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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Patients discovered recumbent, helpless and incapacitated, awake or unresponsive are referred to as "long lie trauma" (LLT) in the German medical jargon. Yet, a characterization of this cohort is missing.We retrospectively analyzed all LLT patients admitted to the emergency department of the University Hospital Cologne from July 2018 to December 2020.A total of 50 LLT patients (median age 76 years, median time on the ground 13.5 h) were identified. The FD was most often attributed to primary cerebral causes in 40% of the cases (20% ischemic stroke, 16% intracranial hemorrhage, 4% epilepsy), intoxication/overdose (12%), and trauma (10%). It was often associated with infection (52%), injury (22%), hypovolemia (66%), acute kidney injury (20%), and severe rhabdomyolysis (creatine kinase ≥ 5000 U/l, 21%) as well as severe hypothermia 32 °C (20%). Overall, 69% of the patients were admitted to an intensive care unit and in-hospital mortality was 50%.The term "long lie trauma" describes a complex clinical situation, in which various conditions lead to an incapacitated state with acute onset, which then causes further adverse health effects. Trauma or tissue damage were no obligatory requirement in this syndrome. Considering the high morbidity and in-hospital mortality, patients should initially be treated in the emergency room by an interdisciplinary team.HINTERGRUND: Bisher fehlen Versorgungsdaten für Patienten mit Liegetrauma (LT).Deskriptive retrospektive Analyse aller rettungsdienstlich mit einem LT der Notaufnahme des Universitätsklinikums Köln von 07.2018 bis 12.2020 zugeführten Patienten.Insgesamt konnten 50 Patienten mit LT (Altersmedian 76 Jahre, Liegedauer im Median 13,5 h) im Untersuchungszeitraum identifiziert werden. Die zugrunde liegende Ursache für das LT war in 40 % primär neurologisch (ischämischer Schlaganfall: 20 %, intrakranielle Blutung: 16 %, Epilepsie: 4 %), in 12 % eine Intoxikation und in 10 % ein häusliches Trauma. Häufige assoziierte Diagnosen waren Infektionen (52 %), Traumafolgen (22 %), Exsikkose (66 %), akute Nierenfunktionsstörung (20 %), schwere Rhabdomyolyse (Kreatininkinase ≥ 5000 U/l, 21 %) und schwere Hypothermie 32 °C (20 %). Insgesamt wurden 69 % der Patienten auf einer Intensivstation aufgenommen und die Krankenhausletalität betrug 50 %.Das LT beschreibt einen Patientenzustand, bei dem infolge vielfältiger Ursachen plötzlich die eigenständige Mobilisierung und ein selbstständiges Hilfeholen verhindert werden und dadurch weitere Gesundheitsschäden entstehen. Bei diesem Syndrom sind Gewebsschäden als Folge des Liegens keine notwendige Voraussetzung für das Vorliegen eines LT. Aufgrund der hohen Morbidität und Letalität sollten diese Patienten in einem nichttraumatologischen Schockraum aufgenommen werden.

Background The identification of new biomarkers in autosomal-dominant polycystic kidney disease (ADPKD) is crucial to improve and simplify prognostic assessment as a basis for patient selection for targeted therapies. Post-Hoc-Analyses of the TEMPO 3:4 study indicated that copeptin could be one of those biomarkers. Methods Copeptin was tested in serum samples from patients of the AD(H)PKD study. Serum copeptin levels were measured using a time-resolved amplified cryptate emission (TRACE) based assay. In total, we collected 711 values from 389 patients without tolvaptan treatment and a total of 243 values (of which 64 were pre-tolvaptan) from 94 patients on tolvaptan. These were associated to rapid progression and disease-causing gene variants and their predictive capacity tested and compared to the Mayo Classification. Results As expected, copeptin levels showed a significant negative correlation with eGFR. Measurements on tolvaptan showed significantly higher copeptin levels (9.871 pmol/l vs. 23.90 pmol/l at 90/30 mg; p Conclusion Copeptin levels are associated with kidney function and independently explained future eGFR slopes. As expected, treatment with tolvaptan strongly increases copeptin levels.

