Search

Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.

The prognosis of allogeneic stem cell transplant recipients admitted to the intensive care unit (ICU) has improved over the last decades. However, data focusing on patients treated in the ICU during the peri-transplant period are scarce. We therefore conducted an analysis comprising 70 patients who had allogeneic stem cell transplantation at the University Hospital Cologne between 2014 and 2020 and were admitted to the ICU between the initiation of conditioning therapy and day 30 after transplantation. The median age was 59 years (range: 18 − 72 years). 50% of patients were female. Sepsis was the most common cause for ICU admission (49%). Mechanical ventilation (MV) was required in 56% of patients, 27% had renal replacement therapy (RRT), and 64% needed vasopressors. The ICU, hospital, 90-day, and 1-year survival rates were 48.6%, 38.6%, 35.7%, and 16.2%, respectively. MV and/or RRT during the ICU stay were associated with an impaired survival (p p n = 23), sepsis and other infectious complications represented the major causes of death (48%). Taken together, the present analysis indicates unfavorable outcomes for allogeneic stem cell transplant recipients admitted to the ICU during the peri-transplant period. The data may help to make informed decisions with patients and their families.

Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapeutic treatment concept that is changing the treatment approach to hematologic malignancies. The development of CAR T-cell therapy represents a prime example for the successful bench-to-bedside translation of advances in immunology and cellular therapy into clinical practice. The currently available CAR T-cell products have shown high response rates and long-term remissions in patients with relapsed/refractory acute lymphoblastic leukemia and relapsed/refractory lymphoma. However, CAR T-cell therapy can induce severe life-threatening toxicities such as cytokine release syndrome, neurotoxicity, or infection, which require rapid and aggressive medical treatment in the intensive care unit setting. In this review, the authors provide an overview of the state-of-the-art in the clinical management of severe life-threatening events in CAR T-cell recipients. Furthermore, key challenges that have to be overcome to maximize the safety of CAR T cells are discussed.

ZusammenfassungDie anhaltende Belastung der Mitarbeiter im Gesundheitsdienst während der COVID-19-Pandemie ist erheblich und stellt die Mitarbeiter vor große emotionale und psychologische Herausforderungen. In einer teaminternen Evaluation (Ärzt:innen und Pflegekräfte) wurden teamspezifische Belastungen, mögliche Entlastungsstrategien, positive und negative Erfahrungen sowie Wünsche für eine Verbesserung der Situation auf einer Intensivstation erhoben. Während beide Berufsgruppen gleich hohe emotionale Belastungsintensitäten wahrnahmen, werden bei der Pflege zusätzlich starke Belastungsintensitäten im organisatorischen und körperlichen Bereich wahrgenommen. Damit erweist sich die Berufsgruppe der Pflegenden als am stärksten durch die COVID-19-Pandemie belastet. Durch die hier herausgearbeiteten Erkenntnisse können für die Zukunft konkrete Handlungsanweisungen abgeleitet werden.

