Influenza-associated pulmonary aspergillosis (IAPA) is a frequent and often fatal complication of severe influenza in critically ill patients. Despite increased recognition, its real global burden and optimal prevention strategies remain uncertain. A structured literature review of studies published between January 2000 and June 2025 was conducted to summarize IAPA incidence, fatality rate and study heterogeneity. Continuous variables were summarized as trimmed medians (central 80

Renal replacement therapy (RRT) is frequently used in critically ill patients with acute kidney injury (AKI). Here, we provide guidelines for the management of RRT in critically ill patients on the intensive care unit (ICU). We convened a systemic literature research and a Delphi process with a bi-national multidisciplinary consensus panel including 22 clinicians of 12 different German-speaking societies (Germany and Austria) with expertise in RRT. This structured guideline process was the basis for the evidence-based statements and recommendations. We identified seven clinical areas needing guidance: (1) start, (2) modality (diffusion and convection), (3) continuous/ intermittent, (4) anticoagulation, (5) dose (6) pharmacotherapy, (7) stopping criteria. The consensus produced 73 statements and recommendations regarding key clinical areas, the most important 47 statements and recommendations are summarized in this overview. This evidence-based bi-national guideline should provide physicians with guidance for delivering best practice to critically ill patients with a dialysis-dependent AKI.

Drug-drug interactions (DDIs) are a significant contributor to adverse drug reactions (ADRs) in clinical practice. Despite established pharmacovigilance systems, underreporting and inconsistent causality assessment remain challenges. Switzerland and Austria offer a unique comparative setting due to similar healthcare infrastructures but different pharmacovigilance system designs. This study aims to compare pharmacovigilance system outcomes of Switzerland and Austria by examining how system designs may influence DDI reporting patterns and report quality. We retrospectively analysed 1,499 individual case safety reports involving DDIs submitted between January 2008 and April 2024 to the national pharmacovigilance systems of Switzerland (n = 1,159) and Austria (n = 340). As indicators of system performance, reports were assessed for demographics, reporter categories, seriousness of outcomes in relation to polypharmacy (expressed as reporting odds ratios [RORs] and confidence intervals [CIs]), ADR types, and pharmacological plausibility. Cross-national disparities were evident: Switzerland reported 3.4 times more DDI cases than Austria (mean 5.8 vs. 1.7 cases/month), with comparable patient demographics and differing reporter proportions. Most reports were classified as serious (80% Switzerland, 84% Austria), with polypharmacy strongly associated with serious outcomes in both countries (Switzerland: ROR 3.71, 95% CI 3.26-4.23, p < 0.0001; Austria: ROR 1.98, 95% CI 1.60-2.44, p < 0.0001). Reported ADRs differed qualitatively, with Switzerland predominantly reporting mechanisms whereas Austria reported more frequently symptoms. Differences were also found in the pharmacological consistency between ADR and associated drugs. These cross-national disparities in DDI reporting volume, content, and quality suggest that pharmacovigilance system design and specialist involvement influence reporting. The integration of clinical pharmacologists and pharmacists in ADR processing warrants further investigation, given its potential to strengthen DDI-related pharmacovigilance practices. These findings provide actionable insights for policymakers and regulatory agencies seeking to strengthen their pharmacovigilance systems through strategic specialist integration.

Die Nierenersatztherapie ist neben der Beatmung das am häufigsten durchgeführte Organersatzverfahren in der Intensivmedizin. Dennoch fehlen bisher konsentierte, evidenzbasierte Empfehlungen zur Durchführung von Nierenersatztherapie nach bestem aktuellen Wissen und Evidenzen. In dieser Leitlinie werden die Themenbereiche Beginn eines Nierenersatzverfahrens, Modalität (Diffusion oder Konvektion, kontinuierliche oder intermittierende Verfahren), Antikoagulation, adäquate Dosis sowie Kriterien zur Beendigung eines Nierenersatzverfahrens beschrieben. Zudem wird die aktuelle Evidenz zur adäquaten antiinfektiven Therapie unter den Besonderheiten der akuten Nierenschädigung und der Nierenersatztherapie dargestellt.

