic kidney disease (CKD) with GFR BMI > 35 kg/m2 with at least one other risk factor (CAD, CKD with GFR Exclusion criteria: Age Unable to give informed consent Pregnant women or breastfeeding mothers Previous transfusion reaction or other contraindication to a plasma transfusion Known hypersensitivity to camostat mesylate and/or severe pancreatitis Volume stress due to CP administration would be intolerable Known IgA deficiency Life expectancy Duration SARS-CoV-2 typical symptoms > 3 days SARS-CoV-2 PCR detection older than 3 days SARS-CoV-2 associated clinical condition ≥ WHO stage 3 (patients hospitalized for other reasons than COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria) Previously or currently hospitalized due to SARS-CoV-2 Previous antiviral therapy for SARS-CoV-2 ALT or AST > 5 x ULN at screening Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial) Chronic kidney disease with GFR Concurrent or planned anticancer treatment during trial period Accommodation in an institution due to legal orders (§40(4) AMG). Any psycho-social condition hampering compliance with the study protocol. Evidence of current drug or alcohol abuse Use of other investigational treatment within 5 half-lives of enrolment is prohibited Previous use of convalescent plasma for COVID-19 Concomitant proven influenza A infection Patients with organ or bone marrow transplant in the three months prior to screening visit Intervention and comparator Participants will be randomized to the following 4 groups: Convalescent plasma (CP), 2 units at screening/baseline visit (day 0) or day 1; CP is defined by the presence of neutralizing anti-SARS-CoV-2 antibodies with titers ≥ 1:160; individuals with body weight ≥ 150 kg will receive a third unit of plasma on day 3 Camostat mesylate (200 mg per capsule, one capsule taken each in the morning, afternoon and evening on days 1–7) Standard of care (SOC, control for CP) Placebo (identical in appearance to camostat mesylate capsules, one capsule taken each morning, afternoon and evening on days 1–7; for camostat mesylate control group) Participants will be monitored after screening/baseline on day 3, day 5, day 8, and day 14. On day 28 and day 56, telephone visits and on day 90, another outpatient visit are scheduled. Adverse events and serious adverse events will be monitored and reported until the end of the study. An independent data safety monitoring committee will review trial progression and safety. Main outcomes The primary endpoint of the study is the cumulative number of individuals who progress to or beyond category 4b on the modified WHO COVID-19 ordinal scale (defined as hospitalization with COVID-19 pneumonia and additional oxygen demand via nasal cannula or mask) within 28 days after randomization. Randomization Participants will be randomized using the Alea-Tool (aleaclinical.com) in a 2:2:1:1 ratio to the treatment arms (1) CP, (2) camostat mesylate, (3) standard of care (SoC), and (4) placebo matching camostat mesylate. Randomization will be stratified by study center. Blinding (masking) The camostat mesylate treatment arm and the respective placebo will be blinded for participants, caregivers, and those assessing outcomes. The treatment arms convalescent plasma and standard of care will not be blinded and thus are open-labeled, unblinded. Numbers to be randomized (sample size) Overall, n = 994 participants will be randomized to the following groups: n = 331 to convalescent plasma (CP), n = 331 to camostat mesylate, n = 166 to standard of care (SoC), and n = 166 to placebo matching camostat mesylate. Trial status The RES-Q-HR protocol (V04F) was approved on the 18 December 2020 by the local ethics committee and by the regulatory institutions PEI/BfARM on the 2 December 2020. The trial was opened for recruitment on 26 December 2020; the first patient was enrolled on 7 January 2021 and randomized on 8 January 2021. Recruitment shall be completed by June 2021. The current protocol version RES-Q HR V05F is from 4 January 2021, which was approved on the 18 January 2021. Trial registration EudraCT Number 2020-004695-18. Registered on September 29, 2020. ClinicalTrial.gov NCT04681430. Registered on December 23, 2020, prior to the start of the enrollment (which was opened on December 26, 2020). Full protocol The full protocol (V05F) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Evaluation and power of seroprevalence studies depend on the performed serological assays. The aim of this study was to assess four commercial serological tests from EUROIMMUN, DiaSorin, Abbott, and Roche as well as an in-house immunofluorescence and neutralization test for their capability to identify SARS-CoV-2 seropositive individuals in a high-prevalence setting. Therefore, 42 social and working contacts of a German super-spreader were tested. Consistent with a high-prevalence setting, 26 of 42 were SARS-CoV-2 seropositive by neutralization test (NT), and immunofluorescence test (IFT) confirmed 23 of these 26 positive test results (NT 61.9% and IFT 54.8% seroprevalence). Four commercial assays detected anti-SARS-CoV-2 antibodies in 33.3-40.5% individuals. Besides an overall discrepancy between the NT and the commercial assays regarding their sensitivity, this study revealed that commercial SARS-CoV-2 spike-based assays are better to predict the neutralization titer than nucleoprotein-based assays are. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04169-7.

