Overall Risk Of Death Research Articles

Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study

ObjectivesTo investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death.DesignThe European Prospective Investigation into Cancer and nutrition...

Mortality rate after open Roux-in-Y gastric bypass: a 10-year follow-up.

The prevalence of obesity has increased to epidemic status worldwide. Thousands of morbidly obese individuals undergo bariatric surgery for sustained weight loss; however, mid- and long-term outcomes of this surgery are still uncertain. Our objective was to estimate the 10-year mortality rate, and determine risk factors associated with death in young morbidly obese adults who underwent bariatric surgery. All patients who underwent open Roux-in-Y gastric bypass surgery between 2001 and 2010, covered by an insurance company, were analyzed to determine possible associations between risk factors present at the time of surgery and deaths related and unrelated to the surgery. Among the 4344 patients included in the study, 79% were female with a median age of 34.9 years and median body mass index (BMI) of 42 kg/m2. The 30-day and 10-year mortality rates were 0.55 and 3.34%, respectively, and 53.7% of deaths were related to early or late complications following bariatric surgery. Among these, 42.7% of the deaths were due to sepsis and 24.3% to cardiovascular complications. Male gender, age ≥50 years, BMI ≥50 kg/m2, and hypertension significantly increased the hazard for all deaths (P<0.001). Age ≥50 years, BMI ≥50 kg/m2, and surgeon inexperience elevated the hazard of death from causes related to surgery. Male gender and age ≥50 years were the factors associated with increased mortality from death not related to surgery. The overall risk of death after bariatric surgery was quite low, and half of the deaths were related to the surgery. Older patients and superobese patients were at greater risk of surgery-related deaths, as were patients operated on by less experienced surgeons.

Improved survival with combined gemcitabine and S‐1 for locally advanced pancreatic cancer: pooled analysis of three randomized studies

The long-term prognosis for localized pancreatic cancer (PC) remains poor. Three randomized trials (GEST phase III, JACCRO PC-01 phase II and GEMSAP phase II) evaluated gemcitabine (Gem) with or without S-1 for patients with metastatic and locally advanced PC. A pooled analysis based on published data examined whether Gem with S-1 (GS) is superior to Gem alone in overall survival (OS) in patients with locally advanced PC. Data were extracted on 193 patients: 31 (JACCRO), 28 (GEMSAP), and 134 (GEST). OS was used for primary endpoint and progression-free survival (PFS) was used for secondary endpoint. A general variance-based method was used to estimate the pooled HR and 95% CI between GS (n = 96) and Gem (n = 97). Meta-analysis demonstrated that the overall risk of death was significantly different between the two chemotherapies (hazard ratio = 0.673, 95% confidence interval: 0.488-0.929, P = 0.016). The median PFSs for GS and GEM in the JACCRO, GEMSAP, and GEST studies were 12.0, 12.6, and 10.7 months, and 4.1, 8.1, and 6.2 months, respectively (P = 0.001). The random-effect pooled estimate for 165 patients showed the objective response rate (ORR) in the GS group (28.4%) was better in the Gem group (8.3%, P = 0.001). GS improved ORR, PFS and OS in patients with locally advanced PC over Gem alone. GS could become one of the front-line chemotherapeutic agents.

Death from cancer: a sobering truth for patients with kidney transplants

Cancer is a major cause of morbidity among those with kidney transplants. Farrugia et al. examined the overall and site-specific risk of cancer death among kidney transplant recipients. Cancer outcomes, particularly for those with a history of cancer prior to transplantation, are poor. The overall risk of death attributed to cancer in patients with kidney transplants is increased at least tenfold over that in cancer patients in the general population.

The Choi response criteria for inferior vena cava tumor thrombus in renal cell carcinoma treated with targeted therapy.

