BACKGROUND:Tsutsugamushi fever is an infection caused by Orientia tsutsugamushi that is rarely diagnosed in Europe but endemic in several Asian countries and in Chile. Its clinical presentation is often nonspecific, ranging from fever, myalgia, lymphadenopathy, and a maculopapular rash to severe disease with multiorgan involvement. CASE REPORT:A 34-year-old man presented with fever, myalgia, lymphadenopathy, and a maculopapular rash after returning from Thailand. Despite empiric antimicrobial therapy, his condition deteriorated rapidly, with respiratory failure, decreased vigilance, and hypotension. PCR testing from peripheral blood confirmed Orientia tsutsugamushi. Treatment with doxycycline, along with meropenem for hospital-acquired pneumonia, resulted in rapid clinical improvement. CONCLUSIONS:This case highlights the importance of considering tsutsugamushi fever in febrile travellers returning from endemic regions. Early presumptive or PCR-based diagnostics and initiation of effective therapy are crucial to prevent severe disease with multiorgan involvement and secondary complications.

A previously healthy traveler of Togolese origin visiting friends and relatives presented with severe dengue complicated by acute liver failure. Despite intensive care management and listing for high-urgency liver transplantation, the patient succumbed to the disease. This case highlights the risk for life-threatening travel-related complications of dengue.

ABSTRACT Background Obtaining non‐directed samples from the upper bronchial tree is easier to perform and poses fewer risks for critically ill patients than deep bronchoalveolar lavage (BAL). Since invasive pulmonary aspergillosis is associated with a high mortality in critically ill patients, timely diagnosis and rapid initiation of treatment are of utmost importance. Objectives The objective of this study was to compare Galactomannan (GM) testing by Enzyme Immunoassay (EIA), GM Lateral Flow Assay (LFA) and the detection of Aspergillus DNA by Polymerase Chain Reaction (PCR) between directed BAL and non‐directed bronchial lavage (BL) in critically ill patients. Methods In this prospective, exploratory pilot study, we analysed 120 samples from 40 patients admitted to 12 mixed intensive care units. Inclusion criteria required either risk factors for IPA or positive Aspergillus assessments and met the criteria published by the European Society of Clinical Microbiology and Infectious Diseases guidelines for IPA diagnosis. Both respiratory secretions and blood were collected. In each patient, LFA and PCR were performed on BAL, BL and blood serum, respectively. The EIA test was applied to the BL and BAL of each patient, and the serum of 24 patients. The study was registered on clinicaltrials.gov (NCT04848831). Results In a total of 80 respiratory samples, Aspergillus GM EIA yielded optical density indices (ODI) ranging from 0.04 to ≥ 3.5. We observed a high correlation between BAL and BL samples for Aspergillus GM EIA (Pearson's r = 0.78 [95% CI 0.62, 0.88]; intraclass correlation coefficient 0.78). At an ODI cutoff of 0.8 for BAL and 1.2 for BL, the sensitivity of Aspergillus GM EIA was 0.94, while the specificity was 0.67. Increasing the BAL cutoff to 1.0 ODI improved the specificity to 0.86. Aspergillus PCR examination showed good agreement between the two compartments, with a Cohen's kappa coefficient of 0.75 (95% CI 0.48, 1.00). The correlation of Aspergillus GM LFA between BAL and BL was weak. Conclusions Our findings demonstrate that the detection of Aspergillus GM using EIA or Aspergillus PCR in BL is comparable to that in BAL. Thus, BL samples can be reliably used for diagnosing invasive pulmonary aspergillosis.

Background:Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterised by uncontrolled immune activation and multi-organ dysfunction. Whilst initially described in paediatric populations, HLH is increasingly recognised in critically ill adults, often triggered by malignancies, infections, or autoimmune diseases. Methods:This single-centre retrospective study analysed 43 adult patients with HLH admitted to the ICU between 2008 and 2024. Clinical characteristics, laboratory parameters, organ support requirements, and outcomes were assessed. Temporal trends in routine parameters surrounding HLH diagnosis were also evaluated. Results:The median age was 45 years (IQR: 33-60), and 65% were male. Respiratory failure (62.8%) and sepsis (41.9%) were the leading causes of ICU admission. Disease severity was high, with a median SOFA score of 14 (IQR: 11-17), and ICU mortality reached 65.1%. Invasive mechanical ventilation was required in 83.7% of patients, and continuous renal replacement therapy in 72.1%. Ferritin levels were markedly elevated, with a median peak of 25,045 μg/l (IQR: 12,771-94,586), with 93% of patients exceeding 6,000 μg/l. The median HScore was 245 (IQR: 210-273) and did not differ significantly between survivors and non-survivors (p = 0.64). Conclusion:HLH in adult ICUs carries high mortality and demands extensive organ support. Existing diagnostic scores provide limited bedside guidance, highlighting the need for ICU-specific validation and improved prognostic markers.

