Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Clinical profile and outcomes in very elderly patients with atrial fibrillation anticoagulated with rivaroxaban: data from the EMIR study

Objectives To analyze the clinical profile,adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial(AF),taking rivaroxaban in clinical practice.Results Out of 1433 patients,453(31.6%)were octogenarians at baseline.Compared to younger patients,octogenarians had more comorbidities,higher CHA2DS2-VASc(4.5±1.3vs.3.0±1.4;P<0.001)and HAS-BLED scores(2.0±1.0vs.1.4±1.0;P<0.001).Overall,the dose of rivaroxaban was adequately prescribed in 83.4%of patients,but more frequently in the younger population(71.1%vs.89.1%;P=0.039).After a mean follow-up of 2.2±0.6 years,annual rates of stroke+systemic embolism+transient ische-mic attack,MACE,cardiovascular death and major bleeding were 1.03%,1.24%,1.03%and 1.75%,respectively,in octogenarian patients.Except for progressive heart failure death and major bleeding,rates of outcomes in octogenarians were similar com-pared to younger patients.In octogenarians,the concomitant use of antiplatelet agents and non-severe dementia were independ-ently associated with the development of ischemic stroke,whereas previous coronary revascularization and heart failure with and higher HAS-BLED score with major bleeding.MACE,Conclusions In clinical practice,around one third of patients taking rivaroxaban are octogenarians.These patients have many comorbidities and a high thromboembolic risk.Despite that,rates of adverse events remain low.Rivaroxaban is adequately pre-scribed in the majority of octogenarians.

Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease

Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.

Analysis of tumor-draining vein secretome: A direct access to tumor-derived extracellular vesicles in surgical lung cancer patients

Tumor-secreted extracellular vesicles(EVs)participate in the metastasis process through different mechanisms,including the preparation of the pre-metastatic niche to grant circulating tumor cells(CTCs)implantation and growth.The study of the metastasis process through the analysis of CTCs and tumor-derived EVs is difficult because of the dilution grade of these elements in peripheral blood.In early-stage lung cancer patients,the tumor-secreted products are even more diluted.An attractive strategy in surgical lung cancer patients is to purify them from a pulmonary tumor-draining vein where they are enriched.The information obtained from the analysis of EVs and CTCs purified from this source could give more accurate information about tumor biology and could be an important source of biomarkers to identify patients at high risk of relapse after curative surgery.

Randomized, Double-Blind, Double-Masked, Parallel Group Clinical Study to Compare the Effectiveness of Diclofenac Potassium 150 mg, LP OD, vs Diclofenac Potassium 50 mg, TID, Three Times a Day, in Knee Osteoarthritis

Background: Osteoarthritis is a chronic disease associated with pain, inflammation, stiffness and synovial effusion, with progressive functional limitation, compromising quality of life. It progressively leads to loss or decrease in joint function. Pharmacological and non-pharmacological therapy seeks symptomatic management, complicated by a lack of adherence. After acetaminophen, non-steroidal anti-inflammatory drugs such as diclofenac are the most widely used medications. Objectives: The primary objective compared the analgesic effect of diclofenac 150 mg once daily vs. 50 mg three times daily in patients with knee osteoarthritis. The secondary objective assessed changes in quality of life. Method: One group received diclofenac 150 mg OD with placebo TTD. Another group received placebo OD and 50 mg active diclofenac (reference) TTD, both for 30 days. The evaluation of pain was carried out by a visual analog scale (VAS), at the beginning, 2, 3, 4, 15 and 30 days, quality of life (the WOMAC scale) and adverse effects, at 15 and 30 days. Results: Pain decreased significantly on days 15 and 30, compared to day 0, in both groups, without differences between groups. The total results in the WOMAC scale showed a very marked improvement at 15 and 30 days, without differences between groups. The most frequent adverse effects were constipation 6% in the reference group, and gastric discomfort 30.3% in the reference group vs 28.1%, in the Test group. Conclusions: Prolonged-release diclofenac 150 mg OD is as effective as diclofenac 50 mg TID for the treatment of patients with knee osteoarthritis.

