Efficacy and Safety of Oral Anticoagulants in Patients With Atrial Fibrillation and Stages 4 or 5 Chronic Kidney Disease.

PURPOSE: The aim of this study was to investigate whether oral anticoagulants can provide efficacy and safety profiles better than no anticoagulant in patients with stages 4 or 5 chronic kidney disease and atrial fibrillation. METHODS: From 2001 to 2017, a cohort of patients with stages 4 or 5 chronic kidney disease and atrial fibrillation based on electronic medical records were selected from Chang Gung Memorial Hospital system in Taiwan. Patients were divided into nonvitamin K antagonist oral anticoagulants (NOACs), warfarin, and nonanticoagulated groups. They were followed from the index date to the occurrence of the study outcomes or for 5 years, whichever occurred first. The outcomes were admissions due to ischemic stroke or systemic embolism or major bleedings. Survival analyses were conducted to estimate the incidence rates of outcomes. RESULTS: A total of 3771 patients with atrial fibrillation and estimated glomerular filtration rate less than 30 mL/min/1.73m2 were enrolled, of whom 2971 were in the nonanticoagulated group, 280 in the NOAC group, and 520 in the warfarin group. About 25% of all subjects (940 patients) were on dialysis. The mean follow-up was 3.2 years. After adjusting for sex, age, comorbidities, and comedication, the warfarin group had a significantly higher risk of ischemic stroke or systemic embolism (adjusted hazard ratio [aHR] 3.1, 95% confidence interval [CI] 2.1-4.6) than the nonanticoagulated group. The NOAC group had a similar risk of ischemic stroke or systemic embolism (aHR 1.1; 95% CI 0.3-3.4) to that of the nonanticoagulated group. Both the warfarin and the NOAC groups had a significantly higher major bleeding risk than the noncoagulated group (aHR 2.8 [95% CI 2.0-3.8] for warfarin; aHR 3.1 [95% CI 1.9-5.2] for NOAC). CONCLUSION: The use of NOACs or warfarin is not more effective than using no anticoagulants at all in reducing the risk of ischemic stroke or systemic embolism. Both NOACs and warfarin are associated with increased risk of major bleeding. Our results do not support the use of anticoagulants in patients with atrial fibrillation and stages 4-5 chronic kidney disease.

Case series: Transplantation of kidneys from donors with renal artery aneurysm.

INTRODUCTION: With the present disparity between organ availability and recipient demands, we reported our experience in transplanting kidneys with renal artery aneurysm after back-table reconstruction. METHODS: Four patients were identified. The repair consisted of excision of the aneurysm with ostial closure, and for one of the cases, an ovarian vein patch was used. We reviewed the safety and outcomes of this procedure. All donors were asymptomatic before surgery and were diagnosed incidentally during living donor evaluation. The nephrectomies performed were hand-assisted laparoscopic approaches. All recipients had followup renal function and ultrasound duplex of renal artery at six and 12 months and then annually. RESULTS: The mean age of the recipients was 28.7 years (range 3-45). The mean size of the aneurysm was 7.4 ± 2.7 mm. All patients had immediate graft function with median serum creatinine of 1.9 ± 1.5 mg/dL at discharge. The average length of hospital stay was 6.25 ± 2.6 days. They also maintained good renal function with an average estimated glomerular filtration rate (eGFR) of 102.8 mL/min/1.73m2 (range 53.4-199 mL/min/1.73m2) and patent vessels at one year. One patient suffered from acute antibody-mediated rejection and lost his graft (medication non-compliance). One patient had two simultaneous benign renal cysts that were resected. Three of the kidneys were right-sided and one left. Mean cold ischemia time was 86 ± 18 minutes. No deaths have been recorded. CONCLUSIONS: Transplanting kidneys with a renal artery aneurysm after ex-vivo repair is safe and the outcomes are encouraging. Also, it may play an important role in expanding the donor pool in the face of current organ shortage.

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis.

BACKGROUND: Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. DESIGN: We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. RESULTS: A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. CONCLUSIONS: These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy.

Gene diversity, agroecological structure and introgression patterns among village chicken populations across North, West and Central Africa.

BACKGROUND: Chickens represent an important animal genetic resource for improving farmers' income in Africa. The present study provides a comparative analysis of the genetic diversity of village chickens across a subset of African countries. Four hundred seventy-two chickens were sampled in 23 administrative provinces across Cameroon, Benin, Ghana, Côte d'Ivoire, and Morocco. Geographical coordinates were recorded to analyze the relationships between geographic distribution and genetic diversity. Molecular characterization was performed with a set of 22 microsatellite markers. Five commercial lines, broilers and layers, were also genotyped to investigate potential gene flow. A genetic diversity analysis was conducted both within and between populations. RESULTS: High heterozygosity levels, ranging from 0.51 to 0.67, were reported for all local populations, corresponding to the values usually found in scavenging populations worldwide. Allelic richness varied from 2.04 for a commercial line to 4.84 for one population from Côte d'Ivoire. Evidence of gene flow between commercial and local populations was observed in Morocco and in Cameroon, which could be related to long-term improvement programs with the distribution of crossbred chicks. The impact of such introgressions seemed rather limited, probably because of poor adaptation of exotic birds to village conditions, and because of the consumers' preference for local chickens. No such gene flow was observed in Benin, Ghana, and Côte d'Ivoire, where improvement programs are also less developed. The clustering approach revealed an interesting similarity between local populations found in regions sharing high levels of precipitation, from Cameroon to Côte d'Ivoire. Restricting the study to Benin, Ghana, and Côte d'Ivoire, did not result in a typical breed structure but a south-west to north-east gradient was observed. Three genetically differentiated areas (P<0.01) were identified, matching with Major Farming Systems (namely Tree Crop, Cereal-Root Crop, and Root Crop) described by the FAO. CONCLUSIONS: Local chickens form a highly variable gene pool constituting a valuable resource for human populations. Climatic conditions, farming systems, and cultural practices may influence the genetic diversity of village chickens in Africa. A higher density of markers would be needed to identify more precisely the relative importance of these factors.

