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Purpose Esophageal perforation is associated with high morbidity and mortality. In addition to surgical treatment, endoscopic endoluminal stent placement and endoscopic vacuum therapy (EVT) are established methods in the management of this emergency condition. Although health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic intervention, not much is known about HRQoL, particularly in the long-term follow-up of patients treated for non-neoplastic esophageal perforation with different treatment strategies. The aim of this study was to evaluate patients' outcome after non-neoplastic esophageal perforation with focus on HRQoL in the long-term follow-up. Methods Patients treated for non-neoplastic esophageal perforation at the University Hospital Cologne from January 2003 to December 2014 were included. Primary outcome and management of esophageal perforation were documented. Long-term quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI), the Health-Related Quality of Life Index (HRQL) for patients with gastroesophageal reflux disease (GERD), and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires for general and esophageal specific QoL (QLQ-C30 and QLQ-OES18). Results Fifty-eight patients were included in the study. Based on primary treatment, patients were divided into an endoscopic (n = 27; 46.6%), surgical (n = 20; 34.5%), and a conservative group (n = 11; 19%). Short- and long-term outcome and quality of life were compared. HRQoL was measured after a median follow-up of 49 months. HRQoL was generally reduced in patients with non-neoplastic esophageal perforation. Endoscopically treated patients showed the highest GIQLI overall score and highest EORTC general health status, followed by the conservative and the surgical group. Conclusion HRQoL in patients with non-neoplastic esophageal perforation is reduced even in the long-term follow-up. Temporary stent

BackgroundMortality after ST-elevation myocardial infarction (STEMI) is dependent from best-medical treatment after initial event. ObjectivesDetermining the impact of prescription of guideline-recommended therapy after STEMI in two cohorts, patients with and without history of arterial hypertension, on survival. Methods1,025 patients of the Cologne Infarction Model registry with invasively adjudicated STEMI were dichotomized according to their history of arterial hypertension. We recorded prescription rates and dosing of RAS-inhibitors, beta-blockers and statins in all patients. The primary outcome was all-cause death. Mean follow-up was 2.5 years. ResultsMean age was 64 +/- 13 years, 246 (25%) were women. 749 (76%) patients had a history of hypertension. All-cause mortality was 24.2%, 30-day and 1-year mortality was 11.3% and 16.6%, respectively. History of hypertension correlated with lower mortality (hazard ratio [HR], @30 days: 0.41 [0.27-0.62], @1 year: 0.37 [0.26-0.53]). After adjusting for age, sex, Killip-class, diabetes mellitus, body-mass index, kidney function and statin prescription at discharge 1-year mortality HR was 0.24 (0.12-0.48). At discharge, prescription rates for RAS-inhibitors, beta-blockers and statins, as well as individual dosing and long-term persistence of RAS-inhibitors were higher in patients with history of hypertension. On the same lines, prescription rates for RAS-inhibitors, beta-blockers and statins at discharge correlated significantly with lower mortality regardless of history of hypertension. ConclusionPatients with history of hypertension show higher penetration of guideline recommended drug therapy after STEMI, which may contribute to better survival. Better tolerance of beta-blockers and RAS-inhibitors in patients with history of hypertension, not hypertension itself, likely explains these differences in prescription and dosing.