Clinical impact of artificial intelligence-based solutions on imaging of the pancreas and liver

Artificial intelligence(AI)has experienced substantial progress over the last ten years in many fields of application,including healthcare.In hepatology and pancreatology,major attention to date has been paid to its application to the assisted or even automated interpretation of radiological images,where AI can generate accurate and reproducible imaging diagnosis,reducing the physicians’workload.AI can provide automatic or semi-automatic segmentation and registration of the liver and pancreatic glands and lesions.Furthermore,using radiomics,AI can introduce new quantitative information which is not visible to the human eye to radiological reports.AI has been applied in the detection and characterization of focal lesions and diffuse diseases of the liver and pancreas,such as neoplasms,chronic hepatic disease,or acute or chronic pancreatitis,among others.These solutions have been applied to different imaging techniques commonly used to diagnose liver and pancreatic diseases,such as ultrasound,endoscopic ultrasonography,computerized tomography(CT),magnetic resonance imaging,and positron emission tomography/CT.However,AI is also applied in this context to many other relevant steps involved in a comprehensive clinical scenario to manage a gastroenterological patient.AI can also be applied to choose the most convenient test prescription,to improve image quality or accelerate its acquisition,and to predict patient prognosis and treatment response.In this review,we summarize the current evidence on the application of AI to hepatic and pancreatic radiology,not only in regard to the interpretation of images,but also to all the steps involved in the radiological workflow in a broader sense.Lastly,we discuss the challenges and future directions of the clinical application of AI methods.

Respiratory muscle training with electronic devices in the postoperative period of hepatectomy:A randomized study

BACKGROUND Many studies have been developed with a focus on surgical techniques and drugs,but few that address the importance of rehabilitation in the pre and postoperative period,and the specific benefits for each surgical procedure or type of neoplasm,aiming to minimize respiratory complications in the postoperative period.AIM To compare the strength of the respiratory muscles in the pre and postoperative periods of hepatectomy by laparotomy and to verify the incidence of postoperative pulmonary complications among the groups studied.METHODS Prospective,randomized,clinical trial study that compared the inspiratory muscle training group(GTMI)with the control group(CG).After the collection of sociodemographic and clinical data,in both groups,preoperatively,on the first and fifth postoperative days,vital signs and pulmonary mechanics were evaluated and recorded.Albumin and bilirubin values were recorded for the albumin-bilirubin(ALBI)score.After randomization and allocation of participants,those in the CG underwent conventional physical therapy and those in the GTMI underwent conventional physical therapy plus inspiratory muscle,in both groups for five postoperative days.RESULTS Of 76 subjects met eligibility criteria.The collection of 41 participants was completed:20 in the CG and 21 in the GTMI.The most frequent diagnosis was 41.5%with liver metastasis,followed by 26.8%with hepatocellular carcinoma.As for respiratory complications in the GTMI,there was no incidence.In the CG,there were three respiratory complications.Patients in the CG classified as ALBI score 3 presented,statistically,a higher energy value compared to patients classified as ALBI score 1 and 2(P=0.0187).Respiratory variables,measured preoperatively and on the first postoperative day,had a significant drop in both groups from the preoperative to the first postoperative day(P≤0.0001).When comparing the preoperative period and the fifth postoperative day between the GTMI and the CG,the maximal inspiratory pressure variable in the GTMI was statistically significant(P=0.0131).CONCLUSION All respiratory measures showed a reduction in the postoperative period.Respiratory muscle training using the Powerbreathe?device increased maximal inspiratory pressure and this may have contributed to a shorter hospital stay and better clinical outcome.