Due to acuteness, time constraints, and psychological pressure as well as changing team compositions, professional communication constitutes a key challenge in the treatment of critically ill patients.The aim of this narrative review is to present the current literature on clinical relevance and current developments of interdisciplinary and interprofessional communication in intensive care and emergency medicine.Effective communication is of great importance in intensive care and emergency medicine, both for ensuring high-quality patient care and work satisfaction as well as mental health of the medical practitioners. Most conflicts occur between the medical and nursing staff, with communicative conflicts predominantly being related to discussions about the patient's prognosis and end-of-life decision-making. Structural measures such as regular team meetings and trainings seem suitable to specifically improve communication. However, the topic is commonly inadequately represented in everyday clinical practice as well as in research.Even though the importance of interprofessional and interdisciplinary communication for high-quality patient care and workload reduction is increasingly being recognized, its routine application in everyday clinical practice is still scarce, particularly in intensive care and emergency medicine. Due to the specific structure and patient population of these fields of patient care, they can benefit more than other specialties from targeted measures to improve communication.HINTERGRUND: Bei der Behandlung kritisch kranker Patient*innen stellt eine professionelle Kommunikation aufgrund der Akuität, des hohen zeitlichen und psychischen Drucks sowie wechselnder personeller Konstellationen verschiedener Berufsgruppen eine besondere Herausforderung dar.Das Ziel ist eine Darstellung der Bedeutung und aktueller Entwicklungen der interdisziplinären und interprofessionellen Kommunikation in der Intensiv- und Notfallmedizin im Rahmen einer narrativen Übersichtsarbeit anhand der aktuellen Literatur.Eine effektive Kommunikation spielt in der Intensiv- und Notfallmedizin eine zentrale Rolle. Dies gilt sowohl für die Qualität der Patient*innenversorgung als auch für die Arbeitszufriedenheit und psychische Gesundheit des Behandlungsteams. Dabei treten die häufigsten Konflikte zwischen ärztlichem und pflegerischem Personal auf und betreffen insbesondere Diskussionen bezüglich Prognose und Entscheidungen am Lebensende. Einfache strukturelle Maßnahmen, wie regelmäßige Teambesprechungen und Schulung kommunikativer Kompetenzen, stellen geeignete Maßnahmen dar, um die Kommunikation gezielt zu verbessern. Aktuell sind diese Maßnahmen in klinischem Alltag und Forschung jedoch zumeist deutlich unterrepräsentiert.Auch wenn die Bedeutung interprofessioneller und interdisziplinärer Kommunikation für die Versorgungsqualität und die Arbeitsbelastung zunehmend erkannt wird, wird diesem Thema im klinischen Alltag zu wenig Aufmerksamkeit geschenkt. Dies gilt insbesondere in der Intensiv- und Notfallmedizin, die fachbedingt immens von gezielten Maßnahmen zur Verbesserung der Kommunikation profitieren kann.

Cancer patients compromise about 15-20 % of all patients on the intensive Care Unit (ICU). Moreover, recent therapeutic developments in hematology oncology as chimeric T-cells (CAR T-cells) regularly require critical care and therefore the amount of cancer patients in the ICU is expected to grow in the coming years. Although their prognosis has dramatically improved over the past decades, the mortality on cancer patients on the ICU is still high compared to non-cancer patients. Therefore, the interdisciplinary management of these patients is crucial in order to accurately identify patients who benefit from transfer to the ICU and to optimize treatment of these vulnerable and often complex patients. Consequently, large cohort studies have shown a positive impact of daily interdisciplinary patient visits including hematology-oncology and critical care medicine on survival of cancer patients on the ICU. This short review summarizes current knowledge and open questions in the critical care management of cancer patients.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) can be associated with adverse events necessitating treatment on the intensive care unit (ICU). Data focusing on patients admitted to the ICU during hospitalization for high-dose chemotherapy and ASCT are scarce. We thus conducted a single-center retrospective analysis comprising 79 individuals who had high-dose chemotherapy and ASCT between 2014 and 2020 and were admitted to the ICU between the initiation of conditioning therapy and day 30 after ASCT. The median age was 57 years (range: 20–82 years); 38% of patients were female. B-cell non-Hodgkin lymphoma (34%) and plasma cell disorders (28%) were the most common indications for high-dose chemotherapy and ASCT. Sepsis represented the major cause for ICU admission (68%). Twenty-nine percent of patients required mechanical ventilation (MV), 5% had renal replacement therapy, and 44% needed vasopressors. The ICU, hospital, 90-day, and 1-year survival rates were 77.2%, 77.2%, 72.2%, and 60.3%, respectively. Stable disease or disease progression prior to the initiation of high-dose chemotherapy (p = 0.0028) and MV (p