Bei leichter bis mittelschwerer Demenz kann durch Bewegungsforderung und Training eine Verbesserung der physischen und psychischen Leistungsfahigkeit erzielt werden. Dieser Ansatz kann die medikamentose und psychologische Therapie unterstutzen und erganzen. Alltagskompetenzen konnen erhalten oder verbessert werden. Die Bewegungs- forderung kann sich aus Gruppen- und Heimtrainings zusammensetzen und durch Onlineangebote erganzt werden. Gezieltes korperliches Training wird im stationaren Pflegealltag meist als physiotherapeutische Masnahme erbracht, dabei ist die Rolle der Pflegenden nicht zu unterschatzen: Bereits wenig aufwendige gezielte Bewegungsablaufe im pflegerischen Alltag konnen schon erfolgreich sein.

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility., Author summary COVID-19, caused by the virus SARS-CoV-2, has claimed millions of lives and affected many more since its emergence. A number of studies have previously suggested that influenza vaccination can provide protection against COVID-19. Although multiple COVID-19 vaccines are currently available, emergence of new variants and inequity in vaccine distribution around the world make it crucial to identify alternative ways that can help in the fight against this pandemic. With this in mind, we investigated if seasonal influenza vaccination had any effect on COVID-19 incidence. Dutch healthcare workers who received the influenza vaccine in the previous flu season had 37% and 49% lower risk of SARS-CoV-2 infection in the first two waves of the pandemic, respectively. We also explored the mechanisms underlying this observation, using various techniques such as single-cell RNA sequencing, proteomics, and stimulation assays. The influenza vaccine reduced systemic inflammation and reprogrammed the immune cells to fine-tune the response against SARS-CoV-2. This study reveals influenza vaccination as a safe and helpful tool to decrease COVID-19 burden.

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response to SARS-CoV-2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS-CoV-2 spike S1 subunit and their neutralization capacity after SARS-CoV-2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 [78-519] BAU/ml versus 1826 [560-3180] BAU/ml for KTRs and controls, p

Context An important clinical feature of Cushing’s syndrome (CS) is proximal muscle myopathy caused by glucocorticoid induced protein metabolism. However, interindividual differences cannot be explained solely by the pure extent of hypercortisolemia. Objective To evaluate the effects of glucocorticoid receptor (GR) polymorphisms (BclI, N363S, ER22/23EK and A3669G), which influence peripheral glucocorticoid sensitivity on muscular function in endogenous CS. Methods 205 patients with proven endogenous CS (128 central, 77 adrenal) from 3 centers of the German Cushing’s Registry and 125 subjects, in whom CS was ruled out, were included. All subjects were assessed for grip strength (via hand grip dynamometer) and performed a chair-rising test (CRT). DNA samples were obtained from peripheral blood leukocytes for GR genotyping. Results In patients with active CS, normalized handgrip strength of the dominant and nondominant hand was higher in A3669G minor allele than in wildtype carriers (P = .006 and P = .021, respectively). CS patients in remission and ruled-out CS showed no differences in handgrip strength regarding A3669G minor allele and wildtype carriers. Male CS patients harboring the ER22/23EK wildtype presented lower hand grip strength than minor allele carriers (P = .049 dominant hand; P = .027 nondominant hand). The other polymorphisms did not influence handgrip strength. CRT showed no differences regarding GR polymorphisms carrier status. Conclusion Handgrip strength seems to be more susceptible to hypercortisolism in A3669G wildtype than in A3669G minor allele carriers. This might partially explain the inter-individual differences of glucocorticoid-induced myopathy in patients with endogenous CS. ER22/23EK polymorphism seems to exert sex-specific differences.

The purpose of basic military training (BMT) is to enable the recruited soldiers to acquire basic military skills and develop the required physical fitness. This training is accompanied by heightened physical stress and the risk of injury and excessive stress symptoms (I&ESS). The objective of this study was to examine the extent to which the level of physical fitness at the beginning of BMT affects the incidence of I&ESS and resultant absence from duty. The data of a total of 774 subjects (age 20.5 ± 2.2) from 8 subsequent BMT quarters were analysed. The medical diagnoses made during the consulting hours of the unit physicians were reviewed for I&ESS and the kinds of injuries incurred and the sick leave pronounced were documented. The level of physical fitness per quarter was then categorised by means of the total numbers of points achieved during the standard basic fitness test (BFT). This categorisation was finally used as a basis for an analysis of the lost days in relation to the level of physical fitness. 255 of the 774 subjects (32.9%) suffered an I&ESS. 60% of all the I&ESS were located at lower extremity. There was a significant increase in the length of absence from duty among the group with the lowest level of physical fitness. The analysis revealed that the level of physical fitness at the beginning of BMT has a significant influence on the length of absence from duty due to I&ESS. Moreover, 60% of the injuries were lower extremity injuries, which show the specific significance they have for limitations during BMT. Overall, this reveals the necessity for appropriate preventive measures (additional fitness training, adjustment of requirements) to be implemented so that recruits with a low level of fitness can complete BMT with as few injuries as possible.