ContextDifferential diagnosis of thiazide-associated hyponatremia (TAH) is challenging. Patients can either have volume depletion or a syndrome of inappropriate antidiuresis (SIAD)-like presentation.ObjectiveTo evaluate the impact of the simplified apparent strong ion difference in serum (aSID; sodium + potassium − chloride) as well as the urine chloride and potassium score (ChU; chloride − potassium in urine) in the differential diagnosis of TAH, in addition to assessment of fractional uric acid excretion (FUA).MethodsPost hoc analysis of prospectively collected data from June 2011 to August 2013 from 98 hospitalized patients with TAH < 125 mmol/L enrolled at University Hospital Basel and University Medical Clinic Aarau, Switzerland. Patients were categorized according to treatment response in volume-depleted TAH requiring volume substitution or SIAD-like TAH requiring fluid restriction. We computed sensitivity analyses with ROC curves for positive predictive value (PPV) and negative predictive value (NPV) of aSID, ChU, and FUA in differential diagnosis of TAH.ResultsAn aSID > 42 mmol/L had a PPV of 79.1% in identifying patients with volume-depleted TAH, whereas a value < 39 mmol/L excluded it with a NPV of 76.5%. In patients for whom aSID was inconclusive, a ChU < 15 mmol/L had a PPV of 100% and a NPV of 83.3%, whereas FUA < 12% had a PPV of 85.7% and a NPV of 64.3% in identifying patients with volume-depleted TAH.ConclusionIn patients with TAH, assessment of aSID, potassium, and chloride in urine can help identifying patients with volume-depleted TAH requiring fluid substitution vs patients with SIAD-like TAH requiring fluid restriction.

Zusammenfassung Hintergrund Die aktuelle COVID-19-Pandemie stellt, trotz der Verfügbarkeit von Schnelltests und des Starts der Impfkampagne, die Notaufnahme weiterhin vor große Herausforderungen. Die strukturierte Erfassung von demographischen, klinischen sowie therapiebezogenen Daten stellt die Grundlage für die Erstellung evidenzbasierter Prozesse und Behandlungskonzepte dar. Ziel der Arbeit Darstellung der systematischen Erfassung klinischer Parameter bei Patienten mit COVID-19-Verdacht im Notaufnahmeregister ReCovER (Registry for COVID-19 in the Emergency Room) sowie deskriptive Darstellung der ersten 1000 Patienten. Material und Methoden In zentralen Notaufnahmen (ZNA) von 6 Universitätskliniken werden kontinuierlich Daten von Patienten mit COVID-19-Verdacht, unabhängig vom Nachweis einer SARS-CoV-2-Infektion, in ein webbasiertes, anonymisiertes Register eingegeben. Ergebnisse Zwischen dem 19.05.2020 und dem 13.01.2021 wurden 1000 Patienten in das Register eingegeben, hiervon waren 594 Patienten (59,4 %) in der SARS-CoV-2-positiven (PG) und 406 Patienten (40,6 %) in der negativen Gruppe (NG). Patienten der PG hatten signifikant weniger Vorerkrankungen und eine deutlich längere Latenz zwischen Symptombeginn und Vorstellung in der ZNA (Median 5 vs. 3 Tage), litten häufiger unter Husten, Myalgien, Fatigue sowie Geruchs/Geschmacksverlust und hatten einen signifikant höheren Sauerstoffbedarf als die NG-Patienten. Die Rate von schweren Krankheitsverläufen war in der PG signifikant erhöht und es bestanden nach Entlassung häufiger persistierende Symptome (11,1 vs. 4,6 %). Schlussfolgerungen Durch die multizentrische Erfassung von umfangreichen klinischen Daten zu COVID-19-Verdachtsfällen in der Notaufnahme können insbesondere auch für die Situation in Deutschland spezifische Aspekte analysiert werden. Dies ist essenziell für eine gezielte Überprüfung und Adaption international publizierter Strategien.

Background Frequent outbreaks around the globe and endemic appearance in different parts of the world emphasize the substantial risk of hantavirus diseases. Increasing incidence rates, trends of changing distribution of hantavirus species and new insights into clinical courses of hantavirus diseases call for multinational surveillance. Furthermore, evidence-based guidelines for the management of hantavirus diseases and scoring systems, which allow stratification of patients into risk categories, are lacking. Methods Hantavirus registry (HantaReg) is a novel registry platform facilitating multinational research of hantavirus-caused diseases, such as haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HantaReg provides an electronic case report form and uses the General Data Protection Regulation compliant platform clinicalsurveys.net, which can be accessed from any internet browser in the world. Having a modular structure, the registry platform is designed to display or hide questions and items according to the documented case (e.g. patient with HFRS versus HCPS) to facilitate fast, but standardized, data entry. Information categories documented in HantaReg are demographics, pre-existing diseases, clinical presentation, diagnostic and therapeutic approaches, as well as outcome. Conclusions HantaReg is a novel, ready-to-use platform for clinical and epidemiological studies on hantavirus diseases and facilitates the documentation of the disease course associated with hantavirus infections. HantaReg is expected to promote international collaboration and contributes to improving patient care through the analysis of diagnostic and treatment pathways for hantavirus diseases, providing evidence for robust treatment recommendations. Moreover, HantaReg enables the development of prognosis-indicating scoring systems for patients with hantavirus disease.