To evaluate the prognostic significance of the Choi criteria for assessing the responses of a renal mass and inferior vena cava (IVC) tumor thrombus in patients with renal cell carcinoma (RCC) receiving targeted therapy. We reviewed the medical records of 22 patients diagnosed with RCC and IVC thrombus between 2005 and 2012. The efficacy of targeted therapy in renal mass and IVC tumor thrombus was evaluated using response evaluation criteria in solid tumors (RECIST) and Choi criteria, respectively. Overall survival was estimated, and the prognostic significance of each variable was estimated using Cox proportional-hazards regression modeling. There were no significant differences in overall survival between patients with partial response (PR) and nonresponse according to RECIST criteria (19.3 vs 43 months; p = 0.212) or Choi criteria (9.0 vs 23.3 months; p = 0.109) in primary tumor. Regarding the response of IVC tumor thrombi, according to Choi criteria, nine patients (40.9 %) demonstrated PR and longer survival than patients with stable disease (7.2 vs 23.3 months; p = 0.014). In multivariable analysis, response to IVC thrombus according to Choi criteria was the only significant predictive factor. Patients with IVC thrombus who demonstrate the PR according to Choi criteria were at 0.35-fold greater overall risk of death compared with patients who did not demonstrate this response (p = 0.043). A response according to Choi criteria in IVC tumor thrombus was an independent prognostic predictor in patients with RCC and IVC thrombus who receive targeted therapy.

Helmet use among Alaskan children involved in off-road motorized vehicle crashes

BackgroundOff-road motorized vehicle crashes are a common source of trauma among Alaska children. Injury morbidity is worse in Alaska Native children than non-Native children, but the reasons are unclear.ObjectiveTo evaluate the differences in helmet use between the Native and the non-Native children, and to assess the impact of helmet use on injury patterns and outcomes.DesignThis retrospective cohort study identified patients aged 17 or younger admitted after all-terrain vehicle, snowmobile or motorbike injury between 2001 and 2011 from the Alaska Trauma Registry. Helmeted and non-helmeted patients were compared with respect to demographics, central nervous system (CNS) injury and the overall risk of death or permanent disability. Logistic regression was used to evaluate predictors of helmet use and the effects of ethnicity and helmet use on outcomes.ResultsOf the 921 injured children, 51% were Alaska Native and 49% were non-Native. Helmet use was lower among Native versus non-Native patients on unadjusted comparison (24% vs. 71%) and multivariable logistic regression (OR 0.17, 95% CI 0.11–0.27, p<0.0001). Prevalence of CNS injury was higher among Native children (39.7% vs. 30.4%, p=0.016). However, on logistic regression with adjustment for helmet use, Native ethnicity was not a significant predictor of CNS injury (OR 1.07, 95% CI 0.68–1.68, p=0.78), whereas helmet use was strongly protective against CNS injury (OR 0.28, 95% CI 0.18–0.44, p<0.0001) as well as death or permanent disability (OR 0.26, 95% CI 0.10–0.67, p=0.006).ConclusionsHelmet use is lower among Alaska Native children involved in off-road motorized vehicle crashes. These ethnic disparities in helmet use contribute to higher rates of CNS injury among Native children. Helmet use significantly improves overall outcome. Helmet promotion efforts should be expanded, especially in Native communities.

Cancer incidence and cause-specific mortality in patients with metal-on-metal hip replacements in Finland

Background and purpose — Metal-on-metal hip implants have been widely used, especially in the USA, Australia, England and Wales, and Finland. We assessed risk of death and updated data on the risk of cancer related to metal-on-metal hip replacements.Patients and methods — A cohort of 10,728 metal-on-metal hip replacement patients and a reference cohort of 18,235 conventional total hip replacement patients were extracted from the Finnish Arthroplasty Register for the years 2001–2010. Data on incident cancer cases and causes of death until 2011 were obtained from the Finnish Cancer Registry and Statistics Finland. The relative risk of cancer and death were expressed as standardized incidence ratio (SIR) and standardized mortality ratio (SMR). SIR/SIR ratios and SMR/SMR ratios, and Poisson regression were used to compare the cancer risk and the risk of death between cohorts.Results — The overall risk of cancer in the metal-on-metal cohort was not higher than that in the non-metal-on-metal cohort (RR = 0.91, 95% CI: 0.82–1.02). The risk of soft-tissue sarcoma and basalioma in the metal-on-metal cohort was higher than in the non-metal-on-metal cohort (SIR/SIR ratio = 2.6, CI: 1.02–6.4 for soft-tissue sarcoma; SIR/SIR ratio = 1.3, CI: 1.1–1.5 for basalioma). The overall risk of death in the metal-on-metal cohort was less than that in the non-metal-on-metal cohort (RR = 0.78, CI: 0.69–0.88).Interpretation — The overall risk of cancer or risk of death because of cancer is not increased after metal-on-metal hip replacement. The well-patient effect and selection bias contribute substantially to the findings concerning mortality. Arthrocobaltism does not increase mortality in patients with metal-on-metal hip implants in the short term. However, metal-on-metal hip implants should not be considered safe until data with longer follow-up time are available.