Background Anaemia is common among cancer patients and they may require red blood cell transfusions. Erythropoiesis-stimulating agents (ESAs) and iron might help in reducing the need for red blood cell transfusions. However, it remains unclear whether the combination of both drugs is preferable compared to using one drug. Objectives To systematically review the effect of intravenous iron, oral iron or no iron in combination with or without ESAs to prevent or alleviate anaemia in cancer patients and to generate treatment rankings using network meta-analyses (NMAs). Search methods We identified studies by searching bibliographic databases (CENTRAL, MEDLINE, Embase; until June 2021). We also searched various registries, conference proceedings and reference lists of identified trials. Selection criteria We included randomised controlled trials comparing intravenous, oral or no iron, with or without ESAs for the prevention or alleviation of anaemia resulting from chemotherapy, radiotherapy, combination therapy or the underlying malignancy in cancer patients. Data collection and analysis Two review authors independently extracted data and assessed risk of bias. Outcomes were on-study mortality, number of patients receiving red blood cell transfusions, number of red blood cell units, haematological response, overall mortality and adverse events. We conducted NMAs and generated treatment rankings. We assessed the certainty of the evidence using GRADE. Main results Ninety-six trials (25,157 participants) fulfilled our inclusion criteria; 62 trials (24,603 participants) could be considered in the NMA (12 different treatment options). Here we present the comparisons of ESA with or without iron and iron alone versus no treatment. Further results and subgroup analyses are described in the full text. On-study mortality We estimated that 92 of 1000 participants without treatment for anaemia died up to 30 days after the active study period. Evidence from NMA (55 trials; 15,074 part

Purpose Esophageal perforation is associated with high morbidity and mortality. In addition to surgical treatment, endoscopic endoluminal stent placement and endoscopic vacuum therapy (EVT) are established methods in the management of this emergency condition. Although health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic intervention, not much is known about HRQoL, particularly in the long-term follow-up of patients treated for non-neoplastic esophageal perforation with different treatment strategies. The aim of this study was to evaluate patients' outcome after non-neoplastic esophageal perforation with focus on HRQoL in the long-term follow-up. Methods Patients treated for non-neoplastic esophageal perforation at the University Hospital Cologne from January 2003 to December 2014 were included. Primary outcome and management of esophageal perforation were documented. Long-term quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI), the Health-Related Quality of Life Index (HRQL) for patients with gastroesophageal reflux disease (GERD), and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires for general and esophageal specific QoL (QLQ-C30 and QLQ-OES18). Results Fifty-eight patients were included in the study. Based on primary treatment, patients were divided into an endoscopic (n = 27; 46.6%), surgical (n = 20; 34.5%), and a conservative group (n = 11; 19%). Short- and long-term outcome and quality of life were compared. HRQoL was measured after a median follow-up of 49 months. HRQoL was generally reduced in patients with non-neoplastic esophageal perforation. Endoscopically treated patients showed the highest GIQLI overall score and highest EORTC general health status, followed by the conservative and the surgical group. Conclusion HRQoL in patients with non-neoplastic esophageal perforation is reduced even in the long-term follow-up. Temporary stent

Background About 70% to 80% of adults with cancer experience chemotherapy -induced nausea and vomiting (CI NV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5hydroxytryptamine-3 (5 -HT,) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK,) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head -to -head comparisons do not allow comparison of all treatments versus another. Objectives In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK, receptor antagonists, 5 -HT, receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy -induced nausea and vomiting in network meta -analysis (NMA) To generate a clinically meaningful treatment ranking according to treatment safety and efficacy In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK, receptor antagonists, 5 -HT, receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapyinduced nausea and vomitingtotreatment combinations including 5 -HT, receptor antagonists and corticosteroids solely, in network meta analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy Search methods We searched CENTRAL, MEDLIN E, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs). Selection criteria We included RCTs including adults with any cancer receiving HEC or MEC (accordi

Background About 70% to 80% of adults with cancer experience chemotherapy -induced nausea and vomiting (CI NV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5hydroxytryptamine-3 (5 -HT,) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK,) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head -to -head comparisons do not allow comparison of all treatments versus another. Objectives In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK, receptor antagonists, 5 -HT, receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy -induced nausea and vomiting in network meta -analysis (NMA) To generate a clinically meaningful treatment ranking according to treatment safety and efficacy In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK, receptor antagonists, 5 -HT, receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapyinduced nausea and vomitingtotreatment combinations including 5 -HT, receptor antagonists and corticosteroids solely, in network meta analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy Search methods We searched CENTRAL, MEDLIN E, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs). Selection criteria We included RCTs including adults with any cancer receiving HEC or MEC (accordi

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.

