Hypervitaminosis A is prevalent in children with CKD and contributes to hypercalcemia

Background

Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia.

Methods

We studied the relationship between vitamin A intake, serum retinoid levels, and serum calcium in 105 children with CKD stages 2–5 on dialysis and posttransplant. Serum retinoid measures included retinol (ROH), its active retinoic acid (RA) metabolites [all-trans RA (at-RA) and 13-cis RA] and carrier proteins [retinol-binding protein-4 (RBP4) and transthyretin (TTR)]. Dietary vitamin A intake was assessed using a food diary.

Results

Twenty-five children were in CKD 2–3, 35 in CKD 4–5, 23 on dialysis and 22 posttransplant; 53 % had vitamin A intake above the Reference Nutrient Intake (RNI) value. Children receiving supplemental feeds compared with diet alone had higher vitamin A intake (p?=?0.02) and higher serum ROH (p?<?0.001). Notably, increased ROH was seen as early as CKD stage 2. For every 10 ml/min/1.73 m² fall in estimated glomerular filtration rate (eGFR), there was a 13 % increase in ROH. RBP4 levels were increased in CKD 3–5 and dialysis patients. The lowest ratios of ROH:RBP4 were seen in dialysis compared with CKD 2–3 (p?=?0.03), suggesting a relative increase in circulating RBP4. Serum ROH, RBP4 and at-RA were associated with serum calcium. On multivariable analysis RBP4 levels and alfacalcidol dose were significant predictors of serum calcium (model R ² 32 %) in dialysis patients.

Conclusions

Hypervitaminosis A is seen in early CKD, with highest levels in children on supplemental feeds compared with diet alone. Serum retinoid levels significantly predict hypercalcemia.

     

Parathyroidectomy Decreases Insulin Resistance Index in Patients with Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) has been considered a cause of insulin resistance (IR) and impaired glucose metabolism. However, there are conflicting results related with the recovery of insulin resistance in patients with PHPT following curative parathyroidectomy. Our aim is to evaluate the effects of curative parathyroidectomy on IR in patients with PHPT. This is a prospective interventional study. Twenty-one consecutive patients with symptomatic PHPT were included into the study. All patients underwent parathyroidectomy. Fasting serum glucose, calcium, phosphorous, parathormone, plasma insulin, and vitamin D levels were measured both at baseline and 2 months after parathyroidectomy. Insulin resistance was calculated by homeostasis of model assessment-insulin resistance (HOMA-IR). Two months after curative parathyroidectomy, serum levels of calcium (p?=?0.001), PTH (p?<?0.001), insulin (p?=?0.003), and HOMA-IR (p?=?0.003) decreased, while phosphorous levels increased (p?=?0.001). During this period, no changes were observed at vitamin D and glucose levels. We concluded that curative parathyroidectomy decreases HOMA-IR index in patients with PHPT. Studies with larger population and longer follow-up period are required to confirm our results.     

Pristane-induced arthritis in dark Agouti rat is a relevant model for mimicking vascular dysfunction and lipid paradox in rheumatoid arthritis

ObjectivesTo understand the pathophysiology of cardiovascular (CV) dysfunction in rheumatoid arthritis (RA) is crucial, but limited by the paucity of animal models able to mimic CV impairments. We wanted to determine if the rat model of Pristane-Induced Arthritis (PIA) reproduced cardiometabolic impairments of RA.MethodsDark Agouti rats received an injection of pristane or saline (controls) at day 0. Reactivity to vasoconstrictors and vasodilators was studied in aortic rings and mesenteric arteries at day 28 (acute) and day 120 post-induction (chronic phase). Circulating markers of inflammation, lipid and glucose levels, arthritis and radiographic scores were assessed.ResultsIn aortic rings, PIA induced a reduced vasoconstriction to phenylephrine and serotonin in both phases of the model. The relaxant effect of acetylcholine was decreased in PIA in acute (P < 0.05) but not in chronic phase. In mesenteric arteries, only the acetylcholine-induced vasorelaxation was impaired in PIA rats in the chronic phase (P < 0.001). Serum interleukin-6 levels were higher, total cholesterol and triglycerides levels were lower in PIA in both phases (P < 0.001) whereas myeloperoxidase activity and blood glucose were unchanged. Adiponectine levels were lower in PIA in acute (P < 0.001) but not in chronic phase. Endothelial function correlated with interleukin-6, total cholesterol levels and arthritis score in aorta but not in mesenteric arteries.ConclusionsAs new information, PIA induces endothelial dysfunction in micro-/macro-vascular beds and low lipid levels, like in RA. This model of chronic arthritis might be useful to study CV pathophysiology and to screen new therapeutic options for reducing CV risk in RA.     

Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis

ObjectiveMany clinical studies have been carried out to investigate the relationship between periodontitis and rheumatoid arthritis (RA). Owing to limited evidence and inconsistent findings among these studies, it is unclear whether periodontitis would increase the risk for RA. This meta-analysis was performed to evaluate whether periodontitis represents a risk factor for RA.MethodsPubMed, Cochrane Library, Embase, Web of Science, and Wanfang were searched for eligible studies that compared periodontitis patients with controls. A pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between periodontitis and RA.ResultsThirteen studies including a total of 706611 periodontitis patients and 349983 control subjects were included. The pooled OR of RA risk between periodontitis and controls was (OR: 1.69; 95% CI: 1.31–2.17; P < 0.0001), indicating that the patients in periodontitis group had a 69% greater risk for RA than people in control group. When stratified by disease type, the pooled results showed periodontitis represents a risk factor for incident RA (OR = 1.70, 95%CI: 0.75–3.85, P < 0.001) and mixed RA (OR = 1.61, 95%CI: 1.26–2.06; P < 0.001). When stratified by disease duration, the pooled results showed periodontitis represents a risk factor for RA disease duration > 5 years (OR = 2.88, 95%CI: 0.66–12.62, P = 0.018), disease duration < 5 years (OR = 2.59, 95%CI: 0.83–8.11, P < 0.001), mixed disease duration (OR = 1.53; 95%CI: 1.05–2.22, P < 0.001).ConclusionOur meta-analysis revealed an increased risk of RA in patients with periodontitis compared to healthy controls. Moreover, when stratified by disease type, there was a higher risk between incident RA and periodontitis. When stratified by disease duration, the patients with periodontitis might be more closely associated with the RA patients with disease duration >5 years.     

Urinary Retinol-Binding Protein 4 is Associated With Renal Function and Rapid Renal Function Decline in Kidney Transplant Recipients

BackgroundUrinary retinol-binding protein 4 (RBP4) has been known as a biomarker of chronic kidney disease. In this study, we evaluated the association of urinary RBP4 with renal function and progression of renal function in kidney transplant recipients (KTRs).MethodsA total 50 KTRs were included in this study. Proteomic analysis with liquid chromatography-mass spectrometry and tandem mass spectrometry was performed to discover potential urinary biomarkers. Several urinary proteins including RBP4 were identified and then validated by enzyme-linked immunosorbent assay. Rapid renal function decline was defined as estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m²/year or initiation of dialysis, and 19 (38%) were included in rapid renal function decline group.ResultsUrinary RBP4/creatinine was inversely correlated with allograft function (r = –0.54, P < .001 with eGFR, and r = 0.49, P < .001 with serum creatinine, respectively). Urinary RBP4/creatinine was higher in rapid renal function decline group than in stable renal function group (184.9 ± 156.7 vs 83.1 ± 99.9, P = .017). Log-transformed urinary RBP4/creatinine was significantly associated with rapid renal function decline in univariate logistic regression analysis (Odds ratio [OR] 7.59, confidence interval [CI] 2.04-36.70, P = .005). In multivariate logistic regression adjusted with recipient age and sex, donor age, number of HLA mismatch, and acute rejection episode, urinary RBP4/creatinine remained a significant factor for rapid renal function decline (OR 9.43, CI 1.99-65.65, P = .010). Receiver operating characteristic analysis showed that the area under the curve of urinary RBP4/creatinine was 0.747 (CI 0.608-0.886, P < .001) for rapid renal function decline.ConclusionsUrinary RBP4 levels are associated with renal function and might be used to predict rapid renal function decline in KTRs.     

