Interim analysis of the COSA (COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter) registry.

BACKGROUND: The Seraph® 100 Microbind® Affinity Blood Filter is a haemoperfusion device that is licensed for the reduction of pathogens, including several viruses, in the blood. It received Emergency Use Authorization for the treatment of severe coronavirus disease 2019 (COVID-19) by the Food and Drug Administration (FDA). Several studies have shown that the blood viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlates with adverse outcomes and removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph® 100 has been recently demonstrated. The aim of this registry was to evaluate the safety and efficacy of Seraph® 100 treatment for COVID-19 patients. METHODS: Twelve hospitals from six countries representing two continents documented patient and treatment characteristics as well as outcome parameters without reimbursement. Additionally, mortality and safety results of the device were reported. A total of 102 treatment sessions in 82 patients were documented in the registry. Four patients were excluded from mortality analysis due to incomplete outcome data, which were available in the other 78 patients. RESULTS: Overall, a 30-day mortality rate of 46.2% in the 78 patients with complete follow-up was reported. The median treatment time was 5.00 h (4.00-13.42) and 43.1% of the treatments were performed as haemoperfusion only. Adverse events of the Seraph® 100 treatment were reported in 8.8% of the 102 treatments and represented the premature end of treatment due to circuit failure. Patients who died were treated later in their intensive care unit (ICU) stay and onset of COVID symptoms. They also had higher ferritin levels. Multivariate Cox regression revealed that delayed Seraph® 100 treatment after ICU admission (>60 h), as well as bacterial superinfection, were associated with mortality. While average predicted mortality rate according to Sequential Organ Failure Assessment (SOFA) score in ICU patients was 56.7%, the observed mortality was 50.7%. In non-ICU patients, Coronavirus Clinical Characterisation Consortium (4C) score average predicted a mortality rate of 38.0%, while the observed mortality rate was 11.1%. CONCLUSIONS: The treatment of COVID-19 patients with Seraph® 100 is well tolerated and the circuit failure rate was lower than previously reported for kidney replacement therapy (KRT) in COVID-19 patients. Mortality correlated with late initiation of Seraph treatment after ICU admission and bacterial superinfection. Compared with predicted mortality according to 4C and SOFA scores, mortality of Seraph® 100-treated patients reported in the registry was lower.

German S3 Guideline: Oxygen Therapy in the Acute Care of Adult Patients.

BACKGROUND: Oxygen (O2) is a drug with specific biochemical and physiological properties, a range of effective doses and may have side effects. In 2015, 14% of over 55,000 hospital patients in the UK were using oxygen. 42% of patients received this supplemental oxygen without a valid prescription. Health care professionals are frequently uncertain about the relevance of hypoxemia and have low awareness about the risks of hyperoxemia. Numerous randomized controlled trials about targets of oxygen therapy have been published in recent years. A national guideline is urgently needed. METHODS: A national S3 guideline was developed and published within the Program for National Disease Management Guidelines (AWMF) with participation of 10 medical associations. A literature search was performed until February 1, 2021, to answer 10 key questions. The Oxford Centre for Evidence-Based Medicine (CEBM) System ("The Oxford 2011 Levels of Evidence") was used to classify types of studies in terms of validity. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the quality of evidence and for grading guideline recommendation, and a formal consensus-building process was performed. RESULTS: The guideline includes 34 evidence-based recommendations about indications, prescription, monitoring and discontinuation of oxygen therapy in acute care. The main indication for O2 therapy is hypoxemia. In acute care both hypoxemia and hyperoxemia should be avoided. Hyperoxemia also seems to be associated with increased mortality, especially in patients with hypercapnia. The guideline provides recommended target oxygen saturation for acute medicine without differentiating between diagnoses. Target ranges for oxygen saturation are based depending on ventilation status risk for hypercapnia. The guideline provides an overview of available oxygen delivery systems and includes recommendations for their selection based on patient safety and comfort. CONCLUSION: This is the first national guideline on the use of oxygen in acute care. It addresses health care professionals using oxygen in acute out-of-hospital and in-hospital settings.

[A cross-sectional study in three German hospitals regarding oxygen therapy characteristics]. / Eine Querschnittsuntersuchung zur Qualität der Sauerstofftherapie in drei deutschen Krankenhäusern.