PURPOSE:The executive summary of the guideline aims to provide the most relevant recommendations on the diagnosis and treatment of invasive pulmonary aspergillosis in critically ill patients in the intensive care unit. METHODS:The guideline's work included a systematic literature search, selection and assessment of the data relevant to the issues identified. Key questions included the areas of epidemiology, risk factors, diagnostics, and therapy. They were discussed analogous to a PICO scheme within the guideline committee, with subsequent working groups proposing recommendations for specific key questions, which were then again discussed and finalized by the entire guideline committee. RESULTS:In addition to the classic risk factors (persistent neutropenia, allogeneic stem cell transplantation, congenital or acquired immunodeficiency, etc.), decompensated liver cirrhosis, COPD, solid tumours and viral pneumonia (influenza, COVID-19) have been established as risk factors for critically ill patients in need of intensive care. If there is no adequate improvement or even further clinical deterioration of the respiratory status in critically ill patients, the presence of IPA should be considered and appropriate diagnostic tests should be initiated. Diagnostics should include a CT scan of the chest and a broncho-alveolar lavage with culture for moulds, testing for galactomannan and PCR. Isavuconazole and voriconazole are recommended as first-line treatment, liposomal amphotericin B as an alternative, with posaconazole (PCZ) or the echinocandins (as an add-on to azole or polyene treatment) being additional options for salvage treatment. CONCLUSION:Invasive aspergillosis in critically ill patients represents a diagnostic and therapeutic challenge. If indicated, invasive aspergillosis should be considered and appropriate diagnostic tests initiated. Isavuconazole and voriconazole are recommended as first-line treatment, liposomal amphotericin B as an alternative.

Objective:Analyze the outcomes of critically ill patients who developed new-onset organ dysfunction and received systemic chemotherapy during their ICU stay. Design:Retrospective cohort study. Setting:A tertiary medical center in Germany with an Intensive Care Medicine department consists of 11 intensive care units comprising 140 beds, serving all subspecialties of adult intensive care medicine. Patients:167 patients receiving systemic oncological treatment from January 1st, 2015 to December 31st, 2021, with a data cut-off on December 31st, 2022. Interventions:None. Measurements and main results:A total of 167 patients were included. The primary reasons for ICU admission were respiratory failure and shock/sepsis, each accounting for 34% of cases, while complications associated with oncological therapy accounted for less than 8%. The median age of hematological patients (n = 129) was 62 years (IQR 50-70), and for solid tumor patients (n = 38), it was 60 years (IQR 52-65). Predominant disease entities included lymphoma (43%) and acute myeloid leukemia (29%) among hematological patients, and lung cancer (47%) and gastrointestinal malignancies (17%) among solid tumor patients. Hematological patients had a significantly higher median Simplified Acute Physiology Score II (47 vs. 39 points; p=0.013), a higher need for invasive mechanical ventilation (59% vs. 50%; p=0.3), renal replacement therapy (54% vs. 24%; p < 0.001), and a higher 1-year mortality rate (64% vs. 53%; p=0.2) compared to solid tumor patients. The hazard ratio for 1 year survival for male sex was 2.34 (1.31-3.49), for mechanical ventilation 2.01 (1.33-3.04), for vasopressor therapy 1.98 (1.27-3.10), and for renal replacement therapy 1.51 (1.03-2.23), respectively. Conclusion:Administering intravenous chemotherapy in an ICU setting remains challenging, and the experience to establish an indication for systemic chemotherapy is still challenging. However, the study demonstrates that, after careful interdisciplinary decision-making, a substantial number of patients can benefit from it.

