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Objective. Scleroderma renal crisis (SRC) is a severe life-threatening manifestation in patients with systemic sclerosis (SSc). However, the knowledge about risk factors for SRC is limited. We determined here the frequency of SRC and identified risk factors for the prediction of SRC. Methods. Based on regular followup data from the German Network for Systemic Scleroderma, we used univariate and multivariate generalized estimating equations to analyze the association between clinical variables, SSc subsets, therapy [i.e., angiotensin-converting enzyme inhibitors (ACEi), corticosteroids], and the occurrence of SRC. Results. Data of 2873 patients with 10,425 visits were available for analysis with a mean number of registry visits of 3.6 +/- 2.8 and a mean time of followup of 3.6 +/- 3.8 years. In total, 70 patients developed SRC (70/ 2873, 2.4%). Of these patients, 57.1% (40/70) were diagnosed with diffuse cutaneous SSc, 31.4% (22/70) with limited cutaneous SSc, and 11.4% (8/70) with SSc- overlap syndromes. Predictive independent factors with the highest probability for SRC were positive anti-RNA polymerase antibodies (RNAP), a history of proteinuria prior to SRC onset, diminished DLCO, and a history of hypertension. Interestingly, positive antitopoisomerase autoantibodies did not predict a higher risk for SRC. Further, patients with SRC were significantly more frequently treated with ACEi and corticosteroids without being independently associated with SRC. Conclusion. In this cohort, SRC has become a rare complication. By far the highest risk for SRC was associated with the detection of anti-RNAP and proteinuria.

Objective Residual paravalvular regurgitation (PVR) has been associated to adverse outcomes after transcatheter aortic valve replacement (TAVR). This study sought to evaluate the impact of device landing zone (DLZ) calcification on residual PVR after TAVR with different next-generation transcatheter heart valves. Methods 642 patients underwent TAVR with a SAPIEN 3 (S3; n=292), ACURATE neo (NEO; n=166), Evolut R (ER; n=132) or Lotus (n=52). Extent, location and asymmetry of DLZ calcification were assessed from contrast-enhanced CT imaging and correlated to PVR at discharge. Results PVR was >= moderate in 0.7% of S3 patients, 9.6% of NEO patients, 9.8% of ER patients and 0% of Lotus patients (p<0.001), and these differences remained after matching for total DLZ calcium volume. The amount of DLZ calcium was significantly related to the degree of PVR in patients treated with S3 (p=0.045), NEO (p=0.004) and ER (p<0.001), but not in Lotus patients (p=0.698). The incidence of PVR >= moderate increased significantly over the tertiles of DLZ calcium volume (p=0.046). On multivariable analysis, calcification of the aortic valve cusps, LVOT calcification and the use of self-expanding transcatheter aortic valve implantation (TAVI) prostheses emerged as predictors of PVR. Conclusions The susceptibility to PVR depending on the amount of calcium was mainly observed in self-expanding TAVI prostheses. Thus, DLZ calcification is an important factor to be considered in prosthesis selection for each individual patient, keeping in mind the trade-off between PVR reduction, risk of new pacemaker implantation and unfavourable valve ha emodynamics.

Objectives. Systemic sclerosis is a heterogeneous, multisystem disease. It can occur at any age, but most patients develop the disease between the age of 40 to 50 years. There is controversial evidence on whether/how the age at disease onset affects their clinical phenotype. We here investigate the relationship between age at disease onset and symptoms in a large cohort of SSc patients (IcSSc, dcSSc and SSc-overlap syndromes). Methods. Clinical data of the registry of the German Network for Systemic Scleroderma including 3281 patients were evaluated and subdivided into three age groups at disease onset (<40years, 40-60 years, >60 years). Results. Among all SSc patients, 24.5% developed their first non-Raynaud phenomenon symptoms at the age <40years, and 22.5% were older than 60 years of age. In particular, older patients at onset developed the IcSSc subset significantly more often. Furthermore, they had pulmonary hypertension more often, but digital ulcerations less often. Remarkably, the course of the disease was more rapidly progressing in the older cohort (>60 years), except for gastrointestinal and musculoskeletal involvement. No significant difference was found for the use of corticosteroids. However, significantly, fewer patients older than 60 years received immunosuppressive treatment. Conclusion. In this large registry, similar to 25% of patients developed SSc at an age above 60years with an increased frequency of IcSSc. In this age group, an onset of internal organ involvement was significantly accelerated across all three subsets. These findings suggest that, in the elderly cohort, more frequent follow-up examinations are required for an earlier detection of organ complications.