Genetic variants in matrix metalloproteinase genes as disposition factors for ovarian cancer risk, survival, and clinical outcome.

Ovarian cancer is one of the leading female cancers in the United States. Challenges remain in early diagnosis of this deadly disease. Matrix metalloproteinases (MMPs) family genes are paradoxically involved in cancer promotion and suppression. We hypothesize that genetic variants in MMP genes are associated with ovarian cancer development, so they could be potential markers for ovarian cancer diagnosis and prognosis. In this study of 417 ovarian cancer cases and 417 healthy controls, we genotyped a comprehensive panel of 266 single nucleotide polymorphisms (SNPs) in 23 MMP genes and analysed their associations with ovarian cancer risk, overall survival and treatment response in ovarian cancer cases who received platinum-based chemotherapy with surgery. In the analysis on 339 Caucasian cases and 349 Caucasian controls, 4 SNPs were significantly associated with cancer risk. The most significant association was observed for rs2292730 (OR = 2.03, 95% CI = 1.39-2.96, P = 0.0002). Classification and regression tree analysis identified four terminal nodes with differential risk of ovarian cancer. Thirty-four SNPs were significantly associated with overall survival and four of which showed significant association with response to chemotherapy. Unfavourable genotype analysis of top SNPs on overall risk of death showed significant gene-dosage effect, survival tree analysis differentiated patients into distinct risk groups based on their genetic profiles with median survival times (MSTs) ranging from 17.7 to 151.7 months. In conclusion, our results suggest that genetic variants in MMP pathway genes may modulate the risk and clinical outcomes of ovarian cancer, both individually and jointly.

Anticoagulants for Cerebral Venous Thrombosis

See related article, p 8. Evidence relating to efficacy and safety of anticoagulants for CVT is only partially available from studies in the peer reviewed medical literature and from the corresponding authors of those studies. Consequently, this article is an opinion piece rather than a systematic review. Cerebral venous thrombosis (CVT) accounts for ≈0.5% of strokes and may occur at any age.1 Risk factors include pregnancy, oral contraceptives, head trauma, malignancy, infection, anemia, and dehydration. In older reports, the incidence of CVT was 3 to 4 per 1 million people per year in Europe and the United States.2 However, a survey published in 2012 found an incidence of CVT of 13.2 per 1 million people per year.3 With modern brain imaging technology, more cases are being discovered that probably would have resolved without medical intervention. Relative to pre-1990 clinical outcomes data, the average prognosis has dramatically improved.4,5 A Cochrane review of anticoagulant therapy for CVT4 based the recommendation in favor of using anticoagulation treatment (full-dose unfractionated heparin [UFH] or low-molecular-weight heparin [LMWH] followed by a vitamin K antagonist [VKA]) on 2 small randomized placebo-controlled trials (RCTs, n=79). These trials demonstrated a non-statistically significant reduction in deaths with anticoagulation (risk ratio, 0.33; 95% confidence interval [CI], 0.08–1.28). Subsequently, the European Federation of Neurological Sciences6 and the American Heart Association/American Stroke Association7 issued clinical practice guidelines calling for full-dose heparin acutely followed by VKAs for ≥3 months. The efficacy and safety of anticoagulants for CVT have not been comprehensively reviewed, with the inclusion of observational studies and the RCTs excluded from the Cochrane review. This review will evaluate published reports from 1990 to 2013 regarding the efficacy and safety of full-dose heparin (UFH or LMWH) during initial hospitalization and subsequent VKA treatment …

C-Reactive Protein, Lipid-soluble Micronutrients, and Survival in Colorectal Cancer Patients

