[Cardiovascular therapy for sepsis: when, how and how much?] / Kreislauftherapie bei Sepsis ­ wann, wie und wie viel?

The management of hemodynamic instability in the context of sepsis or septic shock is at the forefront in emergency care as well as in the intensive care unit. Cardiovascular instability has a dramatic impact on the rate of organ complications and mortality from sepsis. According to the guideline for the treatment of sepsis, mean arterial pressure should not fall below 65 mm Hg. Crystalloid balanced fluid and catecholamines are the cornerstones of therapy management for septic cardiovascular instability. In this article, the most important points of what, when and how much regarding circulation therapy are presented and critically discussed.

Pelvic cellulitis caused by Raoultella planticola in a neutropenic patient.

Raoultella planticola is a gram-negative, encapsulated, aerobic bacterium within the Enterobacteriaceae family. It has been primarily described as pathogen in cases with pneumonia and gastrointestinal infections. Here we describe a case of severe pelvic cellulitis in a patient with neutropenia following induction therapy for myeloid sarcoma. The patient experienced a septic shock and was treated successfully with antibiotic therapy. A literature review is provided to put this case in context with previous reports on R. planticola. This report highlights that awareness for uncommon pathogens is crucial in the clinical management of infections in neutropenic patients.

Consensus statement for cancer patients requiring intensive care support.

This consensus statement is directed to intensivists, hematologists, and oncologists caring for critically ill cancer patients and focuses on the management of these patients.

[Diagnostic management of fever]. / Diagnostisches Management von Fieber.

Fever is a symptom of a wide range of diseases. Its diagnostic management is of crucial importance, whereby the interface between general practitioner and hospital plays an important role. The family practitioner is of particular importance in the detection of life-threatening or complex situations involving fever. The diagnostic algorithm presented here can serve as the basis for rapid and targeted diagnostics. Good communication between the doctor and the hospital doctor is mandatory.

Prospective Analyses of Circulating B Cell Subsets in ABO-Compatible and ABO-Incompatible Kidney Transplant Recipients.

Immunosuppressive strategies applied in renal transplantation traditionally focus on T cell inhibition. B cells were mainly examined in the context of antibody-mediated rejection, whereas the impact of antibody-independent B cell functions has only recently entered the field of transplantation. Similar to T cells, distinct B cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B cell subsets in the peripheral blood of AB0-compatible (n = 27) and AB0-incompatible (n = 10) renal transplant recipients. Activated B cells were transiently decreased and plasmablasts were permanently decreased in patients without signs of rejection throughout the first year. In patients with histologically confirmed renal allograft rejection, activated B cells and plasmablasts were significantly elevated on day 365. Rituximab treatment in AB0-incompatible patients resulted in long-lasting B cell depletion and in a naïve phenotype of repopulating B cells 1 year following transplantation. Acute allograft rejection was correlated with an increase of activated B cells and plasmablasts and with a significant reduction of regulatory B cell subsets. Our study demonstrates the remarkable effects of standard immunosuppression on circulating B cell subsets. Furthermore, the B cell compartment was significantly altered in rejecting patients. A specific targeting of deleterious B cell subsets could be of clinical benefit in renal transplantation.

Nonmyeloablative allogeneic stem cell transplantation for chronic lymphocytic leukaemia offers the possibility of disease control with minimal morbidity and mortality--a single institution experience.

Allogeneic stem cell transplantation is a treatment option for patients with poor risk CLL. We conducted a retrospective analysis of all CLL patients allografted at our institution, the University Hospital of Cologne, Germany. Data was collected on 40 patients from 2004 to 2012. The mean age was 54, and the majority were male (75 %). On average, the patients were diagnosed 6 years (range 2-12) prior to transplant with an average of 4 years (range 1-8) from time of first-line therapy to transplant. The remission states at the time of transplant were complete remission (CR) (n = 4), stable disease (n = 10), partial remission (n = 20) and progressive disease (n = 6). Only reduced intensity conditioning regimens were employed. The average CD34(+) cell dose was 4.16 × 10(6)/kg. Neutrophil engraftment was seen by day +17 (range 10-23) post-transplant, and 88 % achieved 95-100 % donor chimerism by day 100. Overall survival, progression-free survival and non-relapse mortality at 2 years post-transplant were 65, 52.5 and 27.5 %, respectively. A total of 51 % of patients were found to be minimal residual disease (MRD)-negative at 1 year post-transplant. Our single-centre experience confirms the valuable role of allogeneic stem cell transplantation (allo-SCT) in the treatment of poor risk CLL patients with promising long-term survival and acceptable transplant-related mortality. The advent of newer therapeutic agents should not hinder the consideration of allo-SCT for this patient cohort as it remains the only curative option for these patients.

