Adjuvant immunotherapy for locally advanced renal cell carcinoma.

INTRODUCTION: Locally advanced renal cell carcinoma (RCC) presents a therapeutic challenge due to 20-40% relapse risk post-nephrectomy. There has been substantial interest in utilizing immunotherapy interrupting the PD-1/PD-L1 axis in the perioperative space, especially in the adjuvant setting, in order to minimize such risk. AREAS COVERED: We conducted a PubMed search using the terms 'adjuvant' and 'RCC.' We begin by examining landmark studies in the postoperative space for locally advanced RCC, with special emphasis on immunotherapeutic biologics. Important considerations are outlined in an effort to explain the conflicting data on the benefit of adjuvant immunotherapy as well as to adequately assess the magnitude of potential benefit of the recently approved adjuvant pembrolizumab. Relevant contemporary challenges and opportunities as well as future directions of the field are also discussed. EXPERT OPINION: Systemic immunotherapy with monoclonal antibodies targeting the PD-1/PD-L1 axis likely holds promise, either alone or potentially in combinations, in minimizing recurrence risk for locally advanced RCC. However, emphasis on post-protocol care, robust endpoint selection, and continued work and validation on predictive biomarkers are needed to confidently select those patients that may benefit the most and minimize biologic and financial toxicity.

Development and validation of a prognostic nomogram for overall and disease-specific survival in patients with sarcomatoid urothelial carcinoma.

INTRODUCTION: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data guiding prognosis. In this study, we present the first prognostic nomograms in the literature for 3- and 5-year overall survival (OS) and disease-specific survival (DSS), for patients with SUC derived from the surveillance, epidemiology and end results database (SEER). MATERIALS AND METHODS: Patients with SUC were identified by using the ICD-10 topography codes C67.0-C67.9 (bladder cancer), and the morphologic code 8122 (SUC). Patients were randomly divided into a training cohort (TC) and a validation cohort (VC) (7:3 ratio). Variables significantly associated with OS and DSS were identified with multivariate Cox regression and were used to build the nomograms. Harrel's C-statistic with bootstrap resampling and calibration curves were used for internal (TC) and external (VC) validation. Clinical utility of the nomograms was assessed with the decision curve analysis (DCA). Goodness of fit between the nomograms and the AJCC 8th edition staging system was compared with the likelihood ratio test. RESULTS: A total of 741 patients with SUC were included (507 TC, 234 VC). No statistically significant differences in baseline characteristics were identified between the 2 cohorts. Sex, SEER stage, radical cystectomy and chemotherapy were common variables for the OS and the DSS nomograms with the addition of age in the former. Optimism-corrected C-statistic for the nomograms was 0.68 and 0.67 for OS and DSS respectively. In comparison, C-statistic for AJCC was 0.59 for OS and 0.60 for DSS (P < 0.001). Calibration curves constructed for the nomograms showed appropriate consistency between predicted and actual survival. The nomograms demonstrated optimal clinical utility in the DCA, outperforming the AJCC staging system, by maintaining a higher clinical net benefits than treat all, treat none and AJCC curves, across threshold probabilities. CONCLUSION: We present the first prognostic nomograms developed in patients with SUC. Our models demonstrated superior prognostic performance to the AJCC system, by utilizing a set of variables readily available in daily practice and may serve as useful tools for the individualized risk assessment of these patients.

Renal Sarcoma: A Population-Based Study.