Identification of biomarkers associated with survival in patients with cancer is important for elucidating the underlying mechanisms of cancer progression and identifying possible interventions to reduce cancer morbidity and mortality. Using stored patient plasma samples from a multiethnic population-based case-control study of invasive colorectal cancer, we measured posttreatment blood levels of C-reactive protein (CRP) and lipid-soluble micronutrients. Patients (n = 368) were followed after phlebotomy (mean of 8 years), during which time 47% died (25% colorectal cancer specific). HRs were estimated by Cox proportional hazards regression with adjustment for stage, age at diagnosis, ethnicity, sex, smoking status, and month of blood draw. A positive association with overall risk of death was observed for CRP [HR for highest vs. lowest quintile: 1.80; 95% confidence interval (CI), 1.07-3.04; Ptrend = 0.01], whereas inverse associations were generally observed for retinol and carotenoids (HRs for overall risk of death for the highest quintile ranging from 0.5-0.8); these associations were significant for retinol (Ptrend = 0.0002), α-carotene (Ptrend = 0.02), and total carotenoids (Ptrend = 0.02) and were generally consistent across subgroups (sex, ethnicity, cancer anatomical subtype, and stage). HRs for retinol and carotenoids were attenuated somewhat after adjustment for CRP. Similar trends for CRP were observed for colorectal cancer-specific deaths (HR for highest vs. lowest tertile: 2.06; 95% CI, 1.18-3.61; Ptrend = 0.01) as for deaths from all other causes (Pheterogeneity = 0.78). These observations are consistent with a direct relationship between circulating CRP and overall survival among patients with colorectal cancer. These results, if reproduced, suggest that reduction of inflammation should be explored as a potential complementary treatment strategy.

Neurodevelopmental Outcome of Extremely Low Birth Weight Infants with Candida Infection

Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status. ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study. Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047). In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.

An assessment of the impact of geographic variation on resection rates and survival for early-stage pancreatic adenocarcinoma.

e15052 Background: Pancreatic resection is the only known curative option for pancreatic adenocarcinoma. Resection has been previously reported to be underutilized in patients with early stage disease. To develop a better understanding of this issue and control for treatment selection factors, we examined the relationship between geographic area resection rates and survival in patients with stage I/II pancreatic cancer. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) data for patients with stage I/II cancer of the pancreatic head diagnosed from 2004-2009. We excluded patients with less than 3mo survival. Resection rates were calculated within Health Service Areas (HSAs) across all 18 SEER regions. Resection rate was defined as the number of patients who had an operation divided by the total number diagnosed with early stage pancreatic cancer. Multivariate Cox regression was used to estimate the overall survival effect of HSA rates while controlling for age, gender, marital status, poverty level, education, and AJCC stage. Results: 8,323 patients with stage I (n=1,454) and stage II (n=6,869) disease were analyzed. Pancreatectomy was performed in 476 patients (32.7%) with stage I disease and 3,846 (56.0%) with stage II disease. HSA resection rates were arranged into five groups (quintiles) which ranged from 42.7 to 65.7% (Table). Across the quintiles, median overall survival increased from 11 to 14 months, suggesting a positive association with resection rate. Multivariate analysis revealed that for every 10.00% increase in resection rate, the risk of overall death decreased by 5.26% (p&lt;0.001). Conclusions: Patients with early stage pancreatic cancer who live in areas with higher resection rates have longer average survival times. Because geography should not influence treatment response, we conclude that efforts to raise resection rates should increase survival times in patients for whom there is uncertainty about the risk/benefits of resection. [Table: see text]

Surgery in asymptomatic patients with colorectal cancer and unresectable liver metastases: the authors&amp;#39; experience

PurposeIn asymptomatic patients with Stage IV colorectal cancer, the debate continues over the efficacy of primary resection compared to chemotherapy alone. The aim of this study was to define the optimal management for asymptomatic patients with colorectal cancer and unresectable liver metastases.Patients and methodsPatients receiving elective surgery (n = 17) were compared to patients receiving chemotherapy only (n = 31). Data concerning patients’ demographics, location of primary tumor, comorbidities, performance status, Child–Pugh score, extension of liver metastases, size of primary, and other secondary locations were collected.ResultsThirty-day mortality after chemotherapy was lower than that after surgical resection (19.3% versus 29.4%; not significant). In patients with >75% hepatic involvement, mortality at 1 month was higher after receiving surgical treatment than after chemotherapy alone (50% versus 25%). In patients with <75% hepatic involvement, 30-day mortality was similar in both groups (not significant). Thirty-day mortality in patients with Stage T3 was lower in those receiving chemotherapy (16.7% versus 30%; not significant). Overall survival was similar in both groups. The risk of all-cause death after elective surgery (2.1) was significantly higher than in patients receiving chemotherapy only (P = 0.035).ConclusionThis study demonstrated that in palliative treatment of asymptomatic unresectable Stage IV colorectal cancer, the overall risk of death was significantly higher after elective surgery compared to patients receiving chemotherapy alone. However, in the literature, there is no substantial difference between these treatments. New studies are required to better evaluate outcomes.

