Direct cost variance analysis of peroral endoscopic myotomy vs heller myotomy for management of achalasia:A tertiary referral center experience

BACKGROUND Laparoscopic Heller myotomy(LHM)has been the traditional surgical treatment for achalasia.Recently,peroral endoscopic myotomy(POEM)has demonstrated similar clinical outcomes with shorter procedure times.Studies comparing the direct cost-effectiveness of POEM vs LHM are limited.AIM To compare costs of POEM vs LHM.METHODS Haider SA et al.Comparing costs:POEM vs Heller myotomy WJGE https://www.wjgnet.com 594 October 16,2023 Volume 15 Issue 10 This retrospective chart review aimed to compare the outcomes and cost of clinical care between patients who underwent POEM and LHM procedures for achalasia.The study was conducted at a tertiary academic center from January 2019 to December 2020.Clinical outcomes,including post-operative Eckardt scores and adverse events,were assessed and compared between the two groups.Direct cost variance analysis was utilized to evaluate the cost of clinical care incurred by patients undergoing POEM in the year preceding the procedure,during the index admission,and one year post-procedure,in comparison to patients undergoing LHM.RESULTS Of 30 patients were included(15 POEM and 15 LHM)in the study.Patients in the POEM group had a mean Eckardt score of 0.5±0.5 post-procedure,which was no different from patients in the LHM group(0.7±0.6,P=0.17)indicating comparative efficacy.However,the total costs of the admission for the procedure in the LHM group were on average$1827 more expensive than in the POEM group(P<0.01).Total healthcare costs one year prior to index procedure were$7777 higher in the LHM group,but not statistically different(P=0.34).The patients in the LHM group one year after the index procedure had accrued$19730.24 larger total cost,although this was not statistically different from POEM group(P=0.68).CONCLUSION Despite similar clinical outcomes,the cost of the index procedure admission for POEM was significantly lower than for LHM.The difference was primarily related to shorter time increments utilized in the operating room during the index procedure,and shorter length of hospital stay following POEM.

Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Innovative pathways allow safe discharge of mild acute pancreatitis from the emergency room

Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

Global geoepidemiology of gastrointestinal surgery rates in Crohn’s disease

BACKGROUND Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn’s disease(CD)remains limited.AIM To systematically review the global variation in the rates of surgery in CD.METHODS A comprehensive search analysis was performed using multiple electronic databases from inception through July 1,2020,to identify all full text,randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with CD.Outcomes included continent based demographic data,CD surgery rates over time,as well as the geoepidemiologic variation in CD surgery rates.Statistical analyses were conducted using R.RESULTS Twenty-three studies spanning four continents were included.The median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America,Europe,Asia,and Oceania were 30%(range:1.7%-62.0%),40%(range:0.6%-74.0%),17%(range:16.0%-43.0%),and 38%respectively.No clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America(R^(2)=0.035)and Europe(R^(2)=0.100).A moderate,negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time(R^(2)=0.520)in Asia.CONCLUSION There appears to be significant inter-continental variation regarding surgery rates in CD.Homogenous evidencebased guidelines accounting for the geographic differences in managing patients with CD is prudent.Moreover,as a paucity of data on surgery rates in CD exists outside the North American and European continents,future studies,particularly in less studied locales,are warranted.

Targeted medical therapy of biliary tract cancer:Recent advances and future perspectives

The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.

Cost effectiveness of intensive care in a low resource setting: A prospective cohort of medical critically ill patients

AIM: To calculate cost effectiveness of the treatment of critically ill patients in a medical intensive care unit(ICU) of a middle income country with limited access to ICU resources. METHODS: A prospective cohort study and economic evaluation of consecutive patients treated in a recently established medical ICU in Sarajevo, Bosnia and Herzegovina. A cost utility analysis of the intensive care of critically ill patients compared to the hospital ward treatment from the perspective of the health care system was subsequently performed. Incremental cost effectiveness was calculated using estimates of ICU vs non-ICU treatment effectiveness based on a formal systematic review of published studies. Decision analytic modeling was used to compare treatment alternatives. Sensitivity analyses of the key model parameters were performed.RESULTS: Out of 148 patients, seventy patients(47.2%) survived to one year after critical illness with a median quality of life index 0.64 [interquartile range(IQR)0.49-0.76]. Median number of life years gained per patient was 30(IQR 16-40) or 18 quality adjusted life years(QALYs)(IQR 7-28). The cost of treatment of critically ill patients varied between 1820 dollar and20109 dollar per hospital survivor and between 100 dollar and 2514 dollar per QALY saved. Mean factors that influenced costs were: Age, diagnostic category,ICU and hospital length of stay and number and type of diagnostic and therapeutic interventions. The incremental cost effectiveness ratio for ICU treatment was estimated at 3254 dollar per QALY corresponding to35% of per capita GDP or a Very Cost Effective category according to World Health Organization criteria.CONCLUSION: The ICU treatment of critically ill medica patients in a resource poor country is cost effective and compares favorably with other medical interventions.Public health authorities in low and middle income countries should encourage development of critical care services.

