The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Judy Tung ◽  
Musarrat Nahid ◽  
Mangala Rajan ◽  
Lia Logio

Abstract Background Academic medical centers invest considerably in faculty development efforts to support the career success and promotion of their faculty, and to minimize faculty attrition. This study evaluated the impact of a faculty development program called the Leadership in Academic Medicine Program (LAMP) on participants’ (1) self-ratings of efficacy, (2) promotion in academic rank, and (3) institutional retention. Method Participants from the 2013–2020 LAMP cohorts were surveyed pre and post program to assess their level of agreement with statements that spanned domains of self-awareness, self-efficacy, satisfaction with work and work environment. Pre and post responses were compared using McNemar’s tests. Changes in scores across gender were compared using Wilcoxon Rank Sum/Mann-Whitney tests. LAMP participants were matched to nonparticipant controls by gender, rank, department, and time of hire to compare promotions in academic rank and departures from the organization. Kaplan Meier curves and Cox proportional hazards models were used to examine differences. Results There were significant improvements in almost all self-ratings on program surveys (p < 0.05). Greatest improvements were seen in “understand the promotions process” (36% vs. 94%), “comfortable negotiating” (35% vs. 74%), and “time management” (55% vs. 92%). There were no statistically significant differences in improvements by gender, however women faculty rated themselves lower on all pre-program items compared to men. There was significant difference found in time-to-next promotion (p = 0.003) between LAMP participants and controls. Kaplan-Meier analysis demonstrated that LAMP faculty achieved next promotion more often and faster than controls. Cox-proportional-hazards analyses found that LAMP faculty were 61% more likely to be promoted than controls (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.16–2.23, p-value = 0.004). There was significant difference found in time-to-departure (p < 0.0001) with LAMP faculty retained more often and for longer periods. LAMP faculty were 77% less likely to leave compared to controls (HR 0.23, 95% CI 0.16–0.34, p < 0.0001). Conclusions LAMP is an effective faculty development program as measured subjectively by participant self-ratings and objectively through comparative improvements in academic promotions and institutional retention.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Si-wei Pan ◽  
Peng-liang Wang ◽  
Han-wei Huang ◽  
Lei Luo ◽  
Xin Wang ◽  
...  

Background. In gastric cancer, various surveillance strategies are suggested in international guidelines. The current study is intended to evaluate the current strategies and provide more personalized proposals for personalized cancer medicine. Materials and Methods. In the aggregate, 9191 patients with gastric cancer after gastrectomy from 1998 to 2009 were selected from the Surveillance, Epidemiology, and End Results database. Disease-specific survival was analyzed by Kaplan-Meier method and the log-rank test. Cox proportional hazards regression analyses were used to confirm the independent prognostic factors. As well, hazard ratio (HR) curves were used to compare the risk of death over time. Conditional survival (CS) was applied to dynamically assess the prognosis after each follow-up. Results. Comparisons from HR curves on different stages showed that earlier stages had distinctly lower HR than advanced stages. The curve of stage IIA was flat and more likely the same as that of stage I while that of stage IIB is like that of stage III with an obvious peak. After estimating CS at intervals of three months, six months, and 12 months in different periods, stages I and IIA had high levels of CS all along, while there were visible differences among CS levels of stages IIB and III. Conclusions. The frequency of follow-up for early stages, like stages I and IIA, could be every six months or longer in the first three years and annually thereafter. And those with unfavorable conditions, such as stages IIB and III, could be followed up much more frequently and sufficiently than usual.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 584-584
Author(s):  
Weining Wang ◽  
Chin Jin Seo ◽  
Grace Hwei Ching Tan ◽  
Claramae Shulyn Chia ◽  
Khee Chee Soo ◽  
...  

584 Background: Right and left-sided colon cancers are embryonically distinct and present differently. Recently, there has been growing belief that sidedness could be independently associated with survival outcomes. This has important clinical implications regarding the prognostication, management and surveillance of colon cancer patients. Hence, we aim to investigate the impact of sidedness on survival in our patient population in this study. Methods: Patients who had primary treatment naïve colon cancer who underwent curative surgical resection in our institution from September 2002 to December 2010 were included in this study. Demographic and clinicopathological data was collected from electronic records and clinical charts. Tumours arising from the cecum, ascending colon, hepatic flexure and transverse colon were considered right-sided, while those arising from splenic flexure and descending colon were considered left-sided. Cancers of the rectosigmoid junction and rectum were excluded. Kaplan-Meier curves and log-rank test were used to compare overall, locoregional recurrence-free and distant recurrence-free survivals (OS, LRFS, DRFS respectively) between both groups. Multivariate analysis was performed using Cox regression proportional hazards. Results: 389 patients were included in this study. 238 had left-sided tumours while the remaining 151 had right-sided tumours. In our cohort, right-sided tumours were associated with older age and mucinous histology. Kaplan-Meier curves plotted showed improved LRFS in left-sided tumours (p = 0.04, median survival not reached) but no significant difference in OS and DRFS. On multivariate analysis, sidedness was also found to be an independent prognostic factor for LRFS but not OS and DRFS despite factoring in age, size of tumour, pT, pN and histology. Conclusions: Our study suggests that left-sided tumours in primary colon cancer are independently prognostic for improved locoregional survival as compared to the right-sided tumours, even after taking into account other known factors such as age, staging and histology.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S201-S202
Author(s):  
M Kabir ◽  
K Curtius ◽  
P Kalia ◽  
I Al Bakir ◽  
C H R Choi ◽  
...  

