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Background The prevalence of end-stage renal disease of unknown etiology in adult patients is globally high and accounts for almost 20% of all dialysis patients. Recent studies have suggested that the percentage of adult patients with a causal genetic variant has been underestimated so far. Despite severe prognostic and therapeutic implications, awareness about prevalence and manifestations of genetic kidney diseases in adult renal patients is still limited. Methods We recruited 58 individuals from 39 families at our transplantation center, fulfilling at least one of the following criteria: (i) unclear etiology of kidney disease, (ii) clinically suspected genetic kidney disease and (iii) positive family history for nephropathies. The cohort consisted of patients waitlisted for kidney transplantation and patients in the follow-up after transplantation. Detailed documentation of family history and phenotype was obtained before initiating gene panel sequencing of 479 nephropathy-associated genes. Results With this study design, a molecular genetic diagnosis was established in one-third of all patients. Mutations in the collagen COL4A genes, and mutations in MUC1 and UMOD were the most frequent among all detected causal variants. Overall, rare genetic variants were detected in more than half of all cases. Conclusion The combination of detailed phenotyping prior to next-generation sequencing diagnostics was highly efficient. Elucidating the underlying genetic causes in a cohort of adult renal patients has considerable clinical impact on medical management.

Background COPD influences cardiac function and morphology. Changes of the electrical heart axes have been largely attributed to a supposed increased right heart load in the past, whereas a potential involvement of the left heart has not been sufficiently addressed. It is not known to which extent these alterations are due to changes in lung function parameters. We therefore quantified the relationship between airway obstruction, lung hyperinflation, several echo- and electrocardiographic parameters on the orientation of the electrocardiographic (ECG) P, QRS and T wave axis in COPD. Methods Data from the COPD cohort COSYCONET were analyzed, using forced expiratory volume in 1 s (FEV1), functional residual capacity (FRC), left ventricular (LV) mass, and ECG data. Results One thousand, one hundred and ninety-five patients fulfilled the inclusion criteria (mean ± SD age: 63.9 ± 8.4 years; GOLD 0–4: 175/107/468/363/82). Left ventricular (LV) mass decreased from GOLD grades 1–4 (p = 0.002), whereas no differences in right ventricular wall thickness were observed. All three ECG axes were significantly associated with FEV1 and FRC. The QRS axes according to GOLD grades 0–4 were (mean ± SD): 26.2° ± 37.5°, 27.0° ± 37.7°, 31.7° ± 42.5°, 46.6° ± 42.2°, 47.4° ± 49.4°. Effects of lung function resulted in a clockwise rotation of the axes by 25°-30° in COPD with severe airway disease. There were additional associations with BMI, diastolic blood pressure, RR interval, QT duration and LV mass. Conclusion Significant clockwise rotations of the electrical axes as a function of airway obstruction and lung hyperinflation were shown. The changes are likely to result from both a change of the anatomical orientation of the heart within the thoracic cavity and a reduced LV mass in COPD. The influences on the electrical axes reach an extent that could bias the ECG interpretation. The magnitude of lung function impairment should be taken into account to uncover other cardiac disease and to prevent misdiagnosis. Electronic supplementary material The online version of this article (10.1186/s12931-019-1025-y) contains supplementary material, which is available to authorized users.

Background: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference.Methods: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, post-bronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores.Main outcomes: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points.Findings: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points.Conclusions: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Background Mild hypothermia treatment (32–34°C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48h. Patients and methods A total of 34 patients were analysed and received mild therapeutic hypothermia treatment (MTH) according to the current guidelines and irrespective of the initial rhythm. At admission to hospital and in the field in case of OHCA, a 12-lead ECG was performed in all patients. Results During cooling the incidence of ventricular tachycardia was low (8.8%) and in none of the patients Torsade de pointes occurred. The QTc interval was within normal range at first patient contact with EMS in the field (440.00ms; IQR 424.25–476.75; n =17) but during hypothermia treatment the QTc interval was significantly prolonged at 33°C after 24h of cooling (564.47ms; IQR 512.41–590.00; p =0.0001; n =34) and decreased after end of hypothermia to baseline levels (476.74ms; 448.71–494.97; p =0.15). Conclusion The QTc interval was found to be significantly prolonged during MTH treatment, and some severe prolongations >670ms were observed, without a higher incidence of life-threatening arrhythmias, especially no Torsade des pointes were detected. However, routine and frequent ECG recording with respect to the QTc interval should become part of any hypothermia standard operation protocol and should be recommended by official guidelines.