Die Transfusion von Chimaren-Antigenrezeptor(CAR)-T-Zellen hat sich als neue Therapieform in der Onkologie etabliert, geht jedoch regelhaft mit immunvermittelten Nebenwirkungen einher, die auch schwer verlaufen konnen sowie eine spezifische und intensivmedizinische Behandlung erfordern. Literaturrecherche zu CAR-T-Zell-Therapie, Toxizitaten und Nebenwirkungsmanagement. Das „cytokine release syndrome“ (CRS) und das „immune effector cell-associated neurotoxicity syndrome“ (ICANS) treten regelhaft kurz nach einer Therapie mit CAR-T-Zellen auf. Das CRS kann von einer milden grippeahnlichen Symptomatik bis zum Multiorganversagen fuhren. Beim ICANS kann es neben milden Symptomen wie Verwirrtheit und Aphasie auch zu Krampfanfallen und Hirnodem kommen. Das Management von CRS und ICANS orientiert sich am Schweregrad nach dem Grading der American Society for Transplantation and Cellular Therapy (ASTCT). Beim CRS werden Tocilizumab und Kortikosteroide empfohlen; beim ICANS werden Kortikosteroide eingesetzt. Im weiteren Verlauf sind eine persistierende Hypogammaglobulinamie und Zytopenien auch Monate nach der Therapie haufig; diese begunstigen Infektionen auch Monate nach CAR-T-Zell-Therapie. Nach CAR-T-Zell-Therapie kommt es regelhaft zu potenziell schweren Komplikationen. Eine interdisziplinare Zusammenarbeit zwischen Intensivmediziner*innen, Hamatolog*innen, Neurolog*innen und Arzt*innen anderer Fachabteilungen ist fur die optimale Versorgung von CAR-T-Zell-Patient*innen von entscheidender Bedeutung.

Background Contamination of the catheter hub is an important source of central line-associated bloodstream infections (CLABSI); catheter hub caps incorporating a 70% isopropyl alcohol aim are designed to reduce contamination and hence CLABSI rates. Supporting data in high-risk hematological and oncological patients on the clinical effectiveness of this approach are sparse. Methods We conducted a before-after single center study accompanying the introduction of such caps at our department. Retrospective data from the year prior to the introduction were compared to 1 year of prospective data. Results The control and antiseptic barrier cap (ABC) groups consisted of 309 and 289 patients presenting a CLABSI rate of 15.28 and 10.38 per 1,000 catheter days (P= .042), respectively. However, after multivariate analysis, ABCs were not identified as a statistically significant independent protective factor for the occurrence of CLABSI (hazard ratio 0.69, P= .120). There was no significant difference between the groups with respect to time to CLABSI (P= .681), nor the proportion of catheters removed due to suspicion of infection (P= .076). Conclusions The introduction of ABCs in this high-risk population did not significantly alter CLABSI rates.

Both, objective and self-perceived cognitive deficits, are frequently observed in patients with cancer before, during, and after medical treatment [1,2]. This phenomenon, also known as cancer-relat...

ZusammenfassungKrebspatienten haben ein hohes Risiko, eine Infektion zu entwickeln, die eine Behandlung auf einer Intensivstation notwendig macht. Dies ist insbesondere bei hämatologischen Erkrankungen der Fall, da das Immunsystem fast immer am Krankheitsgeschehen beteiligt ist. Das Bild der Infektion kann mitunter sehr bunt sein, ist abhängig sowohl von der Primärerkrankung als auch der Krebstherapie und kann bis hin zum Vollbild einer Sepsis reichen.

Summary Background Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. Methods This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. Findings 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0–7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1–27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3–4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3–4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37–4·57]), bacterial infection (2·12 [1·11–4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05–3·10]). Interpretation Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. Funding Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique.

SARS-CoV-2 (COVID-19) infections have been recently shown to be associated with a high rate of thromboembolic events due to pro-coagulative mechanisms that have not yet been fully understood. This paper reports on a 55-year-old female COVID-19 patient with severe ARDS and pulmonary embolism (PE) complicated by cardiogenic shock after 12 days of hospitalization under initial prophylactic anticoagulation with low molecular weight heparin (LMWH). An ultima-ratio va (veno-arterial) ECMO implantation and subsequent rapid upgrade to vvaECMO due to insufficient oxygenation was performed. The patient developed severe coagulopathy with intrapulmonary bleeding. The present report aims to highlight and discuss the pros and cons of various anticoagulation strategies in COVID-19 patients focusing on current scientific debates to address this frequently observed complication in the current situation worldwide.

