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Background: Remote monitoring is an established, guideline-recommended technology with unequivocal clinical benefits; however, its ability to improve survival is contradictory.
Objective: The aim of our study was to investigate the effects of remote monitoring on mortality in an optimally treated heart failure patient population undergoing cardiac resynchronization defibrillator therapy (CRT-D) implantation in a large-volume tertiary referral center.
Methods: The population of this single-center, retrospective, observational study included 231 consecutive patients receiving CRT-D devices in the Medical Centre of the Hungarian Defence Forces (Budapest, Hungary) from January 2011 to June 2016. Clinical outcomes were compared between patients on remote monitoring and conventional follow-up.
Results: The mean follow-up time was 28.4 (SD 18.1) months. Patients on remote monitoring were more likely to have atrial fibrillation, received heart failure management at our dedicated heart failure outpatient clinic more often, and have a slightly lower functional capacity. Crude all-cause mortality of remote-monitored patients was significantly lower compared with patients followed conventionally (hazard ratio [HR] 0.368, 95% CI 0.186-0.727, P=.004). The survival benefit remained statistically significant after adjustment for important baseline parameters (adjusted HR 0.361, 95% CI 0.181-0.722, P=.004).
Conclusions: In this single-center, retrospective study of optimally treated heart failure patients undergoing CRT-D implantation, the use of remote monitoring systems was associated with a significantly better survival rate.
CD4+ T cell lymphopenia predicts mortality from Pneumocystis pneumonia in kidney transplant patients
(2020)
Background: Pneumocystis jirovecii pneumonia (PcP) remains a life-threatening opportunistic infection after solid organ transplantation, even in the era of Pneumocystis prophylaxis. The association between risk of developing PcP and low CD4+ T cell counts has been well established. However, it is unknown whether lymphopenia in the context of post-renal transplant PcP increases the risk of mortality. Methods: We carried out a retrospective analysis of a cohort of kidney transplant patients with PcP (n = 49) to determine the risk factors for mortality associated with PcP. We correlated clinical and demographic data with the outcome of the disease. For CD4+ T cell counts, we used the Wilcoxon rank sum test for in-hospital mortality and a Cox proportional-hazards regression model for 60-day mortality. Results: In univariate analyses, high CRP, high neutrophils, CD4+ T cell lymphopenia, mechanical ventilation, and high acute kidney injury network stage were associated with in-hospital mortality following presentation with PcP. In a receiver-operator characteristic (ROC) analysis, an optimum cutoff of ≤200 CD4+ T cells/µL predicted in-hospital mortality, CD4+ T cell lymphopenia remained a risk factor in a Cox regression model. Conclusions: Low CD4+ T cell count in kidney transplant recipients is a biomarker for disease severity and a risk factor for in-hospital mortality following presentation with PcP.
Purpose: Dexamethasone (Dex) is the most common corticosteroid to treat edema in glioblastoma (GBM) patients. Recent studies identified the addition of Dex to radiation therapy (RT) to be associated with poor survival. Independently, Tumor Treating Fields (TTFields) provides a novel anti-cancer modality for patients with primary and recurrent GBM. Whether Dex influences the efficacy of TTFields, however, remains elusive. Methods: Human GBM cell lines MZ54 and U251 were treated with RT or TTFields in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We further performed a retrospective analysis of GBM patients with TTFields treatment +/- concomitant Dex and analysed its impact on progression-free (PFS) and overall survival (OS). Results: The addition of Dex significantly reduced the efficacy of RT in U251, but not in MZ54 cells. TTFields (200 kHz/250 kHz) induced massive cell death in both cell lines. Concomitant treatment of TTFields and Dex did not reduce the overall efficacy of TTFields. Further, in our retrospective clinical analysis, we found that the addition of Dex to TTFields therapy did not influence PFS nor OS. Conclusion: Our translational investigation indicates that the efficacy of TTFields therapy in patients with GBM and GBM cell lines is not affected by the addition of Dex.
Background: To evaluate the impact of time to castration resistance (TTCR) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies for mHSPC.
Material and Methods: Of 213 mHSPC patients diagnosed between 01/2013-12/2020 who subsequently developed metastatic castration resistant prostate cancer (mCRPC), 204 eligible patients were analyzed after having applied exclusion criteria. mHSPC patients were classified into TTCR <12, 12-18, 18-24, and >24 months and analyzed regarding OS. Moreover, further OS analyses were performed after having developed mCRPC status according to TTCR. Logistic regression models predicted the value of TTCR on OS.
Results: Median follow-up was 34 months. Among 204 mHSPC patients, 41.2% harbored TTCR <12 months, 18.1% for 12-18 months, 15.2% for 18-24 months, and 25.5% for >24 months. Median age was 67 years and median PSA at prostate cancer diagnosis was 61 ng/ml. No differences in patient characteristics were observed (all p>0.05). According to OS, TTCR <12 months patients had the worst OS, followed by TTCR 12-18 months, 18-24 months, and >24 months, in that order (p<0.001). After multivariable adjustment, a 4.07-, 3.31-, and 6.40-fold higher mortality was observed for TTCR 18-24 months, 12-18 months, and <12 months patients, relative to TTCR >24 months (all p<0.05). Conversely, OS after development of mCRPC was not influenced by TTCR stratification (all p>0.05).