Besides mechanical ventilation, renal replacement therapy is the most frequently performed organ replacement therapy in intensive care medicine. However, there is a lack of consensus- and evidence-based recommendations for the implementation of renal replacement therapy according to the best current knowledge and evidence. This guideline describes the topics of starting a renal replacement therapy, modality (diffusion or convection, continuous or intermittent procedures), anticoagulation, adequate dose, and criteria for stopping renal replacement therapy. In addition, the current evidence on adequate anti-infective therapy is presented under the special features of acute kidney injury and renal replacement therapy.

Background:In critically ill patients, acid-base disorders are common before start of continuous renal replacement therapy. The aim of this study was to determine the influence of a high bicarbonate replacement fluid (30 mmol/L, Phoxilium®) on underlying acid-base disturbances. Methods:This single-center retrospective study included patients treated with continuous veno-venous hemofiltration (CVVH) at a medical ICU from January 2018 to May 2019. All patients received CVVH with regional citrate anticoagulation (RCA) and a high bicarbonate RF (Phoxilium®). Patients were categorized based on their initial pH. Acid-base parameters were closely monitored over 72 h at pre-specified intervals. Results:The study included 64 patients with a median age of 68 years. At the start of CVVH, 56.3% (n = 36) had acidemia, 12.5% (n = 8) had alkalemia and 32.3% (n = 20) had a normal pH. The median pH of patients with acidemia [0 h: 7.28 (interquartile range 7.23-7.33)] was corrected quickly to the normal range within 8 h [7.36 (interquartile range 7.29-7.4)]. The median pH of patients with alkalemia took longer (48 h) to reach normal values and patients with a normal pH showed a further pH increase within the normal range over the 72 h. All patients showed an increasing bicarbonate and base excess from 24 to 72 h. Conclusions:The RF in CVVH with RCA appears to be one of several factors influencing acid-base balance. Patients with different pre-existing acid-base disorders showed distinct correction kinetics. Prospective studies are needed to determine the clinical relevance of these findings and to optimize RF composition for better patient outcomes.

INTRODUCTION:Acid-base disturbances are common issues during continuous veno-venous hemofiltration (CVVH). Especially using regional citrate anticoagulation (RCA), recent studies have shown that control in intracorporal pH and HCO3 concentration may be improved when the replacement fluid is changed to a solution with a lower HCO3− concentration during continuous renal replacement therapy. This prospective trail aimed to compare acid-base balance between a high (HBF) and low (LBF) bicarbonate replacement fluid over a period of 96 h after CVVH initiation using RCA. METHODS:This is a prospective, randomized, controlled, open-label, crossover, phase II, single-center study involving critically ill patients requiring RRT. The two replacement fluids (Phoxilium and Biphozyl) are compared in two groups with 1:1 block randomization and consecutive crossover after 48 h of CVVH. The primary endpoints are the occurrence of at least one pH (>7.45) or HCO3- (>26 mmol/L) excursion within 16-48 h of each treatment phase using a generalized estimating equation approach. The objective was to examine differences of pH and HCO3- between patients who receive LBF and HBF as replacement fluid during CVVH. We hypothesize that during CVVH with LBF, pH, and HCO3- excursion rates are significantly lower compared to HBF. Recruitment of 88 study participants is ongoing, with the trial expected to be completed in 2025. Data cleaning, analysis, and publication preparation will follow thereafter. The trial is registered at ClinicalTrials.gov (NCT04071171) and EudraCT (2019-001262-15). CONCLUSION:Given the broad inclusion and restricted exclusion criteria, we expect the results of the BiPhox-Trial to be broadly applicable to patients in need of CVVH with RCA in the intensive care setting. This trial aims to determine whether the use of LBF results in more stable acid-base parameters compared to HBF during CVVH with RCA in critically ill patients and may guide therapeutic decisions in clinical practice.