Was ist neu? CRS und ICANS als Nebenwirkung von CAR-T-Zellen Das Cytokine-Release-Syndrome (CRS) ist die häufigste Nebenwirkung einer CAR-T-Zell-Therapie und kann von leichtem Fieber bis zu einem Multiorganversagen führen. Pathophysiologisch kommt es beim CRS zu einem Zytokinsturm und trotz einer Therapie mit Tocilizumab sind refraktäre und tödliche Verläufe beschrieben. Die Symptome des Immune-Effector-Cell-associated-Neurotoxicity-Syndrome (ICANS) variieren von leichter Desorientiertheit bis zum lebensbedrohlichen Hirnödem. Die Pathophysiologie und Therapie des ICANS sind noch nicht ausreichend erforscht. Die Differenzialdiagnosen von CRS und ICANS sind komplex und umfassen neben Infektionen und Sepsis unter anderem auch eine Toxizität der vorhergehenden Therapie, ein Tumorlysesyndrom und nicht zuletzt einen Progress der Grunderkrankung. Ein klinischer oder laborchemischer Parameter zum sicheren Beweis oder Ausschluss eines CRS oder ICANS gibt es zum heutigen Zeitpunkt nicht. Intensivmedizinische Relevanz und potenzielle Entwicklungen der CAR-T-Zell-Therapie Erste Auswertungen von Real-world-Daten deuten auf eine höhere Rate an schweren Nebenwirkungen im Rahmen der CAR-T-Zell-Therapie als in den Zulassungsstudien hin. Für die Indikation r/r-DLBCL könnten schätzungsweise bis zu maximal 300 Patienten pro Jahr in Deutschland eine intensivmedizinische Betreuung im Rahmen der CAR-T-Zell-Therapie benötigen. Studien mit wesentlich häufigeren soliden Tumoren könnten die Patientenzahl drastisch erhöhen. Therapieziel bei CAR-T-Zell-Patienten und Entscheidungen bei Therapiezieländerung Aufgrund des neuen Therapiekonzepts kann ein Konflikt zwischen bislang palliativem Patientenkollektiv und nun möglicherweise langfristigen Remissionen entstehen. Eine frühzeitige Aufklärung über potenziell lebensbedrohliche Nebenwirkungen im Rahmen der Therapie und eine interdisziplinäre Besprechung der Therapieziele mit den Patienten ist entscheidend.

COVID-19 continues to challenge health-care systems and ICUs around the globe more than one year into the pandemic and in spite of all advances in diagnosis and treatment of the disease caused by the novel SARS-CoV-2. Many open questions remain concerning optimal medical therapy, respiratory management and resource allocation, particuly in times of limited available health care personell. In the following short article, we summarized current knowlegde on management of COVID-19 in the ICU.

ZusammenfassungDas Management der hämodynamischen Instabilität im Rahmen einer Sepsis bzw. eines septischen Schocks steht in der Notfallversorgung und auf der Intensivstation ganz im Vordergrund. Kreislaufinstabilität hat einen dramatischen Einfluss auf die Rate an Organkomplikationen und die Mortalität bei Sepsis. Nach der Leitlinie zur Therapie der Sepsis soll ein mittlerer arterieller Druck von 65 mm Hg nicht unterschritten werden. Kristalloide balancierte Flüssigkeit und Katecholamine sind die Eckpfeiler des therapeutischen Managements der septischen Kreislaufinstabilität. In diesem Beitrag sollen die wichtigsten Punkte – das Was, Wann und Wieviel – der Kreislauftherapie präsentiert und kritisch diskutiert werden.

