Hepatocellular carcinoma:State of the art diagnostic imaging

Primary liver cancer is the fourth most common malignancy worldwide,with hepatocellular carcinoma(HCC)comprising up to 90%of cases.Imaging is a staple for surveillance and diagnostic criteria for HCC in current guidelines.Because early diagnosis can impact treatment approaches,utilizing new imaging methods and protocols to aid in differentiation and tumor grading provides a unique opportunity to drastically impact patient prognosis.Within this review manuscript,we provide an overview of imaging modalities used to screen and evaluate HCC.We also briefly discuss emerging uses of new imaging techniques that offer the potential for improving current paradigms for HCC character-ization,management,and treatment monitoring.

MicroRNAs in hepatocellular carcinoma treatment:Charting the path forward

MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.

Nomograms and prognosis for superficial esophageal squamous cell carcinoma

In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.

Congophilic fibrils in the glomeruli with polyclonal immunoglobulin gamma staining-another cause for diagnostic overlap:A case report

BACKGROUND Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice,with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities.Renal amyloid heavy and light chain(AHL)is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin(Ig)heavy chain and a single light chain,further supported by mass spectrometry(MS)and serum studies for monoclonal protein.But polyclonal light chain staining can pose a challenge.CASE SUMMARY Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma(IgG)staining pattern by immunofluorescence.The patient is a 62-yearold Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria.Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence,ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm.Congo red was positive while DNAJB9 was negative.MS suggested a diagnosis of amyloid AHL type with IgG and lambda,but kappa light chains were also present supporting the immunofluorescence staining results.Serum immunofixation studies demonstrated IgG lambda monoclonal spike.The patient was started on chemotherapy.The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after.CONCLUSION Tissue diagnosis of AHL amyloid can be tricky.Thorough confirmation using other available diagnostic techniques is recommended in such cases.

Commentary on“The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in the early phase of cutting maneuvers in female athletes”

1.Introduction For decades,substantial disagreement has persisted as to whether dynamic knee valgus is the cause of the majority of anterior cruciate ligament(ACL)injuries or rather the result of the ACL rupture.1 Consequently,great effort and expense has gone into capturing 3-dimensional kinetics and kinematics from live athletes to drive in vitro and in silico models of ACL injury in order to elucidate the actual mechanism of injury,as these factors have been demonstrated to be surrogates of intraarticular structural loading on the ACL.2,3 The elucidation of injury mechanisms for non-contact ACL injuries is of great medical value as such knowledge consequently permits quantified examination and validation of interventions and their respective effectiveness in both prevention and rehabilitation of these traumatic knee injuries.

Astrocyte syncytium:from neonatal genesis to aging degeneration

Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).

Neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma: The need for patient-centered research

Pancreatic ductal adenocarcinoma is an aggressive cancer with high recurrence rates following surgical resection.While adjuvant chemotherapy improves survival,a significant proportion of patients are unable to initiate or complete all intended therapy following pancreatectomy due to postoperative complications or poor performance status.The administration of chemotherapy prior to surgical resection is an alternative strategy that ensures its early and near universal delivery as well as improves margin-negative resection rates and potentially improves long-term survival outcomes.Neoadjuvant therapy is increasingly being recommended to patients with pancreatic ductal adenocarcinoma,however,patient-centered research on its use is lacking.In this review,we highlight opportunities to focus research efforts in the domains of patient preferences,patient-reported outcomes,patient experience,and survivorship.Novel research in these areas may identify relevant barriers and facilitators to the use of neoadjuvant therapy thereby increasing its utilization,improve shareddecision making for patients and providers,and optimize the experience of those undergoing neoadjuvant therapy.

Organ assessment and repair centers: The future of transplantation is near

Solid organ transplantation is limited by suitable donor organ availability and the geographic limitations that lead to prolonged ischemic times. Ex vivo organ perfusion is an evolving technology that enables assessment of organ function prior to transplantation. As a byproduct, overall out of body organ times are able to be extended. The future implications organ assessment and repair centers utilizing this technology are discussed.