Context Primary aldosteronism (PA) is associated with impaired quality of life (QoL). Autonomous cortisol cosecretion (ACS) is a relevant phenotype of PA, which could contribute to depression and anxiety disorders. This has not been investigated so far. Objective To evaluate the prevalence of depression and anxiety in PA patients according to ACS. Methods We performed testing for hypercortisolism and evaluated anxiety, depression and QoL by self-rating questionnaires in newly diagnosed PA patients of the German Conn’s Registry; 298 patients were reevaluated at follow-up. Results In the overall cohort, scores for anxiety (P < .001), depression (P < .001), and QoL (mental P = .021; physical P = .015) improved significantly at follow-up. This improvement was seen in both subgroups of patients with and without ACS, with the exception of the mental subscore in no-ACS patients. Analysis for sex differences showed that anxiety decreased significantly in females with ACS and no-ACS, whereas males with no-ACS failed to improve. Depression improved significantly in males and females with ACS (P = .004, P = 0.011 respectively), but not in those with no-ACS. Physical subscore of QoL improved significantly (P = .023) in females with ACS and mental subscore (P = .027) in males with ACS, whereas no differences were seen for the no-ACS groups. Conclusion Improvement in depression and anxiety scores in response to treatment of PA is more pronounced in patients with ACS in contrast to no-ACS suggesting a role of ACS in the psychopathological symptoms of patients with PA. Furthermore, we observed significant differences in depression and anxiety scores between the sexes.

ObjectivesMitral valve (MV) tenting parameters are indicators of left ventricular remodelling severity and may predict outcome in functional mitral regurgitation (FMR). We hypothesised that indexing of MV tenting area to body surface area (BSA), to mitral annulus diameter or gender-adjusted analysis of tenting parameters may improve their prognostic value.MethodsWe identified retrospectively 240 patients with consecutive FMR (mean age 68±10 years; men=135) from our institutional database who underwent isolated MV annuloplasty during a period of 7 years (2010–2016). Using preoperative two-dimensional transthoracic echocardiographic images, MV tenting parameters including tenting area, tenting height and annulus diameter were systematically assessed. Follow-up protocol consisted of chart review and structured clinical questionnaire. Primary study endpoint was the composite of death and adverse cardiac events (ie, MV reoperation, cardiac resynchronisation therapy implantation, ventricular assist device implantation or heart transplantation).ResultsBSA-indexed MV tenting area was identified as independent predictor of primary study endpoint (HR 1.9; 95% CI 1.1 to 3.5; p=0.02). After cut-off point analysis, BSA-indexed MV tenting area >1.35 cm2/m2 was significantly associated with primary study outcome (HR 2.3; 95% CI 1.3 to 4.0; p=0.003). Annulus-indexed MV tenting area showed only a tendency towards primary study endpoint prediction (HR 2.8; 95% CI 0.6 to 12.6; p=0.17). Between female and male patients, BSA-indexed MV tenting area was similar (1.42±0.4 cm2/m2 vs 1.45±0.4cm2/cm2; p=0.6) and gender was not associated with primary study outcome (HR 0.8; 95% CI 0.5 to 1.4; p=0.5).ConclusionIn our FMR cohort, BSA-indexed MV tenting area showed the strongest association with negative outcomes following isolated MV annuloplasty. Patients with BSA-indexed MV tenting area >1.35cm2/m2 could potentially benefit from additional surgical maneuvers addressing left ventricular remodelling.

Primary aldosteronism (PA) is the cause of arterial hypertension in 4% to 6% of patients, and 30% of patients with PA are affected by unilateral and surgically curable forms. Current guidelines recommend screening for PA ≈50% of patients with hypertension on the basis of individual factors, while some experts suggest screening all patients with hypertension. To define the risk of PA and tailor the diagnostic workup to the individual risk of each patient, we developed a conventional scoring system and supervised machine learning algorithms using a retrospective cohort of 4059 patients with hypertension. On the basis of 6 widely available parameters, we developed a numerical score and 308 machine learning-based models, selecting the one with the highest diagnostic performance. After validation, we obtained high predictive performance with our score (optimized sensitivity of 90.7% for PA and 92.3% for unilateral PA [UPA]). The machine learning-based model provided the highest performance, with an area under the curve of 0.834 for PA and 0.905 for diagnosis of UPA, with optimized sensitivity of 96.6% for PA, and 100.0% for UPA, at validation. The application of the predicting tools allowed the identification of a subgroup of patients with very low risk of PA (0.6% for both models) and null probability of having UPA. In conclusion, this score and the machine learning algorithm can accurately predict the individual pretest probability of PA in patients with hypertension and circumvent screening in up to 32.7% of patients using a machine learning-based model, without omitting patients with surgically curable UPA.

Background The number of patients requiring lead extraction has been increasing in recent years. Despite significant advances in operator experience and technique, unexpected complications may occur. Prophylactic placement of femoral sheaths allows for immediate endovascular access for emergency procedures and may shorten response time in the event of complications. Objective The purpose of this study was to assess the benefits of routine prophylactic femoral access in patients undergoing transvenous lead extraction (TLE) and to evaluate the methods, frequency, and efficacy of the emergency measures used in those patients. Methods We conducted a retrospective analysis of patients who underwent TLE from January 2012 to February 2019. The data were analyzed with regard to procedural complications and deployment of emergency measures via femoral access. Results Two hundred eighty-five patients (mean age 65.3 ± 15.5 years) were included in the study. Median lead dwell time was 84 months (interquartile range 58–144). Overall complication rate was 4.2% (n = 12), with 1.8% major complications (n = 5). Clinical success rate was 97.2%. Procedure-related mortality was 1.1% (n = 3). Femoral sheaths were actively engaged in 9.1% (n = 26) of cases. Deployment of snares was the most common intervention (n = 10), followed by prophylactic (n = 6) or emergency placement (n = 1) of occlusion balloons, temporary pacing (n = 3), venous angioplasty (n = 3), diagnostic venography (n = 3), and extracorporeal membrane oxygenation (n = 1). We did not observe any femoral vascular complications due to prophylactic sheath placement. Conclusion Routine prophylactic placement of femoral sheaths shortens response time and quickly establishes control in the event of various complications that may occur during TLE procedures.

