The genetic framework for development of nephrolithiasis

Over 1%-15% of the population worldwide is affected by nephrolithiasis,which remains the most common and costly disease that urologists manage today.Identification of atrisk individuals remains a theoretical and technological challenge.The search for monogenic causes of stone disease has been largely unfruitful and a technological challenge;however,several candidate genes have been implicated in the development of nephrolithiasis.In this review,we will review current data on the genetic inheritance of stone disease,as well as investigate the evolving role of genetic analysis and counseling in the management of nephrolithiasis.

Management of 220 adolescents and adults with complications of hypospadias repair during childhood

Objective:The goal of hypospadias repair is to achieve normal voiding and good penile cosmesis with minimal complications.Some urethroplasties deteriorate from childhood to adolescence and late stage failures have been reported.We report our experience with adult patients who have had a previous repair during childhood and present with a late complication.Methods:We reviewed the records of 220 patients aged 15e39 years old with a history of hypospadias repair who presented to our clinic.Forty-five patients with chordee,39 with urethral strictures,11 urethral fistulae,five with hairy urethras,three with urethral diverticula,and 117 patients with an abnormal glans or subterminal meatus were repaired.Results:Median follow-up was 14 months.Two patients had persistent chordee.Island skin flap urethroplasty afforded one patient with a urethral fistula and another with a recurrent urethral stricture,while the buccal mucosa group had one fistula which healed spontaneously and two recurrent strictures.For the patients undergoing glanular repairs,seven had dehiscence or breakdown of the repair.All other operations were successful.Conclusion:Complications of childhood hypospadias repair may present later in life as some urethroplasties deteriorate with time.We now recommend to parents of children with repaired proximal hypospadias to come for follow-up as their child transitions to adolescence.

Cost-effectiveness analysis of treatments for metastatic castration resistant prostate cancer

Objective:Treatment options for metastatic castration resistant prostate cancer(mCRPC)have expanded rapidly in recent years.Given the significant economic burden,we sought perform a cost-effectiveness analysis(CEA)of the contemporary treatment paradigm for mCRPC.Methods:We devised a treatment protocol consisting of sipuleucel-T,enzalutamide,abiraterone,docetaxel,radium-223,and cabazitaxel.We estimated number and length of treatments for each therapy using dosing schedules or progression free survival data from published clinical trials.We estimated treatment cost using billing data and Medicare reimbursement values and performed a CEA.Our analysis assumed US$100,000 per life year saved(LYS)as the threshold societal willingness to pay.Results:Incremental cost-effectiveness ratios(ICER)for strategies incorporating sipuleucel-T that were not eliminated by extended dominance exceeded the societal threshold willingnessto-pay of US$100,000 per LYS,the lowest of which was sipuleucel-T+enzalutamide+abiraterone+docetaxel at US$207,714 per LYS.Enzalutamide+abiraterone+docetaxel exhibited the most favorable ICER among strategies without sipuleucel-T at US$165,460 per LYS.Conclusion:Based on the available survival data and current costs of treatment,all treatment strategies greatly exceed a commonly assumed societal willingness-to-pay threshold of US$100,000 per LYS.Improvements in this regard can only comewith a reduction in pricing,better tailoring of treatment or significant enhancements in survival with clinical use of treatment combinations or sequences.

Multi-parametric MRI of the prostate:Factors predicting extracapsular extension at the time of radical prostatectomy

Objective:Extracapsular extension(ECE)of prostate cancer is a poor prognostic factor associated with progression,recurrence after treatment,and increased prostate cancer-related mortality.Accurate staging prior to radical prostatectomy is crucial in avoidance of positive margins and when planning nerve-sparing procedures.Multi-parametric magnetic resonance imaging(mpMRI)of the prostate has shown promise in this regard,but is hampered by poor sensitivity.We sought to identify additional clinical variables associated with pathologic ECE and determine our institutional accuracy in the detection of ECE amongst patients who went on to radical prostatectomy.Methods:mpMRI studies performed between the years 2012 and 2014 were cross-referenced with radical prostatectomy specimens.Predictive properties of ECE as well as additional clinical and biochemical variables to identify pathology-proven prostate cancer ECE were analyzed.Results:The prevalence of ECE was 32.4%,and the overall accuracy of mpMRI for ECE was 84.1%.Overall mpMRI sensitivity,specificity,positive predictive value,and negative predictive value for detection of ECE were 58.3%,97.8%,93.3%,and 81.5%,respectively.Specific mpMRI characteristics predictive of pathologic ECE included primary lesion size((20.73±9.09)mm,mean±SD,p<0.001),T2 PIRADS score(p=0.009),overall primary lesion score(p<0.001),overall study suspicion score(p=0.003),and MRI evidence of seminal vesicle invasion(SVI)(p=0.001).

