Extracorporeal membrane oxygenation in adults receiving haematopoietic cell transplantation: an international expert statement.

Combined advances in haematopoietic cell transplantation (HCT) and intensive care management have improved the survival of patients with haematological malignancies admitted to the intensive care unit. In cases of refractory respiratory failure or refractory cardiac failure, these advances have led to a renewed interest in advanced life support therapies, such as extracorporeal membrane oxygenation (ECMO), previously considered inappropriate for these patients due to their poor prognosis. Given the scarcity of evidence-based guidelines on the use of ECMO in patients receiving HCT and the need to provide equitable and sustainable access to ECMO, the European Society of Intensive Care Medicine, the Extracorporeal Life Support Organization, and the International ECMO Network aimed to develop an expert consensus statement on the use of ECMO in adult patients receiving HCT. A steering committee with expertise in ECMO and HCT searched the literature for relevant articles on ECMO, HCT, and immune effector cell therapy, and developed opinion statements through discussions following a Quaker-based consensus approach. An international panel of experts was convened to vote on these expert opinion statements following the Research and Development/University of California, Los Angeles Appropriateness Method. The Appraisal of Guidelines for Research and Evaluation statement was followed to prepare this Position Paper. 36 statements were drafted by the steering committee, 33 of which reached strong agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and expert panel, and rephrased before an additional round of voting. At the conclusion of the process, 33 statements received strong agreement and three weak agreement. This Position Paper could help to guide intensivists and haematologists during the difficult decision-making process regarding ECMO candidacy in adult patients receiving HCT. The statements could also serve as a basis for future research focused on ECMO selection criteria and bedside management.

Treatment, outcome and re-vaccination of patients with SARS-CoV-2 vaccine-associated immune thrombocytopenia.

PURPOSE: Following the emergency use authorization of BNT162b2 by the Food and Drug administration (FDA) in early December 2020, mRNA- and vector-based vaccines became an important means of reducing the spread and mortality of the COVID-19 pandemic. The European Medicines Agency labelled immune thrombocytopenia (ITP) as a rare adverse reaction of unknown frequency after vector-, but not mRNA-vaccination. Here, we report on the long-term outcome of 6 patients who were diagnosed with de-novo, vaccine-associated ITP (VA-ITP), and on the outcome of subsequent SARS-CoV-2 re-vaccinations. METHODS: Patients were included after presenting to our emergency department. Therapy was applied according to ITP guidelines. Follow-up data were obtained from outpatient departments. Both mRNA- or vector-based vaccines were each used in 3 cases, respectively. RESULTS: In all patients, the onset of symptoms occurred after the 1st dose of vaccine was applied. 5 patients required treatment, 3 of them 2nd line therapy. All patients showed a complete response eventually. After up to 359 days of follow-up, 2 patients were still under 2nd line therapy with thrombopoietin receptor agonists. 5 patients have been re-vaccinated with up to 3 consecutive doses of SARS-CoV-2 vaccines, 4 of them showing stable platelet counts hereafter. CONCLUSION: Thrombocytopenia after COVID-19 vaccination should trigger a diagnostic workup to exclude vaccine-induced immune thrombotic thrombocytopenia (VITT) and, if confirmed, VA-ITP should be treated according to current ITP guidelines. Re-vaccination of patients seems feasible under close monitoring of blood counts and using a vaccine that differs from the one triggering the initial episode of VA-ITP.

Severe Candida glabrata pancolitis and fatal Aspergillus fumigatus pulmonary infection in the setting of bone marrow aplasia after CD19-directed CAR T-cell therapy - a case report.

BACKGROUND: Prolonged myelosuppression following CD19-directed CAR T-cell transfusion represents an important, yet underreported, adverse event. The resulting neutropenia and multifactorial immunosuppression can facilitate severe infectious complications. CASE PRESENTATION: We describe the clinical course of a 59-year-old patient with relapsed/refractory DLBCL who received Axicabtagene-Ciloleucel (Axi-cel). The patient developed ASTCT grade I CRS and grade IV ICANS, necessitating admission to the neurological ICU and prolonged application of high-dose corticosteroids and other immunosuppressive agents. Importantly, neutropenia was profound (ANC < 100/µl), G-CSF-refractory, and prolonged, lasting more than 50 days. The patient developed severe septic shock 3 weeks after CAR transfusion while receiving anti-fungal prophylaxis with micafungin. His clinical status stabilized with broad anti-infective treatment and intensive supportive measures. An autologous stem cell backup was employed on day 46 to support hematopoietic recovery. Although the counts of the patient eventually started to recover, he developed an invasive pulmonary aspergillosis, which ultimately lead to respiratory failure and death. Postmortem examination revealed signs of Candida glabrata pancolitis. CONCLUSIONS: This case highlights the increased risk for fatal infectious complications in patients who present with profound and prolonged cytopenia after CAR T-cell therapy. We describe a rare case of C. glabrata pancolitis associated with multifactorial immunosuppression. Although our patient succumbed to a fatal fungal infection, autologous stem cell boost was able to spur hematopoiesis and may represent an important therapeutic strategy for DLBCL patients with CAR T-cell associated bone marrow aplasia who have underwent prior stem cell harvest.