Cognitive behavioral therapy for psychosis (CBT) is an effective treatment in adult patients with schizophrenia. However, no randomized controlled and blinded trial in adolescents with early-onset psychosis (EOP) has been conducted. Therefore, the present pilot study explores the acceptance, tolerability, feasibility, and safety of a modified CBT in adolescents with EOP. Twenty-five adolescents with EOP were randomized to either 9 months (20 sessions) of CBT + treatment as usual (TAU) or TAU alone. The primary endpoint was the PANSS-positive subscale (P1-7). Secondary endpoints included psychopathology, global functioning, and quality of life (QoL). Acceptance, tolerability, feasibility, and safety were assessed. Blinded assessments took place by the end of the treatment (9 months) and at 24-month follow-up. Despite improvements in both groups and lack of statistical significance between CBT + TAU and TAU regarding the primary endpoint, we observed between-group effect sizes of at leastd = 0.39 in favor of CBT + TAU at post-treatment for delusions, negative symptoms, functioning and QoL after the intervention and effect sizes of at leastd = 0.35 after 24 months. CBT in EOP was highly acceptable (73.5% agreed to randomization), well-tolerated (83.1% attendance rate, no drop-outs), and safe (one serious adverse event (SAE) in CBT + TAU in comparison with six SAEs in TAU). These findings suggest that CBT adapted to the needs of adolescents with EOP is a promising approach regarding negative symptoms, functioning, and QoL. CBT is a safe and tolerable treatment. However, due to the small sample size and the pilot character of the study, these conclusions are limited, and should be tested in a larger, adequately powered randomized controlled trial.

Background Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-line treatment for transplant-ineligible individuals consists of multiple drug combinations of bortezomib (V), tenalidomide (R), or thalidomide (T). However, access to these medicines is restricted in many countries worldwide. Objectives To assess and compare the effectiveness and safety of multiple drug combinations of V. R, and T for adults with newly diagnosed transplant-ineligible multiple myeloma and to inform an application for the inclusion of these medicines into the World Health Organization's (WHO) list of essential medicines. Search methods We searched CENTRAL and MEDLI NE, conference proceedings and study registries on 14 February 2019 for randomised controlled trials (RCTs) comparing multiple drug combinations of V, R and 7 for adults with newly diagnosed transplant-ineligible multiple myeloma. Selection criteria We included RCTs comparing combination therapies of V, R, and T, plus melphatan and prednisone (MP) or dexamethasone (D) for first-line treatment of adults with transplant-ineligible multiple myeloma. We excluded trials including adults with relapsed or refractory disease, trials comparing drug therapies to other types of therapy and trials including second-generation novel agents. Data collection and analysis Two review authors independently extracted data and assessed risk of bias of included trials. As effect measures we used hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) for adverse events. An HR or RR < 1 indicates an advantage for the intervention compared to the main comparator MR Where available, we extracted quality of life (QoL) data (scores of standardised questionnaires). Results quoted are from network meta-analysis (N MA) unless stated. Main results We included 25 studies (148 references) comprising 11,403 participants and 21 treatment regim