INTRODUCTION: Renal sarcomas are exceedingly rare and lack a prognostic stage classification. We thus aimed to investigate the contemporary clinicopathologic characteristics and outcomes of renal sarcomas at a national level. PATIENTS AND METHODS: We utilized the Surveillance, Epidemiology, and End Results database to extract data on patients with renal sarcoma diagnosed between 2004 and 2015. We estimated median, 1-, 3-, and 5-year overall survival (OS) probabilities via Kaplan-Meier curves and used multivariable regression to compare OS between different patient groups. RESULTS: We identified 365 patients; at diagnosis, 104 patients (28.5%) had stage I disease (T1N0M0), 133 patients (36.4%) patients had stage II disease (T2-4N0M0), and 117 patients (32.1%) patients had stage III disease (any T, N1, or M1). Median survival was 105 months (interquartile range [IQR], 29 - not reached) for stage I disease, 46 months (IQR 14-118 months) for stage II disease, 8 months (IQR 3-28 months) for stage III disease, and 32 months (IQR, 8-116 months) for the entire cohort. Patient age (hazard ratio [HR] for death [per year] 1.02, 95% confidence interval [95% CI] 1.00-1.04), stage (II vs. I: HR 1.71, 95% CI 1.00-2.92; III vs. I: HR 4.93, 95% CI 2.68-9.05), grade (grade 3 vs. grade 1: 3.07, 95% CI 1.18-8.00; grade 4 vs. grade 1: HR 3.66, 95% CI 1.41-9.49), and possessing medical insurance (HR 0.40, 95% CI 0.16-0.94) were independently and significantly associated with OS. Performance of nephrectomy also trended towards independently improving OS (HR 0.23, 95% CI 0.05-1.09). CONCLUSION: A novel staging classification for renal sarcomas into a 3-stage system based on Tumor Node Metastasis (TNM) criteria produces distinct survival curves, although further studies are needed to robustly assess its validity.

Adjuvant immunotherapy for muscle-invasive urothelial carcinoma of the bladder.

INTRODUCTION: There are substantial unmet needs with regards to adjuvant therapy for muscle-invasive urothelial carcinoma (UC) of the bladder, including patients with persistent disease histologically following neoadjuvant platinum-based therapy and radical resection, as well as patients who are not eligible for or refuse cytotoxic chemotherapy. As such, increased interest has been developed in advancing the use of systemic immunotherapy in the postoperative setting. AREAS COVERED: We begin by examining current uses of systemic immunotherapy in the treatment of advanced UC. We also review emerging neoadjuvant data and describe current adjuvant approaches. We then report and analyze data on adjuvant immunotherapy, including the recent randomized trials on adjuvant nivolumab and atezolizumab, and conclude with a discussion on the available evidence and likely directions of the field. EXPERT OPINION: Systemic immunotherapy can serve to enhance postoperative therapies for muscle-invasive bladder UC, as exemplified by the recent approval of nivolumab. Further research will serve to define optimal immunotherapy timing and combinations with other systemic therapies, as well as identify predictive biomarkers to allow effective tailoring of therapy for each patient.

Sarcomatoid Urothelial Carcinoma: A Population-Based Study of Clinicopathologic Characteristics and Survival Outcomes.

INTRODUCTION: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data regarding epidemiology and survival. In this study, we explored clinicopathologic factors and oncologic outcomes of patients with SUC derived from Survival, Epidemiology and End Results (SEER) database, in comparison to conventional UC (CUC). MATERIALS AND METHODS: SEER database was searched for patients with invasive (≥T1) SUC or CUC using the topography codes C67.0 to C67.9 for bladder cancer and the morphologic codes 8120/8122 for CUC/SUC respectively. Demographic/clinicopathologic/treatment/survival data were extracted. Disease-specific survival (DSS) was estimated with the Kaplan-Meier method. Chi-squared tests were used for comparative analysis and Cox proportional hazards model for identifying clinical covariates associated with DSS. RESULTS: A total of 569 patients with SUC and 37,740 with CUC were identified. Overall, there was a male predominant population in both cohorts, although a higher proportion of women were noted in the SUC cohort (32 vs. 25%). Patients with SUC had significantly higher incidence of non-bladder confined disease (T3/4, 37% vs. 22%) and nodal invasion (18% vs. 12%) in comparison to those with CUC (all P < .05). Median DSS was 16 months (95% CI: 12.4-19.6) in the SUC vs. 82 months (95% CI; 75.9-88.1) in the CUC cohort. Presence of SUC histology was independently associated with shorter DSS in the multivariate analysis, when adjusted for other significant clinicopathologic factors. CONCLUSION: SUC was associated with advanced stage and shorter DSS compared to CUC. Further studies are needed to better understand biological underpinnings behind its aggressive behavior and the role of novel systemic treatments.