Hospital outcomes and early readmission for the most common gastrointestinal and liver diseases in the United States:Implications for healthcare delivery

BACKGROUND Gastrointestinal(GI)and liver diseases contribute to substantial inpatient morbidity,mortality,and healthcare resource utilization.Finding ways to reduce the economic burden of healthcare costs and the impact of these diseases is of crucial importance.Thirty-day readmission rates and related hospital outcomes can serve as objective measures to assess the impact of and provide further insights into the most common GI ailments.AIM To identify the thirty-day readmission rates with related predictors and outcomes of hospitalization of the most common GI and liver diseases in the United States.METHODS A cross-sectional analysis of the 2012 National Inpatient Sample was performed to identify the 13 most common GI diseases.The 2013 Nationwide Readmission Database was then queried with specific International Classification of Diseases,Ninth Revision,Clinical Modification codes.Primary outcomes were mortality(index admission,calendar-year),hospitalization costs,and thirty-day readmission and secondary outcomes were predictors of thirty-day readmission.RESULTS For the year 2013,the thirteen most common GI diseases contributed to 2.4 million index hospitalizations accounting for about$25 billion.The thirty-day readmission rates were highest for chronic liver disease(25.4%),Clostridium difficile(C.difficile)infection(23.6%),functional/motility disorders(18.5%),inflammatory bowel disease(16.3%),and GI bleeding(15.5%).The highest index and subsequent calendar-year hospitalization mortality rates were chronic liver disease(6.1%and 12.6%),C.difficile infection(2.3%and 6.1%),and GI bleeding(2.2%and 5.0%),respectively.Thirty-day readmission correlated with any subsequent admission mortality(r=0.798,P=0.001).Medicare/Medicaid insurances,≥3 Elixhauser comorbidities,and length of stay>3 d were significantly associated with thirty-day readmission for all the thirteen GI diseases.CONCLUSION Preventable and non-chronic GI disease contributed to a significant economic and health burden comparable to chronic GI conditions,providing a window of opportunity for improving healthcare delivery in reducing its burden.

Effect of transplant center volume on post-transplant survival in patients listed for simultaneous liver and kidney transplantation

AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.

Outcomes of inpatient cholecystectomy among adults with cystic fibrosis in the United States

BACKGROUND Symptomatic biliary and gallbladder disorders are common in adults with cystic fibrosis(CF)and the prevalence may rise with increasing CF transmembrane conductance regulator modulator use.Cholecystectomy may be considered,but the outcomes of cholecystectomy are not well described among modern patients with CF.AIM To determine the risk profile of inpatient cholecystectomy in patients with CF.METHODS The Nationwide Inpatient Sample was queried from 2002 until 2014 to investigate outcomes of cholecystectomy among hospitalized adults with CF compared to controls without CF.A propensity weighted sample was selected that closely matched patient demographics,patient’s individual comorbidities,and hospital characteristics.The propensity weighted sample was used to compare outcomes among patients who underwent laparoscopic cholecystectomy.Hospital outcomes of open and laparoscopic cholecystectomy were compared among adults with CF.RESULTS A total of 1239 inpatient cholecystectomies were performed in patients with CF,of which 78.6%were performed laparoscopically.Mortality was<0.81%,similar to those without CF(P=0.719).In the propensity weighted analysis of laparoscopic cholecystectomy,there was no difference in mortality,or pulmonary or surgical complications between patients with CF and controls.After adjusting for significant covariates among patients with CF,open cholecystectomy was independently associated with a 4.8 d longer length of stay(P=0.018)and an$18449 increase in hospital costs(P=0.005)compared to laparoscopic cholecystectomy.CONCLUSION Patients with CF have a very low mortality after cholecystectomy that is similar to the general population.Among patients with CF,laparoscopic approach reduces resource utilization and minimizes post-operative complications.