Aim Psychological interventions, such as cognitive behavioural therapy (CBT) and supportive counselling (SC), are used to treat people with schizophrenia and people at clinical high risk (CHR) of psychosis. However, little information is available on predictors of treatment response. This study aims to identify such predictors of psychological interventions in CHR. Methods A total of 128 help-seeking CHR outpatients were randomized into two groups-integrated psychological intervention (IPI), including CBT, and SC-for 12 months. Multiple regression analysis was used to identify demographic, symptomatic and functional variables that predict improvement in positive (PANSS Positive), negative (PANSS Negative) and basic symptoms (Basic symptom total score) and improvement in functioning (GAF) at 1-year follow up. Results In the merged group (IPI + SC), people who lived independently, were younger and presented with higher baseline functioning showed more improvement in symptomatic outcomes at follow up. Negative symptoms at baseline predicted less improvement in positive and basic symptoms. Being married or cohabiting and living in the primary family were found to correlate with good functioning at 1-year follow up. Conclusions Younger CHR individuals and those who are functioning well may particularly benefit from early intervention. Treatment might need to be modified for low-functioning CHR and those who already display higher scores of negative symptoms. Registration number: NCT00204087

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage degrees 3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed.What is Known:center dot Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies.center dot Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx.What is New:center dot This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects.center dot The hypothesis is

Background: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm. Methods: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups. Results: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group (P<0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups. Conclusions: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion.

Introduction. The determination of the electrolytes sodium and potassium is essential in critical care. In daily clinical practice, both the blood gas analyzer (ABG) and the laboratory autoanalyzer (AA) are generally applied. However, there is still uncertainty regarding the convergence of the prementioned assays, and data about the comparability dependent on the pH value are still lacking. Materials and Methods. One hundred samples from intensive care unit patients with a range in pH values between 7.20 and 7.49 were evaluated in this retrospective cohort study. All patients suffered an infarct-related cardiogenic shock and were intubated and not under therapeutical hypothermia at the time of blood collection. We used scatter plots to compare different distributions of sodium and potassium values between the methods. Comparability of the analyses was assessed using the Bland-Altmann approach, and intraclass correlations (ICC) as estimates of interrater reliability were calculated. Results. The mean potassium level measured on ABG was 4.33mmol/L (SD 0.48mmol/L), and the value obtained using the AA was 4.40mmol/L (SD 0.55mmol/L). A Bland-Altman comparison for total potassium measurements revealed that the limits of agreement were small (-0.241 to 0.391mmol/L). Total ICC displayed a very good correlation of 0.949. For sodium, we found average values of 140mmol/L (SD 5.20mmol/L) in the AA and 140mmol/L (SD 5.80mmol/L) in the ABG assessment. Contrarily, the Bland-Altman comparison for sodium displayed that the 95% limits of agreement were very wide (-5.99 to 6.59mmol/L) for total measurements as well as in every pH subgroup. Total ICC only reached a value of 0.830. Conclusion. Data from our single-center study indicate that urgent and vital decisions based on potassium measurements can be made by trusting the value obtained on the ABG machine irrespective of pH values.

Aims: This study sought to determine the incidence and identify predictors of acute kidney injury (AKI) following percutaneous edge-to-edge mitral valve repair (PMVR) and compare the risk of AKI between PMVR and surgical mitral valve repair (SMVR). Methods and results: We performed a single-centre analysis of 378 patients receiving treatment for mitral regurgitation (196 consecutive patients undergoing PMVR and 182 patients undergoing SMVR). The incidence of AKI (any stage according to KDIGO) following PMVR was 17.9%. Intervention duration (OR 1.01, 95% CI: 1.00-1.02) and peripheral vascular disease (OR 7.69, 95% CI: 3.25-18.17) predicted AKI after PMVR. Patients suffering from AKI after PMVR demonstrated poorer survival (median follow-up 428 days). SMVR patients were significantly younger, had fewer comorbidities and better renal function at baseline. Nevertheless, AKI occurred numerically more often after SMVR than PMVR (25.8% vs. 17.9%, p=0.060), and a multivariable regression model adjusting for differences between both groups confirmed a significantly lower risk for AKI following PMVR (OR 0.22, 95% CI: 0.11-0.44, p<0.001). Conclusions: These data show a significant incidence of AKI after PMVR that must be taken into account in periprocedural care. Nevertheless, our data suggest that SMVR carries an even higher risk of AKI, which should be considered when a decision has to be made between the two therapies.