Predictive Nomograms for Synchronous Liver and Lung Metastasis in Colon Cancer.

BACKGROUND: The risk of distant metastasis may be estimated using predictive nomograms. The purpose of this study is to develop nomograms that may assess the risk of synchronous metastasis in patients with colon cancer. METHODS: A retrospective analysis of the Surveillance Epidemiology and End Results database between 2010 and 2014. Logistic regression was performed to identify factors associated with synchronous liver and lung metastasis. RESULTS: Overall, 117,934 patients with colon cancer (59,076 [50.1%] males, mean age 68.3 ± 13.7 years) were included, of which 16,135 (13.7%) had liver metastasis and 4601 (3.9%) had lung metastasis at diagnosis. Age, sex, race, tumor location, tumor grade, CEA levels, perineural invasion, and T and N stage were associated with the presence of liver metastasis. Age, sex, race, tumor location, tumor grade, CEA levels, perineural invasion, T stage, N stage, and presence of liver metastasis were associated with the presence of lung metastasis. These variables were used to construct predictive nomograms. The c-indexes for both predictive models were 0.97. CONCLUSIONS: In this study, we constructed predictive nomograms for the presence of synchronous liver and lung metastasis in patients with colon cancer that may be used to quantitatively assess the risk of synchronous metastatic disease.

Sarcomatoid Renal Cell Carcinoma: Population-Based Study of 879 Patients.

BACKGROUND: Sarcomatoid renal cell carcinoma (sRCC) constitutes a rare and aggressive subtype of renal cell carcinoma. We aimed to investigate its clinicopathologic characteristics and outcomes at a national level. PATIENTS AND METHODS: We accessed the National Cancer Institute's Surveillance, Epidemiology, and End Results database (2010-2015) and extracted data on patients with sRCC. We estimated median, 1-, 3-, and 5-year disease-specific survival (DSS) probabilities after generation of Kaplan-Meier curves and used multivariable regression to evaluate variables associated with nephrectomy and DSS. RESULTS: A total of 879 patients with sRCC were identified; 60.9% patients had stage IV disease at diagnosis, and the median tumor size was 8.3 cm (interquartile range, 5.5-12 cm). The 5-year DSS were 77.7%, 67.8%, 35.4%, and 3.5% for patients with stage I, II, III, and IV disease at diagnosis, respectively; median DSS was 9 months (interquartile range, 4-42 months) for the entire cohort. Older age (hazard ratio [HR] = 1.01; 95% confidence interval [CI], 1.00-1.02), higher tumor stage (stage III vs. I: HR = 3.81; 95% CI, 2.18-6.67; stage IV vs. I: HR = 9.89; 95% CI, 5.80-16.98), and performance of nephrectomy (HR = 0.53; 95% CI, 0.43-0.66) were found to independently affect DSS. CONCLUSION: In the largest sRCC cohort to date, we found that most patients present with metastatic disease, and the prognosis for this disease remains extremely poor. Nephrectomy should be considered in all patients with acceptable surgical risk, including cytoreductive nephrectomy in carefully selected patients with metastatic disease.

Risk factors for cardiovascular mortality in patients with colorectal cancer: a population-based study.

BACKGROUND: Patients with colorectal cancer are at increased risk of cardiovascular mortality compared to the general population. The purpose of this study is to identify risk factors of cardiovascular mortality in patients with colorectal cancer. METHODS: A retrospective review of the Surveillance Epidemiology and End Results (SEER) database was performed between 2010 and 2014. Standardized Mortality Ratios (SMRs) for cardiovascular mortality were calculated by comparing the number of expected deaths in the United States according to the National Center for Health Statistics (ICD-10 codes I00-I99) to the number of observed deaths in the database. Logistic regression was used to identify independent risk factors. RESULTS: Overall, 164,719 patients were identified (mean age at diagnosis 67 ± 13.9 years, 52.7% males, 47.3% females), of which 4854 (2.9%) died from cardiovascular disease. The majority of cardiovascular deaths occurred during the first year after diagnosis (2658, 54.8%). SMRs for cardiovascular mortality were 11.7 (95% CI 11.3-12) among all patients, 12.1 (95% CI 11.7-12.6) for male patients and 11.1 (95% CI 10.6-11.6) for female patients, with SMRs being higher for younger patients. Older age, male sex, African-American race, elevated CEA and not undergoing curative surgery were independent risk factors of cardiovascular mortality in patients with colorectal cancer. CONCLUSION: Patients with colorectal cancer are associated with an increased risk of cardiovascular death, especially during the first year after diagnosis. Older age, male sex, African-American race, elevated CEA and not undergoing curative surgery are independent risk factors of cardiovascular death.