Clinical outcomes and complications of single anastomosis duodenal-ileal bypass with sleeve gastrectomy:A 2-year follow-up study in Bogotá,Colombia

BACKGROUND The global prevalence of obesity has increased over the past 40 years,and bariatric surgery has proven to be the most effective therapy for long-term weight loss.Its principles are based on modifying the brain-gut axis by altering the gastrointestinal anatomy and affecting the function of gastrointestinal hormones,thereby modifying satiety signals.Single anastomosis duodeno-ileal bypass with sleeve gastrectomy(SADI-S)combines both techniques and has become an alternative to gastric bypass and biliopancreatic diversion procedures for treating severe obesity and associated metabolic diseases in selected patients.AIM To describe the outcomes and complications of SADI-S.METHODS We retrospectively analyzed the data of patients who underwent SADI-S laparoscopically at the Clínica Reina Sofía in Bogotá,Colombia.This study assessed the therapeutic effectiveness of SADI-S in terms of short-term preoperative clinical characteristics,postoperative complications,comorbidities,nutritional deficiencies,and intraoperative complications during a 2-year follow-up.RESULTS Sixty-one patients with a mean body mass index(BMI)of 50±7.1 kg/m2 underwent laparoscopic SADI-S.The mean operative time and hospital stays were 143.8±42 min and 2.3±0.8 d,respectively.The mean follow-up period was 18 mo,and the mean BMI decreased to 28.5±12.2 kg/m2.The excess BMI loss was 41.8%±13.5%,and the weight loss percentage was 81.1%±17.0%.Resolution of obesity-related comorbidities,including type 2 diabetes mellitus,hypertension,dyslipidemia,and obstructive sleep apnea,was achieved and defined as complete or partial remission.No intraoperative complications were observed.Short-term complications were observed in four(6.8%)patients.However,larger studies with longer follow-up periods are required to draw definitive conclusions.CONCLUSION SADI-S has a low intraoperative and postoperative complication rate and is effective for weight loss and improving obesity-related comorbidities,including hypertension,type 2 diabetes mellitus,dyslipidemia,and sleep apnea syndrome.

Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma

AIM: To investigate the survival rates after transarterial embolization(TAE).METHODS: One hundred third six hepatocellular carcinoma(HCC) patients [90 barcelona clinic liver cancer(BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test.RESULTS: The overall mean survival was 35.8 mo(95%CI: 25.1-52.0). The survival rates of the BCLC A patients(33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo(95%CI: 27.5-52.0). The survival rates of the BCLC B patients(66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo(95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo(95%CI: 32.8-34.3), 28.6 mo(95%CI: 27.5-29.8), 19.0 mo(95%CI: 17.2-20.9) and 13 mo, respectively(P = 0.013).CONCLUSION : The BCLC sub-stagingsystem could add additional prognosis information for postembolization survival rates in HCC patients.

Engineering Fe‑N_(4)Electronic Structure with Adjacent Co‑N_(2)C_(2)and Co Nanoclusters on Carbon Nanotubes for Efficient Oxygen Electrocatalysis

Regulating the local configuration of atomically dispersed transition-metal atom catalysts is the key to oxygen electrocatalysis performance enhancement.Unlike the previously reported singleatom or dual-atom configurations,we designed a new type of binary-atom catalyst,through engineering Fe-N_(4)electronic structure with adjacent Co-N_(2)C_(2)and nitrogen-coordinated Co nanoclusters,as oxygen electrocatalysts.The resultant optimized electronic structure of the Fe-N_(4)active center favors the binding capability of intermediates and enhances oxygen reduction reaction(ORR)activity in both alkaline and acid conditions.In addition,anchoring M-N-C atomic sites on highly graphitized carbon supports guarantees of efficient charge-and mass-transports,and escorts the high bifunctional catalytic activity of the entire catalyst.Further,through the combination of electrochemical studies and in-situ X-ray absorption spectroscopy analyses,the ORR degradation mechanisms under highly oxidative conditions during oxygen evolution reaction processes were revealed.This work developed a new binary-atom catalyst and systematically investigates the effect of highly oxidative environments on ORR electrochemical behavior.It demonstrates the strategy for facilitating oxygen electrocatalytic activity and stability of the atomically dispersed M-N-C catalysts.