Approx. 93 % of COVID-19 infections are mild, and not all severely ill patients are transferred to the intensive care unit. But the Corona crisis implies high demands on intensive care medicine. Many treatment modalities of COVID patients are “best practice”, but some aspects remain unclear at present. This article deals with diagnostics, monitoring and therapy with COVID-19 patients in intensive care units and with a suitable hygiene concepts.A hygiene concept is obligatory and must ensure – in addition to general measures – the training of employees and the hygienic discharge of material. Ideally, a cohort isolation is implemented.Monitoring of patients with COVID-19 is not different from other intensive care patients and should be adapted to the clinical situation of the individual patient. In laboratory analysis the typical abnormality of COVID-19 patients should be taken into account. In case of increasing inflammatory parameters, fungal infections should be tested.Due to the formation of aerosols, disconnection of the respiratory system must be avoided in invasive ventilation. If a disconnection from the respirator is necessary, the tube should be disconnected. After extubation, an intermittent NIV treatment for atelectase prophylaxis can be performed.

Summary Objectives Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID‐19) associated invasive aspergillosis at a single centre in Cologne, Germany. Methods A retrospective chart review of all patients with COVID‐19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany. Results COVID‐19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS. Conclusion Clinicians caring for patients with ARDS due to COVID‐19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co‐infection.

Introduction Patient-level data from Clostridioides difficile infections (CDI) treated in an intensive care setting is limited, despite the growing medical and financial burden of CDI. Methods We retrospectively analyzed data from 100 medical intensive care unit patients at the University Hospital Cologne with respect to demography, diagnostics, severity scores, treatment, and outcome. To analyze factors influencing response to treatment and death, a backward-stepwise multiple logistic regression model was applied. Results Patients had significant comorbidities including 26% being immunocompromised. The mean Charlson Comorbidity Index was 6.3 (10-year survival rate of 2.25%). At the time of diagnosis, the APACHE II was 17.4±6.3 (predicted mortality rate of 25%), and the ATLAS score was 5.2±1.9 (predicted cure rate of 75%). Overall, 47% of CDI cases were severe, 35% were complicated, and 23% were both. At least one concomitant antibiotic was given to 74% of patients. The cure rate after 10 and 90 days was 56% and 51%, respectively. Each unit increment in APACHE II score was associated with poorer treatment response (OR 0.931; 95% CI 0.872–0.995; p = 0.034). Age above 65 years was associated with death (OR 2.533; 95% CI 1.031–6.221; p = 0.043), and overall mortality at 90 days was 56%. Conclusions CDI affects a high-risk population, in whom predictive scoring tools are not accurate, and outcomes are poor despite intensive treatment. Further research in this field is warranted to improve prediction scoring and patient outcomes.

The ongoing strain on personnel in the healthcare system during the COVID-19 pandemic is considerable and poses major emotional and psychological challenges for the personnel. In a team evaluation (physicians and nurses), team-specific stress, possible relief strategies, positive and negative experiences, and wishes for improvement of the situation in an intensive care unit were collected. While both occupational groups perceived equally high emotional stress intensities, nursing additionally perceived high stress intensities in the organizational and physical areas. Thus, the occupational group of nurses proves to be the most stressed by the COVID-19 pandemic. The findings presented here can be used to derive instructions for future actions.Die anhaltende Belastung der Mitarbeiter im Gesundheitsdienst während der COVID-19-Pandemie ist erheblich und stellt die Mitarbeiter vor große emotionale und psychologische Herausforderungen. In einer teaminternen Evaluation (Ärzt:innen und Pflegekräfte) wurden teamspezifische Belastungen, mögliche Entlastungsstrategien, positive und negative Erfahrungen sowie Wünsche für eine Verbesserung der Situation auf einer Intensivstation erhoben. Während beide Berufsgruppen gleich hohe emotionale Belastungsintensitäten wahrnahmen, werden bei der Pflege zusätzlich starke Belastungsintensitäten im organisatorischen und körperlichen Bereich wahrgenommen. Damit erweist sich die Berufsgruppe der Pflegenden als am stärksten durch die COVID-19-Pandemie belastet. Durch die hier herausgearbeiteten Erkenntnisse können für die Zukunft konkrete Handlungsanweisungen abgeleitet werden.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) cause serious infections and aggravate disease progression. Last resort antibiotics are effective against MDR-GNB and are reimbursed by flat rates based on German diagnosis-related groups (G-DRG). From a hospital management perspective, this analysis compared hospital reimbursement for last resort antibiotics with their acquisition costs to outline potential funding gaps. Retrospective analyses based on medical charts and real-life reimbursement data included patients with pneumonia due to MDR-GNB treated in intensive care units (ICU) of a German tertiary care hospital (University Hospital Cologne) between January 2017 and December 2020. Drug-associated hospital reimbursement of G-DRG was compared with drug acquisition costs based on preliminarily approved last resort antibiotics (cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-cilastatin-relebactam) according to label. Funding gaps were determined for the treatment of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and mixed infections, respectively. Most of the 31 patients were infected with Enterobacterales (n = 15; 48.4%) and P. aeruginosa (n = 13; 41.9%). Drug-associated G-DRG reimbursement varied from 44.50 EUR (mixed infection of P. aeruginosa and Enterobacterales) to 2265.27 EUR (P. aeruginosa; mixed infection of P. aeruginosa and Enterobacterales). Drug acquisition costs ranged from 3284.40 EUR in ceftazidime-avibactam (minimum duration) to 15,827.01 EUR for imipenem-cilastatin-relebactam (maximum duration). Underfunding was found for all MDR-GNB, reaching from 1019.13 EUR (P. aeruginosa; mixed infection of P. aeruginosa and Enterobacterales) to 14,591.24 EUR (Enterobacterales). This analysis revealed the underfunding of last resort antibiotics in German hospital treatment. Insufficient reimbursement implies less research in this field, leading to a more frequent use of inappropriate antibiotics. The cycle closes as this contributes to the development of multi-drug resistant bacteria.