Outcomes After Surgical Resection Differ by Primary Tumor Location for Metastatic Gastrointestinal Stromal Tumors (GISTs): a Propensity Score Matching Population Study.

PURPOSE: Primary tumor location has been identified as an important prognostic factor among patients with gastrointestinal stromal tumors (GISTs). The purpose of this study is to identify how primary tumor location may affect outcomes after resection for patients with metastatic GISTs. METHODS: Patients with GISTs and distant metastases at diagnosis were identified in the Surveillance Epidemiology and End Results (SEER) database. Patients that underwent surgery were matched to patients that did not undergo surgery using propensity score matching (PSM) analysis. RESULTS: After PSM, 570 patients were identified (males 334 [58.6%], females 236 [41.4%], age 62 ± 13.9 years). Gastric tumors constituted the majority (325 [57%]), followed by small intestinal (136 [23.9%]), colorectal (19 [3.3%]), and retroperitoneal/peritoneal tumors (23 [4%]). Median follow-up was 25.5 months (95% CI 23-29 months). Undergoing surgery was associated with improved disease-specific survival (DSS) on both univariate (median not reached vs. 51 months, p < 0.001) and multivariate analyses (HR 4.98, 95% CI 2.23-11.12, p < 0.001). A sub-analysis of patients with gastric GISTs showed that undergoing surgery was the only significant factor associated with improved DSS (median not reached vs. 39 months, p < 0.001, HR 2.95, 95% CI 1.92-4.53). In contrast, undergoing surgery was not associated with improved survival for small intestinal, colorectal, or retroperitoneal/peritoneal tumors. CONCLUSIONS: Surgery for gastric metastatic GISTs is associated with improved survival. No discernible benefit after surgical resection was identified for patients with small intestinal, colorectal, retroperitoneal, or peritoneal metastatic GISTs.

Predictors of lymph node metastasis in patients with gastrointestinal stromal tumors (GISTs).

BACKGROUND: Lymph node metastasis is not common among patients with gastrointestinal stromal tumors (GISTs) and its prognostic value is controversial. The purposes of this study are to identify predictors of lymph node metastasis and determine its prognostic associations. METHODS: A retrospective analysis of the surveillance, epidemiology and end results (SEER) database was performed. Patients with GISTs that underwent surgery and pathologic nodal staging were identified. Logistic regression and Cox regression were performed to identify independent predictors and prognostic factors, respectively. RESULTS: Of 1430 patients (age: 61.5 ± 14.5 years, 52% males), 140 (9.8%) had lymph node metastasis. On multivariable analysis, distant metastasis was the only independent predictor of lymph node metastasis (OR 4.95, 95% CI: 2.43-10.08, p < 0.001). In the entire cohort, lymph node metastasis did not reflect a worse overall survival (OS, HR 1.12, 95% CI: 0.49-2.58, p = 0.794) or disease-specific survival (DSS, HR 0.95, 95% CI: 0.31-2.88, p = 0.924), but was an independent predictor of worse OS in 51 patients (25.4% of 201 patients) who presented with both lymph node metastasis and synchronous distant metastasis (HR 2, 95% CI: 1.25-3.21, p = 0.004). Lymph node metastasis was also independently associated with worse survival among patients with small intestinal (OS: HR 1.88, 95% CI: 1.15-3.1, p = 0.013) and colorectal tumors (OS: HR 3.41, 95% CI: 1.56-7.46, p = 0.002, DSS: HR 3.58, 95% CI: 1.27-10.06, p = 0.016). CONCLUSIONS: Metastatic disease is an independent predictor of lymph node metastasis in patients with GISTs. Lymph node metastasis is also associated with worse overall survival in patients with metastatic GISTs.