[Intensive care management of hematological and oncological patients]. / Intensivmedizinisches Management hämatologischer und onkologischer Patienten.

Management of critically ill cancer patients warrants stringent admission criteria and clear concepts concerning duration and limits of intensive care. Recent developments in mechanical ventilation and sepsis therapy can easily be used to improve the outcome of critically ill cancer patients. The incidence and overall prognosis of cancer is constantly growing and, thus, the number of critically ill cancer patients is increasing. Furthermore, novel oncology drugs-in particular immune modulators-produce unexpected and substantial side effects. Therefore, the development of an interdisciplinary algorithm by oncologists and intensivists remains an important and dynamic challenge.

[Proposal for participation in intensive care and emergency medicine studies for patients unable to give informed consent (Cologne Model)]. / Vorschlag für ein Verfahren zur Teilnahme an intensiv- und notfallmedizinischen Studien bei nichteinwilligungsfähigen Patient*innen (Kölner Modell).

When conducting clinical trials in intensive care and emergency medicine, physicians, ethics committees, and legal experts have differing views regarding the inclusion of patients who are incapable of giving consent. These different views on the participation of patients who are not capable of giving consent also complicate how clinical trials are prepared and conducted. Based on the results of a literature search, a consensus model (Cologne Model) was developed by physicians performing clinical research, ethics committees, and lawyers in order to provide patients, those scientifically responsible for the study, ethics committees, and probate (guardianship) judges with a maximum of patient safety and legal certainty, while simultaneously enabling scientific research.

[CARs, CRS and neurotoxicity: severe complications after administration of immunotherapy : Essentials for intensivists]. / CAR, CRS und Neurotoxizität: schwere Komplikationen der Immuntherapie : Was der Intensivmediziner wissen muss.

BACKGROUND: The development of chimeric antigen receptor (CAR) T­cells has shown promising results in relapsed/refractory B­cell acute lymphoblastic leukemia/lymphoma (B-ALL) and diffuse large cell B­cell lymphoma. Complications, especially cytokine release syndrome (CRS) and CAR T­cell related encephalopathy syndrome (CRES), can be life threatening. The management of both plays a key role in CAR T­cell therapy. OBJECTIVES: Diagnosis, clinical presentation and development of complications in the treatment with CAR T­cells. MATERIALS AND METHODS: Summary of incidence, mortality and treatment of severe complications after administration of CAR T­cells referring to current studies and therapy recommendations. RESULTS: Complications after administration of CAR T­cells, especially CRS and CRES, can be life threatening. The timely identification of side effects and their appropriate treatment usually leads to complete recovery. CONCLUSIONS: Using a therapy algorithm in the treatment with CAR T­cells allows safe management of toxicities and can be helpful in recognizing them in time.

[Diagnosis and treatment of immune-related adverse events during checkpoint inhibitor therapy in intensive care medicine]. / Diagnostik und Therapie von immunvermittelten Nebenwirkungen durch Checkpointinhibitoren in der Intensivmedizin.

BACKGROUND: Due to the use of checkpoint inhibitors, intensive care units will be confronted with an increasing number of patients with immune-related adverse events. A broad spectrum of symptoms and potentially lethal consequences make diagnosis and treatment challenging. OBJECTIVES: Diagnosis and treatment of immune-related adverse events in the treatment with checkpoint inhibitors with a special focus on intensive care units. MATERIALS AND METHODS: Review of current publications about incidence, symptoms and treatment of adverse events after the use of checkpoint inhibitors relevant for intensive care medicine. RESULTS: Immune-related adverse events during therapy with checkpoint inhibitors are difficult to diagnose and present with various symptoms. Severe complications can often successfully be treated with early therapy. CONCLUSIONS: The early treatment of immune-related adverse events according to their severity is needed to prevent a potentially life-threatening course.