声辐射力脉冲成像评估2型糖尿病胰岛素抵抗患者肝脏功能

目的应用声辐射力脉冲成像(ARFI)中的声触诊组织量化(VTQ)技术评估2型糖尿病(T2DM)胰岛素抵抗(IR)患者肝脏弹性的改变。方法收集62例T2DM患者,分为IR组(n=32)和非IR组(n=30);检测空腹血糖、空腹胰岛素、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、甘油三酯(TG),并计算稳态模型IR指数;应用VTQ技术测定肝脏剪切波速度(SWV),分析其与IR及脂代谢相关血液指标的相关性。结果 IR组平均肝脏SWV值为(1.33±0.18)m/s,非IR组平均肝脏SWV值为(1.04±0.10)m/s,差异有统计学意义(P0.05)。随着肝脏SWV值升高,TC、TG、LDL-C升高而HDL-C降低。结论 T2DM患者肝脏SWV值与IR情况及血脂水平有密切关系;ARFI技术可用于评估T2DM IR患者的肝脏弹性及脂代谢情况。     

Clinical significance of tocilizumab-related neutropenia in patients with rheumatoid arthritis

ObjectiveTo determine the risks and clinical significance of tocilizumab (TCZ)-related neutropenia, in real-world settings, for patients with rheumatoid arthritis (RA).MethodsMedical records of RA patients treated with TCZ at a tertiary referral hospital in South Korea were collected. Infectious complications were defined as cases confirmed by clinical diagnosis and treated with antibiotics.ResultsA total of 277 RA patients with TCZ treatment (intravenous: 152 [54.9%], subcutaneous: 125 [45.1%]) were included in our study. During the observational period, 22 (7%) patients experienced grade 3 neutropenia. No patients discontinued TCZ due to neutropenia, while the dosage of conventional synthetic DMARD (csDMARD) was either reduced or discontinued for 8 patients. Patients, who experienced neutropenia while using csDMARD, had a higher risk for grade 3/4 neutropenia during TCZ treatment (hazard ratio [HR]: 3.120, 95% CI: 1.189–8.189, P = 0.021). Among infections, pulmonary infections were the most common (10.35 per 100 patient-years). Age over 60 years (HR: 2.133, 95% CI: 1.118–4.071, P = 0.022) and the presence of extra-articular manifestations (adjusted HR: 11.096, 95% CI: 5.353–22.999, P < 0.001), but not neutropenia (adjusted HR: 1.263, 95% CI: 0.269–5.945, P = 0.77), were risk factors for infections during TCZ treatment.ConclusionApproximately 7% of RA patients treated with TCZ developed grade 3 neutropenia. The previous history of neutropenia during csDMARD was a risk factor for TCZ-related neutropenia. Age and extra-articular manifestations, but not neutropenia, were risk factors for infection during TCZ treatment, suggesting that TCZ treatment can be maintained in the presence of neutropenia unless infection occurs.     

Utilization of renal mass biopsy in patients with localized renal cell carcinoma: A population-based study utilizing the National Cancer Database

