Immune-related and adverse drug reactions to low versus high initial doses of Viscum album L. in cancer patients

Background Immune-related adverse drug reactions (ADRs) to immunotherapy agents have been associated with beneficial clinical outcomes in oncology. Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional cancer treatment in Europe. VA has been associated with improved quality of life and a reduction in chemotherapy-related ADRs. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Current guidelines recommend commencing with a low dose and increasing slowly overtime, however, off-label prescribing of high initial doses is common. Purpose We investigated ADR profiles related to subcutaneous VA therapy commencing with low, recommended doses versus higher than recommended doses. Study Design Retrospective cohort study. Methods Medical records of 1361 cancer patients treated between 2003 and 2013 were assessed. Patients were divided into two groups based on whether the dose of their first VA injection adhered to current guidelines. Patient characteristics and suspected VA-related ADRs were compared between dose groups. Results Of 1361 cancer patients, 516 (38%) started with a recommended, low dose of VA(≤0.02 mg) and 845 (62%) started with a higher dose(>0.02 mg). Groups did not differ by age or gender, but significant differences were observed for type (p < 0.001) and stage of cancer (p = 0.05). Starting with a high dose of VA was significantly associated with a higher incidence of VA-related ADRs compared to starting with a low dose (20.7% versus 0.8%, p < 0.001). Adjusting for age, gender, tumour type and stage of disease, produced an odds ratio of 37.5 (95% CI = 15.7–122.8,

High levels of cell-free DNA accurately predict late acute kidney injury in patients after cardiac surgery

Use of cardiopulmonary bypass in cardiac surgery triggers systemic inflammation by neutrophil activation leading to neutrophil extracellular traps (NETs) release. Hence, nuclear DNA released by necrotic and apoptotic cells might contribute to an increase in circulating cell-free DNA (cfDNA). cfDNA/NETs might induce endothelial damage and organ dysfunction. This study focuses on the accuracy of cfDNA to predict acute kidney injury (AKI) after on-pump surgery. 58 cardiac patients undergoing on-pump surgery were prospectively enrolled. Blood samples were taken preoperatively, immediately after surgery, at day 1, 2, 3 and 5 from patients with (n = 21) or without (n = 37) postoperative AKI development. Levels of cfDNA, neutrophil gelatinase-associated lipocalin (NGAL) and creatinine in patients' plasma were quantified. ROC curves were used to assess the predictive value of the biomarkers for AKI. Further baseline characteristics and perioperative variables were analyzed. cfDNA and NGAL levels highly increased in AKI patients and significant intergroup differences (vs. non-AKI) were found until day 3 and day 5 after surgery, respectively. cfDNA levels were significantly elevated in patients who developed late AKI (>24 hours), but not in those with AKI development during the first 24 hours (early AKI). NGAL and creatinine, which were highest in patients with early AKI, accurately predicted during the first 24 postoperative hours (early AKI). At day 3, at a threshold of 260.53 ng/ml cfDNA was the best predictor for AKI (AUC = 0.804) compared to NGAL (AUC = 0.699) and creatinine (AUC = 0.688). NGAL, but not cfDNA, was strongly associated with AKI stages and mortality. Monitoring of cfDNA levels from the first postoperative day might represent a valuable tool to predict late AKI after on-pump surgery

Immune-related and adverse drug reactions to low versus high initial doses of Viscum album L. in cancer patients