[Prevalence of cancer patients in German intensive care units]. / Prävalenz von Krebspatienten auf deutschen Intensivstationen.

INTRODUCTION: Cancer is one of the leading causes of death worldwide. Due to increasing comorbidities, age and aggressive chemotherapy, care of cancer patients in intensive care units (ICUs) is more and more necessary. So far, little is known about the care structure of cancer patients in German ICUs. The aim of this work is to collect and evaluate the prevalence and care data of cancer patients on two reference dates. METHODS: German ICUs were invited to participate in a 2-day, prospective, multicenter point prevalence study in ICU cancer patients. Participation in the study was voluntary and the study was not funded. An ethics vote was obtained to conduct the study. The data were anonymously entered into an eCRF (electronic case report form) by the participating centers. Identification of the patients is therefore not possible. RESULTS: About one in four patients on the ICU/IMC ward had hematological-oncological (HO) disease (n = 316/1319, 24%). The proportion depended significantly on the number of beds in each hospital. The most frequent reasons for admission to the ICU/IMC station were postoperative monitoring (n = 83/221, 37.6%), respiratory instability (n = 79/221, 35.7%), circulatory instability (n = 52/221; 23.5%) and the severe infection with sepsis (n = 47/221; 21.3%). In all, 66.5% (n = 147/221) of the patients had a solid tumor and 21.7% (n = 48/221) had hematological cancer, 78.3% (n = 173/221) of the documented cancer patients received "full-code" intensive management, while 42.5% (n = 94/221) of the HO patients were ventilated and 40.7% (n = 90/221) required catecholamines. The median (mean; IQR) SAPS II score was 35 (37.79, IQR = 24-48) and the median (mean, IQR) TISS score was 10 (13.26, IQR = 10-15). Through the analysis and evaluation of the data available in the context of the prevalence study, it was possible for the first time to determine the Germany-wide cross-center prevalence and care situation of hematological cancer patients in intensive care and intermediate care stations. About one in four patients on German ICUs and IMC wards have a major or minor cancer diagnosis (n = 316/1319 = 24%). Care management is complex in this patient population and requires close interdisciplinary collaboration.

CD40-activated B cells can be generated in high number and purity in cancer patients: analysis of immunogenicity and homing potential.

Cellular adjuvants such as dendritic cells (DC) are in the focus of tumour immunotherapy. In DC-vaccine trials, induction of tumour antigen-specific immunity is observed frequently and well-documented clinical responses have been reported. However, the overall response rate is less than 3%, therefore alternative strategies are being investigated. CD40-activated B cells (CD40-B) have been characterized previously as an interesting alternative because they present antigen efficiently and can be expanded by several logs from small amounts of peripheral blood. To determine the central technical challenges of cell-based vaccines we performed a single-patient analysis of 502 patients from DC-based tumour vaccine trials and identified at least three factors contributing to their limited efficiency: (1) lack of cell numbers; (2) lack of documented purity thus high contamination of bystander cells; and (3) lack of quality control and thus heterogeneous or unknown expression of important surface molecules such as major histocompatibility complex (MHC) and chemokine receptors. Based on these findings we re-evaluated the CD40-B approach in cancer patients. Here, we show that proliferation of B cells from cancer patients is equivalent to that observed in healthy donors. Purity is always > 90% after 2 weeks and remains stable for several weeks. They have comparable antigen-presenting capability determined phenotypically and by allogeneic mixed lymphocyte reaction. Expression of CCR7 and CD62L was detected in all samples and B cells migrated towards the relevant homing chemokines. Taken together, CD40-B cells from cancer patients can be expanded in virtually unlimited numbers at high purity and full function concerning antigen-presentation and migratory properties.

[Hematological-oncological intensive care patients : Treatment without borders]. / Der hämatologisch-onkologische Intensivpatient : Therapie ohne Grenzen.

The number of treatment options and success of treating patients with cancer have both significantly increased in recent years. However, many of these patients require intensive care due to comorbidities, treatment-associated complications, or severe infections. At the same time, the boundaries between what is feasible and sensible are difficult to draw. Over the past few years, awareness of the problems these cancer patients may have in the intensive care unit has increased and discussions have begun. This article intends to offer a discussion basis and also possible solution strategies.