This study aimed to compare a high (HBF) and low (LBF) bicarbonate (HCO3−) replacement fluid over 96 h after continuous veno-venous hemofiltration (CVVH) initiation using regional citrate anticoagulation to determine which fluid achieved better acid–base balance. In this prospective, randomized, controlled, open-label, cross-over, single-center trial, patients were randomized to initially receive either LBF (22 mmol/l HCO3−) or HBF (30 mmol/l HCO3−) for 48 h (first phase), followed by changing to the other fluid for a further 48 h (second phase). Intracorporeal pH and HCO3− changes were analyzed by calculating the rates of levels outside the standard values (excursion rates). Generalized estimating equations were performed to estimate the odds ratios for at least one pH/HCO3− excursion. Time to normalization within the first phase for pH and HCO3− was assessed using Kaplan–Meier curves and log-rank tests. A total of 88 patients were included. The rates for at least one pH and HCO3− excursion were higher in patients treated with HBF compared to LBF (pH: first phase 52

Sepsis causes millions of deaths each year. Rapid, targeted therapy can reduce mortality rates. Both bacterial and viral pathogens can trigger sepsis, but the utility of commonly used inflammatory markers for differentiation remains controversial. Moreover, little is known about the time courses of alternative inflammatory parameters. The aim of this prospective, two-center observational study was to investigate the differences in the course of soluble Neuropilin-1 (sNRP-1) levels between bacterial and viral sepsis over a 7-day period. To be included, adult patients had to meet the SEPSIS-3 criteria and be diagnosed with either a bacterial or viral pathogen. Immunosuppressed patients were excluded. While IL-6, PCT, and CRP levels decreased consistently over time, sNRP-1 levels remained elevated in the bacterial group throughout the entire ICU stay. PCT (p < 0.001) and CRP (p = 0.016) levels were significantly associated with the course of sNRP-1. The AUC of sNRP-1 was 0.777 for discriminating between bacterial and viral infections on day 1. sNRP-1 remained stable and significantly higher in bacterial than in viral infections. Furthermore, the AUC values for discrimination ranged from acceptable to good, depending on the day of the ICU stay. sNRP-1 may serve as a potential tool to differentiate between bacterial and viral pathogens in sepsis.

Bei kritisch Kranken besteht ein hohes Risko für unerwünschte Arzneimittelinteraktionen. Pharmakodynamische Interaktionen können Organtoxizität verstärken. Pharmakokinetische Interaktionen gründen meist auf einer Hemmung oder Induktion von Enzymen des Arzneimittelmetabolismus wie Cytochrom-P-450-Isoenzymen und Transporterproteinen wie P‑Glykoprotein. Inhibitoren dieser Moleküle können so toxische Wirkspiegel der entsprechenden Substrate herbeiführen, Induktoren hingegen subtherapeutische Konzentrationen. Amiodaron, Makrolide, Azol-Antimykotika, direkt wirksame Antikoagulanzien, Vitamin-K-Antagonisten, Immunsuppressiva, Rifampicin und einige ZNS-wirksame Substanzen sind besonders häufig an Interaktionen beteiligt. Eine Überprüfung der Medikation unter strenger Risiko-Nutzen-Abwägung, therapeutisches Drugmonitoring, Verwendung elektronischer Alert-Systeme und Datenbanken zusammen mit klinischer Bewertung können zur Vermeidung unerwünschter Arzneimittelinteraktionen beitragen.

Critically ill patients are at high risk of adverse drug-drug interactions. Pharmacodynamic drug-drug interaction may cause organ damage. Pharmacokinetic interactions are usually caused by inhibition or induction of enzymes of drug metabolism such as cytochrome P-450 isoenzymes or transporter proteins such as P‑glycoprotein. Inhibitors of such molecules can cause toxic levels of the corresponding substrates, while inducers might produce subtherapeutic concentrations. Amiodarone, macrolides, antifungal azoles, direct-acting anticoagulants, vitamin K antagonists, immunosuppressants, rifampicin, and some central nervous system (CNS)-active substances are frequently involved in drug-drug interactions. Sound risk and benefit assessment of the applied medication, therapeutic drug monitoring, the use of electronic alert systems and databases along with clinical evaluation will contribute to avoiding adverse drug-drug interactions.