OBJECTIVES To determine the 5-year outcome in patients treated by isolated transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (sAVR)—a prospective observational cohort study. METHODS A total of 18 010 patients were included (n = 8942 TAVI and n = 9068 sAVR) in the German Aortic Valve Registry (GARY) who were treated in 2011 and 2012 at 92 sites in central Germany. Eligible patients with TAVI and sAVR were matched using propensity scores in a nearest-neighbour approach. Patients with repeat procedures or unequivocal indication for one treatment option (e.g. frailty) were excluded (n = 4785 for TAVI and n = 2 for sAVR). This led to 13 223 patients (4157 TAVI and 9066 sAVR) as an unmatched subcohort. The main outcome measure was the 5-year all-cause mortality. RESULTS TAVI patients were significantly older (80.9 ± 6.1 vs 68.5 ± 11.1 years, P CONCLUSIONS The 5-year follow-up data show that TAVI patients were significantly older and had a higher STS score than sAVR patients. After propensity score matching, TAVI with early-generation prosthesis was associated with significantly higher 5-year all-cause mortality than sAVR.

Every year, influenza causes 290.000 to 650.000 deaths worldwide and vaccination is encouraged to prevent infection in high-risk individuals. Interestingly, cross-protective effects of vaccination against heterologous infections have been reported, and long-term boosting of innate immunity (also termed trained immunity) has been proposed as the underlying mechanism. Several epidemiological studies also suggested cross-protection between influenza vaccination and COVID-19 during the current pandemic. However, the mechanism behind such an effect is unknown. Using an established in-vitro model of trained immunity, we demonstrate that the quadrivalent inactivated influenza vaccine used in the Netherlands in the 2019-2020 influenza season can induce a trained immunity response, including an improvement of cytokine responses after stimulation of human immune cells with SARS-CoV-2. In addition, we found that SARS-CoV-2 infection was less common among Dutch hospital employees who had received influenza vaccination during the 2019/2020 winter season (RR = 0,61 (95% CI, 0.4585 - 0.8195, P = 0.001). In conclusion, a quadrivalent inactivated influenza vaccine can induce trained immunity responses against SARS-CoV-2, which may result in relative protection against COVID-19. These data, coupled with similar recent independent reports, argue for a beneficial effect of influenza vaccination against influenza as well as COVID-19, and suggests its effective deployment in the 2020-2021 influenza season to protect against both infections.

OBJECTIVES Functional mitral regurgitation (FMR) is a sequel of left ventricular (LV) remodelling in heart failure patients. Relocation of both papillary muscles aims to specifically address mitral leaflet tethering to improve long-term durability of modern FMR repair. Nevertheless, the prognostic impact of the underlying cardiomyopathy on the outcome after FMR repair is unknown. METHODS We analysed 84 consecutive heart failure patients with severe FMR, LV ejection fraction 10 mm, who underwent ring annuloplasty and simultaneous bilateral papillary muscles relocation between June 2016 and March 2019. One-year outcome of 54 patients with ischaemic cardiomyopathy (‘ICM group’) was prospectively compared to the remaining 30 patients with dilated cardiomyopathy (‘DCM group’). RESULTS One-year survival was similar in both groups (96% in the ‘ICM group’ vs 97% in the ‘DCM group’; P = 0.93). Furthermore, primary composite outcome (i.e. freedom from death or mitral regurgitation ≥ 2) at 1-year postoperatively was comparable between the study groups (94%in the ‘ICM group’ vs 87% in the ‘DCM group’; P = 0.10). LV end-diastolic diameter 1-year after surgery was significantly reduced, as compared to preoperative values, in the ‘DCM group’ (P = 0.018), but not in the ‘ICM group’ (P = 0.058). Improvement of New York Heart Association functional class and reduction of serum levels of N-terminal pro-B natriuretic peptide at 1 year was comparable in both study groups. CONCLUSIONS Standardized relocation of both papillary muscles to correct FMR resulted in very satisfactory in-hospital and 1-year outcomes, in both ICM and DCM. DCM patients showed similar improvement in heart failure symptoms and LV re-remodelling compared to ICM patients. Subannular repair is developing towards a valid therapeutic option in heart failure patients presenting with severe FMR.