Predictive Nomograms for Synchronous Distant Metastasis in Rectal Cancer.

BACKGROUND: Nomograms may be used to quantitatively assess the probability of synchronous distant metastasis. The purpose of this study is to develop predictive nomograms for the presence of synchronous distant metastasis in patients with rectal cancer. METHODS: A retrospective analysis of the Surveillance Epidemiology and End Results database was performed for cases diagnosed between 2010 and 2014. RESULTS: Overall, 46,785 patients with rectal cancer (27,773 [59.4%] males, mean age 63.9 ± 13.7 years) were identified, of which 6192 (13.2%) had liver metastasis, 2767 (5.9%) had lung metastasis, and 601 (1.3%) had bone metastasis. Age, sex, race, tumor location, tumor grade, primary tumor size, CEA levels, perineural invasion, T stage, N stage, and liver and lung metastasis were found to be associated with the presence of synchronous distant metastasis and were included in the predictive models. The c-indexes of these models were 0.99 for liver metastasis, 0.99 for lung metastasis, and 1 for bone metastasis. CONCLUSIONS: Predictive nomograms for the presence of synchronous liver, lung, and bone metastasis were developed and may be used to predict the probability of distant disease in rectal cancer patients.

Incidence and predictors of synchronous liver metastases in patients with gastrointestinal stromal tumors (GISTs).

BACKGROUND: The liver is the most common metastatic site in patients with gastrointestinal stromal tumors (GISTs). The purpose of this study is to identify the incidence and predictive factors associated with synchronous liver metastases among patients with GISTs. METHODS: A retrospective review of the Surveillance Epidemiology and End Results (SEER) database was performed. RESULTS: Overall, 2757 patients were identified, of which 276 (10%) had synchronous liver metastases. The two-year survival of patients with synchronous liver metastases was 31.9% overall and 37.1% after undergoing surgery with curative intent. Primary tumor size >5 cm (5-10 cm: OR 2.97, 95% CI: 1.03-8.55, p = 0.044, >10 cm: OR 5.59, 95% CI: 1.95-16.07, p = 0.001), presence of nodal metastases (OR 4.09, 95% CI: 2.01-8.33, p < 0.001) and mitotic count >5/50 HPF (OR 1.58, 95% CI: 1.01-2.47, p = 0.044) were associated with the presence of liver metastases. CONCLUSIONS: One out of ten patients with GISTs presents with hepatic metastases. Primary tumor size >5 cm, presence of nodal metastases and mitotic count >5/50 HPF are associated with a higher risk of synchronous hepatic metastases.

Conditional survival analysis for patients with intraductal papillary mucinous neoplasms (IPMNs) undergoing curative resection.

BACKGROUND: Conditional survival (CS) analysis represents a novel method that may provide more clinically relevant perspectives to cancer management compared to conventional survival analysis. The purpose of this study was to evaluate conditional survival for patients with intraductal papillary mucinous neoplasms (IPMNs) undergoing curative resection. METHODS: A retrospective search of the Surveillance Epidemiology and End Results (SEER) database was performed. Three-year conditional survival (i.e. probability that a patient will survive an additional 3 years if they have already survived x years) was calculated using the formula 3-CS(x)=OS(x+3)/OS(x), where OS represents overall survival. RESULTS: Overall, 1303 patients were identified, with mean age of 65.2 ± 12.2 years. 3-CS at 1, 3 and 5 years after diagnosis was 35.8%, 47.5% and 44.7%. Patients with stage III/IV disease demonstrated small differences in 3-CS at 1-3 years after diagnosis compared to patients with stage I/II disease (I/II: 35.1%-46.9%, III/IV: 22.1%-42.3%, d range 0.09-0.28), while their 3-CS was superior at 4-5 years after diagnosis (I/II: 41.5%-45.7%, III/IV: 57.9%-64.7%, d range 0.24-0.47). Differences in 3-CS based on tumor grade displayed a different pattern, with small differences at 1-3 years after diagnosis (well-differentiated (WD)/moderately-differentiated (MD): 34.6%-50%, poorly-differentiated (PD)/undifferentiated (UD): 23.2%-40%, d range 0.18-0.24), before becoming prominent at 4-5 years after diagnosis (WD/MD: 50%-51.7%, PD/UD: 24.1%-30%, d range 0.4-0.55). CONCLUSIONS: Conditional survival for patients with IPMNs undergoing resection improves over time, especially for patients with high-risk features. This information may be used to provide individualized approaches to surveillance and treatment.