Background The aim of the study was to report the impact of our hypothermia protocol on survival and neurological outcome. Furthermore, we were interested in the risk of bleeding complications in patients with acute myocardial infarction (AMI) being treated with percutaneous coronary revascularisation (PCI) and therapeutic hypothermia. Methods and results In a prospective observational study we identified 31 comatose patients (25 male, age 65±13 years) admitted to our intensive care unit with out-of-hospital cardiac arrest due to AMI who were treated with hypothermia. They were compared to 31 historical age- and gender-matched controls (25 male, age 65±12 years) admitted after out-of-hospital cardiac arrest due to AMI in the era prior to hypothermia treatment. Peak creatinine kinase-MB was 118 U/L (94–248) in the hypothermia group and 131 U/L (98–257) in controls ( p =0.51). In the hypothermia group, 19 patients were discharged with a favourable neurological outcome, whereas in controls, such outcome was observed in only six patients ( p =0.002). In both groups, haemoglobin values and platelet counts declined during the first 48 h (all p p =1.0), transfusion requirements ( p =1.0), and the number of transfusions ( p =0.9) were observed between the groups. Conclusions A major improvement in neurological outcome was observed in patients treated with hypothermia. Our results indicate that the combination of reperfusion strategies and the application of hypothermia do not carry an excessive risk of bleeding complications. Patients with AMI and out-of-hospital cardiac arrest should receive the optimal therapy for both conditions, that is, either thrombolysis or PCI and therapeutic hypothermia.

Clotting of the extracorporal system is the main complication of heparin free hemodialysis performed in patients with an increased risk of bleeding. The authors compared thromboxane B2, platelet factor 4, beta-thromboglobulin, and thromboelastography in systemic blood as markers of thrombogenicity during hemodialysis in eight patients with an increased risk of bleeding. Measurements were performed during hemodialysis with and without heparin. Thromboxane B2 levels in centrifuged blood were evaluated by an 125I assay system using a special extraction with mini-columns and magnetic separation (normal 32-64 pg/ml). At the onset of hemodialysis, thromboxane B2 concentrations in the inflow arterial blood line were lower than normal (30 +/- 23 pg/ml). Thromboxane B2 increased (97 +/- 105 versus 40 +/- 26 pg/ml) and was significantly higher during heparin free hemodialysis than during hemodialysis with heparin (p = 0.01, Wilcoxon matched pairs signed rank test). The highest values were observed in 5 cases with signs of clotting (152 +/- 122 pg/ml). Among the investigated parameters, thromboxane B2 proved to be the most significant serum parameter correlated with platelet activation and the consequently increased risk of incipient clotting during heparin free hemodialysis.

Summary Intestinal transplantation (ITX) can be a successful treatment for patients with irreversible intestinal failure and associated severe complications. Because of long waiting periods and organ shortages, the precise identification of eligible patients and their early referral to centers that perform ITX is important. We retrospectively analyzed all patients who were referred to our center between 2000 and 2011 concerning their referral criteria, waitlist characteristics, and outcome. A total of 87 patients (47 male patients, 40 female patients; median age 39.8 ± 13.4 years) were referred to our center. All patients presented with intestinal failure caused by short bowel syndrome or motility disorders. About 80.5% of patients were evaluated for isolated ITX, modified multivisceral (mMVTX), or multivisceral transplantation (MVTX). About 56.3% were listed at EUROTRANSPLANT, 33.3% suffered from severe secondary organ failure requiring MVTX, and 34.5% were transplanted. 14.3% (all MVTX-candidates) died on the waitlist as a result of infectious complications. The high proportion of MVTX candidates underlines the need for early referral to specialized centers. MVTX-candidates have a high waitlist mortality for different reasons. However, the current allocation policy for MVTX does not mirror the severity of disease and may therefore contribute to high waitlist mortality.