Purpose Baroreflex activation therapy (BAT) has been shown to lower blood pressure in patients with resistant hypertension. The purpose of this study was to analyze whether this translates into a reduction of more relevant clinical endpoints. Methods Patients with resistant hypertension were treated with the second-generation BAT system. Records on hospitalization (dates of admission and discharge, main diagnosis) were obtained from medical insurance companies. Results Records on hospitalization were available for a period of 1 year before BAT in two patients and 2 years in 22 patients. The total number of hospitalizations per patient was 3.3 +/- 3.5/year before BAT and 2.2 +/- 2.7/year after BAT (p = 0.03). Hospitalizations related to hypertension were significantly decreased from 1.5 +/- 1.6/year before BAT to 0.5 +/- 0.9/year after BAT (p < 0.01). The cumulative duration of hypertension-related hospital stays was significantly reduced from 8.0 +/- 8.7 days/year before BAT to 1.8 +/- 4.8 days/year after BAT (p < 0.01). Office cuff blood pressure was 183 +/- 27 mmHg over 102 +/- 17 mmHg under 6.6 +/- 2.0 antihypertensive drugs before BAT and 157 +/- 32 mmHg over 91 +/- 20 mmHg (both p < 0.01) under 5.9 +/- 1.9 antihypertensive drugs (p = 0.09 for number of drugs) at latest follow-up. Daytime ambulatory blood pressure was 164 +/- 21 mmHg over 91 +/- 14 mmHg before BAT and 153 +/- 21 mmHg (p = 0.03) over 89 +/- 15 mmHg (p = 0.56) at latest follow-up. Heart rate was 75 +/- 16 bpm before BAT and 72 +/- 12 bpm at latest follow-up (p = 0.35). Conclusions Rate and duration of hypertension-related hospitalizations in patients with severe resistant hypertension were lowered after BAT. Whether the response is mediated through improvements in blood pressure control requires further studies.

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.

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.

Purpose Baroreflex activation therapy (BAT) has been shown to lower blood pressure in patients with resistant hypertension. The purpose of this study was to analyze whether this translates into a reduction of more relevant clinical endpoints. Methods Patients with resistant hypertension were treated with the second-generation BAT system. Records on hospitalization (dates of admission and discharge, main diagnosis) were obtained from medical insurance companies. Results Records on hospitalization were available for a period of 1 year before BAT in two patients and 2 years in 22 patients. The total number of hospitalizations per patient was 3.3 +/- 3.5/year before BAT and 2.2 +/- 2.7/year after BAT (p = 0.03). Hospitalizations related to hypertension were significantly decreased from 1.5 +/- 1.6/year before BAT to 0.5 +/- 0.9/year after BAT (p < 0.01). The cumulative duration of hypertension-related hospital stays was significantly reduced from 8.0 +/- 8.7 days/year before BAT to 1.8 +/- 4.8 days/year after BAT (p < 0.01). Office cuff blood pressure was 183 +/- 27 mmHg over 102 +/- 17 mmHg under 6.6 +/- 2.0 antihypertensive drugs before BAT and 157 +/- 32 mmHg over 91 +/- 20 mmHg (both p < 0.01) under 5.9 +/- 1.9 antihypertensive drugs (p = 0.09 for number of drugs) at latest follow-up. Daytime ambulatory blood pressure was 164 +/- 21 mmHg over 91 +/- 14 mmHg before BAT and 153 +/- 21 mmHg (p = 0.03) over 89 +/- 15 mmHg (p = 0.56) at latest follow-up. Heart rate was 75 +/- 16 bpm before BAT and 72 +/- 12 bpm at latest follow-up (p = 0.35). Conclusions Rate and duration of hypertension-related hospitalizations in patients with severe resistant hypertension were lowered after BAT. Whether the response is mediated through improvements in blood pressure control requires further studies.