Refusal of Cancer-Directed Surgery by Breast Cancer Patients: Risk Factors and Survival Outcomes.

BACKGROUND: It has been reported that some patients with breast cancer may refuse cancer-directed surgery, but the incidence in the United States is not currently known. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with refusal of recommended breast cancer-directed surgery. PATIENTS: A retrospective review of the Surveillance Epidemiology and End Results (SEER) database between 2004 and 2013 was performed. Patients who underwent cancer-directed surgery were compared with patients in whom cancer-directed surgery was refused, even though it was recommended. RESULTS: Of 531,700 patients identified, 3389 (0.64%) refused surgery. An increasing trend was observed from 2004 to 2013 (P = .009). Older age (50-69: odds ratio [OR] 4.96; 95% confidence interval, 1.23-19.96; P = .024, ≥ 70 years: OR 17.27; 95% CI, 4.29-69.54; P < .001), ethnicity (P < .001), marital status (single: OR 2.28; 95% CI, 1.98-2.62; P < .001, separated/divorced/widowed: OR 2.26; 95% CI, 2.01-2.53; P < .001), higher stage (II: OR 2.05; 95% CI, 1.83-2.3; P < .001, III: OR 2.2; 95% CI, 1.87-2.6; P < .001, IV: OR 13.3; 95% CI, 11.67-15.16; P < .001), and lack of medical insurance (OR 2.11; 95% CI, 1.59-2.8; P < .001) were identified as risk factors associated with refusal of surgery. Survival analysis showed a 2.42 higher risk of mortality in these patients. CONCLUSION: There has been an increasing rate of patients refusing recommended surgery, which significantly affects survival. Age, ethnicity, marital status, disease stage, and lack of insurance are associated with higher risk of refusal of surgery.

Correlation of Opioid Mortality with Prescriptions and Social Determinants: A Cross-sectional Study of Medicare Enrollees.

BACKGROUND: The opioid epidemic is an escalating health crisis. We evaluated the impact of opioid prescription rates and socioeconomic determinants on opioid mortality rates, and identified potential differences in prescription patterns by categories of practitioners. METHODS: We combined the 2013 and 2014 Medicare Part D data and quantified the opioid prescription rate in a county level cross-sectional study with data from 2710 counties, 468,614 unique prescribers and 46,665,037 beneficiaries. We used the CDC WONDER database to obtain opioid-related mortality data. Socioeconomic characteristics for each county were acquired from the US Census Bureau. RESULTS: The average national opioid prescription rate was 3.86 claims per beneficiary that received a prescription for opioids (95% CI 3.86-3.86). At a county level, overall opioid prescription rates (p < 0.001, Coeff = 0.27) and especially those provided by emergency medicine (p < 0.001, Coeff = 0.21), family medicine physicians (p = 0.11, Coeff = 0.008), internal medicine (p = 0.018, Coeff = 0.1) and physician assistants (p = 0.021, Coeff = 0.08) were associated with opioid-related mortality. Demographic factors, such as proportion of white (p white < 0.001, Coeff = 0.22), black (p black < 0.001, Coeff = - 0.19) and male population (p male < 0.001, Coeff = 0.13) were associated with opioid prescription rates, while poverty (p < 0.001, Coeff = 0.41) and proportion of white population (p white < 0.001, Coeff = 0.27) were risk factors for opioid-related mortality (p model < 0.001, R 2 = 0.35). Notably, the impact of prescribers in the upper quartile was associated with opioid mortality (p < 0.001, Coeff = 0.14) and was twice that of the remaining 75% of prescribers together (p < 0.001, Coeff = 0.07) (p model = 0.03, R 2 = 0.03). CONCLUSIONS: The prescription opioid rate, and especially that by certain categories of prescribers, correlated with opioid-related mortality. Interventions should prioritize providers that have a disproportionate impact and those that care for populations with socioeconomic factors that place them at higher risk.