ObjectiveTo evaluate trends and factors predicting use of renal mass biopsy (RMB) for localized Renal Cell Carcinoma in the United States (US) in the context of current guidelines recommendations.MethodsWe queried the National Cancer Database for cT1-cT3N0M0 Renal Cell Carcinoma diagnosed between 2004 and 2015. Temporal trends of RMB were characterized based on tumor size, treatment (partial nephrectomy [PN], radical nephrectomy [RN], ablation, and no treatment), age and Charlson Comorbidity Index with slopes compared using analysis of variance. Multivariable analysis was used to determine factors associated with use of RMB.ResultsOf 338,252 patients analyzed, 11.9% (40,276) underwent RMB. Use of RMB increased throughout the study period from 1,586 (7.6%) in 2004 to 5,629 (16.2%) in 2015 (P < 0.001). Use of RMB increased greatest for ablation (27 to 63%, P < 0.001) and tumors 2–4 cm (9 to 20%, P < 0.001). Multivariable analysis showed year of diagnosis (OR = 1.06; P < 0.001), higher education (OR = 1.09; P < 0.001) and insured status (OR = 1.23; P < 0.001) were associated with increased RMB. Compared to tumors ≤2 cm, tumors 2.1–4 cm (OR = 1.36; P=<0.001), 4.1–7 cm (OR = 1.18; P <0.001) and >7 cm (OR = 1.05; P = 0.03) were associated with higher rates of RMB. Compared to RN, PN was not associated with increased RMB (OR = 1.00; P = 0.92), while ablation (OR = 10.90; P < 0.001) and no surgical treatment (OR = 4.83; P < 0.001) were.ConclusionRMB utilization increased overall, with largest increase associated with ablation. Nonetheless, only two-thirds of patients underwent RMB with ablation, suggesting persistent underutilization. Rates of RMB for tumors ≤2 cm and in those undergoing no treatment increased less, suggesting less utilization for surveillance. However, rates for tumors >2–4 cm increased more, suggesting selective utilization of RMB to guide decision-making and risk stratification in small renal masses.     

Prognostic impact of tumor-associated immune cell infiltrates at radical cystectomy for bladder cancer

ObjectivesTo assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC).Material and methodsA total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan–Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10–55).ResultsOf the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence.ConclusionsIn this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer.     

Clinically node-positive (cN+) urothelial carcinoma of the bladder treated with chemotherapy and radical cystectomy: Clinical outcomes and development of a postoperative risk stratification model

Introduction and objectiveAlthough node-positive (cN+) bladder cancer is considered Stage IV disease, a subset of patients is treated with chemotherapy and consolidative radical cystectomy (RC). We examined the clinical outcomes of such patients and developed a risk prediction model to facilitate risk-stratification and management.MethodsWe identified adult patients with cTany cN1-3 M0 urothelial carcinoma of the bladder treated with chemotherapy followed by RC from 2006 to 2013 in the NCDB. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression, and a simplified risk score was developed.ResultsA total of 491 patients received chemotherapy followed by RC. Median number of lymph nodes removed was 16 (interquartile range 9–25). At RC, 10% of patients were ypT0, and 35% were ypN0. Over a median follow-up of 18.7 months, 160 patients died of any cause. 1-, 5-, and 8-year OS were 69%, 34%, and 29%, respectively. On multivariable analysis, pT stage (hazard ratio [HR] 2.18; P = 0.003 for pT3, HR 2.65; P < 0.001 for pT4 vs. <pT2) and pN stage (HR 1.77; P = 0.02 for pN1; HR 2.58; P < 0.001 for pN2; HR 5.09; P < 0.001 for pN3 vs. pN0) were independently associated with worse OS. A risk score was developed based on pT and pN stages, with 5-year OS of 59%, 24%, and 10% for risk score groups of 0-1, 2, and ≥3 points.ConclusionsSurvival for patients with cN+ bladder cancer treated with chemotherapy and RC is highly variable, ranging from 10% to 59% at 5 years. A risk score can facilitate postoperative risk-stratification and selection of patients for adjuvant therapy.     