Background: Stroke has become a treatable condition with increasing evidence of treatment benefits in older people. However, stroke mimics in geriatric patients are especially prevalent, causing incorrect suspicion and consecutive burden to patients and emergency room resources. We therefore examined the dimension of this problem by investigating emergency room admissions from nursing homes for suspected stroke. Methods: We performed a retrospective cohort study of all nursing home residents who were admitted to the neurological emergency room of our primary and tertiary care university hospital between 2013 and 2015. Patients were further divided into those with confirmed stroke and stroke mimics after diagnostic stroke work-up. Results: Of 419 nursing home patients referred to the emergency room, nearly one third had suspected stroke (n = 126; mean age: 78 ± 14 years, polypharmacy rate: 77%). Of those, 43 (34%) had a confirmed stroke (ischaemic: n = 34; haemorrhagic: n = 9) and 83 (66%) had stroke mimics after diagnostic work-up. Only one patient underwent intravenous thrombolysis, followed by mechanical thrombectomy for middle cerebral artery occlusion. Prehospital delay (47%) and multimorbidity-associated contraindications (27%) were the main reasons for withholding recanalization therapy. Among the stroke-mimicking conditions, infectious diseases (24%) and epileptic seizures (20%) were the most frequent. Multivariate analysis identified focal deficits (OR 16.6, 95% CI 4.3–64.0), atrial fibrillation (OR 3.9, 95% CI 1.5–10.5) and previous stroke (OR 3.2, 95% CI 1.2–8.9) as indicators that were associated with stroke. Conclusions: In our region, nursing home referrals for suspected stroke have a high false positive rate and occur delayed, which most often precludes specific stroke treatment in addition to multimorbidity. Such problems may also exist in other centres and highlight the need for targeted educational and organizational efforts. Simple indicators as identified in this study may help to sort out patients with true stroke more efficiently.

Lisa Müller,1 Carolin Hildebrandt,1,2 Erich Müller,3 Renate Oberhoffer,2 Christian Raschner1 1Department of Sport Science, University of Innsbruck, Innsbruck, Austria; 2Department of Sport and Health Science, Preventative Pediatrics, Technical University of Munich, Munich, Germany; 3Department of Sport Science and Kinesiology, University of Salzburg, Salzburg, Austria Background: Studies on injuries and illnesses involving youth ski racers younger than 15 years are lacking in the literature. The aim of this study was prospectively to assess the incidence, prevalence, and severity of traumatic and overuse injuries, as well as illnesses of elite youth ski racers with regard to sex, biological maturity status, and relative age.Subjects and methods: A prospective, longitudinal cohort design was used to monitor the anthropometrics, training characteristics, traumatic and overuse injuries, and illnesses of 82 elite youth ski racers (51 males, 31 females, age 9–14 years) over 2 consecutive years. The exact training exposure (skiing and athletic) was recorded. Relative age and estimated biological maturity status were assessed.Results: Relatively low injury incidence or prevalence (traumatic, 0.86/1,000 hours of training; overuse, 0.28/1,000 hours) and comparably high illness prevalence (2.4/athlete) were reported. The knee was the most commonly affected body part (traumatic injuries 36.5%, overuse injuries 82%). A high number of bone fractures were revealed (46%), while no stress fractures occurred; 66% of the illnesses were respiratory tract infections. No differences were found between males and females, the differing maturity groups, or relative age quartiles. Early-maturing athletes had comparably low traumatic and overuse-injury rates. Relatively younger athletes had low traumatic injury rates.Conclusion: The injury-prevention measures implemented in the training process of youth ski racers seem to contribute to a low incidence of injury. Biological maturity status should be considered in the training process to prevent injuries in late-maturing athletes. Keywords: traumatic and overuse injuries, health problems, youth alpine ski racing, birth quarter, biological development

A once-daily, modified-release hydrocortisone medication reduces BMI and improves glucose metabolism compared with the twice- or thrice-daily standard hydrocortisone treatment in patients with adrenal insufficiency. Now, further evidence emerges that changing to a once-daily, modified-release hydrocortisone medication improves the immune cell profile and results in fewer infections.

Circadian rhythms are highly important not only for the synchronization of animals and humans with their periodic environment but also for their fitness. Accordingly, the disruption of the circadian system may have adverse consequences. A certain number of animals in our breeding stock of Djungarian hamsters are episodically active throughout the day. Also body temperature and melatonin lack 24-h rhythms. Obviously in these animals, the suprachiasmatic nuclei (SCN) as the central pacemaker do not generate a circadian signal. Moreover, these so-called arrhythmic (AR) hamsters have cognitive deficits. Since motor activity is believed to stabilize circadian rhythms, we investigated the effect of voluntary wheel running. Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14 L/10 D lighting regimen. AR animals were selected according to their activity pattern obtained by means of passive infrared motion detectors. In a first step, the daily activity behavior was investigated for 3 weeks each without and with running wheels. To estimate putative photic masking effects, hamsters were exposed to light (LPs) and DPs and also released into constant darkness for a minimum of 3 weeks. A novel object recognition (NOR) test was performed to evaluate cognitive abilities both before and after 3 weeks of wheel availability. The activity patterns of hamsters with low wheel activity were still AR. With more intense running, daily patterns with higher values in the dark time were obtained. Obviously, this was due to masking as LPs did suppress and DPs induced motor activity. When transferred to constant darkness, in some animals the daily rhythm disappeared. In other hamsters, namely those which used the wheels most actively, the rhythm was preserved and free-ran, what can be taken as indication of a reconstitution of circadian rhythmicity. Also, animals showing a 24-h activity pattern after 3 weeks of extensive wheel running were able to recognize the novel object in the NOR test but not so before. The results show that voluntary exercise may reestablish circadian rhythmicity and improve cognitive performance.