Trends in incidence and associated risk factors of suicide mortality among breast cancer patients.

OBJECTIVE: Breast cancer patients are associated with an increased risk for committing suicide. The purpose of this study was to study the trends in the incidence of suicide mortality and identify pertinent risk factors among patients with breast cancer. METHODS: A retrospective examination of the Surveillance Epidemiology and End Results database between years 1973 and 2013 was performed. RESULTS: Overall, 474 128 patients were identified of which 773 had committed suicide. There were no significant differences in the incidence of suicide mortality over the last 3 decades (1984-1993: 0.14%, 1994-2003: 0.16%, 2004-2013: 0.17%, P = 0.173). On logistic regression, younger age (<30 y: OR 6.34, 95% CI: 1.98-20.33, P = 0.002; 30-49 y: OR 10.64, 95% CI: 7.97-14.2, P < 0.001; 50-69 y: OR 4.7, 95% CI: 3.64-6.07, P < 0.001), male sex (OR 4.34, 95% CI: 2.57-7.31, P < 0.001), nonwhite-nonblack race (OR 1.39, 95% CI: 1.01-1.91, P = 0.046), marital status (single: OR 1.35, 95% CI: 1.04-1.76, P = 0.024; separated/divorced/widowed: OR 1.25, 95% CI: 1.01-1.55, P = 0.043), undergoing surgery (OR 2.13, 95% CI: 1.23-3.67, P = 0.007), and short-time elapsed from diagnosis (first year: OR 4.67, 95% CI: 3.39-6.42, P < 0.001; second year: OR 2.35, 95% CI: 1.69-3.27, P < 0.001) were independent risk factors of suicide mortality. CONCLUSIONS: There have been no identifiable improvements in preventing suicide mortality in the United States. Younger age, male sex, race, marital status, and undergoing surgery are independent risk factors for committing suicide, especially in the first year after diagnosis.

Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A Systematic Review and Meta-analysis.

BACKGROUND: Mismanagement of asymptomatic patients with positive urine cultures (referred to as asymptomatic bacteriuria [ASB] in the literature) promotes antimicrobial resistance and results in unnecessary antimicrobial-related adverse events and increased health care costs. METHODS: We conducted a systematic review and meta-analysis of studies that reported on the rate of inappropriate ASB treatment published from 2004 to August 2016. The appropriateness of antimicrobial administration was based on guidelines published by the Infectious Diseases Society of America. RESULTS: A total of 2142 nonduplicate articles were identified, and among them 30 fulfilled our inclusion criteria. The pooled prevalence of antimicrobial treatment among 4129 cases who did not require treatment was 45% (95% CI, 39-50). Isolation of gram-negative pathogens (odds ratio [OR], 3.58; 95% CI, 2.12-6.06), pyuria (OR, 2.83; 95% CI, 1.9-4.22), nitrite positivity (OR, 3.83; 95% CI, 2.24-6.54), and female sex (OR, 2.11; 95% CI, 1.46-3.06) increased the odds of receiving treatment. The rates of treatment were higher in studies with ≥100 000 cfu/mL cutoff values compared with <10 000 cfu/mL for bacterial growth (P, .011). The implementation of educational and organizational interventions designed to eliminate the overtreatment of ASB resulted in a median absolute risk reduction of 33% (rangeARR, 16-36%, medianRRR, 53%; rangeRRR, 25-80%). CONCLUSION: The mismanagement of ASB remains extremely frequent. Female sex and the overinterpretation of certain laboratory data (positive nitrites, pyuria, isolation of gram-negative bacteria and cultures with higher microbial count) are associated with overtreatment. Even simple stewardship interventions can be particularly effective, and antimicrobial stewardship programs should focus on the challenge of differentiating true urinary tract infection from ASB.