Zusammenfassung Die von der Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin (GHUP) federführend aktualisierte Leitlinie „Medizinisch klinische Diagnostik bei Schimmelpilzexposition in Innenräumen – Update 2023“ ist Gegenstand des vorliegenden Beitrags. Schimmelwachstum im Innenraum ist als ein potenzielles Gesundheitsrisiko zu betrachten, auch ohne dass ein quantitativer und/oder kausaler Zusammenhang zwischen dem Vorkommen einzelner Arten und Gesundheitsbeschwerden gesichert werden kann. Es liegt keine Evidenz für einen kausalen Zusammenhang zwischen Feuchte-/Schimmelschäden und Krankheiten des Menschen vor. Wesentliche Gründe dafür sind das ubiquitäre Vorkommen von Schimmelpilzen und und bislang unzureichende diagnostische Methoden. Es liegt lediglich ausreichende Evidenz für folgende Assoziationen von Feuchte-/Schimmelschäden und folgenden Erkrankungen vor: allergische Atemwegserkrankungen, allergische Rhinitis, allergische Rhinokonjunktivitis, Allergische bronchopulmonale Aspergillose (ABPA), andere Allergische bronchopulmonale Mykosen (ABPM), Aspergillom, Aspergillus-Bronchitis, Asthma (Manifestation, Progression, Exazerbation), Begünstigung von Atemwegsinfekten, Bronchitis (akut, chronisch), Community-acquired Aspergillus-Pneumonie, Exogen-allergische Alveolitis (EAA), invasive Aspergillosen, Mykosen, Organic Dust Toxic Syndrome (ODTS) [Arbeitsplatzexposition], pulmonale Aspergillose (subakut, chronisch) und Rhinosinusitis (akut, chronisch invasiv oder granulomatös, allergisch). Dabei ist das sensibilisierende Potenzial von Schimmelpilzen im Vergleich zu anderen Umweltallergenen deutlich geringer einzuschätzen. Aktuelle Studien zeigen europaweit eine vergleichsweise geringe Sensibilisierungsprävalenz von 3–22,5 % gemessen an der Gesamtbevölkerung. Eingeschränkte oder vermutete Evidenz für eine Assoziation liegt vor hinsichtlich des atopischen Ekzems (atopische Dermatitis, Neurodermitis, Manifestation), Befindlichkeitsstörungen, chronisch obstruktive Lungenerkrankung (COPD), Geruchswirkungen, Mucous Membrane Irritation (MMI) und Sarkoidose. Inadäquate oder unzureichende Evidenz für eine Assoziation liegt vor für akute idiopathische pulmonale Hämorrhagie bei Kindern, Arthritis, Autoimmunerkrankungen, chronisches Müdigkeitssyndrom (CFS), Endokrinopathien, gastrointestinale Effekte, Krebs, luftgetragen übertragene Mykotoxikose, Multiple chemische Sensitivität (MCS), Multiple Sklerose, neuropsychologische Effekte, neurotoxische Effekte, plötzlicher Kindstod, renale Effekte, Reproduktionsstörungen, Rheuma, Schilddrüsenerkrankungen, Sick-Building-Syndrom (SBS), Teratogenität und Urtikaria. Das Infektionsrisiko durch die in Innenräumen regelmäßig vorkommenden Schimmelpilzarten ist für gesunde Personen gering, die meisten Arten sind in die Risikogruppe 1 und wenige in 2 (Aspergillus fumigatus, Aspergillus flavus) der Biostoffverordnung eingestuft. Nur Schimmelpilze, die potenziell in der Lage sind, Toxine zu bilden, kommen als Auslöser einer Intoxikation in Betracht. Ob im Einzelfall eine Toxinbildung im Innenraum stattfindet, entscheiden die Umgebungs- und Wachstumsbedingungen und hier vor allem das Substrat. Von Geruchswirkungen und/oder Befindlichkeitsstörungen kann bei Feuchte-/Schimmelschäden im Innenraum grundsätzlich jeder betroffen sein. Hierbei handelt es sich nicht um eine akute Gesundheitsgefährdung. Prädisponierende Faktoren für Geruchswirkungen können genetische und hormonelle Einflüsse, Prägung, Kontext und Adaptationseffekte sein. Prädisponierende Faktoren für Befindlichkeitsstörungen können Umweltbesorgnisse, -ängste, -konditionierungen und -attributionen sowie eine Vielzahl von Erkrankungen sein. Besonders zu schützende Risikogruppen bezüglich eines Infektionsrisikos sind Personen unter Immunsuppression nach der Einteilung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut (RKI), Personen mit schwer verlaufender Influenza, Personen mit schwer verlaufender COVID-19 und Personen mit Mukoviszidose (zystischer Fibrose), bezüglich eines allergischen Risikos Personen mit Mukoviszidose (zystischer Fibrose) und Personen mit Asthma bronchiale. Die rationale Diagnostik beinhaltet die Anamnese, eine körperliche Untersuchung, eine konventionelle Allergiediagnostik einschließlich gegebenenfalls Provokationstests. Zum Vorgehen bei Schimmelpilzinfektionen wird auf die entsprechenden Leitlinien verwiesen. Hinsichtlich der Mykotoxine existieren zurzeit keine brauchbaren und validierten Testverfahren, die in der klinischen Diagnostik eingesetzt werden könnten. Präventivmedizinisch ist wichtig, dass Schimmelpilzbefall in relevantem Ausmaß aus Vorsorgegründen nicht toleriert werden darf. Zur Beurteilung des Schadensausmaßes und zum Vorgehen wird auf den „Schimmelpilzleitfaden“ des Umweltbundesamtes verwiesen.