Comparison of open and closed hyperthermic intraperitoneal chemotherapy: Results from the United States hyperthermic intraperitoneal chemotherapy collaborative

BACKGROUND Cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)for peritoneal carcinomatosis can be performed in two ways:Open or closed abdominal technique.AIM To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes.METHODS Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database.Post-operative,recurrence,and overall survival outcomes were compared between those who received open vs closed HIPEC.RESULTS Of the 1812 patients undergoing curative-intent CRS and HIPEC,372(21%)patients underwent open HIPEC and 1440(79%)underwent closed HIPEC.There was no difference in re-operation or severe complications between the two groups.Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities.On multi-variable analysis,closed HIPEC technique was not a significant predictor for overall survival(hazards ratio:0.75,95%confidence interval:0.51-1.10,P=0.14)or recurrence-free survival(hazards ratio:1.39,95%confidence interval:1.00-1.93,P=0.05)in the entire cohort.These findings remained consistent in the appendiceal and the colorectal subgroups.CONCLUSION In this multi-institutional analysis,the HIPEC method was not independently associated with relevant post-operative or long-term outcomes.HIPEC technique may be left to the discretion of the operating surgeon.

Artificial intelligence:Advances and new frontiers in medical imaging

Artificial intelligence(AI)has been entwined with the field of radiology ever since digital imaging began replacing films over half a century ago.These algorithms,ranging from simplistic speech-to-text dictation programs to automated interpretation neural networks,have continuously sought to revolutionize medical imaging.With the number of imaging studies outpacing the amount of trained of readers,AI has been implemented to streamline workflow efficiency and provide quantitative,standardized interpretation.AI relies on massive amounts of data for its algorithms to function,and with the wide-spread adoption of Picture Archiving and Communication Systems(PACS),imaging data is accumulating rapidly.Current AI algorithms using machine-learning technology,or computer aided-detection,have been able to successfully pool this data for clinical use,although the scope of these algorithms remains narrow.Many systems have been developed to assist the workflow of the radiologist through PACS optimization and imaging study triage,however interpretation has generally remained a human responsibility for now.In this review article,we will summarize the current successes and limitations of AI in radiology,and explore the exciting prospects that deep-learning technology offers for the future.

Salvage locoregional therapies for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the second most common cause of cancerrelated death worldwide.Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies,recurrence rates remain high.In contrast to first-line treatment for HCC,which relies on several factors,including clinical staging,tumor burden,and liver function,there is no consensus or general treatment recommendations for recurrent HCC(R-HCC).Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC.Herein,we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.

Randomized intervention and outpatient follow-up lowers 30-d readmissions for patients with hepatic encephalopathy,decompensated cirrhosis

BACKGROUND We previously reported national 30-d readmission rates of 27% in patients with decompensated cirrhosis(DC).AIM To study prospective interventions to reduce early readmissions in DC at our tertiary center.METHODS Adults with DC admitted July 2019 to December 2020 were enrolled and randomized into the intervention(INT) or standard of care(SOC) arms. Weekly phone calls for a month were completed. In the INT arm, case managers ensured outpatient follow-up, paracentesis, and medication compliance. Thirty-day readmission rates and reasons were compared.RESULTS Calculated sample size was not achieved due to coronavirus disease 2019;240 patients were randomized into INT and SOC arms. 30-d readmission rate was 33.75%, 35.83% in the INT vs 31.67% in the SOC arm(P = 0.59). The top reason for 30-d readmission was hepatic encephalopathy(HE, 32.10%). There was a lower rate of 30-d readmissions for HE in the INT(21%) vs SOC arm(45%, P = 0.03). There were fewer 30-d readmissions in patients who attended early outpatient follow-up(n = 17, 23.61% vs n = 55, 76.39%, P = 0.04).CONCLUSION Our 30-d readmission rate was higher than the national rate but reduced by interventions in patients with DC with HE and early outpatient follow-up. Development of interventions to reduce early readmission in patients with DC is needed.

柚皮素：新一代免疫调节剂

大量研究表明,植物来源的黄酮类化合物具有广泛的生理活性和药理作用,日常摄取适量的黄酮类化合物能够显著降低许多疾病的发生.柚皮素作为一种自然界分布广泛的黄酮类化合物富含于水果、蔬菜、坚果、咖啡、茶和红酒等日常饮食中,与其他黄酮类化合物相比柚皮素易于胃肠道吸收、生物利用度高且安全剂量大.自2004年起我们对柚皮素调节免疫的分子机制进行了深入系统的研究.本文将重点介绍柚皮素作为一种新型免疫调节剂的研究进展.