The salivary microbiome is consistent between subjects and resistant to impacts of short-term hospitalization.

In recent years, a growing amount of research has begun to focus on the oral microbiome due to its links with health and systemic disease. The oral microbiome has numerous advantages that make it particularly useful for clinical studies, including non-invasive collection, temporal stability, and lower complexity relative to other niches, such as the gut. Despite recent discoveries made in this area, it is unknown how the oral microbiome responds to short-term hospitalization. Previous studies have demonstrated that the gut microbiome is extremely sensitive to short-term hospitalization and that these changes are associated with significant morbidity and mortality. Here, we present a comprehensive pipeline for reliable bedside collection, sequencing, and analysis of the human salivary microbiome. We also develop a novel oral-specific mock community for pipeline validation. Using our methodology, we analyzed the salivary microbiomes of patients before and during hospitalization or azithromycin treatment to profile impacts on this community. Our findings indicate that azithromycin alters the diversity and taxonomic composition of the salivary microbiome; however, we also found that short-term hospitalization does not impact the richness or structure of this community, suggesting that the oral cavity may be less susceptible to dysbiosis during short-term hospitalization.

Extended-spectrum ß-lactamase-producing Enterobacteriaceae colonisation in long-term care facilities: a systematic review and meta-analysis.

The objectives of this study were to estimate the colonisation rate by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) among residents of long-term care facilities (LTCFs) and to identify pertinent risk factors. A systematic search of PubMed and EMBASE databases for studies published up to May 2016 that provided raw data for gastrointestinal colonisation by ESBL-PE among LTCF residents was performed. Twenty-three studies reporting data on 9775 screened subjects met the inclusion criteria. The pooled prevalence of ESBL-PE among LTCF residents was 18% [95% confidence interval (CI) 12-24%]. Risk factors for colonisation included recent antibiotic use (within 6 months) [odds ratio (OR) = 2.06, 95% CI 1.78-2.38], previous hospitalisation (within 2.5 years) (OR = 1.50, 95% CI 1.04-2.15), history of invasive procedures (within 2 years) (OR = 2.79, 95% CI 1.66-4.70), previous ESBL-PE colonisation or infection (OR = 6.77, 95% CI 1.33-34.62), history of urinary tract infection (OR = 2.66, 95% CI 1.76-4.01) and urinary catheter use (OR = 2.55, 95% CI 1.29-5.04). In conclusion, almost one in five LTCF residents is colonised with ESBL-PE, and colonised residents are more likely to have a history of recent antibiotic use or healthcare facility utilisation. Strict adherence to antimicrobial stewardship in LTCFs is needed to address these high resistance rates.

Urinary tract infections caused by ESBL-producing Enterobacteriaceae in renal transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Urinary tract infections (UTIs) are the most common infectious complications among renal transplant recipients (RTR). UTIs caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) have been associated with inferior clinical outcomes and increased financial burden. METHODS: We performed a systematic review and meta-analysis by searching through the PubMed and EMBASE databases (to May 20, 2016) and identifying studies that reported data on the number of RTR who developed an ESBL-PE UTI. RESULTS: Our analysis included seven studies, out of 357 non-duplicate articles, that provided data on 2824 patients. Among them, 10% (95% confidence interval [CI] 4%-17%) developed an ESBL-PE UTI over their follow-up periods. The proportion of RTR affected by an ESBL-PE UTI was 2% in North America (95% CI 1%-3%), 5% in Europe (95% CI 4%-6%), 17% in South America (95% CI 10%-27%), and 33% in Asia (95% CI 27%-41%). In addition, patients affected with an ESBL-PE UTI were 2.75-times (95% CI 1.97-3.83) more likely to suffer a recurrent UTI. CONCLUSIONS: Based on a limited number of studies, one in 10 RTR will develop a UTI caused by an ESBL-PE, and these patients face an almost 3 times greater risk of recurrence. A more rigorous monitoring of RTR, both during and after resolution of their infection, should be evaluated in order to reduce the incidence and the clinical impact of these resistant infections.