Shunting,optic nerve sheath fenestration and dural venous stenting for medically refractory idiopathic intracranial hypertension:systematic review and meta-analysis

Background:Cerebrospinal fluid(CSF)-diversion procedures have traditionally been the standard of treatment for patients with medically refractive idiopathic intracranial hypertension(IIH).However,dural venous sinus stent(VSS)placement has been described as a safe and effective procedure for the management of medically refractive IIH.We performed a meta-analysis comparing outcomes and complications of CSF-diversion procedures,VSS and optic nerve sheath fenestration(ONSF)for the treatment of medically refractive IIH.Methods:Electronic searches were performed using six databases from 1988 to January 2017.Data was extracted and meta-analysed from the identified studies.Results:From 55 pooled studies,there were 538 CSF-diversion cases,224 dural venous stent placements,and 872 ONSF procedures.Similar improvements were found in terms of postoperative headaches(CSF vs.VSS vs.ONSF:84%vs.78%vs.62%,P=0.223),papilledema(CSF vs.VSS vs.ONSF:71%vs.86%vs.77%,P=0.192),whilst visual acuity changes favored venous stenting(CSF vs.VSS vs.ONSF:55%vs.69%vs.44%,P=0.037).There was a significantly lower rate of subsequent procedures with venous stent placement(CSF vs.VSS vs.ONSF:37%vs.13%vs.18%,P<0.001),but other complication rates were similar(CSF vs.VSS vs.ONSF:13%vs.8%vs.14%,P=0.28).Subgroup analysis of lumbar-peritoneal vs.ventriculoperitoneal shunts found no differences in symptom improvements,complications and subsequent procedure rates.Conclusions:Our findings suggest that dural venous sinus stenting may be a viable alternative to traditional surgical interventions in patients who are refractory to medical treatment.

Molecular hallmarks of long non-coding RNAs in aging and its significant effect on aging-associated diseases

Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.

Burden of bone disease in chronic pancreatitis:A systematic review and meta-analysis

BACKGROUND Bone disease is an under-recognized cause of morbidity in chronic pancreatitis(CP).Over the past decade,publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem.AIM To quantify the prevalence of osteopenia,osteoporosis,and fragility fractures in CP patients and investigate the associated clinical features and outcomes.METHODS A systematic search identified studies investigating bone disease in CP patients from Cochrane Library,Embase,Google Scholar,Ovid Medline,PubMed,Scopus,and Web of Science,from inception until October 2022.The outcomes included prevalence of osteopenia,osteoporosis,and fragility fractures,which were metaanalyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features.RESULTS Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis.The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2%(95%CI:35.2%-47.3%)and 20.9%(95%CI:14.9%-27.6%),respectively.The pooled prevalence of fragility fractures described among CP was 5.9%(95%CI:3.9%-8.4%).Metaregression revealed significant association of pancreatic enzyme replacement therapy(PERT)use with prevalence of osteoporosis[coefficient:1.7(95%CI:0.6-2.8);P<0.0001].We observed no associations with mean age,sex distribution,body mass index,alcohol or smoking exposure,diabetes with prevalence of osteopenia,osteoporosis or fragility fractures.Paucity of data on systemic inflammation,CP severity,and bone mineralization parameters precluded a formal metaanalysis.CONCLUSION This meta-analysis confirms significant bone disease in patients with CP.Other than PERT use,we observed no patient or study-specific factor to be significantly associated with CP-related bone disease.Further studies are needed to identify confounders,at-risk population,and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