PI-RADS score is associated with biochemical control and distant metastasis in men with intermediate-risk and high-risk prostate cancer treated with radiation therapy

BackgroundNovel methods of risk stratification are needed for men with prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) uses multiparametric MRI (mpMRI) to assign a score indicating the likelihood of clinically significant prostate cancer. We evaluated pretreatment mpMRI findings, including PI-RADS score, as a marker for outcome in patients treated with primary radiation therapy (RT).MethodsOne hundred and twenty-three men, 64% and 36% of whom had National Comprehensive Cancer Network (NCCN) intermediate-risk and high-risk disease, respectively, underwent mpMRI prior to RT. PI-RADS score and size of the largest nodule were analyzed with respect to freedom from biochemical failure (FFBF) and freedom from distant metastasis.ResultsA PI-RADS score of ≤3, 4, or 5 was defined in 7%, 49%, and 44%; with a median nodule size of 0, 8, and 18 mm, respectively (P < 0.001). Median follow-up was 67 months. Men with PI-RADS ≤ 3, 4, or 5 disease had 7-year FFBF of 100%, 92%, and 65% (P = 0.002), and a 7-year freedom from distant metastasis of 100%, 100%, and 82%, respectively (P = 0.014). PI-RADS (Hazard Ratio 5.4 for PI-RADS 5 vs. 4, P = 0.006) remained associated with FFBF when controlling for NCCN risk category (P = 0.063) and receipt of androgen deprivation therapy (P = 0.535). Nodule size was also associated with FFBF (Hazard Ratio 1.08 per mm, P < 0.001) after controlling for NCCN risk category (P = 0.156) and receipt of androgen deprivation therapy (P = 0.776).ConclusionmpMRI findings, including PI-RADS score and nodule size, may improve risk stratification in men treated with primary RT     

The effect of gender and age on kidney cancer survival: Younger age is an independent prognostic factor in women with renal cell carcinoma

ObjectiveGender-specific differences in incidence of renal cell carcinoma (RCC) and its outcome have previously been reported. We used age as a surrogate to test whether this might be hormone-related in a large international RCC cohort.Methods and MaterialsThis study included patients treated by nephrectomy at 10 international academic centers. Clinicopathologic features were assessed using chi-square and the Student t-tests. Kaplan-Meier survival estimates and Cox proportional hazards models addressed the effect of gender and age on disease-specific survival.ResultsOf the 5,654 patients, 3,777 (67%) were men and 1,877 (33%) were women. Generally, women presented at lower T stages (P<0.001), had fewer metastases (P<0.001), and had lower-grade tumors (P<0.001). Women more frequently had clear-cell (87% vs. 82%) and less frequently had papillary RCC (7% vs. 12%) than men (P<0.001). Women had a 19% reduced risk of death from RCC than men (hazard ratio 0.81, 95% confidence interval 0.73–0.90, P<0.001). The survival advantage for women was present to the greatest degree in the age group<42 years (P = 0.0136) and in women aged 42 to 58 years (P<0.001), but was not apparent in patients aged 59 years and older (P = 0.248). Age was an independent predictor of disease-specific survival in women (hazard ratio 1.011, 95% confidence interval 1.004–1.019, P = 0.004), but not in men.ConclusionsAs a group, women present with less advanced tumors, leading to a 19% reduced risk of RCC-specific death compared with men. This survival difference is present only in patients aged<59 years. Because this gender-based survival difference is not related to pathologic features, the role of hormonal effects on the development and progression of RCC needs to be investigated.     

非酒精性脂肪肝患者血清视黄醇结合蛋白4的变化及意义

目的研究非酒精性脂肪肝患者血清视黄醇结合蛋白4（RBP4）的变化及其与胰岛素抵抗（IR）的关系。方法采用ELISA法测定26例健康对照者及34例非酒精性脂肪肝患者血清RBP4水平。结果非酒精性脂肪肝患者血清RBP4水平[（25．6±11．2）mg／L]较健康对照者[（18．5±9．7）mg／L]明显升高,差异有统计学意义（P〈0．01）。相关分析显示RBP4与腰围、腰臀比、体重指数、总胆固醇、三酰甘油、空腹血糖、空腹血清胰岛素、稳态模型评估法胰岛素抵抗指数（HOMA-IR）有显著相关性（r=0．457、0．361、0．387、0．259、0．366、0．342、0．338、0．379,P〈0．01）。结论非酒精性脂肪肝患者血清RBP4水平升高,且与HOMA—IR呈正相关,提示RBP4在IR的发展中可能起一定的作用。     