Effects of energy drinks on the cardiovascular system

Throughout the last decade, the use of energy drinks has been increasingly looked upon with caution as potentially dangerous due to their perceived strong concentration of caffeine aside from other substances such as taurine, guarana, and L-carnitine that are largely unknown to the general public. In addition, a large number of energy drink intoxications have been reported all over the world including cases of seizures and arrhythmias. In this paper, we focus on the effect of energy drinks on the cardiovascular system and whether the current ongoing call for the products' sales and regulation of their contents should continue.

Geometric comparison of the mitral and tricuspid valve annulus:Insights from three dimensional transesophageal echocardiography

AIM To apply real time three-dimensional transesophageal echocardiography(RT3D TEE) for quantitative and qualitative assessment of the mitral valve annulus(MVA) and tricuspid valve annulus(TVA) in the same patient.METHODS Our retrospective cohort study examined the MVA and TVA in 49 patients by RT3 D TEE. MVA and TVA shape were examined by TEE. The MVA and TVA volume data set images were acquired in the mid esophageal 4-chamber view. The MVA and TVA were acquired separately, with optimization of each for the highest frame rate and image quality. The 3D shape of the annuli was reconstructed using the Philips~? Q lab, MVQ ver. 6.0 MVA model software. The end-systolic frame was used. The parameters measured and compared were annular area, circumference, high-low distances(height), anterolateralposterolateral(ALPM), and anteroposterior(AP) axes. RESULTS A total of 49 patients(mean age 61 ± 14 years, 45% males) were studied. The ALPM and the AP axes of the MVA and TVA are not significantly different. The ALPM axis of the MVA was 37.9 ± 6.4 mm and 38.0 ± 5.6 mm for the TVA(P = 0.70). The AP axis of the MVA was 34.8 ± 5.7 mm and 34.9 ± 6.2 mm for the TVA(P = 0.90). The MVA and the TVA had similar circumference and area. The circumference of the MVA was 127.9 ± 16.8 mm and 125.92 ± 16.12 mm for the TVA(P = 0.23). The area of the MVA was 1103.7 ± 307.8 mm^2 and 1131.7 ± 302.0 mm^2 for the TVA(P = 0.41). The MVA and TVA are similar oval structures, but with significantly different heights. The ALPM/AP ratio for the MVA was 1.08 ± 0.33 and 1.09 ± 0.28 for the TVA(P < 0.001). The height for the MVA and TVA was 9.23 ± 2.11 mm and 4.37 ± 1.48 mm, respectively(P < 0.0001). CONCLUSION RT3 D TEE plays an unprecedented role in the management of valvular heart disease. The specific and exclusive shape of the MVA and TVA was revealed in our study of patients studied. Moreover, the intricate codependence of the MVA and the TVA depends on their distinctive shapes. This realization seen from our study will allow us to better understand the role valvular disease plays in disease states such as hypertrophic cardiomyopathy and pulmonary hypertension.

Challenges in Cardiovascular Risk Prediction and Stratifi cation in Women

There has been an appropriate focus,since the turn of the 21 st century,on sex-and gender-specifi c cardiovascular disease(CVD)as increasing evidence suggests that there are substantial differences in the risk factor profi le,social and environmental factors,clinical presentation,diagnosis,and treatment of ischemic heart disease in women compared with men.As a result of increased awareness,detection,and treatment of ischemic heart disease in women,there has been signifi cant reduction(greater than 30%)in cardiovascular mortality,and in 2013,more US men than US women died of CVD.Nevertheless,continued efforts are required as CVD remains the leading cause of cardiovascular morbidity and death of women in the Western world,and in women younger than 55 years there has been a rise in cardiovascular mortality.In this article,we review several of the contributing factors that continue to cause challenges in accurate risk prediction and risk stratifi cation in women.

Retinal vein occlusion associated with combined hormonal contraceptive vaginal ring use

Dear Editor,We read with interest your recent article on the impact of combined oral contraceptives on ocular tissues.We report a case of a branch retinal vein occlusion（BRVO）associated with use of an etonogestrel/ethinyl estradiol vaginal ring（NuvaR ing）,an implantable combined hormonal contraceptive,in a young healthy female with no other identifiable risk factors.