Abstract Background Racial disparities in inflammatory bowel disease (IBD) phenotypic presentations and outcomes are recognised. However, there are conflicting data from Western population-based cohort studies as to whether racial differences in colitis-associated colorectal cancer (CRC) incidence exists. To our knowledge this is the first study to investigate the impact of ethnicity on the natural history of dysplasia in ulcerative colitis (UC). Methods We performed a retrospective multi-centre cohort study of adult patients with UC whose first low-grade dysplasia (LGD) diagnosis within the extent of colitis was made between 1 January 2001 and 30 December 2018. Only patients with at least one follow-up colonoscopy or colectomy by 30 August 2019 were included. The study end point was time to CRC or end of follow-up. Statistical differences between groups were evaluated using Mann-Whitney U tests and Chi-squared tests. Survival analyses were performed using Kaplan-Meier estimation and multivariate Cox proportional hazards models. Results 408 patients met the inclusion criteria (see Figure 1 for patient and clinical demographics). More patients from a Black or Asian (BAME) background progressed to CRC [13.4% vs. 6.4%; p=0.036] compared to their White Caucasian counterparts, despite having surveillance follow-up. Figure 2 displays Kaplan-Meier curves demonstrating the probability of remaining CRC-free after LGD diagnosis and categorised by ethnicity. BAME patients were more likely to have moderate-severe inflammatory activity on colonic biopsy within the 5 preceding years [42.0% vs. 28.9%; p=0.023], but no significant differences in medication use and a longer median time interval from LGD diagnosis to colectomy date [32 months vs. 11 months; p=0.021]. After adjusting for sex, age and UC duration at time of LGD diagnosis and presence of moderate-severe histological inflammation, being Black or Asian was a predictive factor for CRC progression on multivariate Cox proportional hazard analysis [HR 2.97 (95% CI 1.22 – 7.20); p = 0.016]. However, ethnicity was no longer predictive of CRC progression on sub-analysis of the 317 patients who did not have a colectomy during the follow-up period. Conclusion In this UK multi-centre cohort of UC surveillance patients diagnosed with LGD, delays in receiving cancer preventative colectomy may contribute to an increased CRC incidence in certain ethnic groups. Further work is required to elucidate whether these delays are related to institutional factors (e.g. inequity in the content of decision-making support given or access to healthcare) or cultural factors.


2021 ◽  
Author(s):  
Pingping Ren ◽  
Qilong Zhang ◽  
Yixuan Pan ◽  
Yi Liu ◽  
Chenglin Li ◽  
...  

Abstract Background: Studies on the correlation between serum uric acid (SUA) and all-cause mortality in peritoneal dialysis (PD) patients were mainly based on the results of baseline SUA. We aimed to analyze the change of SUA level post PD, and the correlation between follow-up SUA and prognosis in PD patients. Methods: All patients who received PD catheterization and maintaining PD in our center from March 2, 2001 to March 8, 2017 were screened. Kaplan-Meier and Cox proportional-hazards regression models were used to analyze the effect of SUA levels on the risks of death. We graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months post PD by mean of SUA plus or minus a standard deviation as cut-off values, and compared all-cause and cardiovascular mortality among patients with different SUA grades. Results: A total of 1402 patients were included, 763 males (54.42%) and 639 females (45.58%). Their average age at PD start was 49.50±14.20 years. The SUA levels were 7.97±1.79mg/dl at baseline, 7.12±1.48mg/dl at 6 months, 7.05±1.33mg/dl at 12 months, 7.01±1.30mg/dl at 18 months, and 6.93±1.26mg/dl at 24 months. During median follow-up time of 31 (18, 49) months, 173 (12.34%) all-cause deaths occurred, including 68 (4.85%) cardiovascular deaths. There were no significant differences on all-cause mortality among groups with graded SUA levels at baseline, 12 months, 18 months and 24 months during follow-up or on cardiovascular mortality among groups with graded SUA levels at baseline, 6 months, 12 months, 18 months and 24 months during follow-up. At 6 months post PD,Kaplan Meier analysis showed there was significant difference on all-cause mortality among graded SUA levels (c2=11.315, P=0.010), and the all-cause mortality was lowest in grade of 5.65mg/dl≤SUA<7.13mg/dl. Conclusion: SUA level decreased during follow up post PD. At 6 months post PD, a grade of 5.65mg/dl≤SUA<7.13mg/dl was appropriate for better patients’ survival.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Fukunaga ◽  
K Hirose ◽  
A Isotani ◽  
T Morinaga ◽  
K Ando