Background: Immune-related adverse drug reactions (ADRs) to immunotherapy agents have been associated with beneficial clinical outcomes in oncology. Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional cancer treatment in Europe. VA has been associated with improved quality of life and a reduction in chemotherapy-related ADRs. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Current guidelines recommend commencing with a low dose and increasing slowly overtime, however, off-label prescribing of high initial doses is common. Purpose: We investigated ADR profiles related to subcutaneous VA therapy commencing with low, recommended doses versus higher than recommended doses. Study Design: Retrospective cohort study. Methods: Medical records of 1361 cancer patients treated between 2003 and 2013 were assessed. Patients were divided into two groups based on whether the dose of their first VA injection adhered to current guidelines. Patient characteristics and suspected VA-related ADRs were compared between dose groups. Results: Of 1361 cancer patients, 516 (38%) started with a recommended, low dose of VA(≤0.02 mg) and 845 (62%) started with a higher dose(>0.02 mg). Groups did not differ by age or gender, but significant differences were observed for type (p < 0.001) and stage of cancer (p = 0.05). Starting with a high dose of VA was significantly associated with a higher incidence of VA-related ADRs compared to starting with a low dose (20.7% versus 0.8%, p < 0.001). Adjusting for age, gender, tumour type and stage of disease, produced an odds ratio of 37.5 (95% CI = 15.7–122.8, p < .001). Almost all ADRs, irrespective of the initial VA dose, were of mild or moderate intensity. Most ADRs were immune-related, general disorders and administration site conditions, many of which are desired reactions, such as pyrexia and local reactions. Overall, no serious ADRs occurred. Conclusions: Starting VA therapy with a higher than recommended dose was associated with a high frequency of ADRs, however, nearly all ADRs were expected, of mild to moderate intensity and most were desired reactions. Future research is necessary to investigate whether higher incidences of immune-related events are indicators of beneficial immunomodulation and better clinical outcomes

Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis

Background Stage IV non-small cell lung cancer (NSCLC) is associated with a five-year survival rate of around 1%. Treatment with Viscum album L. (VA) extracts has been shown to reduce chemotherapy (CTx)-related adverse events, decrease CTx dose reductions and improve quality of life in a number of cancers. Recent data suggest a beneficial effect of add-on treatment with Viscum album L. (VA, European mistletoe) on survival in cancer patients. The objective of this study was to evaluate the effect of VA in addition to chemotherapy on survival in stage IV NSCLC patients. Methods The observational study was conducted using data from the Network Oncology clinical registry which is an accredited conjoint clinical registry of German oncological hospitals, practitioners and out-patient centers.Patients were included if they had stage IV NSCLC at diagnosis, lived at least for four weeks post-diagnosis and received chemotherapeutic treatment. Patients with EGFR mutations as well as patients receiving tyrosine kinase inhibitors or immune checkpoint inhibitors were not included. Overall survival and impact on hazard in patients with chemotherapy (CTx) to patients receiving CTx plus VA were compared. To identify factors associated with survival and to address potential sources of bias a multivariate analyses using Cox proportional hazard model was performed. Results The median age of the population was 64.1 years with 55.7% male patients. The highest proportion of patients had adenocarcinoma (72.2%) and most of the patients were current or past smokers (70.9%). Of 158 stage IV NSCLC patients, 108 received CTx only and 50 additional VA. Median survival was 17.0 months in the CTx plus VA group (95%CI: 11.0–40.0) and was 8.0 months (95%CI: 7.0–11.0) in the CTx only group (χ = 7.2, p = .007). Overall survival was significantly prolonged in the VA group (HR 0.44, 95%CI: 0.26–0.74, p = .002). One-year and three-year overall survival rates were greater with CTx plus VA compared to CTX alone (1y: 60.2% vs. 35.5%; 3y: 25.7% vs. 14.2%). Conclusion Our findings suggest that concomitant VA is positively associated with survival in stage IV NSCLC patients treated with standard CTx. These findings complement pre-existing knowl-dedge of add-on VA’s clinical impact, however, results should be interpreted with caution in light of the study’s observational character

Implementation of an Integrative Oncological Concept in the Daily Care of a German Certified Breast Cancer Center

Background: In recent decades the concept of integrative medicine has attracted growing interest in patients and professionals. At the Gemeinschaftskrankenhaus Havelhöhe (GKH), a hospital specialized in anthroposophical medicine, a breast cancer center (BCC) has been successfully certified for more than 5 years. The objective of the present study was to analyze how integrative strategies were implemented in the daily care of primary breast cancer patients. Methods: Clinical, demographic, and follow-up data as well as information on non-pharmacological interventions were analyzed. In addition, BCC quality measures were compared with data of the National Breast Cancer Benchmarking Report 2016. Results: Between 2011 and 2016, 741 primary breast cancer patients (median age 57.4 years) were treated at the GKH BCC. 91.5% of the patients showed Union for International Cancer Control (UICC) stage 0, I, II, or III and 8.2% were in UICC stage IV. 97% of the patients underwent surgery, 53% radiation, 38% had hormone therapy, and 25% received cytostatic drugs. 96% of the patients received non-pharmacological interventions and 32% received Viscum album L. therapy. Follow-up was performed in up to 93% of the patients 2 years after first diagnosis. Compared to nationwide benchmarking BCCs, the GKH BCC met the requirements in central items. Conclusions: The results of the present study show that integrative therapies offered by the concept of anthroposophical medicine can be implemented in the daily care and treatment of a certified BCC. However, as national guidelines on integrative concepts in oncology are missing, further studies are needed for a systematic evaluation of integrative treatment and care concepts in this field