Objectives Coronavirus disease 2019 (COVID-19) is currently a worldwide major health threat. Recognizing hypoxia in patients early on can have a considerable effect on therapy success and survival rate. Methods We collected data using a standard blood gas analyzer from 50 patients and analyzed measurements of partial pressure of carbon dioxide-pCO2, partial pressure of oxygen-pO2 and oxygen saturation-sO2, bicarbonate concentrations-HCO3− as well as ionized calcium concentrations. We further examined PCR test results for SARS-CoV-2 of the patients and analyzed differences between patients tested positive and those tested negative for the virus. Results Venous pCO2 was significantly higher whereas pO2 and sO2 were significantly lower in patients who tested positive for SARS-CoV-2. The pH, and ionized calcium concentrations of patients tested positive for the virus were significantly lower than in those tested negative. Conclusions Symptomatic SARS-CoV-2-positive patients upon admission to the emergency room exhibit lower venous blood levels of oxygen, pH, and calcium and higher levels of carbon dioxide compared to symptomatic SARS-CoV-2-negative patients. This blood gas analysis constellation could help in identifying SARS-CoV-2-positive patients more rapidly and identifying early signs of hypoxia.

In the situation of a shortage of ventilation beds, ethically justifiable, transparent and comprehensible decisions must be made. This concept proposes that all patients are first intubated depending on necessity and then assessed by a triage team afterwards. In this situation newly admitted COVID patients compete with newly admitted Non-COVID patients as well as patients already treated in intensive care units for a ventilator. The combination of short-term and long-term prognoses should enable the interprofessional triage team to make comprehensible decisions. The aim of the prioritization concept is to save as many human lives as possible and to relieve the treatment team of the difficult decision on prioritization.In der Situation des Beatmungsbettenmangels sind ethisch begründbare, transparente und nachvollziehbare Entscheidungen zu treffen. Dieses Konzept sieht vor, dass zunächst alle Patienten nach Notwendigkeit intubiert und dann von einem Triage-Team beurteilt werden. Dabei stehen neu aufgenommene COVID-Patienten mit neu aufgenommenen Nicht-COVID-Patienten und bereits intensivmedizinisch behandelte Patienten in Konkurrenz um ein Beatmungsgerät. Die Kombination der kurz- und langfristigen Prognose soll dem interprofessionellen Triage-Team ermöglichen, nachvollziehbare Entscheidungen zu treffen. Ziel des Priorisierungskonzeptes ist es, möglichst viele Menschenleben zu retten und die Behandlungsteams von der schwierigen Entscheidung der Priorisierung zu entlasten.

The management of older and multimorbid patients with complex care requires a personalised and comprehensive approach. The main diagnosis is often registered as the cause of hospitalisation, yet poor health-related quality of life (HRQoL) as well as multimorbidity may represent the underlying cause and markedly influence prognosis. To analyse the association of HRQoL and clinical prognosis over time as assessed by a Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI) in older patients admitted to the emergency department (ED). We used data from the prospective MPI–HOPE (Influence of the MPI on the Hospitalisation of Older Patients admitted to the Emergency department) study. Data from 165 patients (≥ 75 years) admitted to the ED of the University Hospital of Cologne, Germany, between Oct 2017 and Jan 2018 were included. Clinical prognosis was calculated by the MPI and HRQoL by the EQ5D-5L. Follow-up interviews assessed HRQoL up to 6 months after discharge. Most patients were multimorbid and presented with several geriatric syndromes. At admission, HRQoL was highest in patients with the best clinical prognosis. The MPI showed a negative correlation with the EQ-Index at admission (rs(86) = − 0.50, p

Caloric Restriction (CR) extends lifespan and augments cellular stress-resistance from yeast to primates, making CR an attractive strategy for organ protection in the clinic. Translation of CR to patients is complex, due to problems regarding adherence, feasibility and safety concerns in frail patients. Novel tailored dietary regimens, which modulate the dietary composition of macro- and micronutrients rather than reducing calorie intake promise similar protective effects and increased translatability. However, a direct head-to-head comparison to identify the most potent approach for organ protection as well as overlapping metabolic consequences has not been performed. We systematically analyzed six dietary preconditioning protocols - fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chained amino acids (BCAA), two dietary regimens restricting sulfur-containing amino acids (SR80/100) and CR - in a rodent model of renal ischemia-reperfusion injury (IRI) to quantify diet-induced resilience in kidneys. Of the administered diets, FMD, SR80/100 and CR efficiently protect from kidney damage after IRI. Interestingly, these approaches show overlapping changes in oxidative and hydrogen sulfide (H2S)-dependent cysteine catabolism as a potential common mechanism of organ protection.