Abstract Background Relationship between atrial fibrillation (AF) and heart failure (HF) is often compared with proverbial question of which came first, the chicken or the egg. Some patients showing AF at the HF admission result in restoration of sinus rhythm (SR) at discharge. It is not well elucidated that the restoration into SR during hospitalization can render the preventive effect for rehospitalization. Purpose To investigate the impact of restoration into SR during hospitalization for readmission rate of the HF patients showing AF. Methods We enrolled consecutive 640 HF patients hospitalized from January 2015 to December 2015. Patients data were retrospectively investigated from medical record. Patients showing atrial fibrillation on admission but unrecognized ever were defined as “incident AF”; patients with AF diagnosed before admission were defined as “prevalent AF”. Primary endpoint was a composite of death from cardiovascular disease or hospitalization for worsening heart failure. Secondary endpoints were death from cardiovascular disease, unplanned hospitalization related to heart failure, and any hospitalization. Results During mean follow up of 19 months, 139 patients (22%) were categorized as incident AF and 145 patients (23%) were categorized as prevalent AF. Among 239 patients showing AF on admission, 44 patients were discharged in SR (39 patients in incident AF and 5 patients in prevalent AF). Among incident AF patients, the primary composite end point occurred in significantly fewer in those who discharged in SR (19% vs. 42% at 1-year; 23% vs. 53% at 2-year follow-up, p=0.005). To compare the risk factors related to readmission due to HF with the cox proportional-hazards model, AF only during hospitalization [Hazard Ratio (HR)=0.37, p<0.01] and prevalent AF (HR=1.67, p=0.04) was significantly associated. There was no significant difference depending on LVEF. Conclusion Newly diagnosed AF with restoration to SR during hospitalization was a good marker to forecast future prognosis.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Fujita ◽  
K Takabayashi ◽  
K Iwatsu ◽  
K Matsumura ◽  
T Ikeda ◽  
...  

Abstract Background Polypharmacy creates an increased patient's burden by drug-drug interactions and poor adherence. However, there are very few studies available evaluating the association of polypharmacy with hospital readmission in patients with heart failure (HF). Purpose The aim of this study was to investigate the impact of polypharmacy on hospital readmission for HF. Methods We enrolled 1253 patients who were hospitalized with acute heart failure (AHF) or acute exacerbation of chronic heart failure in the Kitakawachi Clinical Background and Outcome of Heart Failure Registry (KICKOFF Registry) from April 2015 to July 2018 (age 78.1±11.5 years, male 51.4%). Our Registry is a prospective multicenter community-based cohort study of HF patients in Japan. The inclusion criteria for the registry was a diagnosis of HF during hospitalization according to the Framingham criteria, and there were no exclusion criteria. From data at discharge, we collected data on clinical characteristics, medication schedule, and social backgrounds. We defined polypharmacy as the use of seven or more medications. The primary end point was HF rehospitalization within 1 year after discharge. Cox proportional hazards regression analysis was used to describe the association between polypharmacy and 1-year HF rehospitalization, controlling for potential confounding factors. Results In this study, the prevalence of polypharmacy was 59.7% of all patients. Patients with polypharmacy were more likely to have comorbidities such as hypertension, dyslipidemia, diabetes, chronic kidney disease, coronary artery disease and dementia. They also had lower EF (50.9±0.64 vs 53.6±0.80, p<0.01), compared to patients without polypharmacy. There was no significant difference in age, gender and BMI, compared to patients without polypharmacy. During the follow-up period, a total of 278 patients (24.9%) were readmitted for HF. In Kaplan-Meier analyses, hospital readmission for HF during 1-year follow-up was significantly higher in patients with polypharmacy (p<0.01) (figure). After adjusting for gender, age, EF, and the other co-morbidities, polypharmacy was independently associated with higher risk of rehospitalization for HF (hazard ratio 1.28, 95% confidence interval, 1.07–1.52, p<0.01). Conclusion Polypharmacy is an independent predictor of hospital readmission for HF. Our study suggests the need for developing an effective strategy to choose the appropriate drugs in patients with HF. Acknowledgement/Funding Nakajima Steel Pipe