Listeria monocytogenes causes severe bacterial infections with the highest mortality rate among foodborne pathogens in Europe. Combination treatment with ampicillin and gentamicin is recommended for invasive manifestations. However, evidence to support this treatment approach remains limited due to a lack of randomised controlled trials. To explore this critical issue further, we conducted this retrospective, single-center study. We identified all patients hospitalized with invasive listeriosis at the University Medical Center Hamburg-Eppendorf between 2009 and 2020 and analyzed the effect of gentamicin combination treatment versus monotherapy on 90-day mortality. In total, 36 patients with invasive listeriosis were included, of which 21 patients received gentamicin combination treatment and 15 received monotherapy. The mean age-adjusted Charlson Comorbidity Index (aaCCI) value was lower in the gentamicin combination treatment group (5.4 vs. 7.4). Neurolisteriosis was more common in the gentamicin group (81

Acute kidney injury (AKI) is a frequent and challenging clinical condition associated with high morbidity and mortality and represents a common complication in critically ill patients with COVID-19. In AKI, renal tubular epithelial cells (TECs) are a primary site of damage, and recovery from AKI depends on TEC plasticity. However, the molecular mechanisms underlying adaptation and maladaptation of TECs in AKI remain largely unclear. Here, our study of an autopsy cohort of patients with COVID-19 provided evidence that injury of TECs by myoglobin, released as a consequence of rhabdomyolysis, is a major pathophysiological mechanism for AKI in severe COVID-19. Analyses of human kidney biopsies, mouse models of myoglobinuric and gentamicin-induced AKI, and mouse kidney tubuloids showed that TEC injury resulted in activation of the glucocorticoid receptor by endogenous glucocorticoids, which aggravated tubular damage. The detrimental effect of endogenous glucocorticoids on injured TECs was exacerbated by the administration of a widely clinically used synthetic glucocorticoid, dexamethasone, as indicated by experiments in mouse models of myoglobinuric- and folic acid-induced AKI, human and mouse kidney tubuloids, and human kidney slice cultures. Mechanistically, studies in mouse models of AKI, mouse tubuloids, and human kidney slice cultures demonstrated that glucocorticoid receptor signaling in injured TECs orchestrated a maladaptive transcriptional program to hinder DNA repair, amplify injury-induced DNA double-strand break formation, and dampen mTOR activity and mitochondrial bioenergetics. This study identifies glucocorticoid receptor activation as a mechanism of epithelial maladaptation, which is functionally important for AKI.

Medical history A 25-year-old female outpatient presenting with fever and micro-hematuria was treated for urinary tract infection. Her condition worsened over 3 days at home. After experiencing multiple falls caused by leg weakness and mental confusion, she was admitted to a hospital with high fever. Diagnostics Initial laboratory findings showed hemolytic anemia, pancytopenia, and acute kidney injury, suggesting hemolytic uremic syndrome. However, a detailed fever evaluation revealed her recent return from Afrika. This prompted a malaria test, which confirmed Plasmodium falciparum infection with 80 % parasitemia. Therapy and progress Despite the quick reduction of parasitemia following treatment with intravenous administered artesunate and oral Artemether-Lumefantrine, her condition worsened, leading to a septic shock. This required renal replacement and kinetic ventilation therapy, as well as blood transfusions due to persistent hemolysis until the laboratory values normalized after 48 days post-admission. Conclusion The evaluation of fever is often challenging, but most often a detailed patient history is key to early diagnosis and treatment preventing deathly outcomes in severe cases.

PURPOSE OF REVIEW:This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS:Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY:We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.

The global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species. Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed. Using a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75