Background In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. Methods Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). Results A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was − 14% [CI (− 11)–(− 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [− 16%; CI (− 13)–(− 19)], less urgent [− 18%; CI (− 12)–(− 22)] and non-admitted cases [− 17%; CI (− 13)–(− 20)] in particular during the second wave. During the entire observation period admissions for chest pain [− 13%; CI (− 21)–2], myocardial infarction [− 2%; CI (− 9)–11] and heart failure [− 2%; CI (− 10)–6] were less affected and remained comparable to the previous year. Conclusions ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies. Graphical abstract

Short-term dietary restriction (DR) may prevent organ damage from ischemic or toxic insults in animals, but clear evidence in humans is missing. While especially intraarterial administration of contrast media represents a cause of hospital-acquired acute kidney injury (AKI), targeted preventive strategies are not available. This trial investigated the feasibility and effectiveness of pre-interventional DR for preventing AKI in patients undergoing percutaneous coronary intervention (PCI). Patients were randomized to receive a formula diet containing 60% of daily energy requirement (DR group) or ad-libitum food during the 4-day-interval before PCI. Primary endpoint was change of serum creatinine 48 h after PCI (Δcreatinine). Further analyses included incidence of AKI and safety evaluation. Δcreatinine post PCI in the DR group vs. the control group did not show any difference (DR: 0.03(−0.15,0.14)mg/dL vs. control: 0.09(−0.03,0.22)mg/dL;p = 0.797). Subgroup analyses revealed a significant beneficial impact of DR in patients that received ≤100 ml of contrast agent (DR n = 26: Δcreatinine −0.03(−0.20,0.08)mg/dL vs. control n = 24: Δcreatinine 0.10(−0.08,0.24)mg/dL; p = 0.041) and in patients with ≤2 risk factors for AKI (DR: n = 27; Δcreatinine −0.01(−0.18,0.07)mg/dL vs. control n = 31: Δcreatinine 0.09(−0.03,0.16)mg/dl; p = 0.030). Although the primary endpoint was not met, the results of this trial suggest a beneficial impact of DR in low-to-moderate risk patients.

This observational study investigated the impact of hyponatremia resolution on the results of a comprehensive geriatric assessment (CGA) in 150 patients with age ≥70 years and serum sodium 0.2) in the overall analysis for ΔADL and ΔMMSE and moderate (i.e., >0.5) for ΔMMSE in the euvolemic subgroup. Beneficial effects on ΔADL and ΔMMSE were only observed in the subgroup of patients in which [Na+] was raised by >5 mEq/L and multivariable linear regression analysis confirmed [Na+] increase to be an independent predictor of MMSE improvement. Resolution of hyponatremia has a beneficial impact on the geriatric patients’ overall functional status, in particular in euvolemic cases.

Caloric Restriction (CR) extends lifespan and augments cellular stress-resistance from yeast to primates, making CR an attractive strategy for organ protection in the clinic. Translation of CR to patients is complex, due to problems regarding adherence, feasibility and safety concerns in frail patients. Novel tailored dietary regimens, which modulate the dietary composition of macro- and micronutrients rather than reducing calorie intake promise similar protective effects and increased translatability. However, a direct head-to-head comparison to identify the most potent approach for organ protection as well as overlapping metabolic consequences has not been performed. We systematically analyzed six dietary preconditioning protocols - fasting mimicking diet (FMD), ketogenic diet (KD), dietary restriction of branched chained amino acids (BCAA), two dietary regimens restricting sulfur-containing amino acids (SR80/100) and CR - in a rodent model of renal ischemia-reperfusion injury (IRI) to quantify diet-induced resilience in kidneys. Of the administered diets, FMD, SR80/100 and CR efficiently protect from kidney damage after IRI. Interestingly, these approaches show overlapping changes in oxidative and hydrogen sulfide (H2S)-dependent cysteine catabolism as a potential common mechanism of organ protection. Importantly, these metabolic changes can be recapitulated in patients preconditioned by a diet limiting sulfur-containing amino acids indicating conserved diet-induced mechanisms of stress-resistance that may ultimately lead to clinical application.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents AKI can be prevented effectively through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans) longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, in particular arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Acute kidney injury is a frequent complication in the clinical setting and associated with significant morbidity and mortality. Preconditioning with short-term caloric restriction is highly protective against kidney injury in rodent ischemia reperfusion injury models. However, the underlying mechanisms are unknown hampering clinical translation. Here, we examined the molecular basis of caloric restriction-mediated protection to elucidate the principles of kidney stress resistance. Analysis of an RNAseq dataset after caloric restriction identified Cyp4a12a, a cytochrome exclusively expressed in male mice, to be strongly downregulated after caloric restriction. Kidney ischemia reperfusion injury robustly induced acute kidney injury in male mice and this damage could be markedly attenuated by pretreatment with caloric restriction. In females, damage was significantly less pronounced and preconditioning with caloric restriction had only little effect. Tissue concentrations of the metabolic product of Cyp4a12a, 20-hydroxyeicosatetraenoic acid (20-HETE), were found to be significantly reduced by caloric restriction. Conversely, intraperitoneal supplementation of 20-HETE in preconditioned males partly abrogated the protective potential of caloric restriction. Interestingly, this effect was accompanied by a partial reversal of caloric restriction--induced changes in protein but not RNA expression pointing towards inflammation, endoplasmic reticulum stress and lipid metabolism. Thus, our findings provide an insight into the mechanisms underlying kidney protection by caloric restriction. Hence, understanding the mediators of preconditioning is an important prerequisite for moving towards translation to the clinical setting.