This article is an abridged version of the updated AWMF mould guideline "Medical clinical diagnostics in case of indoor mould exposure - Update 2023", presented in July 2023 by the German Society of Hygiene, Environmental Medicine and Preventive Medicine (Gesellschaft fur Hygiene, Umweltmedizin und Praventivmedizin, GHUP), in collaboration with German and Austrian scientific medical societies, and experts. Indoor mould growth is a potential health risk, even if a quantitative and/or causal relationship between the occurrence of individual mould species and health problems has yet to be established. There is no evidence for a causal relationship between moisture/mould damage and human diseases, mainly because of the ubiquitous presence of fungi and hitherto inadequate diagnostic methods. Sufficient evidence for an association between moisture/mould damage and the following health effects has been established for: allergic respiratory diseases, allergic rhinitis, allergic rhino-conjunctivitis, allergic bronchopulmonary aspergillosis (ABPA), other allergic bronchopulmonary mycosis (ABPM), aspergilloma, Aspergillus bronchitis, asthma (manifestation, progression, exacerbation), bronchitis (acute, chronic), community-acquired Aspergillus pneumonia, hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis (EEA)), invasive Aspergillosis, mycoses, organic dust toxic syndrome (ODTS) [workplace exposure], promotion of respiratory infections, pulmonary aspergillosis (subacute, chronic), and rhinosinusitis (acute, chronically invasive, or granulomatous, allergic). In this context the sensitizing potential of moulds is obviously low compared to other environmental allergens. Recent studies show a comparatively low sensitization prevalence of 3-22,5 % in the general population across Europe. Limited or suspected evidence for an association exist with respect to atopic eczema (atopic dermatitis, neurodermatitis; manifestation), chronic obstructive pulmonary disease (COPD), mood disorders, mucous membrane irritation (MMI), odor effects, and sarcoidosis. (iv) Inadequate or insufficient evidence for an association exist for acute idiopathic pulmonary hemorrhage in infants, airborne transmitted mycotoxicosis, arthritis, autoimmune diseases, cancer, chronic fatigue syndrome (CFS), endocrinopathies, gastrointestinal effects, multiple chemical sensitivity (MCS), multiple sclerosis, neuropsychological effects, neurotoxic effects, renal effects, reproductive disorders, rheumatism, sick building syndrome (SBS), sudden infant death syndrome, teratogenicity, thyroid diseases, and urticaria. The risk of infection posed by moulds regularly occurring indoors is low for healthy persons; most species are in risk group 1 and a few in risk group 2 ( Aspergillus fumigatus , A. flavus ) of the German Biological Agents Act (Biostoffverordnung). Only moulds that are potentially able to form toxins can be triggers of toxic reactions. Whether or not toxin formation occurs in individual cases is determined by environmental and growth conditions, water activity, temperature and above all the growth substrates. In case of indoor moisture/mould damage, everyone can be affected by odor effects and/or mood disorders. However, this is not an acute health hazard. Predisposing factors for odor effects can include genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for mood disorders may include environmental concerns, anxiety, condition, and attribution, as well as various diseases. Risk groups to be protected particularly regarding infection risk are immunocompromised persons according to the classification of the German Commission for Hospital Hygiene and Infection Prevention (Kommission fur Krankenhaushygiene und Infektionspravention, KRINKO) at the Robert Koch-Institute (RKI), persons suffering from severe influenza, persons suffering from severe COVID-19, and persons with cystic fibrosis (mucoviscidosis); with regard to allergic risk, persons with cystic fibrosis (mucoviscidosis) and patients with bronchial asthma must be protected. The rational diagnostics include the medical history, physical examination, and conventional allergy diagnostics including provocation tests if necessary; sometimes cellular test systems are indicated. In the case of mould infections, the reader is referred to the specific guidelines. Regarding mycotoxins, there are currently no useful and validated test procedures for clinical diagnostics. From a preventive medical point of view, it is important that indoor mould infestation in relevant magnitudes cannot be tolerated for precautionary reasons. For evaluation of mould damage in the indoor environment and appropriate remedial procedures, the reader is referred to the mould guideline issued by the German Federal Environment Agency (Umweltbundesamt, UBA).