Management of bone fragility in patients with rheumatoid arthritis in France: An analysis of a national health insurance claims database

ObjectivesRheumatoid arthritis (RA) is considered a major risk factor for fragility fractures. We examined the quality of management of bone fragility in RA patients in a real-life setting.MethodsWe performed a longitudinal case-control retrospective study in a 1/97th random sample of French health care claims database from 2014 to 2016 to determine the extent of bone fragility management in patients with RA compared with non-RA matched controls.ResultsCompared to their non-RA controls (n = 4652), RA patients (n = 1008; mean age: 61.1 years; methotrexate: 69.7%; other conventional disease-modifying antirheumatic drugs (cDMARDs): 26.8%; biologic: 26.0%; corticosteroids: 36.9%) had more reimbursements for bone mineral density (BMD) measurements (21.6 vs. 9.2%; OR = 2.7 [2.3; 3.3]; P < 0.01) and for bisphosphonates (7.1 vs. 3.6%, OR = 2.0 [1.5; 2.7]; P < 0.05). In patients exposed to corticosteroids, RA patients underwent more BMD assessments than non-RA controls (28.0 vs. 18.8%; OR = 1.7 [1.3; 2.2]; P < 0.05). RA patients exposed to corticosteroids were more likely to sustain fracture than non-exposed RA patients (5.7 vs. 2.4%, P < 0.01). In addition, only when comparing patients exposed to corticosteroids, was there statistical evidence of an association between RA and an increased fracture rate (6.2 vs. 3.5%, P < 0.05).ConclusionPatients with RA exposed to corticosteroids are at high risk of fracture. Patients with RA had more bone fragility management than controls.     

Dutasteride monotherapy in men with serologic relapse following radical therapy for adenocarcinoma of the prostate: A pilot study

ObjectiveThe objective of this study was to assess the effect of dutasteride on serum prostate specific antigen (PSA) levels in men with serologic relapse following radical prostatectomy and/or radiation therapy for clinically localized adenocarcinoma of the prostate.MethodsA prospective, single institution, IRB approved trial was conducted. Entry criteria required that all participants have serologic disease relapse only with serum PSA levels between 0.4 and 10.0 ng/ml. Enrolled participants were treated with 0.5 mg dutasteride daily. The primary endpoints were serum PSA level and clinical recurrence. The rate of durable decline in PSA was assessed according to the recommendations of the Prostate-Specific Antigen Working Group.ResultsThirty-five patients provided informed consent and participated in the present study. At a median follow-up duration of 27 months (range, 4–42 months), 46% of enrolled men had a serum PSA decrease of greater than 10%, and 25% had a serum PSA decrease of greater than 50% (P < 0.001). Pre-study PSA doubling time (PSADT) (≥12 months vs. <12 months), and Gleason score (≤6 vs. ≥7) were associated with a better response to dutasteride, but only PSADT was statistically significant (P < 0.001). Thirty percent of patients experienced PSA progression (increase in serum PSA of greater than 50%). Two (6%) patients developed bone metastasis. No patient was removed from the study for drug-related toxicity.ConclusionsIn the present pilot study, treatment with dutasteride resulted in a significant decrease in serum PSA in men with serologic relapse following radical treatment for adenocarcinoma of the prostate. These data appear to suggest that dutasteride may delay or prevent progression of prostate cancer in some men with biochemical relapse after radical therapy. These findings require confirmation in the setting of a larger, longer trial.     