Objectives One major goal of the emergency department (ED) is to decide, whether patients need to be hospitalised or can be sent home safely. We aim at providing criteria for these decisions without knowing the SARS-CoV-2 test result in suspected cases.Setting Tertiary emergency medicine.Participants All patients were treated at the ED of the Charité during the pandemic peak and underwent SARS-CoV-2 testing. Patients with positive test results were characterised in detail and underwent a 14-day-follow-up.Primary and secondary outcome measures Logistic regression and classification and regression tree (CART) analyses were performed to identify predictors (primary endpoint), which confirm safe discharge. The clinical endpoint was all-cause mortality or need for mechanical ventilation during index stay or after readmission.Results The primary test population of suspected COVID-19 consisted of n=1255 cases, 45.2% were women (n=567). Of these, n=110 tested positive for SARS-CoV-2 (8.8%). The median age of SARS-CoV-2-positive cases was 45 years (IQR: 33–66 years), whereas the median age of the group tested negative for SARS-CoV-2 was 42 years (IQR: 30–60 years) (p=0.096). 43.6% were directly admitted to hospital care.CART analysis identified the variables oxygen saturation (

The current COVID-19 pandemic, despite the availability of rapid tests and the start of the vaccination campaign, continues to pose major challenges to emergency departments (ED). Structured collection of demographic, clinical, as well as treatment-related data provides the basis for establishing evidence-based processes and treatment concepts.To present the systematic collection of clinical parameters in patients with suspected COVID-19 in the Registry for COVID-19 in the Emergency Room (ReCovER) and descriptive presentation of the first 1000 patients.Data from patients with suspected COVID-19, regardless of evidence of SARS-CoV‑2 infection, are continuously entered into a web-based, anonymized registry in ED at six university hospitals.Between 19 May 2020 and 13 January 2021, 1000 patients were entered into the registry, of whom 594 patients (59.4%) were in the SARS-CoV‑2 positive group (PG) and 406 patients (40.6%) were in the negative group (NG). Patients of the PG had significantly fewer pre-existing conditions and a significantly longer latency between symptom onset and presentation to the ED (median 5 vs. 3 days), were more likely to suffer from cough, myalgia, fatigue, and loss of smell/taste and had significantly higher oxygen requirements than NG patients. The rate of severe disease progression was significantly higher in the PG, and persistent symptoms were more common after discharge (11.1 vs. 4.6%).The multicenter collection of comprehensive clinical data on COVID-19 suspected cases in the ED allows analysis of aspects specific to the situation in Germany in particular. This is essential for a targeted review and adaptation of internationally published strategies.HINTERGRUND: Die aktuelle COVID-19-Pandemie stellt, trotz der Verfügbarkeit von Schnelltests und des Starts der Impfkampagne, die Notaufnahme weiterhin vor große Herausforderungen. Die strukturierte Erfassung von demographischen, klinischen sowie therapiebezogenen Daten stellt die Grundlage für die Erstellung evidenzbasierter Prozesse und Behandlungskonzepte dar.Darstellung der systematischen Erfassung klinischer Parameter bei Patienten mit COVID-19-Verdacht im Notaufnahmeregister ReCovER (Registry for COVID-19 in the Emergency Room) sowie deskriptive Darstellung der ersten 1000 Patienten.In zentralen Notaufnahmen (ZNA) von 6 Universitätskliniken werden kontinuierlich Daten von Patienten mit COVID-19-Verdacht, unabhängig vom Nachweis einer SARS-CoV-2-Infektion, in ein webbasiertes, anonymisiertes Register eingegeben.Zwischen dem 19.05.2020 und dem 13.01.2021 wurden 1000 Patienten in das Register eingegeben, hiervon waren 594 Patienten (59,4 %) in der SARS-CoV-2-positiven (PG) und 406 Patienten (40,6 %) in der negativen Gruppe (NG). Patienten der PG hatten signifikant weniger Vorerkrankungen und eine deutlich längere Latenz zwischen Symptombeginn und Vorstellung in der ZNA (Median 5 vs. 3 Tage), litten häufiger unter Husten, Myalgien, Fatigue sowie Geruchs/Geschmacksverlust und hatten einen signifikant höheren Sauerstoffbedarf als die NG-Patienten. Die Rate von schweren Krankheitsverläufen war in der PG signifikant erhöht und es bestanden nach Entlassung häufiger persistierende Symptome (11,1 vs. 4,6 %).Durch die multizentrische Erfassung von umfangreichen klinischen Daten zu COVID-19-Verdachtsfällen in der Notaufnahme können insbesondere auch für die Situation in Deutschland spezifische Aspekte analysiert werden. Dies ist essenziell für eine gezielte Überprüfung und Adaption international publizierter Strategien.