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.

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

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

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

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.

Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It may cause a variety of symptoms and is associated with longer hospitalizations and higher mortality. However, to date, only little is known about the extent of hyponatremia in patients with incurable diseases and whether it is associated with physical symptoms in this patient group. This study aims to describe the prevalence of hyponatremia, associated symptoms, and symptom intensity in inpatients with hyponatremia receiving specialist palliative care (SPC). This is a retrospective study. Demographic and clinical data as well as symptoms, scored symptom intensity, and laboratory values were collected. All inpatients of a large German University Hospital receiving SPC in 2013 with documented sodium values were included. In 2013, 789 inpatients received SPC of which 710 had documented sodium values. The prevalence of hyponatremia was 38.7% (275/710). A mild degree showed 220 (31,0%), 44 (6.2%) had a moderate, and 11 (1.6%) a severe form. Hyponatremia patients experienced significantly more symptoms than normonatremic patients (mean = 7.71 vs 6.63; p < 0.001). Breathlessness, depressiveness, nausea, vomiting, poor appetite, constipation, and weakness were significantly more frequent in patients with hyponatremia. Furthermore, hyponatremia severity was associated with higher symptom intensity (mean = 13.29 vs 11.28; p < 0.001). More than one third of all SPC patients showed a hyponatremia, and the hyponatremia grade was associated with symptom burden and symptom intensity. A prospective analysis is needed to further examine this association and the possible influence of hyponatremia correction on symptom burden reduction.

The treatment of testicular cancer (TC) requires a multimodal approach. We retrospectively evaluated the diagnostic work-up, treatment, and outcomes of 131 patients with respect to the European Association of Urology guidelines. Of 131 patients, 18% had received non-guideline-concordant treatment, with under-treatment having a negative effect on relapse-free survival. Thus, implementation of guidelines is needed to decrease the mortality of TC. Introduction: The management of testicular cancer (TC) requires a complex multimodal therapeutic approach. Despite the availability of regularly updated guidelines, non-guideline-concordant treatment of TC still occurs. The purpose of the present study was to evaluate the compliance patterns in diagnosis and therapy and their potential effects on patient outcomes with respect to the guidelines of the European Association of Urology. Patients and Methods: We performed a retrospective analysis of 131 patients diagnosed with TC who had been referred to our department from September 2015 to October 2016. Patient characteristics were compared with European Association of Urology guideline recommendations. Results: Of the 131 primary treated patients, 23 (18%) had received a non-guideline-concordant treatment. The most common error was undertreatment (n = 12; 52%), mainly due to missing chemotherapy cycles. Overtreatment occurred in 30% of patients (n = 7); however, inappropriate treatment (n = 2; 9%) and misdiagnosis (n = 2; 9%) were rarely observed. In salvage therapy, non-guideline-concordant treatment was observed less frequently compared to patients receiving primary therapy (12% vs. 18%). Of the 131 patients, 35 developed a relapse, 23 of whom were treated correctly and 6 of whom were undertreated. Undertreatment of patients resulted in significantly reduced relapse-free survival compared with guideline-concordant management in primary treated patients (P = .005). Conclusion: Despite the standardization of treatment by interd

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: Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures. Methods: Forty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman's rank correlation coefficient rho (rho). Results: Average age of the population was 57.8 +/- 16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS (rho = - 0.467) and Ramsay Scores (rho = 0.476). Serum concentrations of sufentanil correlated weakly with RASS (rho = - 0.312) and Ramsay Scores (rho = 0.295). Correlations between BIS index and serum concentrations of midazolam (rho = - 0.252) and sufentanil (rho = - 0.166) were low. Conclusion: Correlations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients.

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.

Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It may cause a variety of symptoms and is associated with longer hospitalizations and higher mortality. However, to date, only little is known about the extent of hyponatremia in patients with incurable diseases and whether it is associated with physical symptoms in this patient group. This study aims to describe the prevalence of hyponatremia, associated symptoms, and symptom intensity in inpatients with hyponatremia receiving specialist palliative care (SPC). This is a retrospective study. Demographic and clinical data as well as symptoms, scored symptom intensity, and laboratory values were collected. All inpatients of a large German University Hospital receiving SPC in 2013 with documented sodium values were included. In 2013, 789 inpatients received SPC of which 710 had documented sodium values. The prevalence of hyponatremia was 38.7% (275/710). A mild degree showed 220 (31,0%), 44 (6.2%) had a moderate, and 11 (1.6%) a severe form. Hyponatremia patients experienced significantly more symptoms than normonatremic patients (mean = 7.71 vs 6.63; p < 0.001). Breathlessness, depressiveness, nausea, vomiting, poor appetite, constipation, and weakness were significantly more frequent in patients with hyponatremia. Furthermore, hyponatremia severity was associated with higher symptom intensity (mean = 13.29 vs 11.28; p < 0.001). More than one third of all SPC patients showed a hyponatremia, and the hyponatremia grade was associated with symptom burden and symptom intensity. A prospective analysis is needed to further examine this association and the possible influence of hyponatremia correction on symptom burden reduction.

The treatment of testicular cancer (TC) requires a multimodal approach. We retrospectively evaluated the diagnostic work-up, treatment, and outcomes of 131 patients with respect to the European Association of Urology guidelines. Of 131 patients, 18% had received non-guideline-concordant treatment, with under-treatment having a negative effect on relapse-free survival. Thus, implementation of guidelines is needed to decrease the mortality of TC. Introduction: The management of testicular cancer (TC) requires a complex multimodal therapeutic approach. Despite the availability of regularly updated guidelines, non-guideline-concordant treatment of TC still occurs. The purpose of the present study was to evaluate the compliance patterns in diagnosis and therapy and their potential effects on patient outcomes with respect to the guidelines of the European Association of Urology. Patients and Methods: We performed a retrospective analysis of 131 patients diagnosed with TC who had been referred to our department from September 2015 to October 2016. Patient characteristics were compared with European Association of Urology guideline recommendations. Results: Of the 131 primary treated patients, 23 (18%) had received a non-guideline-concordant treatment. The most common error was undertreatment (n = 12; 52%), mainly due to missing chemotherapy cycles. Overtreatment occurred in 30% of patients (n = 7); however, inappropriate treatment (n = 2; 9%) and misdiagnosis (n = 2; 9%) were rarely observed. In salvage therapy, non-guideline-concordant treatment was observed less frequently compared to patients receiving primary therapy (12% vs. 18%). Of the 131 patients, 35 developed a relapse, 23 of whom were treated correctly and 6 of whom were undertreated. Undertreatment of patients resulted in significantly reduced relapse-free survival compared with guideline-concordant management in primary treated patients (P = .005). Conclusion: Despite the standardization of treatment by interd

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: Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures. Methods: Forty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman's rank correlation coefficient rho (rho). Results: Average age of the population was 57.8 +/- 16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS (rho = - 0.467) and Ramsay Scores (rho = 0.476). Serum concentrations of sufentanil correlated weakly with RASS (rho = - 0.312) and Ramsay Scores (rho = 0.295). Correlations between BIS index and serum concentrations of midazolam (rho = - 0.252) and sufentanil (rho = - 0.166) were low. Conclusion: Correlations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients.

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.

The study of Kampfenkel et al. investigated whether differences in overall survival could be found in patients with intestinal cancer who were treated in certified centers compared to those treated in non-certified hospitals. We consider some of the limitations of the study, which we believe must be taken into account when interpreting the results of these and similar future studies. Although secondary data evaluations with matched claims and register data can be fundamentally valuable for the description of the health care reality, standards are urgently needed to facilitate the classification of the results and to avoid misleading interpretations.