Venous thromboembolism in patients with pancreatic cancer: Incidence and effect on survival in east Asian ethnic groups.

151 Background: Pancreatic cancer is known to be most frequently associated with venous thromboembolism (VTE), with the incidence of 10~20% in Western countries. As for the East Asian ethnic groups, just one small retrospective study showed lower incidence (5.3%) than other ethnic groups. However, there have been no large retrospective cohort studies of VTE in pancreatic cancer of East Asian ethnic group. Methods: We retrospectively reviewed the medical records of patients diagnosed with pancreatic adenocarcinoma in 2005~2010 at Severance Hospital, Seoul, Korea. Principal outcomes were incident VTE events and mortality. Cox proportional hazards models were used to analyze associations between specific risk factors and principal outcomes. Results: We investigated 1334 patients with pancreatic adenocarcinoma and 218 (16.3%) patients were excluded due to incomplete medical records and loss to follow-up. Among 1116 eligible patients, the overall and 1-year cumulative VTE incidence were 13.9% and 11.2% respectively. The incidence rate during the half year, 1-year and 2-years were 23.4, 17.7, 15.6 events per 100 person-years, respectively. Among total of 155 VTE patients, abdominal VTE was 52.9%, deep vein thrombosis was 21.3%, pulmonary thromboembolism was 19.4%, and head and neck VTE was 18.7%. In multivariable analyses, significant predictors of developing VTE included advanced metastatic stage (HR=2.08, 95% CI 1.37 to 3.17) and treatment of chemotherapy or radiotherapy, including CCRT (HR=1.52, 95% CI 16 to 1.99). VTE was a significant risk factor of 1-year and overall mortality (HR=1.44, 95% CI 1.15 to 1.79 and HR=1.45, 95% CI 1.21 to 1.73). Among 155 VTE patients, head and neck (H&amp;N) VTE revealed highest risk of overall mortality (HR=2.05, 95% CI 1.27 to 3.33, versus non-H&amp;N VTE). Conclusions: Approximately 13.9% of pancreatic adenocarcinoma patients developed VTE in East Asian ethnic group and this incidence was not significantly different from other ethnic groups. Advanced metastatic stage was the strongest predictor of VTE which would be a significant risk factor of 1-year mortality. Among VTE patients, head and neck VTE was 18.7% and showed the highest risk of overall death.

Aortic aneurysm disease vs. aortic occlusive disease - differences in outcome and intensive care resource utilisation after elective surgery

Abdominal aortic surgery is a high-risk procedure, with aortic aneurysm and aortic occlusive diseases being the main indications. These groups are often regarded as having equal perioperative risk profiles. Previous reports suggest that the haemodynamic and inflammatory response to aortic clamping is more pronounced in patients with aortic aneurysm disease, which may affect outcome. The aim of this observational cohort study was to evaluate outcome after open elective abdominal aortic surgery, hypothesising a higher 30-day mortality, a higher incidence of postoperative organ dysfunction and a longer length of stay in patients with aortic aneurysm compared with aortic occlusive disease. Cohort observational study based on prospective registrations from national databases. Eight Danish hospitals, including four university and four non-university centres, from 1 January 2007 to 1 March 2010. One thousand two hundred and ninety-three patients scheduled for primary open elective, aortoiliac bypass or aortofemoral bypass procedures or abdominal aortic aneurysm repair. Mechanical ventilation, acute dialysis, use of vasopressors or inotropes, ICU stay more than 24 h, hospital length of stay and mortality. Compared with aortic occlusive disease, more patients with aortic aneurysm disease had ICU stays more than 24 h (62 vs. 45%, P < 0.001) and more often needed acute dialysis or ventilatory support (17 vs. 11%, P = 0.04). No difference was found in hospital length of stay, 30-day mortality or overall risk of death. Mortality after 1 year was higher in patients with aortic aneurysm disease (8 vs. 4.7%, P = 0.04). Patients with abdominal aortic aneurysms were at higher risk of developing postoperative organ dysfunction and required more ICU resources than patients with occlusive disease, despite no differences in hospital length of stay or 30-day mortality. Distinguishing between these two diseases may be useful in planning and distribution of ICU resources and for in future studies.

Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d’étude des Tumeurs Endocrines (GTE) cohort study

Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.

