Summarizing the evidence for robotic-assisted bladder neck reconstruction: Systematic review of patency and incontinence outcomes

Objective:Bladder neck contracture and vesicourethral anastomotic stenosis are difficult to manage endoscopically,and open repair is associated with high rates of incontinence.In recent years,there have been increasing reports of robotic-assisted bladder neck reconstruction in the literature.However,existing studies are small,heterogeneous case series.The objective of this study was to perform a systematic review of robotic-assisted bladder neck reconstruction to better evaluate patency and incontinence outcomes.Methods:We performed a systematic review of PubMed from first available date to May 2023 for all studies evaluating robotic-assisted reconstructive surgery of the bladder neck in adult men.Articles in non-English,author replies,editorials,pediatric-based studies,and reviews were excluded.Outcomes of interest were patency and incontinence rates,which were pooled when appropriate.Results:After identifying 158 articles on initial search,we included only ten studies that fit all aforementioned criteria for robotic-assisted bladder neck reconstruction.All were case series published from March 2018 to March 2022 ranging from six to 32 men,with the median follow-up of 5e23 months.A total of 119 patients were included in our analysis.A variety of etiologies and surgical techniques were described.Patency rates ranged from 50%to 100%,and pooled patency was 80%(95/119).De novo incontinence rates ranged from 0%to 33%,and pooled incontinence was 17%(8/47).Our findings were limited by small sample sizes,relatively short follow-ups,and heterogeneity between studies.

Ultrasound shear wave elastography and liver fibrosis: A Prospective Multicenter Study

AIM To assess the accuracy of shear wave elastography(SWE) alone and in combination with aminotransferase platelet ratio index(APRI) score in the staging of liver fibrosis.METHODS A multicenter prospective study was conducted to assess the accuracy of SWE(medians) and APRI to predict biopsy results. The analysis focused on distinguishing the different stages of liver disease, namely, F0 from F1-4, F0-1 from F2-4, F0-2 from F3-4 and F0-3 from F4; F0-F1 from F2-F4 being of primary interest. The area under the receiver operating characteristic(AUROC) curve was computed using logistic regression model. The role of age, gender and steatosis was also assessed.RESULTS SWE alone accurately distinguished F0-1 from F2-4 with a high probability. The AUROC using SWE alone was 0.91 compared to 0.78 for using the APRI score alone.The APRI score, when used in conjunction with SWE, did not make a significant contribution to the AUROC. SWE and steatosis were the only significant predictors that differentiated F0-1 from F2-4 with an AUROC of 0.944.CONCLUSION Our study validates the use of SWE in the diagnosis and staging of liver fibrosis. Furthermore, the probability of a correct diagnosis is significantly enhanced with the addition of steatosis as a prognostic factor.

Validation of Treatment Planning Dose Calculations: Experience Working with Medical Physics Practice Guideline 5.a.

Recently published Medical Physics Practice Guideline 5.a. (MPPG 5.a.) by American Association of Physicists in Medicine (AAPM) sets the minimum requirements for treatment planning system (TPS) dose algorithm commissioning and quality assurance (QA). The guideline recommends some validation tests and tolerances based primarily on published AAPM task group reports and the criteria used by IROC Houston. We performed the commissioning and validation of the dose algorithms for both megavoltage photon and electron beams on three linacs following MPPG 5.a. We designed the validation experiments in an attempt to highlight the evaluation method and tolerance criteria recommended by the guideline. It seems that comparison of dose profiles using in-water scan is an effective technique for basic photon and electron validation. IMRT/VMAT dose calculation is recommended to be tested with some TG-119 and clinical cases, but no consensus of the tolerance exists. Extensive validation tests have provided the better understanding of the accuracy and limitation of a specific dose calculation algorithm. We believe that some tests and evaluation criteria given in the guideline can be further refined.

一种以超分辨率理论为基础的磁共振眼球成像方法

磁共振成像(MRI)是一种无电离辐射的非介入性的眼内肿瘤检测方法,但分辨率和运动伪影是成像过程中不易克服的困难.以往的扫描方法或是不可避免的引入运动伪影,或是需要受试者做精确的配合,增加了成像的难度,给受试者带来不舒适的体验.本文提出了一种以超分辨率理论为基础的新的磁共振眼球成像方法,使用一种特制的眼球线圈,对眼部区域扫描一系列动态的图像,使得不同方向上的采集分辨率互补.最后经过预处理、配准、超分辨率重建等操作,得到高质量的磁共振眼球图像.实验结果表明,这种方法可以在不需要受试者做额外配合工作的情况下,得到更加清晰的磁共振眼球图像.

Hypoxia inducible factor in hepatocellular carcinoma:A therapeutic target

Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.