MG53——肌细胞损伤的“分子绷带”

细胞生命活动中始终经历着动态的膜损伤与修复过程，细胞膜损伤后影响其功能．膜损伤修复是一个南多种蛋白和信号途径参与的受损细胞膜的结构和功能快速修正的过程[1-3]。最近研究发现了一种骨骼肌和心肌特异性的膜修复蛋白MG53（Mitsugumin53）．它与几种肌肉特异性膜修复蛋白dysferlin和caveolin-3（Cav3）等在功能上协同作用形成膜“分子创可贴”．完成肌膜损伤后的快速修复[4]．有人称其为肌细胞损伤的“分子绷带”[5]．

脑电图光刺激的光驱反应频谱研究(英文)

目的借助数字化脑电图(DigitalEEG)易于定量分析脑电功率的优势,提高EEG间歇性闪光刺激诱发试验的临床诊断价值。方法本组共60例,男38例,女22例,年龄24～67岁。对60例常规EEG(-)的患者包括:癫痫20例、头痛20例和神经精神障碍20例进行了digitalEEG检查,在枕部01,0z和02处分别测量10s安静时和间歇性闪光刺激(IPS)5,10以及15Hz的α波绝对和相对功率。结果所有患者的α功率在IPS5,15Hz时减退,IPS10Hz时增高,其中癫痫患者表现最显著,而神经精神障碍患者最不明显。前者安静、IPS5,10,15Hz时枕中Oz所测绝对功率(μV2)、相对功率(%)分别为330±40,39.7±2.8,176±24,30.0±1.9,207±29,32.5±2.0和164±25,26.7±2.0;后者则分别为189±28,22.2±2.7,140±21,21.7±1.3,176±22,22.8±1.6和127±16,17.7±1.6。两者安静时的Oz处相对功率比较,P,t分别为9.85×10-24,22.75;2.42×10-29,32.5,差异有显著性意义(P<0.05)。结论DigitalEEG能够定量测定IPS的脑电功率谱变化,提高IPS的临床诊断价值。

医学分子生物学进展诠释着病毒的起源和进化

在人类依然抗争着禽流感病毒、艾滋病病毒以及SARS病毒等对生命威胁和享受现代医学及分子生物学的最新研究成果的同时,思考病毒的起源和进化的分子机理是痛定思痛且必须关心审视的医学科学问题。病毒是介于生命与非生命间的非细胞生命体,关于它的起源及进化有3种观点:1自起源理论,病毒先于细胞产生于生命前地球,然后进化成原核细胞及真核细胞;2平行进化理论,病毒和细胞是在生命前环境条件下同时平行起源而成,进化过程中形成寄生于细胞的关系;3细胞源退化理论或逆向理论,病毒是细胞形成之后,向外"抛出"的大分子或其复合体,来源于并寄生于细胞。近些年的分子生物学的一些进展揭示:理解并接受病毒起源的多元性,认同病毒在生命历史起源进化的多机制特征,是回答自然赋予的这一生物医学课题命题的最合理答案。

间歇闪光定量脑电图在精神疾病患者中的应用

目的 :探讨定量脑电图 (QEEG)在精神疾病中的应用。方法 :对 6 0例常规EEG正常的精神疾病病人进行了QEEG检查 ,其中精神分裂症、双相情感障碍及儿童期和青春期行为障碍各 2 0例。分别测量枕部O1、Oz和O2 处安静时和 5Hz、10Hz及 15Hz间歇性闪光刺激 (IPS)的光驱反应 10s区间的α波绝对和相对功率。结果 :与安静时α功率相比较 ,所有病人的α功率在 5Hz、15HzIPS时减退 ,10HzIPS时增高 ,以精神分裂症病人表现最明显 ,并在Oz处最显著 ,可能为精神病理学的一种表达式。但 3类病人之间的α波绝对或相对功率相比较 ,差异无统计学意义 (P >0 0 5 )。结论 :QEEG能够定量测定光驱反应的脑电功率谱变化 ,对常规EEG正常的精神疾病有一定的临床诊断价值。