Intensive care management of influenza-associated pulmonary aspergillosis.

BACKGROUND: Severe pulmonary infections are among the most common reasons for admission to intensive care units (ICU). Within the last decade, increasing reports of severe influenza pneumonia resulting in acute respiratory distress syndrome (ARDS) complicated by Aspergillus infection were published. OBJECTIVES: To provide a comprehensive review of management of influenza-associated pulmonary aspergillosis in patients with ARDS. SOURCES: Review of the literature pertaining to severe influenza-associated pulmonary aspergillosis. PubMed database was searched for publications from the database inception to January 2019. CONTENT: In patients with lower respiratory symptoms, development of respiratory insufficiency should trigger rapid and thorough clinical evaluation, in particular in cases of suspected ARDS, including electrocardiography and echocardiography to exclude cardiac dysfunction, arrhythmias and ischaemia. Bronchoalveolar lavage should obtain lower respiratory tract samples for galactomannan assay, direct microscopy, culture, and bacterial, fungal and viral PCR. In case of positive Aspergillus testing, chest CT is the imaging modality of choice. If influenza pneumonia is diagnosed, neuraminidase inhibitors are the preferred approved drugs. When invasive aspergillosis is confirmed, first-line therapy consists of isavuconazole or voriconazole. Isavuconazole is an alternative in case of intolerance to voriconazole, drug-drug interactions, renal impairment, or if a spectrum of activity including the majority of Mucorales is desired. Primary anti-mould prophylaxis with posaconazole is recommended in haematology patients at high-risk. It may be considered in newly diagnosed influenza and ARDS, but ideally in clinical trials. IMPLICATIONS: The rising reports of influenza-associated pulmonary aspergillosis in patients with ARDS, who are otherwise not considered at risk for fungal pneumonia demands heightened clinical awareness. Tracheobronchitis and Aspergillus in respiratory tract samples should prompt suspicion of invasive fungal infection and further work-up. The management algorithm should comprise bronchoalveolar lavage, CT imaging, sophisticated ventilator-management, rescue extracorporeal membrane oxygenation, and antifungal and antiviral therapy. To decrease the burden of influenza-related illness, vaccination is of utmost importance, specifically in patients with co-morbidities.

[Antifreeze poisoning : The case of a patient with repeated ethylene glycol poisoning]. / Intoxikation nach Frostschutzmittelaufnahme : Der Fall eines Patienten nach wiederholter Ethylenglykolintoxikation.

Ethylene glycol poisoning of incidental or suicidal intention can cause life-threatening metabolic acidosis, diverse secondary damage, and even lead to death. Beside hemodialysis effective therapy consists of the administration of fomepizole and ethanol. We describe a patient after repeated ethylene glycol poisoning with high anion gap metabolic acidosis and acute renal failure. Using hemodialysis, with dialysate containing a specific amount of ethanol, and intravenous ethanol administration we were able to prevent severe secondary organ damage.

[Mortality of hematology-oncology patients with neutropenia in intensivecare]. / Letalität hämatoonkologischer Patienten in Neutropenie auf der Intensivstation.

BACKGROUND: Febrile neutropenia remains one of the most common reasons for hospital admission of patients with underlying oncologic disease. These patients have an up to 10-fold increased risk of developing sepsis, which often leads to these patients being transferred to the intensive care unit (ICU). The survival of neutropenic patients with sepsis in particular has improved in recent years, due to advanced therapy in intensive care (surviving sepsis campaign); however few large international studies of neutropenic cancer patients in the ICU are available. METHODS: In a retrospective study, 59 episodes of neutropenic cancer patients in the internal medicine ICU at the University Hospital of Cologne over a period of 2 years were analyzed. RESULTS: Pneumonia with or without sepsis are the main admission diagnoses of neutropenic cancer patients in the ICU. The mortality rate of these patients is very high (50.8 %). Pneumonia and sepsis, stem cell transplantation, mechanical ventilation, and acute renal failure with or without dialysis are correlated with mortality. CONCLUSION: Cancer patients should be admitted immediately to the ICU if they have signs of sepsis for early monitoring and treatment. Neutropenic patients have an increased risk for infectious complications and a risk for sepsis with higher mortality rates.