Annals of hematology 101(10), 2317-2324 (2022). doi:10.1007/s00277-022-04958-w, Published by Springer, Berlin

Objectives: Patients with classical Hodgkin lymphoma (cHL) relapsing after second-line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre-)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL). Methods: Patients ≥18 years with histologically confirmed r/r cHL who failed second-line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28-day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT-based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression-free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2-stage phase 2 design (Simon 1989). Results: Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1-year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported. Conclusion: Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1. in press

Purpose: The question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors. Methods: 297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted. Results: Patients had a median age of 56 (IQR 44–65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1–32.4%). Low platelet count (HR 0.997, 95% CI 0.996–0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012–1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081–3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044–2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO. Conclusion: The overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.

The alpha variant of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is associated with higher transmissibility and possibly higher mortality compared with wild-type SARS-CoV-2. However, few data are available on the clinical course of infections with the alpha variant compared with wild-type SARS-CoV-2 in critically ill patients in intensive care units (ICUs). Therefore, we retrospectively analyzed patients admitted to our ICU due to SARS-CoV-2 Alpha variant infection and compared characteristics and course to patients with SARS-CoV-2 wild-type infection. The median age of patients with Alpha variant infections was 57 years compared to 62 years in the wild-type group. ICU survival was 41/80 (51%) in the Alpha variant group and 35/80 (44%) in the wild-type group (p = 0.429). Results of a matched-pair analysis based on age and sex illustrated that 45/58 patients (77.6%) in the Alpha variant group and 38/58 (65.5%) patients in the wild-type group required mechanical ventilation (p = 0.217). ICU survival was documented for 28/58 patients (48.3%) in the Alpha variant group and 27/58 patients (46.6%) in the wild-type group (p = 1). Thus, ICU mortality among patients with SARS-CoV-2 infections remains high. Although the Alpha variant group included younger patients requiring mechanical ventilation, no significant differences between patients with the SARS-CoV-2 Alpha variant and the SARS-CoV-2 wild-type, respectively, were detected with respect to clinical course and ICU mortality. For future VOCs, we believe it would be important to obtain valid and rapid data on the clinical course of critically ill patients who test positive for COVID-19 in order to perform appropriate epidemiological planning of intensive care capacity.

COVID-19 continues to challenge health-care systems and ICUs around the globe more than one year into the pandemic and in spite of all advances in diagnosis and treatment of the disease caused by the novel SARS-CoV-2. Many open questions remain concerning optimal medical therapy, respiratory management and resource allocation, particuly in times of limited available health care personell. In the following short article, we summarized current knowlegde on management of COVID-19 in the ICU.