[Characteristics and outcome of 70 ventilated COVID-19 patients : Summary after the first wave at a university center]. / Charakteristika und Outcome von 70 beatmeten COVID-19-Patienten : Bilanz nach der ersten Welle an einem universitären Zentrum.

BACKGROUND: In a pandemic situation the overall mortality rate is of considerable interest; however, these data must always be seen in relation to the given healthcare system and the availability of local level of care. A recently published German data evaluation of more than 10,000 COVID-19 patients treated in 920 hospitals showed a high mortality rate of 22% in hospitalized patients and of more than 50% in patients requiring invasive ventilation. Because of the high infection rates in Bavaria, a large number of COVID-19 patients with considerable severity of disease were treated at the intensive care units of the LMU hospital. The LMU hospital is a university hospital and a specialized referral center for the treatment of patients with acute respiratory distress syndrome (ARDS). OBJECTIVE: Data of LMU intensive care unit (ICU) patients were systematically evaluated and compared with the recently published German data. METHODS: Data of all COVID-19 patients with invasive and noninvasive ventilation and with completed admission at the ICU of the LMU hospital until 31 July 2020 were collected. Data were processed using descriptive statistics. RESULTS: In total 70 critically ill patients were included in the data evaluation. The median SAPS II on admission to the ICU was 62 points. The median age was 66 years and 81% of the patients were male. More than 90% were diagnosed with ARDS and received invasive ventilation. Treatment with extracorporeal membrane oxygenation (ECMO) was necessary in 10% of the patients. The median duration of ventilation was 16 days, whereby 34.3% of patients required a tracheostomy. Of the patients 27.1% were transferred to the LMU hospital from external hospitals with reference to our ARDS/ECMO program. Patients from external hospitals had ARDS of higher severity than the total study population. In total, nine different substances were used for virus-specific treatment of COVID-19. The most frequently used substances were hydroxychloroquine and azithromycin. Immunomodulatory treatment, such as Cytosorb® (18.6%) and methylprednisolone (25.7%) were also frequently used. The overall in-hospital mortality rate of ICU patients requiring ventilation was 28.6%. The mortality rates of patients from external hospitals, patients with renal replacement therapy and patients with ECMO therapy were 47.4%, 56.7% and 85.7%, respectively. CONCLUSION: The mortality rate in the ventilated COVID-19 intensive care patients was considerably different from the general rate in Germany. The data showed that treatment in an ARDS referral center could result in a lower mortality rate. Low-dose administration of steroids may be another factor to improve patient outcome in a preselected patient population. In the authors' opinion, critically ill COVID-19 patients should be treated in an ARDS center provided that sufficient resources are available.

[Caring for The Critically Ill Cancer Patient in 2019]. / Intensivmedizinische Versorgung des kritisch kranken Tumorpatienten ­ Status Quo 2019.

In Europe, up to 25 % of the ICU patients suffer from malignant diseases. Recent studies have shown that the short term prognosis of critically ill cancer patients is determined by the severity of the acute complication leading to ICU admission, but not by the underlying malignancy. Long-term prognosis of cancer patients surviving the ICU however is given by the underlying disease and comparable to cancer patients never admitted to the ICU. In particular, survival rates of tumor patients admitted after surgery are equal to those from surgical non-tumor patients. Despite this favorable trend the ICU admission of patients suffering from malignancy is still debatable.To define admission criteria a triage system has been developed taking into account the prognosis of the underlying disease, the overall performance status, patient will and the severity of complications. Those criteria allow us to categorize patients and to grade the intensity of treatment into "full code" treatment, a limited "ICU trial", or palliative care without ICU intervention. In addition to those, additional factors of adverse prognosis as low performance status, number of comorbidities, admission due to cardiorespiratory arrest, organ failure due to malignancy, aspergillosis or admission after allogeneic stem cell transplantation have been identified.This complexity requires an interdisciplinary cooperation between oncologists/haematologists and intensive care specialists and seems to be an essential clue to successfully manage critically ill cancer patients. For the future the improvement of education and training, the development of individualized therapies, and to seize the opportunity to use modern tools of data analytics and machine learning are important goals in this field.