Invasive mold diseases are devastating systemic infections which demand meticulous care in selection, dosing, and therapy monitoring of antifungal drugs. Various circumstances regarding PK/PD properties of the applied drug, resistance/tolerance of the causative pathogen or host intolerability can lead to failure of the initial antifungal therapy. This necessitates treatment adaption in the sense of switching antifungal drug class or potentially adding another drug for a combination therapy approach. In the current state of drastically limited options of antifungal drug classes adaption of therapy remains challenging. Current guidelines provide restricted recommendations only and emphasize individual approaches. However, novel antifungals, incorporating innovative mechanisms of action, show promising results in late stage clinical development. These will expand options for salvage therapy in the future potentially as monotherapy or in combination with conventional or other novel antifungals. We outline current recommendations for salvage therapy including PK/PD considerations as well as elucidate possible future treatment options for invasive aspergillosis and mucormycosis.

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. We present a 22-year-old Caucasian woman with CVID and granulomatous lymphocytic interstitial lung disease who contracted COVID-19 and was successfully treated with sotrovimab and molnupiravir. This treatment may have contributed to the relatively mild disease course of COVID-19 in our patient.

(1) Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns to contribute to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. (2) Methods: Here, we assessed Aspergillus culture-positive and culture-negative respiratory tract specimens via direct fungal microscopy (gold standard) and compared the results with galactomannan enzyme immunoassay (GM-EIA) and Aspergillus PCR. (3) Results: 241 respiratory samples from patients suffering from SARS-CoV-2 pneumonia were evaluated. Results showed both diagnostic tools, Aspergillus PCR and GM-EIA, to be positive or negative displaying a sensitivity of 0.90, a specificity of 0.77, a negative predictive value (NPV) of 0.95, and a positive predictive value (PPV) of 0.58 in Aspergillus sp. culture and microscopic-positive specimens. Non-bronchoalveolar lavage (BAL) samples, obtained within a few days from the same patient, showed a high frequency of intermittent positive or negative GM-EIA or Aspergillus PCR results. Positivity of a single biomarker is insufficient for a proper diagnosis. A broad spectrum of Aspergillus species was detected. (4) Conclusions: Our study highlights the challenges of combined biomarker testing as part of diagnosing CAPA. From the results presented, we highly recommend the additional performance of direct microscopy in respiratory specimens to avoid overestimation of fungal infections by applying biomarkers.

Introduction Acute kidney injury is a frequent complication in critically ill patients with and without COVID-19. The aim of this study was to evaluate the incidence of, and risk factors for, acute kidney injury and its effect on clinical outcomes of critically ill COVID-19 patients in Tyrol, Austria. Methods This multicenter prospective registry study included adult patients with a SARS-CoV-2 infection confirmed by polymerase chain reaction, who were treated in one of the 12 dedicated intensive care units during the COVID-19 pandemic from February 2020 until May 2022. Results In total, 1042 patients were included during the study period. The median age of the overall cohort was 66 years. Of the included patients, 267 (26%) developed acute kidney injury during their intensive care unit