Anesthésies et analgésies pratiquées dans les maternités françaises

ObjectiveTo assess the rate of epidural analgesia (EA) for parturition and the techniques of anaesthesia for Caesarean section (CS).Study designRetrospective study.PatientsA series of 84,235 deliveries.MethodsThe series was extracted from a total of 770,054 deliveries carried out in 1991, according to the number of births in each hospital (1/1 if the births were ≤ 100 per year, up to 1/25 if they were ≥ 2,000 per year). The data analyzed included: anaesthesia technique, wheher or not there was an anaesthetist on night duty at the hospital, birth rate in the hospital, type of hospital: university (UH), general (GH) or private (PH). For vaginal deliveries, the mode of labour commencement (spontaneous or induced), the multiplicity of pregnancies and a history of past CS were also noted.ResultsVaginal deliveries: the overall rate of EA was 37.2%. EA were not carried out in 5% of maternity hospitals. In cases of spontaneous labour, the average rate was 32.1%, significantly less than for induced labour (59.6%, P < 0.0001) and in cases of previous CS (39%, P < 0.05). There was no statistical difference in cases of multiple pregnancies (35.7%). The average rate of EA was correlated to the number of annual births (P < 0.001) and was increased when the anaesthetist was present in hospital at night (P < 0.001). It was also significantly lower in GH (P < 0.001) than in UH or PH, which were equivalent.Scheduled CS:general anaesthesia (GA) was carried out at a significantly higher rate than regional anaesthesia (RA) (49.7% vs 48.4%, P< 0.05). In 15.1% of hospitals, RA was not available. The incidence of RA was influenced neither by the rate of annual births nor by the presence of the anaesthetist in the hospital during night. However, RA was significantly less frequent in GH (46.3%, P < 0.001) than in UH (48.6%) and in PH (53.6%) which were equivalent.CS during labour: the incidence of RA was significantly higher than GA (53.2% vs 44.1%, P< 0.001). In 17.1% of hospitals, RA was never carried out. The rate of RA was correlated to the size of the maternity hospital, and significantly higher (P < 0.001) when the anaesthetist was present in hospital during night. The differences between UH, GH and EP were the same than for scheduled CS.ConclusionIn France in 1991, the average rate of 37.2% for EA for obstetrics was high when compared to the rate in United Kingdom. It was equivalent to those in United States and Ontario, Canada. The discrepancies between hospitals were mainly related to structural and organizational factors. The influence of the size of the maternity hospital, the 24-hour service of EA was also shown in other studies. However, the difference between GA and UH and PH is a French particularity. The high rate of GA for CS differs largely with those in the UK or the USA. The time saving aspect of GA was probably an important factor for the choice of this technique. This study must be reactualized and enlarged to determine the demand of EA for labour by parturients and obstetricians.     

Elevated hemoglobin is associated with poor prognosis in Tibetans with poor-grade aneurysmal subarachnoid hemorrhage after clipping: A Retrospective Case-Control Study

ObjectivesHigh hemoglobin (HGB) concentration is frequently seen in Tibetans in clinical practice; however, the impact on postsurgical prognosis in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is not precisely known. Thus, we sought to understand the association between high HGB level and postoperative outcome in Tibetans with poor-grade aSAH.Patients and methodsResults of clipping in consecutive Tibetan patients with poor-grade aSAH were analyzed retrospectively for the period January 2012 to January 2017. Based on the upper limit (160 g/L) of normal hemoglobin levels, patients were divided to a high (HHC) and a normal (NHC) HGB-level cohort according to the first routine blood result on admission. Propensity score matching was used for baseline matching in the 2 cohorts. Postoperative complications in the 2 groups were compared. Prognosis after ictus, including 6-month neurological functional status and mortality at 30 days and 6 months were also assessed.ResultsRisk of ischemia, pulmonary embolism and lower-limb deep venous thrombosis (DVT) was higher in HHC than NHC (62.88% vs. 21.64%; P < 0.001; 10.30% vs. 1.31%, P < 0.005; 24.74% vs. 7.21%, P < 0.001, respectively). Hospital stay also differed significantly (15.82 ± 3.86 vs. 10.37 ± 4.80 days; P < 0.001). Out of the 194 patients, 150 survived at 6 months. At 6-month neurological functional follow-up, 8 NHC patients had favorable modified Rankin scale (mRS) scores ≤ 2 at discharge, versus only 1 HHC patient, showing better outcome in NHC than HHC (8.25% vs. 1.03%; P = 0.035). In-hospital mortality was significantly greater in HHC than NHC (17.52% vs. 7.22%; P = 0.029). 30-day post-ictus mortality was 30.93% in HHC versus 14.43% in NHC (P < 0.006). There was also a significant difference in mortality at 6 months post-ictus (47.42% vs. 18.56%; P < 0.001).ConclusionHigh HGB level was associated with increased risk of postsurgical cerebral ischemia, pulmonary embolism and lower-limb DVT and poor prognosis in poor-grade aSAH patients. Preoperative hemodilution therapy might be beneficial in reducing operative complications, reducing hospital stay and improving short-term prognosis for neurological functional recovery in aSAH patients with high HGB concentration, but further detailed research is needed.     