NGAL在急性药物相关性间质性肾炎中的表达及其意义

目的了解急性药物相关性间质性肾炎(acutedruginducedinterstitialnephritis,AIN)患者肾组织中NGAL的表达及NGAL与肾小管间质病理损害程度的关系。方法免疫组化观察正常肾组织和AIN患者肾组织NGAL的表达,以及NGAL阳性强度与小管间质病理损害程度的关系。结果AIN患者肾组织表达NGAL较正常组增多、增强;其小管NGAL阳性强度与小管间质病理损害程度呈负相关。结论NGAL在AIN肾小管间质病理损害中起重要作用。

重组AdPD-L1腺病毒的构建表达及鉴定

目的 构建程序性死亡配体 1(PD L1)重组腺病毒载体,以期用于体内实验研究。方法 酶切含有小鼠全长PD L1cDNA的pcDNA3 .1 PD L1质粒,亚克隆到穿梭质粒pAdtrack CMV上,在BJ5 183细胞内和AdEasy 1同源重组,筛选阳性克隆,酶切、测序鉴定正确,线性化后脂质体法转染2 93细胞进行包装、扩增,利用报告基因EGFP对病毒滴度进行监测,氯化铯密度梯度离心纯化病毒。PCR、Westernblot鉴定AdPD L1感染2 93细胞后PD L1的表达,同时进行野生型腺病毒的检测和PD L1在混合淋巴细胞反应中的作用。结果 测序、酶切证实PD L1基因重组腺病毒载体构建成功。RT PCR、Westernblot检测AdPD L1感染的2 93细胞,均有PD L1的表达。无野生型腺病毒的产生,PD L1能显著抑制小鼠混合淋巴增殖反应。结论 成功构建了含小鼠PD L1基因的重组腺病毒载体,这种膜结合性的PD L1与其相应受体结合后,对T细胞可起到负性调控的作用,为下一步体内基因治疗实验奠定了基础。

可溶性尿激酶受体的表达、纯化和结晶

克隆尿激酶受体可溶区域(suPAR)到果蝇胚胎细胞分泌表达载体pMT/Bip/v5-his,重组质粒与pCoHygro共转染果蝇S2细胞,筛选多拷贝稳定表达细胞系suPARS2.suPAR表达蛋白经尿激酶N端片段亲和柱、ResourceQ阴离子交换柱两步纯化后,得到高纯度的、稳定的suPAR单体.纯化后的蛋白质,与其抗体ATN615及尿激酶N端片段结构域等摩尔混合,浓缩至10g/L,以透析法进行该三元复合物晶体生长,获得衍射分辨率为1.9#的蛋白质晶体.

心肺耦合分析:基于心电的睡眠分析方法

随着科技的发展和人们对睡眠医学认识的深入,越来越多的便携、家用、远程的睡眠评估方法不断问世且备受关注,虽然简化了仪器,但是患者仍需克服一些不适。心肺耦合分析是一种简化了信号收集和处理的过程,且可提供可靠、实用的睡眠评估报告,目前已在评估睡眠质量和判断睡眠呼吸暂停事件发生等方面得到较好应用。本文旨在介绍这一方法的原理和机制,并简要综述其已有的临床和科研应用。

睡眠信念/信心与睡眠态度的国内外研究现状

良好睡眠的重要性以及失眠所致的诸多问题正在引起越来越多的关注。治疗失眠的方法也是多种多样。睡眠信心、睡眠信念、睡眠态度、睡眠心理等词语在近年来的文献中越来越多地出现,尤其是英文文献中,有很多关于这方面的研究和报道。这些对于解决如失眠一类的睡眠障碍给予了新启示。而中文的相关文献却屈指可数。本文中,我们重点总结回顾了中英文文献中的相关报道,并且对目前国内外的睡眠信念和睡眠信心、态度等的研究现状做了简单回顾。中医心理学对于睡眠信心和睡眠态度的关注尚不足,而发展和创制好的量表可以细化诊断并指导临床。

基于经验模式分解的心肺耦合技术在儿童睡眠分析中的应用

目的探讨基于经验模式分解的心肺耦合分析技术(Cardio-Pulmonary Coupling,HHT-CPC)对儿童睡眠呼吸紊乱(Sleep-Disordered Breathing,SDB)的诊断价值。方法回顾性分析整夜Hypno PTT监测的儿童患者数据63例,根据鼻气流呼吸紊乱指数(Respiratory Disturbance Index,RDI)区分不同严重程度SDB组。比较各组的Hypno PTT睡眠参数、OSA-18量表评分及心肺耦合指标,观察新方法与临床SDB诊断方法的相关性与一致性;应用ROC曲线评价HHT-CPC的SDB诊断效率。结果疾病程度增加导致HHT-CPC的低频耦合、升高式低频耦合指标显著升高,而高频耦合明显降低,这些指标与Hypno PTT睡眠呼吸参数均体现出较强的相关性。其中HHT-CPC的RDI与Hypno PTT的RDI、3%氧减指数的相关性最强(r=0.844和0.770,P<0.001),且Bland-Altman分析结果体现出较高的一致性。在疾病诊断方面,ROC曲线下面积0.93,敏感度与特异度分别为0.85和0.90。结论HHT-CPC与Hypno PTT诊断儿童SDB具有较好的一致性,具有较高的诊断价值。