stay. In total, 12.3% ( n = 126) required renal replacement therapy with a median duration of 9 (IQR 3–18) days. In patients with acute kidney injury the rate of invasive mechanical ventilation was significantly higher with 85% ( n = 227) compared to 41% ( n = 312) in the no acute kidney injury group ( p < 0.001). The most important risk factors for acute kidney injury were invasive mechanical ventilation (OR = 4.19, p < 0.001), vasopressor use ( OR = 3.17, p < 0.001) and chronic kidney disease (OR = 2.30, p < 0.001) in a multivariable logistic regression analysis. Hospital and intensive care unit mortality were significantly higher in patients with acute kidney injury compared to patients without acute kidney injury (Hospital mortality: 52.1% vs. 17.2%, p < 0.001, ICU-mortality: 47.2% vs. 14.7%, p < 0.001). Conclusion As in non-COVID-19 patients, acute kidney injury is clearly associated with increased mortality in critically ill COVID-19 patients. Among known risk factors, invasive mechanical ventilation has been identified as an independent and strong predictor of acute kidney injury. Graphical abstract

BackgroundCoronavirus Disease-19 (COVID-19) convalescents are at risk of developing a de novo mental health disorder or worsening of a pre-existing one. COVID-19 outpatients have been less well characterized than their hospitalized counterparts. The objectives of our study were to identify indicators for poor mental health following COVID-19 outpatient management and to identify high-risk individuals.MethodsWe conducted a binational online survey study with adult non-hospitalized COVID-19 convalescents (Austria/AT: n = 1,157, Italy/IT: n = 893). Primary endpoints were positive screening for depression and anxiety (Patient Health Questionnaire; PHQ-4) and self-perceived overall mental health (OMH) and quality of life (QoL) rated with 4 point Likert scales. Psychosocial stress was surveyed with a modified PHQ stress module. Associations of the mental health and QoL with socio-demographic, COVID-19 course, and recovery variables were assessed by multi-parameter Random Forest and Poisson modeling. Mental health risk subsets were defined by self-organizing maps (SOMs) and hierarchical clustering algorithms. The survey analyses are publicly available (https://im2-ibk.shinyapps.io/mental_health_dashboard/).ResultsDepression and/or anxiety before infection was reported by 4.6% (IT)/6% (AT) of participants. At a median of 79 days (AT)/96 days (IT) post-COVID-19 onset, 12.4% (AT)/19.3% (IT) of subjects were screened positive for anxiety and 17.3% (AT)/23.2% (IT) for depression. Over one-fifth of the respondents rated their OMH (AT: 21.8%, IT: 24.1%) or QoL (AT: 20.3%, IT: 25.9%) as fair or poor. Psychosocial stress, physical performance loss, high numbers of acute and sub-acute COVID-19 complaints, and the presence of acute and sub-acute neurocognitive symptoms (impaired concentration, confusion, and forgetfulness) were the strongest correlates of deteriorating mental health and poor QoL. In clustering analysis, these variables defined subsets with a particularly high propensity of post-COVID-19 mental health impairment and decreased QoL. Pre-existing depression or anxiety (DA) was associated with an increased symptom burden during acute COVID-19 and recovery.ConclusionOur study revealed a bidirectional relationship between COVID-19 symptoms and mental health. We put forward specific acute symptoms of the disease as “red flags” of mental health deterioration, which should prompt general practitioners to identify non-hospitalized COVID-19 patients who may benefit from early psychological and psychiatric intervention.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT04661462].