Hintergrund: Der biologische Entwicklungsstand spielt eine grose Rolle im Sport, da dieser die Leistungsfahigkeit und die Talentselektion in vielen Sportarten beeinflusst. Es werden vermehrt weiter entwickelte Athleten fur regionale und nationale Kader ausgewahlt. Deshalb sollte der biologische Entwicklungsstand in der Talentselektion Berucksichtigung finden. Es bestehen verschiedene Methoden zur Erhebung dessen, diese sind aber oft sehr teuer und schwer umsetzbar. Deshalb war das Ziel dieser Studie, eine einfach anwendbare, dennoch genaue Methode zur Erhebung des biologischen Entwicklungsstandes (Vorhersage des Alters, wann der individuell groste Wachstumsschub erreicht wird = APHV) mit der Goldstandardmethode zur Erhebung des biologischen Alters (Handwurzelknochenrontgen) zu vergleichen. Methoden: In dieser Studie wurden 75 osterreichische Schuler (40♂, 35♀) im Alter von 10 – 13 Jahren untersucht. Die Gruppe bestand aus 30 Schulern einer bekannten Ski-Mittelschule (17♂, 13♀) und 45 Schulern (23♂, 22♀) einer nicht sportbetonten Neuen Mittelschule. Es wurden Handwurzelknochenrontgen (Greulich-Pyle-Methode) der linken Hand durchgefuhrt, um das biologische Alter zu erheben. Auserdem wurden verschiedene anthropometrische Parameter (Grose, Sitzgrose, Gewicht) erhoben und anhand der Formeln von Mirwald und Mitarbeitern das APHV berechnet. Eine Bland-Altman-Analyse, der Korrelationskoeffizient in Klassen (ICC [1,3]) sowie eine lineare Regressionsanalyse wurden durchgefuhrt, um die beiden Methoden miteinander zu vergleichen. Anhand beider Methoden wurden die Teilnehmer in fruh, normal oder spat entwickelt unterteilt und Unterschiede in dieser Klassifizierung wurden mittels chi2-Tests berechnet. Ergebnisse: Die Bland-Altman-Analyse (95 % der Punkte im Plot liegen innerhalb der Ubereinstimmungsgrenzen) und der ICC (p = 0,002; ICC [95 % CI] = 0,48 [0,13 – 0,69]) zeigten eine gute Ubereinstimmung der beiden Methoden. Es konnten keine signifikanten Unterschiede aufgezeigt werden in der anhand der beiden Methoden durchgefuhrten Klassifizierung in fruh, normal oder spat entwickelte Schuler (p = 0,404). Schlussfolgerung: Die Formeln zur Vorhersage des APHV stellen eine valide Methode zur Erhebung des biologischen Entwicklungsstandes bei Sportlern im Alter von 10 – 13 Jahren dar. Folglich kann diese einfach anwendbare, aber dennoch genaue Methode in Zukunft im Talentselektionsprozess eingesetzt werden. Dies soll dazu beitragen, dass spat entwickelte Sportler nicht diskriminiert und ausgeschlossen werden.

Purpose Return to activity remains the most common concern following an injury. To facilitate the decision regarding a patient’s return to sport, we developed a standardized and easy-to-use test battery to enable an objective evaluation of knee function. Methods The test battery consisted of seven functional tests: the two-leg stability test, one-leg stability test (OL-ST), two-leg countermovement jump (CMJ), one-leg CMJ (OL-CMJ), plyometric jumps, speedy test and quick feet test. For each test, the reliability was determined based on the intraclass correlation coefficient. For all one-leg tests, the limb symmetry index (LSI) was calculated. Results All tests showed a moderate-to-high reliability. Normative data from 434 participants were included in the analysis. The subjects were categorized according to age as follows: children (10–14 years), youth (15–19 years), young adults (20–29 years) and adults (30–50 years). The establishment of the functional test values allowed the classification into five normative categories. The LSI for the OL-ST (98 %) indicated a better performance of the non-dominant leg. In contrast, high LSI values were found for the OL-CMJ (124 %), indicating a better performance of the dominant leg. Conclusion Each test was found to be reliable and simple to perform. The better performance of the non-dominant leg in stability tasks must be considered when interpreting side-to-side differences. The established norm data from healthy individuals of each test battery represents an important basis for a clinical setting. Test results from an ACL-reconstructed patient should be at least classified as a functionally average outcome to support a safe return to sports. Level of evidence IV.