Circular smooth muscle contributes to esophageal shortening during peristalsis

AIM:To study the angle between the circular smooth muscle(CSM) and longitudinal smooth muscle(LSM) fibers in the distal esophagus.METHODS:In order to identify possible mechanisms for greater shortening in the distal compared to proximal esophagus during peristalsis,the angles between the LSM and CSM layers were measured in 9 cadavers.The outer longitudinal layer of the muscularis propria was exposed after stripping the outer serosa.The inner circular layer of the muscularis propria was then revealed after dissection of the esophageal mucosa and the underlying muscularis mucosa.Photographs of each specimen were taken with half of the open esophagus folded back showing both the outer longitudinal and inner circular muscle layers.Angles were measured every one cm for 10 cm proximal to the squamocolumnar junction(SCJ) by two independent investigators.Two human esophagi were obtained from organ transplant donors and the angles between the circular and longitudinal smooth muscle layers were measured using micro-computed tomography(micro CT) and Image J software.RESULTS:All data are presented as mean ± SE.The CSM to LSM angle at the SCJ and 1 cm proximal to SCJ on the autopsy specimens was 69.3 ± 4.62 degrees vs 74.9 ± 3.09 degrees,P = 0.32.The CSM to LSM angle at SCJ were statistically significantly lower than at 2,3,4 and 5 cm proximal to the SCJ,69.3 ± 4.62 degrees vs 82.58 ± 1.34 degrees,84.04 ± 1.64 degrees,84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees,P = 0.013,P = 0.008,P = 0.004,P = 0.009 respectively.The CSM to LSM angle at SCJ was also statistically significantly lower than the angles at 6,7 and 8 cm proximal to the SCJ,69.3 ± 4.62 degrees vs 80.18 ± 2.09 degrees,81.81 ± 1.75 degrees and 80.96 ± 2.04 degrees,P = 0.05,P = 0.02,P = 0.03 respectively.The CSM to LSM angle at 1 cm proximal to SCJ was statistically significantly lower than at 3,4 and 5 cm proximal to the SCJ,74.94 ± 3.09 degrees vs 84.04 ± 1.64 degrees,84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees,P = 0.019,P = 0.008,P = 0.02 respectively.At 10 cm above SCJ the angle was 80.06 ± 2.13 degrees which is close to being perpendicular but less than 90 degrees.The CSM to LSM angles measured on virtual dissection of the esophagus and the stomach on micro CT at the SCJ and 1 cm proximal to the SCJ were 48.39 ± 0.72 degrees and 50.81 ± 1.59 degrees.Rather than the angle of the CSM and LSM being perpendicular in the esophagus we found an acute angulation between these two muscle groups throughout the lower 10 cm of the esophagus.CONCLUSION:The oblique angulation of the CSM may contribute to the significantly greater shortening of distal esophagus when compared to the mid and proximal esophagus during peristalsis.

非典型抗精神病药物治疗住院精神分裂症或双相障碍患者急性激越和敌对的疗效:一项系统综述的结果（英文）

急性激越和敌对是双相障碍和精神分裂症患者的常见症状。本综述中,我们讨论在双相障碍或精神分裂症患者中上述症状的发生率、临床评估策略、治疗方案以及目前国内外针对这些症状的治疗指南。在现有的方法中,有使用肌肉注射的抗精神病药物和最近获得批准的口服非典型抗精神病药物治疗双相障碍或精神分裂症住院患者的急性激越和敌对,我们详细讨论了支持这些方法的最新证据,并强调各个抗精神病药物之间的一些差异。

Combination therapy for inflammatory bowel disease

Biologic therapies such as infliximab and adalimumab have become mainstays of treatment for inflammatory bowel disease. Early studies suggested that combination therapy(CT) with infliximab and an immunomodulator drug such as azathioprine may help optimize biologic pharmacokinetics, minimize immunogenicity, and improve outcomes. The landmark SONIC trial in Crohn's disease and the UC SUCCESS trial in ulcerative colitis demonstrated CT with infliximab and azathioprine to be superior to monotherapy with either agent alone at inducing clinical remission in treatment na?ve patients with moderate to severe disease. However, many unanswered questions linger. The role of CT in non-naive patients as well as the optimal duration of CT remains unknown. The effectiveness of CT with alternate biologics and/or alternate immunomodulators is not as clear, and it is unknown whether SONIC's conclusions can be extrapolated beyond infliximab and azathioprine. Also looming are the risks of CT including opportunistic infection and malignancy; specifically, lymphoma. This review lays out the evidence as it pertains to the risks and benefits of CT as well as the areas that require further research. With this information in hand, the practitioner may develop a treatment strategy that best suits each individual patient.