睡眠生理讯号的非线性特征及复杂度理论的潜在应用

人体中有许许多多潜在的讯号,他们与体内生理系统有着密切的关系,而这些生理讯号可以反映出生物体内各个器官、系统的生理或病理特征.现代医学通过应用特定的设备测量生理讯号可以客观地描述生理或病理状态,然后就需要通过科学的量化方法来提供评测指标.在目前备受关注且发展迅速的睡眠医学中,生理讯号就是主要的日常采集数据之一.

人巨细胞病毒临床分离株感染血管内皮细胞伴肾素基因表达

目的探讨巨细胞病毒(Cytomegalovirus,CMV)是否感染血管内皮细胞伴肾素表达。方法(1)用107pfu(空斑形成单位)/ml CMV临床分离株BI-5和实验室型CMV AD169分别与106腹主动脉内皮细胞和人脐静脉内皮细胞共同孵育,在23小时后、第3天、第7天、第10天和第14天分别收集培养上清200μl,第14天用PBS缓冲液洗细胞3次,收获细胞。每组实验均设培养液代替病毒液的无感染对照;(2)COBAS定量PCR检测培养上清中CMV DNA拷贝数;(3)PCR检测感染细胞中CMVpol基因;(4)RT-PCR、Real time RT-PCR和Western blot检测肾素在感染细胞内的表达。结果(1)BI-5和AD169感染静脉和动脉细胞后,其形态学变化相似,无细胞裂解病理效应;(2)AD169感染细胞不同时间培养上清中CMV DNA拷贝数无明显增加,BI-5呈增殖趋势;(3)BI-5感染动脉细胞CMV DNA拷贝数和肾素表达量均大于静脉细胞。结论临床分离株CMV以非裂解形式在血管内皮细胞持续存在并诱导肾素基因表达,血管内皮细胞分泌肾素可能是CMV感染引起心血管疾病的新机制。

巨细胞病毒临床分离株感染血管内皮细胞伴肾素基因表达

目的探讨巨细胞病毒（Cytomegalovirus，CMV）是否感染血管内皮细胞伴肾素表达。方法①用10^7pfu（空斑形成单位）／mLCMV临床分离株BI-5和实验室型CMVA D169分别与10^6腹主动脉内度细胞和人脐静脉内皮细胞共同孵育，在23h后、d3、d7、d10和d14分别收集培养上清200μL，d14用PBS缓冲液洗细胞3次，收获细胞。每组实验均设培养液代替病毒液的无感染对照；②COBAS定量PCR检测培养上清中CMV DNA拷贝数；③PCR检测感染细胞中CMVpol基因；@RT-PCR、Real time RT-PCR和Western blot检测肾素在感染细胞内的表达。结果①BI-5和AD169感染静脉和动脉细胞后，其形态学变化相似，无细胞裂解病理效应；②AD169感染细胞不同时间培养上清中CMVDNA拷贝数无明显增加，BI-5呈增殖趋势；③BI-5感染动脉细胞CMVDNA拷贝数和肾素表达量均大于静脉细胞。结论临床分离株CMV以非裂解形式在血管内皮细胞持续存在并诱导肾素基因表达，血管内皮细胞分泌肾素可能是CMV感染引起心血管疾病的新机制。

神经肽Y与心血管疾病的研究进展

神经肽Y(neuropeptide Y,NPY)是由36个氨基酸构成的多肽,广泛存在于大脑、周围交感神经和肾上腺髓质,在心血管疾病发生、发展等方面有多种作用。NPY对血压有双向调节作用。在中枢神经系统,NPY抑制血压升高,外周NPY则增强血管平滑肌收缩,升高血压。NPY在动脉粥样硬化的进程中有利亦有弊。NPY还能调节水钠潴留,影响心肌和血管重塑。