An Exploratory Graphical Method for Identifying Associations in r x c Contingency Tables

On finding a significant association between rows and columns of an r x c contingency table, the next step is to study the nature of the association in more detail. The use of a scree plot to visualize the largest contributions to Χ2 among all cells in the table in order to determine the nature of the association in more detail is proposed

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation

PurposeModern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer.Methods and materialsA large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan–Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes.ResultsA total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir.ConclusionUtilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation

Purpose Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. Methods and materials A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan–Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. Results A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Conclusion Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity

Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure

IntroductionBrain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear.MethodsThis single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher’s exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure.ResultsA total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure.DiscussionAn optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy

Analysis of the clinical indications for opiate use in inflammatory bowel disease

Background/Aims: Opiate use for inflammatory bowel disease (IBD), particularly high-dose (HD) use, is associated with increased mortality. It's assumed that opiate use is directly related to IBD-related complaints, although this hasn't been well defined. Our goal was to determine the indications for opiate use as a first step in developing strategies to prevent or decrease opiate use.Methods: A retrospective cohort was formed of adults who were diagnosed with IBD and for whom outpatient evaluations from 2009 to 2014 were documented. Opiate use was defined if opiates were prescribed for a minimum of 30 days over a 365-day period. Individual chart notes were then reviewed to determine the clinical indication(s) for low-dose (LD) and HD opiate use.Results: After a search of the electronic records of 1,109,277 patients, 3,226 patients with IBD were found. One hundred four patients were identified as opiate users, including 65 patients with Crohn's and 39 with ulcerative colitis; a total of 134 indications were available for these patients. IBD-related complaints accounted for 49.25% of the opiate indications, with abdominal pain (23.13%) being the most common. Overall, opiate use for IBD-related complaints (81.40% vs. 50.82%; P=0.0014) and abdominal pain (44.19% vs. 19.67%; P=0.0071) was more common among HD than among LD.Conclusions: Our findings show that most IBD patients using opiates, particularly HD users, used opiates for IBD-related complaints. Future research will need to determine the degree to which these complaints are related to disease activity and to formulate non-opiate pain management strategies for patients with both active and inactive IBD

Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after non-ST-elevation myocardial infarction.

Prior studies demonstrated the association between the major adverse cardiovascular outcomes and both higher platelet and lower lymphocyte counts. Our study explores the value of the platelet/lymphocyte ratio (PLR) as a marker of long-term mortality in patients presented with non-ST segment elevation myocardial infarction (NSTEMI). This is an observational study with a total 619 NSTEMI patients admitted to a tertiary center between 2004 and 2006. Patients were stratified into equal tertiles according to their admission PLR. The primary outcome, 4 year all-cause mortality, was compared among the PLR tertiles. The first, second and third PLR tertiles were PLR \u3c 118.4, 118.4 ≤ PLR ≤ 176, and PLR \u3e 176, respectively) included 206, 206 and 207 patients, respectively. There was a significant higher 4 year all-cause mortality in the higher PLR tertiles (the mortalities were 17, 23 and 42 % for the first, second and third PLR tertiles respectively, p \u3c 0.0001). After exclusion of patients expired in the first 30 days, patients in the first PLR tertile had a significant lower 4 year mortality (33/205, 16 %) versus those in the third PLR tertile (72/192, 38 %), p \u3c 0.0001. After controlling for Global Registry of Acute Coronary Events risk scores and other confounders, the hazard ratio of mortality increased 2 % per each 10 U increase of PLR (95 % CI 1.01-1.03, p \u3c 0.0001). In patients with PLR ≥ 176, the mortality rate was statistically higher in those received mono-antiplatelet (30/60 = 50 %) compared to those received dual antiplatelet therapy (48/149 = 32 %), p = 0.0018. However in PLR \u3c 176, the mortality was not significantly different between mono-antiplatelet group (20/94 = 21 %) versus dual antiplatelets group (53/213 = 25 %), p = 0.56. The PLR is a significant independent predictor of long-term mortality after NSTEMI. Among patients with PLR \u3e 176, patients with dual antiplatelet therapy had lower mortality versus those with mono-platelet therapy. Further studies are needed to clarify these findings

The Effect of BAFF Inhibition on Autoreactive B-Cell Selection in Murine Systemic Lupus Erythematosus

Abstract The goal of this study was to determine how B-cell-activating factor of the TNF family (BAFF) availability influences selection of the autoreactive B-cell repertoire in NZB/W and NZW/BXSB lupus-prone mice bearing the site-directed heavy-chain transgene 3H9 that encodes for anti-dsDNA and anti-cardiolipin (CL) autoantibodies. We used a bone marrow chimera system in which autoreactive 3H9 transgenic B cells were allowed to mature in competition with wild-type cells and could be identified by green fluorescent protein. The light-chain repertoire associated with the 3H9 heavy chain in naive and antigen-activated B-cell subsets was assessed using single-cell polymerase chain reaction. We found that deletion of autoreactive transgenic B cells occurred in the bone marrow of both strains regardless of BAFF availability, and there were only modest and physiologically non-relevant effects on the naive B-cell repertoire. BAFF inhibition had different effects on selection of the germinal center repertoire in the two strains. In the NZW/BXSB strain, BAFF inhibition phenocopied the loss of one TLR7 allele in that it influenced the selection of 3H9-encoded autoreactive B cells in the germinal center but did not prevent somatic mutation. In the NZB/W strain, BAFF inhibition did not alter the selection of 3H9-encoded B cells in the germinal center, but it influenced selection of a subset of germinal center cells into the plasma cell compartment. Our data underscore the complexity of regulation of the autoreactive B-cell repertoire by BAFF and may help to explain the heterogeneity of responses observed after BAFF inhibition in humans