BACKGROUND: Oxygen (O2) therapy is one of the most commonly applied medications in German hospitals and rescue services. Both hypoxemia and hyperoxemia can be associated with complications. There is currently a lack of reliable data on the use, documentation and surveillance of O2-therapy in German hospitals. METHODS: We conducted a cross-sectional study on the use of O2 in three hospitals in Hannover, Germany. RESULTS: Of 343 patients included in this study, 20 % received O2 therapy. Twenty-nine percent of patients receiving O2 were at increased risk for hypercapnia. A standard operating procedure (SOP) for O2 therapy was available in only 68 % of patients. In 22 % patients the applied O2-therapy was appropriate in the context of the documented vital parameters. A complete documentation of vital parameters was conducted in only 30 % of all patients and 41 % of patients receiving O2-therapy. A surveillance of O2-therapy using capillary or arterial blood gas analysis was performed in 76 % of patients. Here, 64 % of patients showed normoxemia, 17 % showed hyperoxemia and 19 % of patients showed hypoxemia. The only identifiable predictor for an adequate O2-therapy was a previous invasive ventilation. DISCUSSION: Our data point towards and inadequate prescription, application and documentation of O2 therapy. The recently released German S3-guideline should be used to increase awareness among physicians and nursing staff regarding the use of O2-therapy to improve O2 therapy and consequently patient safety.

[German S3 Guideline - Oxygen Therapy in the Acute Care of Adult Patients]. / S3-Leitlinie Sauerstoff in der Akuttherapie beim Erwachsenen.

BACKGROUND: Oxygen (O2) is a drug with specific biochemical and physiologic properties, a range of effective doses and may have side effects. In 2015, 14 % of over 55 000 hospital patients in the UK were using oxygen. 42 % of patients received this supplemental oxygen without a valid prescription. Healthcare professionals are frequently uncertain about the relevance of hypoxemia and have low awareness about the risks of hyperoxemia. Numerous randomized controlled trials about targets of oxygen therapy have been published in recent years. A national guideline is urgently needed. METHODS: A S3-guideline was developed and published within the Program for National Disease Management Guidelines (AWMF) with participation of 10 medical associations. Literature search was performed until Feb 1st 2021 to answer 10 key questions. The Oxford Centre for Evidence-Based Medicine (CEBM) System ("The Oxford 2011 Levels of Evidence") was used to classify types of studies in terms of validity. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used and for assessing the quality of evidence and for grading guideline recommendation and a formal consensus-building process was performed. RESULTS: The guideline includes 34 evidence-based recommendations about indications, prescription, monitoring and discontinuation of oxygen therapy in acute care. The main indication for O2 therapy is hypoxemia. In acute care both hypoxemia and hyperoxemia should be avoided. Hyperoxemia also seems to be associated with increased mortality, especially in patients with hypercapnia. The guideline provides recommended target oxygen saturation for acute medicine without differentiating between diagnoses. Target ranges for oxygen saturation are depending on ventilation status risk for hypercapnia. The guideline provides an overview of available oxygen delivery systems and includes recommendations for their selection based on patient safety and comfort. CONCLUSION: This is the first national guideline on the use of oxygen in acute care. It addresses healthcare professionals using oxygen in acute out-of-hospital and in-hospital settings. The guideline will be valid for 3 years until June 30, 2024.

[A cross-sectional study in three German hospitals regarding oxygen therapy characteristics]. / Eine Querschnittsuntersuchung zur Qualität der Sauerstofftherapie in drei deutschen Krankenhäusern.

BACKGROUND: Oxygen (O2) therapy is one of the most commonly applied medications in German hospitals and rescue services. Both hypoxemia and hyperoxemia can be associated with complications. There is currently a lack of reliable data on the use, documentation and surveillance of O2-therapy in German hospitals. METHODS: We conducted a cross-sectional study on the use of O2 in three hospitals in Hannover, Germany. RESULTS: Of 343 patients included in this study, 20 % received O2 therapy. Twenty-nine percent of patients receiving O2 were at increased risk for hypercapnia. A standard operating procedure (SOP) for O2 therapy was available in only 68 % of patients. In 22 % patients the applied O2-therapy was appropriate in the context of the documented vital parameters. A complete documentation of vital parameters was conducted in only 30 % of all patients and 41 % of patients receiving O2-therapy. A surveillance of O2-therapy using capillary or arterial blood gas analysis was performed in 76 % of patients. Here, 64 % of patients showed normoxemia, 17 % showed hyperoxemia and 19 % of patients showed hypoxemia. The only identifiable predictor for an adequate O2-therapy was a previous invasive ventilation. DISCUSSION: Our data point towards and inadequate prescription, application and documentation of O2 therapy. The recently released German S3-guideline should be used to increase awareness among physicians and nursing staff regarding the use of O2-therapy to improve O2 therapy and consequently patient safety.

[Oxygen in the acute care of adults : Short version of the German S3 guideline]. / Sauerstoff in der Akuttherapie beim Erwachsenen : Kurzversion der S3-Leitlinie.