Prevalence and out-patient medical costs of comorbid conditions in patients with rheumatoid arthritis

ObjectivesTo evaluate the prevalence, types, and out-patient direct medical costs of comorbid conditions in patients with RA in Thailand.MethodsInformation of the patients with RA treated by rheumatologists with at least one disease modifying antirheumatic drugs (DMARDs), including demographic data, RA-related medication types and treatment costs, comorbidity-related medication types and treatment costs, and total direct medical costs, was captured from King Chulalongkorn Memorial Hospital databases.ResultsThe data from 684 patients with RA were included for analysis. The majority of the patients were prescribed combined DMARDs, while only 2.5% received biologics. Comorbid conditions were reported in 434 patients (63.5%). The most common comorbid condition was hypertension (51.2%). Advanced age and presence of healthcare coverage was associated with comorbid conditions. The average annual cost of non-RA-related treatments in patients with comorbid diseases was 15 times the cost in those without comorbidities (1546 vs. 104 USD; P < 0.001) while the total direct medical cost in patients with comorbid conditions was twice that in patients without comorbid diseases (4118 vs. 2045 USD; P < 0.001). Parameters that influenced total direct medical costs were RA medications costs, comorbidity, healthcare coverage, patient's age, and types of DMARDs.ConclusionsComorbid conditions were common in this study. However, the major cost component incurred in RA patients was the costs of RA medications and services, while the out-patient costs of comorbid conditions accounted for approximately 38% of the total costs.     

Predictive value of low testosterone concentrations during and prior to enzalutamide treatment in metastatic castration-resistant prostate cancer

BackgroundEnzalutamide is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC) patients. However, variances in responses are observed and there is a need for biomarkers predicting treatment outcome and selection. In this study, we aimed to explore the predictive value of testosterone for first-line enzalutamide treatment of mCRPC.MethodsA retrospective analysis of 72 mCRPC patients with no prior abiraterone or docetaxel treatment was performed. Serum testosterone was measured using a liquid chromatography tandem-mass spectrometry method. Association of pre- and during-enzalutimide treatment testosterone levels with progression-free survival (PFS) and failure-free survival (FFS) was investigated using univariate and multivariate Cox models. Testosterone levels were dichotomized into a low (Q1) and high (interquartile range-Q4) group.ResultsMedian PFS (7.4 v. 20.8 months, P<0.0001) and FFS (6.6 v. 17.7 months, P<0.0001) were shorter for patients with low testosterone levels (<0.217 nmol/L) during enzalutamide treatment. Furthermore, univariate Cox proportional hazards models revealed that low testosterone levels were associated with shorter PFS (HR 3.5, 95%CI 1.9-6.3; P<0.001) and FFS (HR 3.1, 95%CI 1.7–5.5; P<0.001). Pre-treatment testosterone levels were lower than during-treatment levels (P<0.0001) and low pre-treatment testosterone levels (<0.143 nmol/L) were associated with shorter median PFS (12.6 v. 20.5 months, P<0.01) and FFS (12.6 v. 22.5 months, P<0.01).ConclusionThe results of this study suggest that low serum testosterone levels during and prior to enzalutamide treatment can predict progression in mCRPC patients and identifies tumors resistant to next-in-line enzalutamide treatment. Validation in a prospective cohort is warranted.