Therapeutic hypothermia after cardiac arrest is a treatment with a high level of evidence. In 2003 the International Liaison Committee on Resuscitation (ILCOR) recommended such treatment for all comatose survivors of out-of-hospital cardiac arrest when the initial rhythm was ventricular fibrillation [1]. However, recent studies have shown that only a minority of resuscitated patients are treated with therapeutic hypothermia in both American and European intensive care units [2-4]. A letter recently published in Critical Care reported the use of therapeutic hypothermia in Germany in only 38% of departments treating patients after cardiac arrest [5]. To improve adherence to the ILCOR guidelines we developed a written standard operating procedure (SOP) for patients after cardiac arrest admitted to our 38-bed medical intensive care unit. Starting in December 2005 the SOP was to be applied to all comatose patients after cardiac arrest, irrespective of the initial rhythm. Since then the SOP has been applied in 28 out of 34 eligible patients. For four patients the physician in charge did not consider therapeutic hypothermia despite clear indication. In two other patients hypothermia was considered to be contraindicated because of extensive coronary vasospasm or massive pulmonary bleeding of a bronchial carcinoma, respectively. In all the remaining 28 patients surface cooling with technical devices (CritiCool from MTRE, Yavne Israel, and ArcticSun from Medivance, Louisville, KY, USA) was used to induce and maintain hypothermia for 24 hours. The target temperature of 33°C was reached in 6.0 ± 3.2 hours (mean ± SD). In none of the patients were serious adverse events potentially related to therapeutic hypothermia, such as clinically relevant bleeding episodes or arrhythmias, observed. In 12 out of 28 patients (42.9%) treated with therapeutic hypothermia a favourable neurologic outcome was reached (Cerebral Performance Category 1 or 2). Although our limited experience does not yet permit a valid statistical evaluation of the impact of therapeutic hypothermia on the neurological outcome of the patients, initial results are encouraging. We are currently trying to shorten the time to target temperature, which we feel was still too long in some patients. However, the simple availability of a written SOP has already led to the application of therapeutic hypothermia in the vast majority of our patients after cardiac arrest. All physicians caring for such patients should be encouraged to establish their own protocol for therapeutic hypothermia at their institutions, to facilitate the widespread application of this evidence-based treatment.

Background— Chlamydia pneumoniae stimulates chronic inflammation in vascular cells. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may have an ameliorating effect. We investigated possible mechanisms. Methods and Results— We infected human macrophages that in coculture spread infection to vascular smooth muscle cells (VSMCs). Cerivastatin (250 nmol/L) reduced VSMC infection by 33%. Western blotting made it apparent that VSMC infection resulted in increased cell membrane-associated RhoA and Rac1, implying increased prenylation of these proteins. This effect was blocked by statin but circumvented by mevalonate. Cytochrome C assays showed that infected VSMCs produced increased reactive oxygen species that was blocked by statin. Infection increased nuclear transcription factor-κB expression in VSMCs that was dose-dependently suppressed by statin. Infected VSMCs produced and released RANTES and MCP-1. Statin dose-dependently blocked this production both at the mRNA and protein levels. Mevalonate and M geranylgeranylpyrophosphate circumvented these effects. Conclusions— C pneumoniae can be transmitted from macrophages to VSMCs. VSMCs showed an activation profile typical of atherosclerosis, namely Rac1 and RhoA prenylation, nuclear transcription factor-κB activation, reactive oxygen species production, and chemokine production. Statin reduces macrophage-mediated C pneumoniae -induced signaling and transmission.

Seasonal Affective Disorder (SAD) has received formal research attention only within the last eight years. Diagnostic criteria for SAD include many characteristics typical of depression: sadness, low self-esteem, lack of energy, social withdrawal, and suicide ideation, and features of atypical depression: carbohydrate craving, overeating, weight gain, and hypersomnia. Differential diagnosis of the disorder depends on an onset in fall/winter and remission in spring/summer. It was hypothesized that spinal cord injury (SCI) patients would have a higher incidence of the disorder in the northern latitudes because of decreased outdoor activities in winter and because of such light-depriving winter survival tactics as installing opaque plastic for storm windows. SCI patient responded to a postal survey which included Rosenthal's Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI). Results showed a substantially higher rate of SAD among SCI patients than in the normative sample.