Clinical relevance and utility of cetuximab-related changes in magnesium and calcium serum levels.

Hypomagnesemia and hypocalcemia are common adverse events during cetuximab treatment. The influence of the chemotherapeutic combination on serum levels is unknown and the predictive value is currently under discussion. This analysis investigated 79 patients who had received cetuximab for at least 6 weeks in the day clinic of the Comprehensive Cancer Center, University of Munich. Calcium and magnesium serum levels were analyzed weekly; tumor response and adverse events were followed. Thirty-eight patients had metastatic colorectal cancer (mCRC) and the predictive value of hypomagnesemia was tested in these patients. During therapy, calcium serum levels decreased to about 97% of the baseline levels and were maintained for the duration of treatment. Magnesium levels showed a significant time-dependent decrease. Serum levels of magnesium were lower when cetuximab was combined with a platinum derivative. After a treatment duration of 12 weeks, magnesium levels decreased to 70% in platinum-treated patients, whereas they decreased to only 90% of baseline in patients who did not receive platinum therapy. In patients treated for mCRC, a decrease of serum magnesium below 95% of the baseline levels 14 days after initiating treatment separated patients significantly in terms of survival times. Magnesium levels decrease in a time-dependent manner during cetuximab therapy. As hypomagnesemia was more prominent in patients receiving platinum agents, magnesium measurements may be advised in these patients. In mCRC patients treated with cetuximab, day-14 magnesium serum levels correlated with treatment efficacy.

Prolonged overall survival after pulmonary metastasectomy in patients with breast cancer.

BACKGROUND: We investigated whether overall survival (OS) in patients with primary breast cancer (BC) is prolonged by pulmonary metastasectomy and which prognostic criteria may facilitate the decision in favor of thoracic surgical intervention. METHODS: We assessed the median OS of 81 women after resection of pulmonary primary BC metastases by means of Kaplan-Meier estimators. Statistical interferences regarding prognostic factors were based on univariate log-rank tests and multivariate Cox proportional hazards regression. Matched patients who had not undergone resection from the Munich Tumor Registry served as controls. RESULTS: Between 1982 and 2007, 81 patients were recruited prospectively. In 81.5% of the patients R0 resection was achieved, which was associated with significantly longer median OS than occurred after R1 or R2 resection (103.4 months versus 23.6 months versus 20.2 months, respectively; p<0.001). Multivariate analysis revealed R0 resection, number (n≥2), size (≥3 cm), and estrogen receptor (ER) and/or progesterone receptor (PR) positivity of metastases as independent prognostic factors for long-term survival. Presence of metastases in mediastinal and hilar lymph nodes correlated with decreased survival only in the univariate analysis (32.1 versus 103.4 months; p=0.095). Matched pair analysis confirmed that pulmonary metastasectomy significantly improved survival. CONCLUSIONS: OS in patients with isolated pulmonary primary BC metastasis is prolonged by metastasectomy. Patients with multiple pulmonary lesions or metastases with negative hormone receptor (HR) status are at greater risk of disease relapse and should be followed closely. Moreover, additive treatment tailored to the biological subtype defined by HR expression should be considered for this group.

Analysis of orthopedic surgery of bone metastases in breast cancer patients.

BACKGROUND: Breast cancer is the most common malignancy and the second leading cause of death in women. Because bone metastases are a common finding in patients with breast cancer, they are of major clinical concern. METHODS: In 115 consecutive patients with bone metastases secondary to breast cancer, 132 surgical procedures were performed. Medical records and imaging procedures were reviewed for age, treatment of the primary tumor, clinical symptoms, surgical treatment, complications, and survival. RESULTS: The overall survival of patients with metastatic breast cancer was dependent on the site and the amount of the metastases. Age was not a prognostic factor for survival. If the result of the orthopaedic surgery was a wide resection (R0) survival was significantly better than in the R1 (marginal resection - tumor resection in sane tissue) or R2 (intralesional resection) situation. Concerning the orthopaedic procedures there was no survival difference. CONCLUSION: In conclusion a wide (R0) resection and the absence of pathological fracture and visceral metastases were predictive for longer survival in univariate analysis. Age and the type of orthopaedic surgery had no impact on survival in multivariate analysis. The resection margins lost significance. The standard of care for patients with metastatic breast cancer to the bone requires a multidisciplinary approach.