2013 ◽  
Vol 62 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Cláudia Débora Silberman ◽  
Cláudia Soares Rodrigues ◽  
Eliasz Engelhardt ◽  
Jerson Laks

OBJECTIVE: The aim of this study is to evaluate the survival rate in a cohort of Parkinson's disease patients with and without depression. METHODS: A total of 53 Parkinson's disease subjects were followed up from 2003-2008 and 21 were diagnosed as depressed. Mean time of follow up was 3.8 (SD 95% = 1.5) years for all the sample and there was no significant difference in mean time of follow up between depressed and nondepressed Parkinson's disease patients. Survival curves rates were fitted using the Kaplan-Meier method. In order to compare survival probabilities according to the selected covariables the Log-Rank test was used. Multivariate analysis with Cox regression was performed aiming at estimating the effect of predictive covariables on the survival. RESULTS: The cumulative global survival of this sample was 83% with nine deaths at the end of the study - five in the depressed and four in the nondepressed group, and 55.6% died in the first year of observation, and none died at the fourth and fifth year of follow up. CONCLUSION: Our finding point toward incremental death risk in depressed Parkinson's disease patients.


2021 ◽  
Author(s):  
Judy Tung ◽  
Musarrat Nahid ◽  
Mangala Rajan ◽  
Lia Logio

Abstract BackgroundAcademic medical centers invest considerably in faculty development efforts to support the career success and promotion of their faculty and to minimize faculty attrition. This study evaluated the impact of a faculty development program called the Leadership in Academic Medicine Program (LAMP) on participants’ (1) self-ratings of efficacy, (2) promotion in academic rank, and (3) institutional retention. MethodParticipants from the 2013-2020 LAMP cohorts were surveyed pre and post program to assess their level of agreement with statements that spanned domains of self-awareness, self-efficacy, satisfaction with work and work environment. Pre and post responses were compared using McNemar’s tests. Changes in scores across gender were compared using Wilcoxon Rank Sum/Mann-Whitney tests.LAMP participants were matched to nonparticipant controls by gender, rank, department, and time of hire to compare promotions in academic rank and departures from the organization. Kaplan Meier curves and Cox proportional hazards models were used to examine differences. ResultsThere were significant improvements in almost all self-ratings on program surveys (p < 0.05). Greatest improvements were seen in “understand the promotions process” (36% vs. 94%), “comfortable negotiating” (35% vs. 74%), and “time management” (55% vs. 92%). There were no statistically significant differences in improvements by gender, however women faculty rated themselves lower on all pre-program items than men.There was significant difference found in time-to-next promotion (p = 0.003) between LAMP participants and controls. Kaplan-Meier analysis demonstrated that LAMP faculty achieved next promotion more often and faster than controls. Cox-proportional-hazards analyses found that LAMP faculty were 61% more likely to get promoted than controls (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.16-2.23, p-value= 0.004).There was significant difference found in time-to-departure (p<0.0001) with LAMP faculty retained more often and for longer periods. LAMP faculty were 77% less likely to leave compared to controls (HR 0.23, 95% CI 0.16-0.34, p<0.0001).ConclusionsLAMP is an effective faculty development program as measured subjectively by participant self-ratings and objectively through comparative improvements in academic promotions and institutional retention.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 598-598
Author(s):  
Koshi Fujikawa ◽  
Satoshi Yuki ◽  
Takahide Sasaki ◽  
Yasuo Takahashi ◽  
Ichiro Iwanaga ◽  
...  

598 Background: Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Although IRI-based chemotherapy combined with Cmab or Pmab has demonstrated the effectiveness in salvage-line, there has been no reported trials comparing these antibodies directly. Methods: Data of 96 pts with mCRC treated by Cmab plus IRI-based chemotherapy (Cmab/IRI) from HGCSG 0901 and 27 pts treated by Pmab plus IRI-based chemotherapy (Pmab/IRI) from HGCSG1002 were retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab/IRI vs. Pmab/IRI); male/female 58/38 vs. 16/11, median age (range) 63(38-80) vs. 64(49-81), PS 0/1/2 52/35/9 vs. 21/6/0, number of metastatic organs 1/2/3- 29/37/30 vs. 6/12/7, prior bevacizumab administration 62.5% vs. 92.6% (p = 0.002). MST was 9.9 months in the Cmab/IRI and 14.9 months in the Pmab/IRI (p = 0.196). PFS was 4.8 months in the Cmab/IRI, as compared with 5.4 months in the Pmab (p = 0.083); the corresponding RR was 25.0 % and 18.5% (p = 0.611). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.908, 95% CI 0.513-1.610, p = 0.742), nor PFS (HR 0.732, 95% CI 0.447-1.199, p = 0.732). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab with IRI-based chemotherapy in the salvage-line treatment of pts with mCRC.


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