Magnesium in Women’s Health and Gynecology

Magnesium is well known in the world of obstetrics for many important uses. It has been utilized in treating pre-eclampsia, eclampsia, and preventing preterm labor, though it has been found recently that prolonged magnesium administration in pregnant women may result in adverse outcomes to fetal bone metabolism, resulting in a new FDA warning [1]. Outside of obstetrics, magnesium is recommended for treating the arrhythmias torsades de pointes and rapid atrial fibrillation, treating severe acute asthma, improving migraine symptoms, and for treating dyspepsia and constipation [2]. Many women in our modern society are magnesium deficient due to low dietary intake, and low dietary magnesium intake resulting in hypomagnesaemia has recently been shown to have many deleterious effects. Magnesium’s uses are wide-reaching, touching many areas of women’s health and gynecology from pre-menstrual syndrome to menopause, PCOS to endometriosis, and beyond.

三种精子处理方法对精子存活时间的影响

目的:探讨浓度梯度离心法、上游法和未经处理精子三种不同精子处理方法对精子存活时间的影响。方法:随机研究男科实验室患者15例,手淫取精后精液标本分为三组6份,未经处理的精子组为A组;浓度梯度离心法处理精子为B组;上游法处理精子为C组。每组又分为室温(25℃)和体温(37℃)组。每天(间隔24 h)光学显微镜观察精子的活率、前向运动,EY(伊红)染色评估精子死亡情况,直到精子全部死亡后2天。结果:三组在25℃室温与37℃体温下比较,显著延长精子存活时间,差异有统计学意义(P<0.05);B、C组与A组比较,体温及室温均(B组:11.6和28天;C组:9.5和26.7天;A组3.1和18.9天)显著延长精子存活时间,差异有统计学意义(P<0.05)。结论:精子处理后显著延长其存活时间,包括活率和前向运动;精子在25℃室温较37℃体温下显著延长精子存活时间。

放射性核素显像在肌肉骨骼感染中的研究进展

目前已有多种影像学检查可用于肌肉骨骼感染的诊断。X光片作为常规检查,即便有时不能提供诊断性信息,但可提供感兴趣区的解剖概况,利于后续影像学方法的选择和诊断。MRI的灵敏度很高,可提供详细的解剖细节。骨显像可不受基础病变的影响,准确诊断骨髓炎。67Ga主要用于脊柱骨髓炎的诊断。体外标记白细胞显像作为一种放射性核素检查方法,可用于糖尿病足骨髓炎和人工关节感染等复杂性骨髓炎的诊断,但不能用于诊断脊柱骨髓炎。抗粒细胞抗体和抗体片段具有一定的局限性,且不能广泛供应。^(111)In-生物素可用于脊柱骨髓炎的诊断。放射性标记抗菌肽泛素合成片段是一种有前景的特异性感染显像剂。^(18)F-脱氧葡萄糖(FDG)可用于脊柱骨髓炎的诊断,但其在糖尿病足骨髓炎和人工关节感染诊断方面的价值尚不明确。初步研究表明,^(68)Ga或可用于肌肉骨骼感染的诊断。^(124)I-fialuridine最初被认为可用作特异性感染显像剂,但随后的研究结果令人失望。PET/CT和SPECT/CT显像融合了解剖成像和功能显像,彻底改变了诊断影像学。这2种融合显像系统可提高诊断的准确性,并影响患者治疗方案的选择,从而重新定义了诊断学组在疑似或确诊感染和炎性反应患者中的价值。

Cold-inducible RNA-binding protein activates splenic T cells during sepsis in a TLR4-dependent manner

Cold-inducible RNA-binding protein (CIRP) is a novel inflammatory mediator that stimulates the release of proinflammatory cytokines from macrophages in sepsis. Given the immune dysregulation that characterizes sepsis, the effect of CIRP on other immune cells is an area of increasing interest that has not yet been studied. In the present study, we hypothesized that extracellular CIRP promotes activation of T lymphocytes in the spleen during sepsis. We observed that mice subjected to sepsis by cecal ligation and puncture showed significantly higher expression of the early activation markers CD69 and CD25 at 20 h on CD4+ splenic T cells, and significantly higher CD69 expression on CD8+ splenic T cells compared with sham-operated controls. Furthermore, at 20 h after receiving intravenous injection of recombinant murine CIRP (rmCIRP, 5 mg/kg body weight (BW)) or PBS (vehicle), those mice receiving rmCIRP showed significantly increased expression of CD69 and CD25 on both CD4+ and CD8+ splenic T cells. This effect, however, was not seen in TLR4-deficient mice after rmCIRP injection. In addition, treatment with CIRP predisposed CD4+ T cells to a Th1 hyperinflammatory response profile, and influenced CD8+ T cells toward a cytotoxic profile. Taken together, our findings indicate that CIRP is a proinflammatory mediator that plays an important role in T-cell dysregulation during sepsis in a TLR4-dependent manner.