Introduction: Admission to the intensive care unit severely affects inflammatory bowel disease (IBD) patients. This study aimed to determine factors associated with mortality in IBD patients admitted to the intensive care unit. Methods: A retrospective cohort study was performed, analyzing data of all IBD patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf between 2013 and 2022. Bivariate comparisons and multivariate regression analyses were performed to identify factors associated with mortality. Results: Overall, 439 IBD patients were admitted to the intensive care unit, representing 0.56% of total admissions. In 98 of these patients, IBD-associated complications were accountable for admission (22.3%). In detail, 39 (40.8%) patients were admitted after IBD-related surgery, 36 (35.7%) due to infections, and 23 (23.5%) due to medical conditions such as bleeding or electrolyte derangement. A total of 16 (16.3%) of these patients died within 90 days after admission. Parameters associated with increased mortality were age (p < 0.001), later age at diagnosis (p 0.026), catecholamine therapy (p 0.003), mechanical ventilation (p < 0.001), renal replacement therapy (p < 0.001), and parenteral nutrition (p 0.002). Prior treatment with anti-TNF therapy was associated with a higher chance of survival (p 0.018). There was no association between prior immunosuppressant therapy and admission because of infections (p 0.294). Conclusions: 16.3% of IBD patients admitted to the intensive care unit died within 90 days after admission. Prior treatment with anti-TNF therapy was associated with a higher chance of survival.

Anamnese Eine 25-jährige Patientin wurde bei Fieber und Mikrohämaturie wegen des Verdachts auf eine Harnwegsinfektion ambulant behandelt. Ihr Zustand verschlechterte sich jedoch über 3 Tage zunehmend, sodass sie aufgrund von ausgeprägter Schwäche und Verwirrtheit mehrfach stürzte und mit hohem Fieber in ein Krankenhaus eingewiesen wurde. Diagnostik Die initialen Laborbefunde zeigten eine hämolytische Anämie, Panzytopenie und ein akutes Nierenversagen, was als ein hämolytisch-urämisches Syndrom diagnostiziert wurde. Erst eine nochmalige detaillierte Anamnese offenbarte eine Reiserückkehr aus Afrika. Ein Malaria-Test zeigte dann eine Infektion mit Plasmodium falciparum mit einer Parasitämie von 80 %. Therapie und Verlauf Intravenöses Artesunat und oral verabreichtes Artemether-Lumefantrin reduzierten die Parasitämie schnell. Dennoch entwickelte die Patientin infolge der Malaria einen septischen Schock, der eine Nierenersatz- sowie eine kinetische Beatmungstherapie und die Gabe von Bluttransfusionen bei anhaltender Hämolyse – bis zur Normalisierung der Laborwerte nach 48 Tagen – erforderte. Folgerung Bei Fieber ist die Anamnese oft herausfordernd, aber wegweisend, um den wichtigen frühzeitigen Behandlungsbeginn der Malaria nicht zu verzögern und tödliche Ausgänge bei komplizierten Fällen zu verhindern.

CAR-T cell (chimeric antigen receptor T) therapy is now part of standard of care treatment of B‑cell lineage malignancies. Although it is an effective treatment, it comes along with adverse side effects and toxicities that may require intensive care therapy. The costs related to critical care therapy in critically ill patients after CAR‑T administration have not been evaluated. Retrospective analysis of all patients who had received CAR‑T therapy and were admitted to the intensive care unit (ICU) of a tertiary care university medical centre in Germany between 1 January 2019 and 31 December 2022. Cause of admission and ICU therapy as well as treatment and total hospitals costs were evaluated. Thirty patients with a history of CAR-T cell therapy for underlying haematological malignancy were included. The median age of all patients was 60 years (interquartile range [IQR] 50–70) and 37

Journal Article Corrected proof Daratumumab as rescue therapy in life-threatening granulomatosis with polyangiitis Get access Martin Krusche, Martin Krusche III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Correspondence to: Martin Krusche, Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20251 Hamburg, Germany. E-mail: m.krusche@uke.de https://orcid.org/0000-0002-0582-7790 Search for other works by this author on: Oxford Academic PubMed Google Scholar Tim Oqueka, Tim Oqueka II Department of Medicine for Oncology and Pulmonology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Dominic Wichmann, Dominic Wichmann Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Stefan Kluge, Stefan Kluge Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany https://orcid.org/0000-0001-8391-3988 Search for other works by this author on: Oxford Academic PubMed Google Scholar Tobias B Huber, Tobias B Huber III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Ina Kötter, Ina Kötter III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Christian Schmidt-Lauber Christian Schmidt-Lauber III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyHamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyResearch Center On Rare Kidney Diseases (RECORD), University Hospital Erlangen, Erlangen, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, kead474, https://doi.org/10.1093/rheumatology/kead474 Published: 09 September 2023 Article history Accepted: 29 August 2023 Published: 09 September 2023 Corrected and typeset: 23 September 2023