Clinical features,histology,and histogenesis of combined hepatocellular-cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma(CHC) is a rare tumor with poor prognosis,with incidence ranging from 1.0%-4.7% of all primary hepatic tumors.This entity will be soon renamed as hepato-cholangiocarcinoma.The known risk factors for hepatocellular carcinoma(HCC) have been implicated for CHC including viral hepatitis and cirrhosis.It is difficult to diagnose this tumor pre-operatively.The predominant histologic component within the tumor largely determines the predominant radiographic features making it a difficult distinction.Heterogeneous and overlapping imaging features of HCC and cholangiocarcinoma should raise the suspicion for CHC and multiple core biopsies(from different areas of tumor) are recommended before administering treatment.Serum tumor markers CA19-9 and alpha-fetoprotein can aid in the diagnosis,but it remains a challenging diagnosis prior to resection.There is sufficient data to support bipotent hepatic progenitor cells as the cell of origin for CHC.The current World Health Organization classification categorizes two main types of CHC based on histo-morphological features:Classical type and CHC with stem cell features.Liver transplant is one of the available treatment modalities with other management options including transarterial chemoembolization,radiofrequency ablation,and percutaneous ethanol injection.We present a review paper on CHC highlighting the risk factors,origin,histological classification and therapeutic modalities.

T1ρ/T2 mapping and histopathology of degenerative cartilage in advanced knee osteoarthritis

AIM To investigate whether normal thickness cartilage in osteoarthritic knees demonstrate depletion of proteoglycan or collagen content compared to healthy knees.METHODS Magnetic resonance(MR) images were acquired from5 subjects scheduled for total knee arthroplasty(TKA)(mean age 70 years) and 20 young healthy control subjects without knee pain(mean age 28.9 years). MR images of T1ρ mapping, T2 mapping, and fat suppressed proton-density weighted sequences were obtained.Following TKA each condyle was divided into 4 parts(distal medial, posterior medial, distal lateral, posterior lateral) for cartilage analysis. Twenty specimens(bone and cartilage blocks) were examined. For each joint,the degree and extent of cartilage destruction was determined using the Osteoarthritis Research Society International cartilage histopathology assessment system.In magnetic resonance imaging(MRI) analysis, 2 readers performed cartilage segmentation for T1ρ/T2 values and cartilage thickness measurement.RESULTS Eleven areas in MRI including normal or near normal cartilage thickness were selected. The corresponding histopathological sections demonstrated mild to moderate osteoarthritis(OA). There was no significant difference in cartilage thickness in MRI between control and advanced OA samples [medial distal condyle, P = 0.461;medial posterior condyle(MPC), P = 0.352; lateral distal condyle, P = 0.654; lateral posterior condyle, P = 0.550],suggesting arthritic specimens were morphologically similar to normal or early staged degenerative cartilage.Cartilage T2 and T1ρ values from the MPC were significantly higher among the patients with advanced OA(P= 0.043). For remaining condylar samples there was no statistical difference in T2 and T1ρ values between cases and controls but there was a trend towards higher values in advanced OA patients. CONCLUSION Though cartilage is morphologically normal or near normal, degenerative changes exist in advanced OA patients. These changes can be detected with T2 and T1ρ MRI techniques.

Minimally invasive local therapies for liver cancer

Primary and metastatic liver tumors are an increasing global health problem,with hepatocellular carcinoma(HCC)now being the third leading cause of cancer-related mortality worldwide.Systemic treatment options for HCC remain limited,with Sorafenib as the only prospectively validated agent shown to increase overall survival.Surgical resection and/or transplantation,locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments,providing improved survival outcomes for both primary and metastatic tumors.Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors.For patients with low volume disease,these therapies have now been established into consensus practice guidelines.This review highlights technical aspects and outcomes of commonly utilized,minimally invasive local therapies including laparoscopic liver resection(LLR),radiofrequency ablation(RFA),microwave ablation(MWA),high-intensity focused ultrasound(HIFU),irreversible electroporation(IRE),and stereotactic body radiation therapy(SBRT).In addition,the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.

WJH 6^(th) Anniversary Special Issues(2): Hepatocellular carcinoma Mammalian target of rapamycin inhibition in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.

Fecal DNA testing for colorectal cancer screening:molecular targets and perspectives

The early detection of colorectal cancer with effective screening is essential for reduction of cancer-specific mortality. The addition of fecal DNA testing in the armamentarium of screening methods already in clinical use launches a new era in the noninvasive part of colorectal cancer screening and emanates from a large number of previous and ongoing clinical investigations and technological advancements. In this review, we discuss the molecular rational and most important genetic alterations hallmarking the early colorectal carcinogenesis process. Also, representative DNA targets-markers and key aspects of their testing at the clinical level in comparison or/and association with other screening methods are described. Finally, a critical view of the strengths and limitations of fecal DNA tests is provided, along with anticipated barriers and suggestions for further exploitation of their use.