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999-2006.

Information on the impact of bone metastasis and skeletal-related events (SREs) on mortality among prostate cancer patients is limited. Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified men aged 65 years or older diagnosed with prostate cancer between July 1 1999 and December 31 2005 and followed to determine deaths through December 31 2006. We classified subjects as having bone metastasis and SREs as indicated by Medicare claims. Using Cox regression, we estimated mortality hazards ratios (HR) among men with bone metastasis with or without SRE, compared with men without bone metastasis. Among 126,978 men with prostate cancer (median follow-up, 3.3 years), 9746 (7.7%) had bone metastasis at prostate cancer diagnosis (1.7%) or during follow-up (5.9%). SREs occurred in 4296 (44%) men with bone metastasis. HRs for risk of death were 6.6 (95% CI=6.4-6.9) and 10.2 (95% CI=9.8-10.7), respectively, for men with bone metastasis but no SRE and for men with bone metastasis plus SRE, compared with men without bone metastasis. Bone metastasis was associated with mortality among prostate cancer patients. This association appeared to be stronger for bone metastasis plus SRE than for bone metastasis without SRE.

Pre-diagnostic NSAID use but not hormone therapy is associated with improved colorectal cancer survival in women.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone therapy (HT) independently decrease the risk of colorectal cancer. However, their role in altering survival after a colorectal cancer diagnosis is not well established. METHODS: We examined the association between the use of these common medications before diagnosis and colorectal cancer survival among women in western Washington State diagnosed with incident colorectal cancer from 1997 to 2002. Cases were ascertained using the Surveillance, Epidemiology and End Results cancer registry; mortality follow-up was completed through linkages to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We observed no overall association between colorectal cancer survival and pre-diagnostic NSAID use. However, when stratified by tumour sub-site, NSAID use was associated with a reduced risk of colorectal cancer mortality for women diagnosed with proximal (HR=0.55; 95% CI: 0.32-0.92), but not distal or rectal (HR=1.32; 95% CI: 0.83-2.10) tumours. The usage of HT was not associated with colorectal cancer survival overall or by tumour sub-site. CONCLUSION: Usage of NSAIDs before diagnosis may be associated with improved colorectal cancer survival among women diagnosed with proximal tumours. The usage of HT does not appear to have a function in altering colorectal cancer mortality.

Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes.

It has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p'-dichlorodiphenyldichloroethylene, chlordane-related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01-3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p-interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45-55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions < 0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.

Obesity, diabetes, and other factors in relation to survival after endometrial cancer diagnosis.

Endogenous and exogenous sources of estrogen and characteristics altering these hormone levels have been related to endometrial cancer risk; however, their relationship to survival following diagnosis is less clear. In a population-based study, we examined whether mortality after endometrial cancer diagnosis was affected by prediagnosis obesity, diabetes, smoking, oral contraceptive use, parity, or postmenopausal hormone (PMH) use. Eligible women, aged 40-79 years, diagnosed from 1991-1994 with incident invasive endometrial cancer and identified through the Wisconsin statewide mandatory cancer registry were invited to participate. Of 745 eligible cases, 166 women were deceased after 9.3 years of follow-up, with 43 attributable to endometrial cancer, based upon vital records linkage. Hazard rate ratios (HRR) and 95% confidence intervals were adjusted for age at diagnosis, menopausal status, stage of disease, and other exposures of interest. Obese women (body mass index [BMI] >or=30 kg/m(2)) prior to endometrial cancer diagnosis had an increased risk of both all-cause (HRR=1.6, 95% CI 1.0-2.5) and endometrial cancer (HRR=2.0, 95% CI 0.8-5.1) mortality, compared with nonoverweight women (BMI<25 kg/m(2)). Endometrial cancer cases with diabetes also had an increased risk of all-cause mortality compared with nondiabetic women (HRR=1.7, 95% CI 1.1-2.5), although there was no association with endometrial cancer mortality. There were no associations between PMH use, oral contraceptive use, parity, or smoking and mortality from any cause. The results suggest that history of obesity and diabetes may increase risk of mortality after endometrial cancer diagnosis; modification of these characteristics may improve survival after endometrial cancer diagnosis.

Recombinant factor VIIa after amniotic fluid embolism and disseminated intravascular coagulopathy.

This case report illustrates the successful use of activated recombinant factor VIIa in the management of severe postpartum hemorrhage secondary to amniotic fluid embolism.

Raman spectroscopy applications of an imaging photomultiplier tube.

A Raman spectroscopy system having an unprecedented combination of high sensitivity and low noise has been built incorporating an imaging (2-D) photomultiplier tube. The number of photons detected for a vibrational band approaches the theoretical limit set by the Raman cross section and experimental configuration. A detector dark count of 10(-4) counts/s/pixel is the major electronic source of noise. The spectrum of air reveals low concentration gas components, specifically (16)O(18)O and CO(2). Vibrational Raman spectra are obtained from solid samples as thin as 20 nm with low laser powers, e.g., 6.5 mW. The imaging photomultiplier yields 1-D (along the focused laser beam) Raman images of interfaces or concentration gradients.