Alpine ski racing is known to be a sport with a high risk of injuries. Because most studies have focused mainly on top-level athletes and on traumatic injuries, limited research exists about injury risk factors among youth ski racers. The aim of this study was to determine the intrinsic risk factors (anthropometrics, biological maturity, physical fitness, racing technique) for injury among youth alpine ski racers. Study participants were 81 youth ski racers attending a ski boarding school (50 males, 31 females; 9–14 years). A prospective longitudinal cohort design was used to monitor sports-related risk factors over two seasons and traumatic (TI) and overuse injuries (OI). At the beginning of the study, anthropometric characteristics (body height, body weight, sitting height, body mass index); biological maturity [status age at peak height velocity (APHV)]; physical performance parameters related to jump coordination, maximal leg and core strength, explosive and reactive strength, balance and endurance; and ski racing technique were assessed. Z score transformations normalized the age groups. Multivariate binary logistic regression (dependent variable: injury yes/no) and multivariate linear regression analyses (dependent variable: injury severity in total days of absence from training) were calculated. T-tests and multivariate analyses of variance were used to reveal differences between injured and non-injured athletes and between injury severity groups. The level of significance was set to p < 0.05. Relatively low rates of injuries were reported for both traumatic (0.63 TI/athlete) and overuse injuries (0.21 OI/athlete). Athletes with higher body weight, body height, and sitting height; lower APHV values; better core flexion strength; smaller core flexion:extension strength ratio; shorter drop jump contact time; and higher drop jump reactive strength index were at a lower injury risk or more vulnerable for fewer days of absence from training. However, significant differences between injured and non-injured athletes were only observed with respect to the drop jump reactive strength index. Regular documentation of anthropometric characteristics, biological maturity and physical fitness parameters is crucial to help to prevent injury in youth ski racing. The present findings suggest that neuromuscular training should be incorporated into the training regimen of youth ski racers to prevent injuries.

Circadian rhythms have been shown to influence learning and memory. In this study, cognitive functions of Djungarian hamsters revealing different circadian phenotypes were evaluated using a novel object recognition (NOR) task. Wild type (WT) animals show a clear and well-synchronized daily activity rhythm, whereas DAO hamsters are characterized by a delayed activity onset. The phenomenon is caused by a diminished ability of photic synchronization. In arrhythmic (AR) hamsters, the suprachiasmatic nuclei (SCN) do not generate a circadian signal at all. The aim of this study was to investigate consequences of these deteriorations for learning and memory processes. Hamsters were bred and kept under standardized housing conditions with food and water ad libitum and a 14 L/10 D lighting regimen. Experimental animals were assigned to different groups (WT, DAO and AR) according to their activity pattern obtained by means of infrared motion sensors. Activity onset of DAO animals was delayed by 3 ± 0.5 h. NOR tests were performed in an open arena and consisted of habituation, training (two identical objects) and test sessions (one of the two objects being replaced). The training-test interval was 60 min. Tests were performed at different Zeitgeber times (ZT 0 = light-on). Every hamster was tested at all times with an interval of one week between experiments. As activity onset of DAO animals is delaying continuously day by day, they could be tested at only three times (ZT 13, ZT 16 and ZT 19). The times animals did explore the novel and the familiar objects were recorded, and the discrimination index as a measure of cognitive performance was calculated. Behavioral analyzes revealed that, WT hamsters were able to discriminate between familiar and novel objects at ZT 13, ZT 16 and ZT 19, i.e. one hour before and during their activity period. In accordance with their delayed activity onset, DAO hamsters could discriminate between objects only at ZT 16 and ZT 19 what corresponds also to 1 h before and 2 h after their activity onset. In contrast, AR hamsters were not able to perform the NOR task at any time. The results show that the SCN modulate learning and memory in a circadian manner. Moreover, the loss of circadian rhythmicity results in cognitive impairments.

Hintergrund Die Refixation von kleinen Knochenfragmenten an den Phalangen stellt nach wie vor eine besondere Herausforderung dar. In der vorliegenden Studie wurde eine klinische und radiologische Evaluation nach operativer Versorgung mit der Minihakenplatte durchgefuhrt. Ebenfalls wurde der DASH-Fragebogen genutzt.

Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.

Frakturen der proximalen Ulna in Kom-bination mit einer proximalen radioulna-ren Dissoziation und Luxation des Radi-uskopfchens werden seit Bado [, 2] nach ihrem Erstbeschreiber Giovanni Batista Monteggia, 762–85, [2] als „Monteg-gia-Frakturen“ bezeichnet. Mit einer In-zidenz von 2–5% der Frakturen des proxi-malen Unterarms treten sie vergleichswei-se selten auf [7]. Trotz des verbesserten biomechanischen Verstandnisses und der Fortschritte in der operativen Frak-turversorgung sind Komplikationen, Re-visionseingriffe und unbefriedigende funktionelle Ergebnisse nach Monteggia- frakturen nach wie vor haufig [7, 20, 26, 37, 40]. In der Literatur existieren bis-her kaum grosere Studien, die sich aus-schlieslich mit diesem Verletzungsmus-ter und dem therapeutischen Konzept beim Erwachsenen beschaftigen. Auser-dem sind kritische Analysen der Ursa-chen unbefriedigender funktioneller Er-gebnisse nach Monteggia-Frakturen sel-ten zu finden. Zudem wurden in der Ver-gangenheit haufiger die Ergebnisse nach Monteggia-Frakturen im Erwachsenenal-ter mit denen im Kindesalter zusammen-gefasst [2, 8, 9, 39], obwohl weder Frak-turformen, Behandlungsgrundsatze und Prognose ubereinstimmen [36].