Isolation of confirmed or suspected coronavirus disease 2019 (COVID-19) cases is essential but, as symptoms of COVID-19 are non-specific and test results not immediately available, case identification at admission remains challenging. To inform optimization of triage algorithms, patient flow and patient care, we analyzed characteristics of patients admitted to an isolation ward, both severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) positive patients and patients in which initial suspicion was not confirmed after appropriate testing.Data from patients with confirmed or suspected COVID-19 treated in an isolation unit were analyzed retrospectively. Symptoms, comorbidities and clinical findings were analyzed descriptively and associations between patient characteristics and final SARS-CoV-2 status were assessed using univariate regression.Eighty three patients (49 SARS-CoV-2 negative and 34 positive) were included in the final analysis. Of initially suspected COVID-19 cases, 59% proved to be SARS-CoV-2-negative. These patients had more comorbidities (Charlson Comorbidity Index median 5(interquartile range [IQR] 2.5, 7) vs 2.7(IQR 1, 4)), and higher proportion of active malignancy than patients with confirmed COVID-19 (47% vs 15%; P = .004), while immunosuppression was frequent in both patient groups (20% vs 21%; P = .984). Of SARS-CoV-2 negative patients, 31% were diagnosed with non-infectious diseases.A high proportion of patients (59%) triaged to the isolation unit were tested negative for SARS-CoV-2. Of these, many suffered from active malignancy (47%) and were immunosuppressed (20%). Non-infectious diseases were diagnosed in 31%, highlighting the need for appropriate patient flow, timely expert medical care including evaluation for differential diagnostics while providing isolation and ruling out of COVID-19 in these patients with complex underlying diseases.

BackgroundRapid and extensive testing of large parts of the population and specific subgroups is crucial for proper management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decision-making in times of a pandemic outbreak. However, point-of-care (POC) testing in places such as emergency units, outpatient clinics, airport security points or the entrance of any public building is a major challenge. The need for thermal cycling and nucleic acid isolation hampers the use of standard PCR-based methods for this purpose.MethodsTo avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including loop-mediated isothermal amplification (LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK).ResultsWhilst specificity of standard LAMP assays appears to be satisfactory, sensitivity does not reach the current gold-standard quantitative real-time polymerase chain reaction (qPCR) assays yet. We describe a novel multiplexed LAMP approach and validate its sensitivity on primary samples. This approach allows for fast and reliable identification of infected individuals. Primer optimization and multiplexing helps to increase sensitivity significantly. In addition, we directly compare and combine our novel LAMP assays with SHERLOCK.ConclusionIn summary, this approach reveals one-step multiplexed LAMP assays as a prime-option for the development of easy and cheap POC test kits.

Acute kidney injury is a common clinical disorder resulting in significantly increased morbidity and mortality. However, despite extensive research, strategies for prevention or treatment are still lacking in routine clinical practice. Already decades ago, several preconditioning strategies (e. g. ischemic/hypoxic preconditioning and calorie restriction) have been published and their extraordinary effectiveness - especially in rodents - has raised the hope for powerful clinical tools to prevent acute kidney injury. However, the underlying mechanisms are still not completely understood and translation to the clinics has not been successful yet. In this review, the most attractive strategies and the current mechanistic concepts are introduced and discussed. Furthermore, we present clinical trials evaluating the feasibility of preconditioning in the clinical setting.

Eine akzidentielle oder (para)suizidale Intoxikation mit Ethylenglykol kann zu einer schweren Acidose, zu verschiedenen Organsystemschaden und zum Tod fuhren. Wirksame Therapien stellen die Hamodialyse und die sofortige Gabe von Fomepizol bzw. von Ethanol dar. Wir beschreiben einen Patienten nach wiederholter Ethylenglykolintoxikation mit einer schweren metabolischen Acidose und einem akuten Nierenversagen. Durch Hamodialyse mit ethanolhaltigem Dialysat und i. v.-Gabe von Ethanol konnten wir gravierende Folgeschaden verhindern.