Pre-microRNA variants predict HPV16-positive tumors and survival in patients with squamous cell carcinoma of the oropharynx

To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor specimens and genotyped four SNPs in pre-miRNAs (hsa-mir-146a rs2910164 G>C, hsa-mir-149 rs2292832 G>T, hsa-mir-196a2 rs11614913 C>T, and hsa-mir-499 rs3746444 A>G) in 309 SCCOP patients. Unconditional logistic regression models were used for calculation of odds ratio (OR) and 95% confidence intervals (CIs), and Kaplan–Meier analysis and Cox proportional hazards regression were used to evaluate associations. We found that statistically significant associations with HPV16-positive SCCOP and survival were found for hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913, while such similar associations were not observed for hsa-mir-149 rs2292832 and hsa-mir499 rs3746444. Compared with those with corresponding hsa-mir-146a CG/CC and has-mir-196a2 CC genotypes, the hsa-mir-146a GG and hsa-mir-196a2 CT/TT wild-type genotypes were significantly associated with HPV16-positive tumor status (adjusted OR, 2.4; 95% CI, 1.4–4.1 and adjusted OR, 2.1, 95% CI, 1.2–3.6), respectively. Patients having hsa-mir-146a rs2910164 GG and hsa-mir196a2 rs11614913 CT/TT genotypes had significantly better overall, disease-specific, and disease-free survival compared with those having the corresponding CG/CC and CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders including HPV status, smoking, and stage. Our findings indicate pre-miRNA polymorphisms may predict tumor HPV16-positive SCCOP cases and may be prognostic biomarkers for SCCOP.

A clinicopathological analysis in a large cohort of Chinese patients with renal amyloid light-chain amyloidosis

The aim of the study is to investigate the association between clinical and pathological features in a large cohort of Chinese patients with renal immunoglobulin light-chain amyloidosis (AL). A series of 186 patients with renal AL amyloidosis diagnosed between 1990 and 2011 were retrospectively reviewed. The extent of amyloid deposition in glomeruli, blood vessels and tubulointerstitium were evaluated semiquantitatively. The renal amyloid load was defined by the sum of glomerular, vascular and interstitial deposits. The associations between the clinical manifestations and pathological features were analyzed. The extent of glomerular amyloid deposition was positively correlated with the level of proteinuria. Patients with codeposition of amyloid and immune complexes (ICs) in glomeruli had higher levels of proteinuria than those without ICs. Advanced glomerular amyloid deposition was an independent pathological factor associated with renal insufficiency at diagnosis. The degree of vascular amyloid (VA) deposition was positively correlated with cardiac involvement and hepatic involvement. Patients with AL-κ showed a higher prevalence of hepatic involvement and more severe VA deposition than patients with AL-λ. High renal amyloid load independently predicted the increased risk for overall death after adjusting for recognized confounders. The degree and localization of amyloid deposits in the kidney of AL patients were associated with the degree of proteinuria and renal insufficiency, as well as extrarenal organs involvement. There were some differences between AL-κ and AL -λ in clinical and pathological characteristics. The renal amyloid load was an independent predictor for overall mortality.

Competing Risks of Death in Patients with Localized Renal Cell Carcinoma: A Comorbidity Based Model

Multiple risks compete with cancer as the primary cause of death. These factors must be considered against the benefits of treatment. We constructed a model of competing causes of death to help contextualize treatment trade-off analyses in patients with localized renal cell carcinoma. We identified 6,655 individuals 66 years old or older with localized renal cell carcinoma in the linked SEER (Surveillance, Epidemiology and End Results)-Medicare data set for 1995 to 2005. We used Fine and Gray competing risks proportional hazards regression to predict probabilities of competing mortality outcomes. Prognostic markers included race, gender, tumor size, age and the Charlson comorbidity index score. At a median followup of 43 months, age and comorbidity score strongly correlated with patient mortality and were most predictive of nonkidney cancer death, as measured by concordance statistics. Patients with localized, node negative kidney cancer had a low 3 (4.7%), 5 (7.5%) and 10-year (11.9%) probability of cancer specific death but a significantly higher overall risk of death from competing causes within 3 (10.9%), 5 (20.1%) and 10 years (44.4%) of renal cell carcinoma diagnosis, depending on comorbidity score. Informed treatment decisions regarding patients with solid tumors must integrate not only cancer related variables but also factors that predict noncancer death. We established a comorbidity based predictive model that may assist in patient counseling by allowing quantification and comparison of competing risks of death in patients 66 years old or older with localized renal cell carcinoma who elect to proceed with surgery.

Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials

BackgroundThe active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death...