BACKGROUND: Oxygen is a drug with specific properties, a defined dose-effect range and side effects. In 2015, in a sample of UK hospital patients, 14% were treated with oxygen, of which only 42% had a prescription. Health care workers are often uncertain about the relevance of hypoxemia, and there is limited awareness of the risks of hyperoxemia. Numerous randomized controlled trials on oxygen therapy have recently been published. METHODS: As part of the guideline program of the Working Group of Scientific Medical Societies e. V. (AWMF), this S3 guideline was developed with the participation of 10 medical societies on the basis of a literature search up to 02/01/2021. The system of the Oxford Centre for Evidence-Based Medicine (CEBM) (The Oxford 2011 Levels of Evidence) was used to evaluate the literature. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE), and a formal consensus process of recommendations was performed. RESULTS: The guideline contains 34 evidence-based recommendations on the indication, prescription, monitoring, and discontinuation of oxygen therapy in acute care. The indication for oxygen is mainly hypoxemia. Hypoxemia and hyperoxemia should be avoided, since both increase mortality. The guideline recommends target ranges of oxygen saturation for acute oxygen therapy without differentiating between different diagnoses. Target areas depend on the risk for hypercapnia and ventilation status. The guideline provides an overview of available oxygen delivery systems and contains recommendations for their selection based on patient safety and comfort. CONCLUSION: This is the first German guideline on the use of oxygen in acute care. It is aimed at medical professionals who use oxygen in and outside hospitals and is valid until June 30th, 2024.

Treatment of a Critically Ill COVID-19 Patient with the Seraph 100 Microbind Affinity Filter.

The coronavirus disease 2019 (COVID-19) pandemic has a serious impact on health and economics worldwide. Even though the majority of patients present with moderate and mild symptoms, yet a considerable portion of patients need to be treated in the intensive care unit. Aside from dexamethasone, there is no established pharmacological therapy. Moreover, some of the currently tested drugs are contraindicated for special patient populations like remdesivir for patients with severely impaired renal function. On this background, several extracorporeal treatments are currently explored concerning their potential to improve the clinical course and outcome of critically ill patients with COVID-19. Here, we report the use of the Seraph 100 Microbind Affinity filter, which is licensed in the European Union for the removal of pathogens. Authorization for emergency use in patients with COVID-19 admitted to the intensive care unit with confirmed or imminent respiratory failure was granted by the U.S. Food and Drug Administration on April 17, 2020. A 53-year-old Caucasian male with a severe COVID-19 infection was treated with a Seraph Microbind Affinity filter hemoperfusion after clinical deterioration and commencement of mechanical ventilation. The 70-minute treatment at a blood flow of 200 mL/minute was well tolerated, and the patient was hemodynamically stable. The hemoperfusion reduced D-dimers dramatically. This case report suggests that the use of Seraph 100 Microbind Affinity filter hemoperfusion might have positive effects on the clinical course of critically ill patients with COVID-19. However, future prospective collection of data ideally in randomized trials will have to confirm whether the use of Seraph 100 Microbind Affinity filter hemoperfusion is an option of the treatment for COVID-19.

Sarcoid-Like Lesions Mimicking Pulmonary Metastasis: A Case Series and Review of the Literature.

BACKGROUND: The association of sarcoid-like lesions and malignancy is well described. Nonetheless, pulmonary lesions in malignant disease are typically presumed metastatic, and do not routinely receive histological validation. Here, we report on pulmonary sarcoid-like lesions identified in patients with a primary malignancy where pulmonary metastatic disease was suspected. METHODS: Patients who underwent thoracic surgical procedures for confirmation or treatment of suspected pulmonary metastasis were retrospectively analysed. RESULTS: In 8/186 patients (4.3%), histology revealed sarcoid-like lesions. In these cases, there were no clinical symptoms suggestive of sarcoidosis. All underlying primary malignancies in the sarcoid-like patients were treated with curative intent. The median age of patients with sarcoid-like lesions was 46.3 years (range 26-61). The median interval between primary diagnosis of malignancy and diagnosis of pulmonary lesions was 188 days (range 0-794), with thoracic surgical intervention performed at a median of 250 days (range 183-675). FDG-avidity was demonstrated in the sarcoid-like lesions in 2 out of 3 patients who underwent PET-CT. CONCLUSION: Sarcoid-like lesions may be challenging to identify and can mimic pulmonary metastases. Therefore, considering sarcoidosis as a differential diagnosis whenever first pulmonary metastasis is suspected is warranted. Carefully considered, histological validation of initial suspected pulmonary metastasis may avoid subsequent over- or undertreatment.

Lung transplantation for severe pulmonary hypertension--awake extracorporeal membrane oxygenation for postoperative left ventricular remodelling.