Conclusion: Patients with TTCR <12 months are at the highest OS disadvantage in mHSPC. This OS disadvantage persisted even after multivariable adjustment. Interestingly, TTCR stratified analyses did not influence OS in mCRPC patients.
Introduction: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void. Materials and Methods: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004–2016). Patients were divided between historical (2004–2013) versus contemporary (2014–2016). Chemotherapy rates were plotted over time. Kaplan–Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses. Results: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001). Conclusions: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.
Background: To examine overall survival rates within a large cohort of German prostate cancer (PCa) patients and to compare these with life-expectancy (LE) predictions derived from German life tables. We hypothesized that the advantage of good general health in radical prostatectomy (RP) patients combined with favorable cancer outcomes might lead to even higher overall survival rates over 10 years compared to the LE of a general population.
Methods: A total of 6483 patients were treated with RP between 1992 and 2007 at the Martini-Klinik Prostate Cancer Center. Preoperative risk classification was performed according to D'Amico. Postoperative risk classification was performed according to the Cancer of the Prostate Risk Assessment score (CAPRA-S). A simulated cohort was created that resembled the exact age distribution of the RP population using Monte Carlo simulation which was based on data derived from official male German life tables (1992–2017). Markov chain was used to represent natural age progression of the simulated cohort. Kaplan–Meier plots were created to display the differences between 10-year observed overall survival (OS) and the simulated, predicted LE.
Results: For D'Amico low risk and intermediate risk, 10-year OS was 12.0% and 9.2% above predicted LE in the simulated cohort, respectively. For D'Amico high risk, OS was virtually the same as predicted LE (0.8% difference in favor of RP treated patients). For CAPRA-S low and intermediate risk, OS was 11.8% and 9.7% above predicted LE. For CAPRA-S high risk, OS was virtually the same as predicted LE (0.3% difference in favor of the simulated cohort).
Conclusions: Low- and intermediate risk PCa patients treated with RP can expect a very favorable overall survival, that even exceeds LE predictions. High risk patients' overall survival perfectly aligns with LE predictions.
Simple Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Clinical phenotypes of frequent mutations and their impact on patient outcome are well established. However, the role of rare mutations often remains elusive. We retrospectively analyzed 1529 newly diagnosed and intensively treated AML patients for mutations of BCOR and BCORL1. We report a distinct co-mutational pattern that suggests a role in disease progression rather than initiation, especially affecting mechanisms of DNA-methylation. Further, we found loss-of-function mutations of BCOR to be independent markers of poor outcomes in multivariable analysis. Therefore, loss-of-function mutations of BCOR need to be considered for AML management, as they may influence risk stratification and subsequent treatment allocation.
Abstract: Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
Uterine cervical cancer is one of the leading causes of cancer-related mortality in women worldwide. Each year, over half a million new cases are estimated, resulting in more than 300,000 deaths. While less-invasive, fertility-preserving surgical procedures can be offered to women in early stages, treatment for locally advanced disease may include radical hysterectomy, primary chemoradiotherapy (CRT) or a combination of these modalities. Concurrent platinum-based chemoradiotherapy regimens remain the first-line treatments for locally advanced cervical cancer. Despite achievements such as the introduction of angiogenesis inhibitors, and more recently immunotherapies, the overall survival of women with persistent, recurrent or metastatic disease has not been extended significantly in the last decades. Furthermore, a broad spectrum of molecular markers to predict therapy response and survival and to identify patients with high- and low-risk constellations is missing. Implementation of these markers, however, may help to further improve treatment and to develop new targeted therapies. This review aims to provide comprehensive insights into the complex mechanisms of cervical cancer pathogenesis within the context of molecular markers for predicting treatment response and prognosis.
Background: To test for rates of other cause mortality (OCM) and cancer-specific mortality (CSM) in elderly prostate cancer (PCa) patients treated with the combination of radical prostatectomy (RP) and external beam radiation therapy (EBRT) versus RP alone, since elderly PCa patients may be over-treated. Methods: Within the Surveillance, Epidemiology and End Results database (2004–2016), cumulative incidence plots, after propensity score matching for cT-stage, cN-stage, prostate specific antigen, age and biopsy Gleason score, and multivariable competing risks regression models (socioeconomic status, pathological Gleason score) addressed OCM and CSM in patients (70–79, 70–74, and 75–79 years) treated with RP and EBRT versus RP alone. Results: Of 18,126 eligible patients aged 70–79 years, 2520 (13.9%) underwent RP and EBRT versus 15,606 (86.1%) RP alone. After propensity score matching, 10-year OCM rates were respectively 27.9 versus 20.3% for RP and EBRT versus RP alone (p < .001), which resulted in a multivariable HR of 1.4 (p < .001). Moreover, 10-year CSM rates were respectively 13.4 versus 5.5% for RP and EBRT versus RP alone. In subgroup analyses separately addressing 70–74 year old and 75–79 years old PCa patients, 10-year OCM rates were 22.8 versus 16.2% and 39.5 versus 24.0% for respectively RP and EBRT versus RP alone patients (all p < .001). Conclusion: Elderly patients treated with RP and EBRT exhibited worrisome rates of OCM. These higher than expected OCM rates question the need for combination therapy (RP and EBRT) in elderly PCa patients and indicate the need for better patient selection, when combination therapy is contemplated.