Conversion total hip arthroplasty: Primary or revision total hip arthroplasty

Total hip arthroplasty(THA) is an increasingly common procedure among elderly individuals.Although conversion THA is currently bundled in a diagnosis related group(DRG) with primary THA,there is a lack of literature supporting this classification and it has yet to be identified whether conversion THA better resembles primary or revision THA.This editorial analyzed the intraoperative and postoperative factors and functional outcomes following conversion THA,primary THA,and revision THA to understand whether the characteristics of conversion THA resemble one procedure or the other,or are possibly somewhere in between.The analysis revealed that conversion THA requires more resources both intraoperatively and postoperatively than primary THA.Furthermore,patients undergoing conversion THA present with poorer functional outcomes in the long run.Patients undergoing conversion THA better resemble revision THA patients than primary THA patients.As such,patients undergoing conversion THA should not be likened to patients undergoing primary THA when determining risk stratification and reimbursement rates.Conversion THA procedures should be planned accordingly with proper anticipation of the greater needs both in the operating room,and for in-patient and followup care.We suggest that conversion THA be reclassified in the same DRG with revision THA as opposed to primary THA as a step towards better allocation of healthcare resources for conversion hip arthroplasties.

Esophageal stent fracture:case report and review of the literature

Endoscopic esophageal stent placement is widely used in the treatment of a variety of benign and malignant esophageal conditions.Self expanding metal stents(SEMS)are associated with significantly reduced stent related mortality and morbidity compared to plastic stents for treatment of esophageal conditions;however they have known complications of stent migration,stent occlusion,tumor ingrowth,stricture formation,reflux,bleeding and perforation amongst others.A rare and infrequently reported complication of SEMS is stent fracture and subsequent migration of the broken pieces.There have only been a handful of published case reports describing this problem.In this report we describe a case of a spontaneously fractured nitinol esophageal SEMS,and review the available literature on the unusual occurrence of SEMS fracture placed for benign or malignant obstruction in the esophagus.SEMS fracture could be a potentially dangerous event and should be considered in a patient having recurrent dysphagia despite successful placement of an esopha-geal SEMS.It usually requires endoscopic therapy and may unfortunately require surgery for retrieval of a distally migrated fragment.Early recognition and prompt management may be able to prevent further problems.

星形胶质细胞糖原和乳酸：学习和记忆机制探索新发现

记忆功能是生存的必备能力,获得的各种信息需要通过记忆来保存。目前,有关记忆形成和储存的分子和细胞研究主要集中在神经元。但除了神经元,大脑中还包含其他多种细胞和系统,包括胶质细胞和脉管系统。近来一些研究开始关注大脑中的非神经元细胞在记忆形成中的作用。研究结果显示,所有的胶质细胞(星形胶质细胞、少突胶质细胞和小胶质细胞)都在记忆的形成和储存中发挥了重要作用。最新研究显示,在长期记忆的形成过程中,神经元会持续产生变化,星形胶质细胞为神经元的这种变化提供能量。本综述即对相关研究结果进行总结和分析,主要有3点。第一,在长期记忆的形成过程中,星形胶质细胞和神经元之间存在葡萄糖代谢以及学习和活动依赖的代谢偶联。第二,星形胶质细胞的葡萄糖代谢在情绪激动的过程中有重要的作用,而情绪激动是形成持久和详细记忆的重要组成部分。第三,因为在大脑的早期形成过程中需要大量的能量,我们还会探讨星形胶质细胞和神经元葡萄糖代谢在早期记忆形成过程中的作用。根据这些研究结果,我们对未来维护脑健康和治疗脑疾病提供新的方向和思路。星形胶质细胞糖原分解和乳酸在记忆的形成中有重要的作用。引起强烈的情绪波动的经历会形成深刻的记忆,其机制与星形胶质细胞β2肾上腺素受体激活及其乳酸分泌增加有关。在发育过程中,大脑所需要的能量高于其他时期,因此糖原分解和星形胶质细胞-神经元代谢偶联在发育过程中的记忆形成中可能也发挥了重要作用。

Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up

AIM: To determine the prevalence of bipolar disorder(BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder(ADHD) through 14 years' follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type Ⅰ?and Ⅱ diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD(MTA). We used the diagnostic interview schedule for children(DISC), administered to both parents(DISC-P) and youth(DISCY). We compared the MTA study subjects with ADHD(n = 579) to a local normative comparison group(LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts(TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic(PM) and non-specific manic(NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD(1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time(df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability(BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG(χ2 = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM(df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2(A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies.