Objective:To determine the effectiveness of exercise in improving sensorimotor function and functional performance, crucial parts of activities of daily living in healthy older adults.Design:RCT.Setting:Laboratory.Participants:39 subjects (M = 71.8 years, range: 61–89 years).Intervention:Task-oriented visual feedback balance training.Primary outcome measure:Timed Up & Go (TUG).Secondary outcome measures:Chair stand test (CST), self-paced walk test, maximum isometric torque, quiet stand posturography, and dynamic balance (DB).Results:Postintervention comparison of the treatment group (TG) and control group (CG) showed better TUG (p < .01), CST (p < .001), and DB (p < .025) for the TG. Pre–post intervention comparison of the TG showed better clinically-relevant outcomes in TUG (p < .001), CST (p < .001), and DB (p < .001).Conclusion:Active driven visual feedback balance training is effective in improving functional performance and dynamic balance in older adults.

The sensorimotor system (SMS) plays an important role in sports and in every day movement. Several tools for assessment and training have been designed. Many of them are directed to specific populations, and have major shortcomings due to the training effect or safety. The aim of the present study was to design and assess a dynamic sensorimotor test and training device that can be adjusted for all levels of performance. The novel pneumatic-driven mechatronic device can guide the trainee, allow independent movements or disrupt the individual with unpredicted perturbations while standing on a platform. The test-reliability was evaluated using intraclass correlation coefficient (ICC). Subjects were required to balance their center of pressure (COP) in a target circle (TITC). The time in TITC and the COP error (COPe) were recorded for analysis. The results of 22 males and 14 females (23.7 ± 2.6 years) showed good to excellent test–retest reliability. The newly designed Active Balance System (ABS) was then compared with the Biodex Balance System SD® (BBS). The results of 15 females, 14 males (23.4 ± 1.6 years) showed modest correlation in static and acceptable correlation in dynamic conditions, suggesting that ABS could be a reliable and comparable tool for dynamic balance assessments.

Introduction The role of allogeneic stem cell transplantation (allo-HSCT) in the treatment algorithms for patients with multiple myeloma remains controversial although it is the only potentially curative approach currently available. Here we present the retrospective analysis of 95 allo-HSCT performed between 1994 and 2013 at Ulm University Hospital. We focused on the impact of cytogenetics, graft-versus-host disease (GvHD) and intensity of conditioning on overall survival (OS), progression- free survival (PFS), relapse and non-relapse mortality (NRM). Study population Median age at initial diagnosis was 49 years (range 25-64), median age at time of allo-HSCT was 51 years (range 26-65). Median time from initial diagnosis to allo-HSCT was 13 months (range 3-106). Indications for allo-HSCT were 1) primary allo-HSCT after induction therapy (11 pts), 2) planned tandem auto-allo-HSCT (44 pts), 3) relapse after single allo-HSCT (25 pts), 4) relapse after tandem-auto-HSCT (15 pts). The conditioning regimen in 60 pts was a reduced intensity conditioning (RIC), in 35 pts myeloablative conditioning (MAC). In 68 pts cytogenetic data were available: 13 pts were stratified into standard-, 39 pts into the intermediate- and 16 pts into the high-risk group according to the mSMART recommendations. Results: Median follow-up was 70 months (95% CI, 64,5-75,5). The estimate 1-, 2- and 5-year OS was 87,4 %, 74,7 % and 46,4 % with a median OS of 36 months (95 % CI, 19,7 -52,2). For both, RIC and MAC median OS was 36 months (95% CI, 24,4–47,6 versus 95% CI, 0-108,4). The cumulative incidence of TRM was not different for RIC and MAC but there was a trend for lower relapse in patients receiving MAC (p=0,0612). With respect to the indication for allo–HSCT outcomes were as follows: Median OS was 89 months for primary allo-HSCT, 47 months for tandem auto-allo-HSCT, 20 months for relapse after auto-HSCT and 26 months for relapse after double auto-HSCT. OS did not differ significantly. Median OS in the standard risk group was 20 months (95% CI, 6,7-33,3), in the intermediate group 41 months (95% CI, 17,3-64,7) and in the high-risk group 7 months (95% CI, 0-14,8), showing no statistical significance. 1-year OS was 61,5% vs 66,7% vs 43,8%, 2-year OS was 35,9% vs 66,7% vs 43,8% and 5-year OS was 35,9% vs 43,2% vs 11,7% (standard vs intermediate vs high risk). The median PFS was 12 months (95% CI 8,4-15,6). 1-year PFS was 49,2%, 2-year PFS 32,9% and 5-year PFS was 21,8%. PFS according to the cytogenetic aberration showed a median PFS of 20 vs 14 vs 5 months, 1-year PFS was 53,8% vs 51,3 % vs 30 %, 2-year PFS with 35,9% vs 30,8% vs 7,5%, and 5-year PFS with 26,9% vs 11,5 % vs 7,5% (standard vs intermediate vs high risk). These differences are not statistically significant. Considering the impact acute GvHD, OS significantly differed between the groups with no aGvHD or aGvHD grade I and aGvHD grade II-IV with inferior survival for patients suffering from aGvHD grade II-IV. Chronic GvHD had no impact on outcome. Conclusion Our data of a 19 year experience in treatment of patients with advanced multiple myeloma with allo-HSCT showed an effective treatment option with a curative potential even for patients after intensive pretreatment including autologous stem cell transplantation. Patients who received MAC had a trend for lower cumulative incidence of relapse compared to RIC without increasing TRM in our study. Disclosures No relevant conflicts of interest to declare.