Sudden cardiac arrest is still one of the most frequent causes of death. Teaching resuscitation in schools was already successfully implemented in Scandinavian countries. Following a recommendation of the conference of german stateministers of education in June 2014, additional tuition for resuscitation is to be implemented in german schools starting in seventh grade. The present study aimed to assess the level of knowledge of seventh grade students in the field of life support and to implement curricular standards for resuscitation courses in secondary schools. Using a standardized questionnaire, students in seventh grade of five schools in Cologne were interrogated about their knowledge on resuscitation and defibrillation. This assessment was taken as basis for developing a curricular teaching concept by the Cologne heart centre in cooperation with the department of biology and technical didactics at the University of Cologne. This tutorial concept was integrated in scholar plans for the first time in the school year 2014/2015. At the end of the school year the students' knowledge got reevaluated. As expected, the technical knowledge of the interviewed students is low, however confidence in their own abilities is high. Most of the interviewed persons would be willing to perform chest compressions (72,26%) and dare using an automated external defibrillator (AED, 64,38%). The exact position of defibrillator pads cannot be precisely indicated by most students (8,40%), compression point, -depth and -frequency are known by just one third of students. Already one-time performance of the live-saving lesson resulted in a clear increase of knowledge about resuscitation. The willingness to perform resuscitation measures and confidence in their own abilities are high in seventh grade students. Therefore, the recommendation of the conference of german stateministers of education in June 2014 addresses the right target group. Long-term success of the presented educational conc

Background This study evaluates whether preoperative statin therapy improves clinical outcomes in patients referred to coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS). Methods A total of 1,151 patients undergoing CABG for ACS were prospectively entered into the North-Rhine-Westphalia surgical myocardial infarction registry and subdivided into two groups according to their preoperative statin status (statin naive vs. statin group). A logistic regression model was employed to analyze the impact of a statin therapy and dose for the endpoints in-hospital mortality and major adverse cardiac events (MACE). Results Demographics, pre- and intraoperative data of the statin-naive group (n = 208; 18%) and statin-treated group (n = 943, 82%) did not differ. In-hospital mortality (12.6 vs. 6.3%, p = 0.002) and MACE rates (22.1 vs. 9.7%, p < 0.001) were significantly higher in statin naive when compared with statin-treated patients with ACS, respectively. Mevalonic acid revealed that both low- and high-dose statin treatment was associated to a reduction in in-hospital mortality and MACE, without a dose-dependent statin effect. Conclusion Statin therapy in patients with ACS undergoing CABG reduces in a dose-independent manner in-hospital mortality and MACE.

Background: Patients undergoing transcatheter aortic valve replacement (TAVR) are mostly elderly patients with substantial comorbidities. Established risk scores are not validated for TAVR and collectives with elderly patients making periprocedural risk stratification difficult. Serum albumin is known to be an indicator for malnutrition and frailty and is simple to measure, independent of physician's bias. Using serum albumin as a preoperative marker for postoperative complications might help estimating morbidity and mortality of these patients. Methods: A total of 457 patients with severe symptomatic aortic stenosis undergoing TAVR at our institution in a period from January 2014 to December 2015 were included in this retrospective study. Baseline characteristics as well as preoperative laboratory parameters were registered. Postoperative morbidity and 30-day mortality were analyzed as primary end points. Enrolled patients with preoperative low serum albumin (<3.5 g/dL) were compared with those revealing normal serum albumin (>= 3.5 g/dL). Results: Among 457 patients, 51 (11%) presented pre-procedural low serum albumin and 406 (89%) had normal serum albumin. Patients' mean age was 81=6 years and 50% of them were male. Postoperative complications such as requirement of blood transfusions (63% versus 33%, P<0.001), infection (53% versus 24%, P<0.001), acute kidney injury (41% versus 19%, P=0.001) and 30-day mortality (10% versus 3%, P=0.045) showed significant differences between preoperative low and normal albumin groups. Conclusions: Preoperative low serum albumin might be an indicator for higher morbidity and mortality in patients undergoing TAVR.