Die schwere akute Hyponatriamie ist eine lebensbedrohliche Erkrankung. Wir berichten uber den Fall einer 38-jahrigen Patientin, die im Rahmen einer isovolamischen Hyponatriamie innerhalb kurzer Zeit ein Hirnodem mit letaler Einklemmung entwickelte.

Alternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, −4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, −11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.

Hyponatremia is a frequently encountered clinical finding, and by far the most common disorder of electrolyte and water homeostasis throughout the world. Given the complex pathophysiology of hyponatremia as well as its clinical implications, which range from apparently asymptomatic presentations to life-threatening conditions, a comprehensive understanding of its possible causes and of the frequencies of occurrence of the various types of hyponatremia in distinct clinical settings is essential for successful disease management. In this chapter, the diverse etiologies of hyponatremia are summarized, explained, and classified according to the patients' extracellular volume status. An in-depth review of the existing literature on epidemiologic data on incidence and prevalence of hyponatremia is provided covering the general population as well as the patient groups with community-acquired and hospital-acquired hyponatremia. Selected clinical scenarios that are described in detail are: hyponatremia in the geriatric population, in the emergency department, in the postoperative state, and in the intensive care setting. Distinct diseases and circumstances that are often associated with hyponatremia are reviewed briefly, while a more detailed discussion is covered in later chapters.

The coronavirus disease (COVID-19) pandemic has caused tremendous pressure on hospital infrastructures such as emergency rooms (ER) and outpatient departments. To avoid malfunctioning of critical services because of large numbers of potentially infected patients seeking consultation, we established a COVID-19 rapid response infrastructure (CRRI), which instantly restored ER functionality. The CRRI was also used for testing of hospital personnel, provided epidemiological data and was a highly effective response to increasing numbers of suspected COVID-19 cases.

Background: Germany is among the countries with the highest numbers of SARS-CoV-2 infections in Europe To slow the spread of SARS-CoV-2 a combination of measur

BackgroundRapid and extensive testing of large parts of the population and specific subgroups is crucial for proper management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decision-making in times of a pandemic outbreak. However, point-of-care (POC) testing in places such as emergency units, outpatient clinics, airport security points or the entrance of any public building is a major challenge. The need for thermal cycling and nucleic acid isolation hampers the use of standard PCR-based methods for this purpose.MethodsTo avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK).ResultsWhilst specificity of standard RT-LAMP assays appears to be satisfactory, sensitivity does not reach the current gold-standard quantitative real-time polymerase chain reaction (qPCR) assays yet. We describe a novel multiplexed RT-LAMP approach and validate its sensitivity on primary samples. This approach allows for fast and reliable identification of infected individuals. Primer optimization and multiplexing helps to increase sensitivity significantly. In addition, we directly compare and combine our novel RT-LAMP assays with SHERLOCK.ConclusionIn summary, this approach reveals one-step multiplexed RT-LAMP assays as a prime-option for the development of easy and cheap POC test kits.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents, AKI can be effectively prevented through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans), longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, particularly arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Background: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Methods: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na+] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH). Results: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na+] change (Δdaily[Na+]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δdaily[Na+] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived. Conclusions: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH.

Background The impact of chronic moderate and profound hyponatremia on neurocognitive performance, motor skills, and mood stability has not been investigated systematically so far, and results regarding mild to moderate hyponatremia are inconsistent. Furthermore, it is not known whether treatment has an effect on outcome in these patients. Methods A total of 130 hospitalized patients with confirmed euvolemic hyponatremia ( Results The scores of all tested domains were significantly worse in the hyponatremia group (median serum sodium [Na+] 122 (119-126) mEq/L) as compared to the reference group (P Conclusion We demonstrate a clear association between lower levels of Na+ beyond mild hyponatremia and impairment of neurocognitive and motor performance as well as mood disorders. Our analysis further suggests a causal role of hyponatremia in this context. However, there are apparent differences between the distinct tested domains warranting further investigations.

Hyponatremia is a frequently encountered clinical finding, and by far the most common disorder of electrolyte and water homeostasis throughout the world. Given the complex pathophysiology of hyponatremia as well as its clinical implications, which range from apparently asymptomatic presentations to life-threatening conditions, a comprehensive understanding of its possible causes and of the frequencies of occurrence of the various types of hyponatremia in distinct clinical settings is essential for successful disease management. In this chapter, the diverse etiologies of hyponatremia are summarized, explained, and classified according to the patients' extracellular volume status. An in-depth review of the existing literature on epidemiologic data on incidence and prevalence of hyponatremia is provided covering the general population as well as the patient groups with community-acquired and hospital-acquired hyponatremia. Selected clinical scenarios that are described in detail are: hyponatremia in the geriatric population, in the emergency department, in the postoperative state, and in the intensive care setting. Distinct diseases and circumstances that are often associated with hyponatremia are reviewed briefly, while a more detailed discussion is covered in later chapters.

