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Abstract Background Progress in recent years strengthened the concept of cellular tumor vaccinations. However, a crucial barrier to successful cancer immunotherapy is tumor-mediated immunosuppression. Tumor-derived soluble factors such as IL-10, TGF-β, and VEGF suppress effector cells either directly or indirectly by disruption of dendritic cell (DC) differentiation, migration and antigen presentation. Human B cells acquire potent immunostimulatory properties when activated via CD40 and have been shown to be an alternative source of antigen-presenting cells (APCs) for cellular cancer vaccines. Nevertheless, in contrast to DCs little knowledge exists about their susceptibility to tumor derived immunosuppressive factors. Thus, we assessed whether IL-10, TGF-β, or VEGF do affect key aspects of the immunostimulatory function of human CD40-activated B cells. Methods Cell surface expression of adhesion and costimulatory molecules and the proliferation capacity of CD40-activated B cells were compared to untreated controls by flow cytometry. Migration towards important chemokines of secondary lymph organs was measured with or without exposure to the immunosuppressive cytokines. Finally, an influence on T cell stimulation was investigated by allogeneic mixed lymphocyte reactions. For statistical analysis Student’s t test or two-way analysis of variance followed by Bonferroni's post-hoc test was used to compare groups. P values of Results Neither cell adhesion nor the expression of MHC class II and costimulatory molecules CD80 and CD86 was inhibited by addition of IL-10, TGF-β, or VEGF. Likewise, the proliferation of CD40-activated B cells was not impaired. Despite being exposed to IL-10, TGF-β, or VEGF the B cells migrated equally well as untreated controls to the chemokines SLC and SDF-1α. Most importantly, the capacity of CD40-activated B cells to stimulate CD4+ and CD8+ T cells remained unaffected. Conclusion Our findings suggest that key immunostimulatory functions of CD40-activated B cells are resistant to inhibition by the immunosuppressive factors IL-10, TGF-β, and VEGF. This supports considerations to use ex vivo generated CD40-activated B cells as a promising alternative or additional APC for cellular immunotherapy, especially in settings where these immunosuppressive cytokines are present in tumor environment.

Abstract Introduction In patients with chronic myeloid leukemia, tyrosine kinase inhibitors suppress the BCR-ABL+ clone and often induce complete molecular remissions. Megakaryocytes in such patients have been shown to be derived from the BCR-ABL+ clone, and abnormal platelet function is frequent in chronic myeloid leukemia. However, little is known about the influence of modern targeted therapy on chronic myeloid leukemia-associated platelet disorders. Case presentation We report the case of a massive hemorrhage in a 32-year-old Caucasian man caused by chronic myeloid leukemia-associated platelet dysfunction, which improved after treatment with imatinib. Conclusion This report demonstrates that platelet dysfunction and bleeding disorder in BCR-ABL+ chronic myeloid leukemia can successfully be treated with imatinib. We suggest the monitoring of platelet function in future studies using imatinib to treat patients with chronic myeloid leukemia.

Abstract Background Currently the majority of cancer patients are considered ineligible for intensive care treatment and oncologists are struggling to get their patients admitted to intensive care units. Critical care and oncology are frequently two separate worlds that communicate rarely and thus do not share novel developments in their fields. However, cancer medicine is rapidly improving and cancer is eventually becoming a chronic disease. Oncology is therefore characterized by a growing number of older and medically unfit patients that receive numerous novel drug classes with unexpected side effects. Discussion All of these changes will generate more medically challenging patients in acute distress that need to be considered for intensive care. An intense exchange between intensivists, oncologists, psychologists and palliative care specialists is warranted to communicate the developments in each field in order to improve triage and patient treatment. Here, we argue that "critical care of cancer patients" needs to be recognized as a medical subspecialty and that there is an urgent need to develop it systematically. Conclusion As prognosis of cancer improves, novel therapeutic concepts are being introduced and more and more older cancer patients receive full treatment the number of acutely ill patients is growing significantly. This development a major challenge to current concepts of intensive care and it needs to be redefined who of these patients should be treated, for how long and how intensively.