Regularly reported patient surveys are an important dimension of hospital quality management. This study investigates whether providing hospital staff with interim feedback on patient survey results following a best practices workshop can help hospitals improve patient centeredness. Standardized surveys with consecutive patient samples were administered in accredited breast cancer center (BCC) hospitals in one German state (18 million inhabitants), over a 6-month period, in 2012. Two studies were conducted by applying a combination of regression point displacement (RPD) and interrupted time series (ITS) designs. In Study 1, 2 of the 27 hospitals that had previously participated in a best practices workshop to discuss patient-centeredness issues were randomly chosen and were provided interim feedback of patient survey results and workshop minutes. In Study 2, 4 randomly chosen hospitals of 32 that had not participated in the workshop also received interim feedback but no workshop minutes. Control hospitals in both studies neither received feedback nor workshop minutes. The impact of interim feedback was evaluated by applying graphical assessments and multiple regression analyses. Both graphical assessments (locally weighted scatterplot smoothing (LOESS) lines, RPD plots) suggested an effect of interim feedback. Multiple regression results did not unambiguously support these findings. The suggested design approach may prove particularly useful to assess effects in pilot studies, when resources are not available to conduct a randomized study or when its conduct is contingent on initial, positive evidence.

Purpose: The aim of the FEELING-ON-ICU study was to compare mortality estimations of critically ill patients based on 'gut feeling' of medical staff and by Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA). Materials and methods: Medical staff estimated patients' mortality risks via questionnaires. APACHE II, SAPS II and SOFA were calculated retrospectively from records. Estimations were compared with actual in-hospital mortality using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Results: 66 critically ill patients (60.6% male, mean age 63 +/- 15 years (range 30-86)) were evaluated each by a nurse (n = 66, male 32.4%) and a physician (n = 66, male 67.6%). 15 (22.7%) patients died on the intensive care unit. AUC was largest for estimations by physicians (AUC 0.814 (95% CI 0.705-0.923)), followed by SOFA (AUC 0.749 (95% CI 0.629-0.868)), SAPS II (AUC 0.723 (95% CI 0.597-0.849)), APACHE II (AUC 0.721 (95% CI 0.595-0.847)) and nursing staff (AUC 0.669 (95% CI 0.529-0.810)) (p < 0.05 for all results). Conclusions: The concept of physicians' 'gut feeling' was comparable to classical objective scores inmortality estimations of critically ill patients. Concerning practicability physicians' evaluations were advantageous to complex score calculation. (C) 2017 Elsevier Inc. All rights reserved.

Estimating the quantitative effect of transcatheter mitral valve repair on functional parameters and quality of life is important for individual treatment decision-making. We combined data from a prospective monocentric cohort study (N = 215) with data from a systematic literature review (PubMed search term mitraclip, till 30.04.2016) on patients undergoing MitraClip with at least mortality after discharge reported as an outcome. Effects on functional parameters were reported as range of mean change. 36 observational studies and 1 randomized controlled trial were identified. Due to substantial heterogeneity of effect estimates (I (2)-heterogeneity > 75%) and inadequate quality of studies with a lack of comparison group in 97.4% and lack of an independent assessment of outcomes in 86.8%, no pooled estimates were calculated. All studies reported improvements of mean New York Heart Association (NYHA) class (0.5-1.9 classes), Short-Form (SF)-12/36 scores (4.4-9.2 for physical component score, 2.6-8.9 for mental component score), 6-min walk distance [(6MWD) 2-336 m] and Minnesota Living with Heart failure questionnaire (MLWHFQ) score (-7 to -18 points), with improvements regarded as clinically relevant in 20 of 29 studies for NYHA class, in all of 7 studies for SF12/36, in 9 of 15 studies for 6MWD and in all of 8 studies for MLWHFQ. MitraClip therapy provides improvements in physical capacity, physical and mental functioning and disease-specific quality of life in the majority of patients. However, more comparative and high-quality studies are required for understanding the heterogeneity of results, which is crucial for optimal patient selection.