Impact of Different Aortic Entry Tear Sites on Early Outcomes and Long-Term Survival in Patients with Stanford A Acute Aortic Dissection

Background Stanford A acute aortic dissection (AAD) is a life-threatening emergency. The aim of this study was to compare the impact of three different aortic entry tear sites on early outcomes and long-term survival of patients with Stanford A AAD. Methods From January 2006 to April 2015, a total of 240 consecutive patients with diagnosed Stanford A AAD underwent emergent, isolated surgical aortic repair in our center. Patients were divided into three groups comprising isolated ascending aorta, proximal aortic arch, and distal aortic arch entry tear site and were followed up for up to 9 years. Results Thirty-day mortality as well as major cerebrovascular events were significantly different between the three groups ( p =0.007 and p =0.048, respectively). Overall cumulative short- and long-term survival of all patients revealed significant differences (Log-Rank p =0.002), whereas survival of all patients free from major cerebrovascular events was similar (Log-Rank p =0.780). Subgroup analysis of short- and long-term survival of patients showed significant differences in terms of men (Log-Rank p =0.043), women (Log-Rank p =0.004), patients over 65 years of age (Log-Rank p =0.007), and hypertensive patients (Log-Rank p =0.003). Kaplan-Meier survival estimation plots significantly showed poorest survival for distal aortic arch entry tear site group. Conclusion The location of the primary entry tear in patients with Stanford A AAD significantly influences early outcomes, short- and long-term survival of patients, whereas survival of patients free from major cerebrovascular events showed similar results among the three groups. Distal aortic entry tear site showed poorest outcomes and survival

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Severity of Presentation, Not Sex, Increases Risk of Surgery for Infective Endocarditis

Background. Cardiac surgery for infective endocarditis (IE) is associated with substantial short- and long-term mortality, and female sex seems to be associated with even worse outcomes. The aim of our study was to analyze the impact of sex on 30-day and long-term mortality and to identify sex-related risk factors in IE patients requiring cardiac surgery. Methods. Relevant clinical data of all consecutive 305 patients undergoing cardiac surgery for IE between 2009 and 2016 were extracted from our institutional database and retrospectively analyzed. Infective endocarditis was defined according to the recent modified Duke criteria and surgery indicated in compliance with current European Society of Cardiology guidelines. Sex-related postoperative outcomes including 30-day and 1-year mortality were recorded. Univariate and multivariable analysis was performed to identify potential sex-dependent risk factors. Results. In all, 229 male patients (75.1%) and 76 female patients (24.9%) underwent surgery for IE. Female patients showed significantly more mitral valve infection (52.6% versus 33.6%, p = 0.003), and Staphylococcus aureus as causative microorganisms was diagnosed in 44.7% of female patients compared with 24.5% of male patients (p = 0.001). Female sex was associated with a higher 30-day mortality (18.4% versus 8.3%, p = 0.014) and 1-year mortality (46.1% versus 27.1%, p = 0.002). Multivariable analysis revealed not female sex, but European System for Cardiac Operative Risk Evaluation II score, reexploration for bleeding, and postoperative acute kidney injury as independent risk factors for 30-day mortality and preoperative dialysis for 1-year mortality, respectively. Conclusions. In this study, female sex was associated with more severe manifestations of IE and significantly higher 30-day and 1-year mortality. After multivariable analysis, not female sex, but the underlying comorbidities seem to determine clinical outcomes. (C) 2019 by The Society of Thoracic Surgeon