Acute kidney injury (AKI) leads to significant morbidity and mortality; unfortunately, strategies to prevent or treat AKI are lacking. In recent years, several preconditioning protocols have been shown to be effective in inducing organ protection in rodent models. Here, we characterized two of these interventions—caloric restriction and hypoxic preconditioning—in a mouse model of cisplatin-induced AKI and investigated the underlying mechanisms by acquisition of multi-layered omic data (transcriptome, proteome, N-degradome) and functional parameters in the same animals. Both preconditioning protocols markedly ameliorated cisplatin-induced loss of kidney function, and caloric restriction also induced lipid synthesis. Bioinformatic analysis revealed mRNA-independent proteome alterations affecting the extracellular space, mitochondria, and transporters. Interestingly, our analyses revealed a strong dissociation of protein and RNA expression after cisplatin treatment that showed a strong correlation with the degree of damage. N-degradomic analysis revealed that most posttranscriptional changes were determined by arginine-specific proteolytic processing. This included a characteristic cisplatin-activated complement signature that was prevented by preconditioning. Amyloid and acute-phase proteins within the cortical parenchyma showed a similar response. Extensive analysis of disease-associated molecular patterns suggested that transcription-independent deposition of amyloid P-component serum protein may be a key component in the microenvironmental contribution to kidney damage. This proof-of-principle study provides new insights into the pathogenesis of cisplatin-induced AKI and the molecular mechanisms underlying organ protection by correlating phenotypic and multi-layered omics data.

Background Data are lacking on the relative incidence of thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS) caused by Shiga toxin–producing Escherichia coli (STEC) and atypical HUS (aHUS) in patients presenting with thrombotic microangiopathies (TMAs). Methods This was a prospective, cross-sectional, multicentre and non-interventional epidemiological study. Patients fulfilling criteria for TMAs (platelet consumption, microangiopathic haemolytic anaemia and organ dysfunction) were included in the study. The primary objective was to assess the relative incidence of TTP, STEC-HUS, aHUS and ‘other’ physician-defined diagnoses. The secondary objective was to develop an algorithm to predict a severe deficiency in ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (≤10%) using routine laboratory parameters. A post hoc classification using the recent Kidney Disease: Improving Global Outcomes diagnostic criteria was then undertaken to further classify patient groups. Results aHUS was diagnosed with a relative incidence of 61%, whereas TTP, STEC-HUS and ‘other’ were diagnosed in 13, 6 and 20% of patients, respectively. In the post hoc analysis, 27% of patients with a TMA were classified as ‘primary aHUS’ and 53% as ‘secondary aHUS’. Multivariate analysis revealed that severe deficiency in ADAMTS13 activity (≤10%) was unlikely to underlie TMA if platelet and serum creatinine were above threshold values of 30 × 109/L and 1.8 mg/dL, respectively (negative predictive value of 92.3 and 98.1, respectively, if one or both values were above the threshold). Conclusions In this study, aHUS was the most common single diagnosis among patients presenting with a TMA. In the absence of an ADAMTS13 activity result, platelet count and serum creatinine may aid in the differential diagnosis.

Objectives We investigated the trend in usage of post-exposure prophylaxis (PEP) after HIV-1 risk exposure and evaluated PEP prescription decision making of physicians according to guidelines. Methods All PEP consultations from January 2014 to December 2016 in patients presenting at the University Hospital of Cologne (Germany) were retrospectively analysed. HIV risk contacts included sexual and occupational exposure. The European AIDS Clinical Society (EACS) Guidelines for HIV PEP (version 9.0, 2017) were used for assessment. Results A total of 649 patients presented at the emergency department (ED) or the clinic for infectious diseases (IDC) for PEP consultations. A continuous increase in the number of PEP requests was recorded: 189 in 2014, 208 in 2015 and 252 in 2016. PEP consultations in men who have sex with men (MSM) showed a remarkable increase in 2016 (2014, n = 96; 2015, n = 101; 2016, n = 152). Decisions taken by physicians with a specialization in infectious diseases (n = 547) included 61 (11%) guideline-discordant prescriptions [2014: 14% (n = 22); 2015: 9% (n = 16); 2016: 11% (n = 23)]. Among these, sexual exposure accounted for 45 (74%) cases, including 15 cases of nonconsensual sex, while occupational exposure accounted for 14 (23%) cases and other exposure two cases (3%). The main reason for guideline-discordant PEP prescriptions was emotional stress of the patient (n = 37/61). Conclusions PEP prescriptions are increasing and decision making is influenced by patients' emotional stress, but PEP prescriptions should be strictly administered according to risk assessment.