Objectives: To investigate characteristics and outcomes of critically ill cancer patients with marked hyperferritinemia. Methods: A single‐center retrospective analysis comprising cancer patients with a ferritin level >10.000 μg/L treated in the intensive care unit (ICU) between 2012 and 2022 was conducted. Results: A total of 117 patients were included in the analysis. The median age was 59 years (range: 15–86 years). Females accounted for 48% of cases. 90% of patients had a hematologic malignancy. The median maximum ferritin level was 27.349 μg/L (range: 10.300–426.073 μg/L). The diagnostic criteria of septic shock were fulfilled in 51% of cases; 31% of patients had hemophagocytic lymphohistiocytosis (HLH) according to the HLH‐2004 criteria. Mechanical ventilation, renal replacement therapy and the use of vasopressors were necessary in 59%, 35% and 70% of cases, respectively. The ICU, hospital, 90‐day and 1‐year survival rates were 33.3%, 23.1%, 23.7% and 11.7%. Patients with septic shock had a worse survival than those without septic shock (p =.001); the survival of patients who fulfilled the HLH‐2004 criteria did not differ from those who did not (p =.88). Conclusion: Critically ill cancer patients with marked hyperferritinemia have poor outcomes. The present data may help to make informed decisions for this patient group. [ABSTRACT FROM AUTHOR]

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare disorder typically characterized by the clinical triad including a sudden onset of fever, painful skin lesions, and neutrophilia. The histopathological findings are a dense neutrophilic infiltrate and oedema of the dermis and epidermis without evidence of a vasculitis. Besides treatment of the underlying cause, sweet syndrome is typically treated with high‐dose corticosteroids leading to a relapse‐free response in 70% of patients. However, if left unrecognized or untreated, the condition may lead to serious complications. Here, we report on the case of a 38‐year‐old patient in whom, under the assumption of the presence of necrotizing fasciitis, exarticulation of the right arm was performed. In the absence of pathogen detection and insufficient response to anti‐infective therapies, the diagnosis of a sweet syndrome was assumed and, later, confirmed by an excellent response to high‐dose administration of systematic glucocorticoids. The case emphasizes the need to be aware of this rare syndrome, which can be easily misdiagnosed due to its close resemblance to infection and stresses the need of further research to define distinct diagnostic tools. [ABSTRACT FROM AUTHOR]

Background: There are limited and partially contradictory data on the effects of airway pressure release ventilation (APRV) in COVID-19-associated acute respiratory distress syndrome (CARDS). Therefore, we analyzed the clinical outcome, complications, and longitudinal course of ventilation parameters and laboratory values in patients with CARDS, who were mechanically ventilated using APRV. Methods: Respective data from 4 intensive care units (ICUs) were collected and compared to a matched cohort of patients receiving conventional low tidal volume ventilation (LTV). Propensity score matching was performed based on age, sex, blood gas analysis, and APACHE II score at admission, as well as the implementation of prone positioning. Findings: Forty patients with CARDS, who were mechanically ventilated using APRV, and 40 patients receiving LTV were matched. No significant differences were detected for tidal volumes per predicted body weight, peak pressure values, and blood gas analyses on admission, 6 h post admission as well as on day 3 and day 7. Regarding ICU survival, no significant difference was identified between APRV patients (40%) and LTV patients (42%). Median duration of mechanical ventilation and duration of ICU treatment were comparable in both groups. Similar complication rates with respect to ventilator-associated pneumonia, septic shock, thromboembolic events, barotrauma, as well as the necessity for hemodialysis were detected for both groups. Clinical characteristics that were associated with increased mortality in a Cox proportional hazards regression analysis included age (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04-1.1; P <.001), severe acute respiratory distress syndrome (HR 2.62, 95% CI 1.02-6.7; P =.046) and the occurrence of septic shock (HR 17.18, 95% CI 2.06-143.2; P =.009), but not the ventilation mode. Interpretation: Intensive care unit survival, duration of mechanical ventilation, and ICU treatment as well as ventilation-associated complication rates were equivalent using APRV compared to conventional LTV in patients with CARDS. [ABSTRACT FROM AUTHOR]

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.