Summary Background There are conflicting results concerning sex-specific differences in the post-cardiac arrest period. We investigated the sex distribution of patients after successful cardiopulmonary resuscitation (CPR), differences in treatment, complications, outcome and sex-specific performance of biomarkers for prognostication of neurological outcome. Methods Prospective observational study including cardiac-arrest (CA) patients treated with mild therapeutic hypothermia (MTH) at 33 °C for 24 h or normothermia. We investigated common complications including pneumonia and acute kidney injury (AKI) and neuron-specific enolase, secretoneurin and tau protein as biomarkers of neurological outcome, which was assessed with the cerebral performance categories score at hospital discharge. Results Out of 134 patients 26% were female. Women were significantly older (73 years, interquartile range (IQR) 56–79 years vs. 62 years, IQR 53–70 years; p = 0.038), whereas men showed a significantly higher rate of pneumonia (29% vs. 6%; p = 0.004) and a trend towards higher rates of AKI (62% vs. 45%; p = 0.091). Frequency of MTH treatment was not significantly different (48% vs. 31%; p = 0.081). Female sex was not associated with neurological outcome in multivariable analysis ( p = 0.524). There was no significant interaction of sex with prognostication of neurological outcome at 24, 48 and 72 h after CPR. At the respective time intervals p interaction for neuron-specific enolase was 0.524, 0.221 and 0.519, for secretoneurin 0.893, 0.573 and 0.545 and for tau protein 0.270, 0.635, and 0.110. Conclusion The proportion of female patients was low. Women presented with higher age but had fewer complications during the post-CA period. Female sex was not associated with better neurological outcome. The performance of biomarkers is not affected by sex.

INTRODUCTION:The epidemiology of invasive Candida infections is evolving. Infections caused by non-albicans Candida spp. are increasing; however, the antifungal pipeline is more promising than ever and is enriched with repurposed drugs and agents that have new mechanisms of action. Despite progress, unmet needs in the treatment of invasive candidiasis remain, and there are still too few antifungals that can be administered orally or that have CNS penetration.AREAS COVERED:The authors shed light on those antifungal agents active against Candida that are in early- and late-stage clinical development. Mechanisms of action and key pharmacokinetic and pharmacodynamic properties are discussed. Insights are offered on the potential future roles of the investigational agents MAT-2203, oteseconazole, ATI-2307, VL-2397, NP-339, and the repurposed drug miltefosine.EXPERT OPINION:Ibrexafungerp and fosmanogepix have novel mechanisms of action and will provide effective options for the treatment of Candida infections (including those caused by multiresistant Candida spp). Rezafungin, an echinocandin with an extended half-life allowing for once weekly administration, will be particularly valuable for outpatient treatment and prophylaxis. Despite this, there is an urgent need to garner clinical data on investigational drugs, especially in the current rise of azole-resistant and multidrug-resistant Candida spp.