BACKGROUND: Bilateral lung transplantation (BLTx) is an established treatment for end-stage pulmonary hypertension (PH). Ventilator weaning failure and death are more common as in BLTx for other indications. We hypothesized that left ventricular (LV) dysfunction is the main cause of early postoperative morbidity or mortality and investigated a weaning strategy using awake venoarterial extracorporeal membrane oxygenation (ECMO). METHODS: In 23 BLTx for severe PH, ECMO used during BLTx was continued for a minimum of 5 days (BLTx-ECMO group). Echocardiography, left atrial (LA) and Swan-Ganz catheters were used for monitoring. Early extubation after transplantation was attempted under continued ECMO. RESULTS: Preoperatively, all patients had severely reduced cardiac index (mean, 2.1 L/min/m2). On postoperative day 2, reduction of ECMO flow resulted in increasing LA and decreasing systemic blood pressures. On the day of ECMO explantation (median, postoperative day 8), LV diameter had increased; LA and blood pressures remained stable. Survival rates at 3 and 12 months were 100% and 96%, respectively. Data were compared to two historic control groups of BLTx without ECMO (BLTx ventilation) or combined heart-lung transplantation for severe PH. CONCLUSION: Early after BLTx for severe PH, the LV may be unable to handle normalized LV preload. This can be effectively bridged with awake venoarterial ECMO.

Outcome of critically ill lung transplant candidates on invasive respiratory support.

PURPOSE: Lung transplantation (LTx) of patients on mechanical ventilation (MV) or extracorporeal support (ECS) is controversial because of impaired survival. Prognostic factors to predict survival should be identified. METHODS: A retrospective analysis was performed in a single centre of all ventilated LTx-candidates awarded an Eurotransplant (ET) high-urgency (HU) status between November 2004 and July 2009. Clinical data were collected on the first day of HU-status from intubated patients with an approved HU status. Single parameters as well as the lung allocation score (LAS), the Sequential Organ Failure Assessment score (SOFA) and the Simplified Acute Physiology Score (SAPS 2) were calculated. The association of these variables with survival was evaluated. RESULTS: A total of 100 intubated patients (median age 38 years, 56 % female) fulfilled the inclusion criteria, of whom 60 also required ECS. The main indications were cystic fibrosis (25 %) and idiopathic pulmonary fibrosis (24 %). Median time with HU status was 12 days [interquartile range (IQR) 6-21 days]. Sixty patients were transplanted, five were weaned from mechanical ventilation and 38 died while on the wait list. One-year-survival rates were 57, 36 and 5 % for transplanted patients, all candidates and non-transplanted candidates, respectively (p < 0.001). A SAPS score >24 (median 30, IQR 27-35), a procalcitonin level of >0.5 µg/l (median 0.4, IQR 0.1-1.4 µg/l) and any escalation of bridging strategy were independently associated with mortality (p = 0.021, = 0.003, and < 0.001, respectively). The LAS (median 88, IQR 8-90) did not predict survival (p = 0.92). CONCLUSIONS: High-urgency LTx improves survival in critically ill intubated candidates. Higher SAPS scores, escalating therapy and an abnormal procalcitonin level were associated with a poor outcome.

Detection of Epstein-Barr virus DNA in peripheral blood is associated with the development of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: The long-term success of lung transplantation is limited by the development of bronchiolitis obliterans syndrome (BOS). Virus infections may be involved in the development of BOS. OBJECTIVES: The study intended to investigate whether there is an association of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human adenovirus (HAdV) with the development of BOS and to identify risk factors for EBV detection in blood. STUDY DESIGN: A prospective cohort study was conducted in lung and heart-lung transplant recipients (LTR) who are followed in our outpatient clinic. 385 LTR were monitored for CMV pp65 antigen, EBV and HAdV DNA in blood at follow-up visits for 6 months. The development of BOS was recorded for a median of 21 months. RESULTS: EBV DNA, HAdV DNA and CMV pp65 antigen were detected at least once in, respectively, 202/385 LTR (52.5%), 10/382 LTR (2.6%) and 19/385 LTR (4.9%). Repeated EBV DNA detection and acute rejection were associated with the development of BOS. Variables associated with EBV DNA detection in blood were the diagnosis of BOS before study entry, retransplantation and immunosuppressive therapy with sirolimus or everolimus. CONCLUSIONS: EBV reactivation is frequent in LTR. The variables found associated with EBV reactivation probably reflect increased immunosuppression. Repeated EBV DNA detection in blood, possibly reflecting chronic EBV replication, is associated with the development of BOS. The elucidation of whether and how EBV DNAemia triggers the development of BOS could improve long-term survival of LTR.