A new tool for monitoring brain function: eye tracking goes beyond assessing attention to measuring central nervous system physiology

Concussion and other forms of brain injury are not always detectable with conventional means such as radiographic imaging.The lack of accurate diagnostics,biomarkers,and outcome measures has a devastating impact.Individual patients may suffer in obscurity,self-medicate into an addictive spiral,have impaired professional activity,and develop failed interpersonal relationships.

Gastrointestinal problems, mechanisms and possible therapeutic directions in Gulf war illness: a mini review

By its nature, Gulf war illness(GWI) is multi-symptomatic and affects several organ systems in the body. Along with other symptoms, veterans who suffer from GWI commonly report chronic gastrointestinal issues such as constipation,pain, indigestion, etc. However, until recently, most attention has been focused on neurological disturbances such as cognitive impairments, chronic fatigue, and chronic pain among affected veterans. With such high prevalence of gastrointestinal problems among Gulf war(GW) veterans, it is surprising that there is little research to investigate the mechanisms behind these issues. This review summarizes all the available works on the mechanisms behind gastrointestinal problems in GWI that have been published to date in various databases. Generally, these studies,which were done in rodent models, in vitro and human cohorts propose that an altered microbiome, a reactive enteric nervous system or a leaky gut among other possible mechanisms are the major drivers of gastrointestinal problems reported in GWI. This review aims to draw attention to the gastrointestinal tract as an important player in GWI disease pathology and a potential therapeutic target.

Imaging Beyond the Angiogram in Women with Suspected Myocardial Infarction and No Obstructive Coronary Artery Disease

A subset of women referred to the cardiac catheterization lab for suspected myocardial infarction thought to be due to a culprit artery are found to have no obstructive coronary artery disease by angiography.The mechanism by which these women have myocardial injury varies and is not usually clear by history and angiography alone.Additional imaging,including modalities such as cardiac MRI,intravascular imaging,and computed tomography may be helpful to clarify diagnoses and direct treatment.

SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity

Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OCP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2（encoded by Ptpn11） affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using ＂Cre-lox P＂-mediated gene excision.SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.

一株多种耐药结核菌在纽约全市的暴发流行

背景:1992年纽约市医院耐两种或更多种药物的活动性结核病情况。目的:检查纽约市1992年结核发病高峰期间,经鉴定命名为公共卫生研究所(PHRI)W株的具有高度耐药且有17条IS6110印迹带的结核菌在全市的分布情况。同时还将此W株与其它纽约市常见菌株加以比较。设计:应用双盲回归法对保存的结核菌培养物进行限定性片段长度多态性(RFLP)DNA指纹分析。结果:1992年中,我们在21所医院的住院病人中共分离112株W印迹株和8个变株。几乎所有的分离株均对四种一线药物和卡那霉素(KAN)耐药。1992年此单一菌株至少占纽约市多种耐药(MDR)结核病的22％,远高于其它任何一株。几乎所有的W株病例均是AIDS患者。该菌群为纽约市耐药程度最高且迄今为止与其它地区比较所鉴定出的最大的具有IS6110指纹相似性的菌群。结论:由于推荐的四药化疗方案对此高度耐药的菌群不能有效杀灭,因此90年代初在纽约AIDS患者中发生因W株感染而引起的结核暴发流行。其它常见菌株并非呈现高度耐药,甚至于令人惊奇的是表现为全敏感。单一多种耐药菌株能够在AIDS和结核均常见的地区引起广泛的播散。

Temporal and Qualitative Differences in the Development of Allodynic Behaviors between Mice and Rats in a Peripheral Nerve Injury Model

The spared nerve injury (SNI) model of neuropathic pain was first developed by Decosterd and Woolf in 2000 in Sprague Dawley rats to enhance reproducibility of injury and behavioral responses resulting from a partial nerve injury. Given the differences in methodology and inconsistent behavioral data published in the SNI model of neuropathic pain in mice, and given that interspecies behavioral comparisons using the same peripheral nerve injury are presently lacking, in this study we assessed the development of mechanical and cold allodynia for five weeks in C57BL/6 mice and Sprague Dawley rats that underwent SNI. In rats and mice, the tibial and peroneal branches were ligated then severed, leaving the sural branch intact. By controlling several factors in the surgical procedure and behavioral tests, we found that rats developed and maintained strong mechanical and robust cold allodynia immediately following the injury that was maintained for the duration of the experiment (five weeks). In comparison, mice developed mechanical allodynia to a lesser magnitude which peaked at 2 weeks, but did not develop cold allodynia. We found both temporal and qualitative differences in the development of allodynic behaviors between SNI-mice and SNI-rats. Parallel analysis of interspecies differences can be exploited to reveal novel molecular players leading to divergent pain behaviors.