Comparison between endoscopic sclerotherapy and band ligation for hemostasis of acute variceal bleeding

AIM:To compare band ligation(BL) with endoscopic sclerotherapy(SCL) in patients admitted to an emergency unit for esophageal variceal rupture. METHODS:A prospective,randomized,single-center study without crossover was conducted.After endoscopic diagnosis of esophageal variceal rupture,patients were randomized into groups for SCL or BL treatment.Sclerotherapy was performed by ethanolamine oleate intravascular injection both above and below the rupture point,with a maximum volume of 20 mL.For BL patients,banding at the rupture point was attempted,followed by ligation of all variceal tissue of the distal esophagus.Primary outcomes for both groups were initial failure of bleeding control(5 d) ,early re-bleeding(5 d to 6 wk),and complications,including mortality.From May 2005 to May 2007,100 patients with variceal bleeding were enrolled in thestudy:50 SCL and 50 BL patients.No differences between groups were observed across gender,age,ChildPugh status,presence of shock at admission,mean hemoglobin levels,and variceal size. RESULTS:No differences were found between groups for bleeding control,early re-bleeding rates,complications,or mortality.After 6 wk,36(80%) SCL and 33(77 %) EBL patients were alive and free of bleeding.A statistically significant association between Child-Pugh status and mortality was found,with 16%mortality in Child A and B patients and 84%mortality in Child C patients(P<0.001) . CONCLUSION:Despite the limited number of patients included,our results suggest that SCL and BL are equally efficient for the control of acute variceal bleeding.

Differential colorectal carcinogenesis:Molecular basis and clinical relevance

Colorectal cancer(CCR) is one of the most frequent cancers in developed countries.It poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal cancer.It has been established that sporadic CCRs can arise from at least two different carcinogenic pathways.The traditional pathway,also called the suppressor or chromosomal instability pathway,follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes,such as K-ras,adenomatous polyposis coli,deleted in colorectal cancer,or p53.Alterations in the Wnt pathway are also very common in this type of tumour.The second main colorectal carcinogenesis pathway is the mutator pathway.This pathway is present in nearly 15% of all cases of sporadic colorectal cancer.It is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes,mostly in hMLH1 or hMSH2.These two pathways have clear molecular differences,which will be reviewed in this article,but they also present distinct histopathological features.More strikingly,their clinical behaviours are completely different,having the "mutator" tumours a better outcome than the "suppressor" tumours.

Treatment of chronic hepatitis B in clinical practice with entecavir or tenofovir

Results from phaseⅢclinical trials clearly demonstrate the efficacy and safety of entecavir and tenofovir in the controlled environment of randomized clinical studies.There are several studies with both drugs performed in clinical practice(also called"real life studies").Despite the pros and cons,studies performed in real life conditions represent everyday practice and add important information about long term treatment effectiveness and safety in this clinical setting.This review shows that patients treated with first line nucleos(t)ide analogs at referral centres,with good clinical follow-up and adherence to international guidelines,can achieve high treatment response rates with a very low rate of adverse events.

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease.

Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil:A national survey

AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods.METHODS The primary antibiotic resistance rates of Helicobacter pylori(H. pylori) were determined from November 2012 to March 2015 in the Southern,South-Eastern,Northern,North-Eastern,and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female,mean age 43 years(range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using Geno Type Helico DR(Hain Life Science,Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies,multiplex amplification,and reverse hybridization. RESULTS Clarithromycin resistance was found in 83(16.9%) patients,and fluoroquinolone resistance was found in 66(13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones(P = 0.55 and P = 0.06,respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3%(21/490) of patients. The A2147 G mutation was present in 90.4%(75/83),A2146 G in 16.9%(14/83) and A2146 C in 3.6%(3/83) of clarithromycin-resistant patients. In 10.8%(9/83) of clarithromycin-resistant samples,more than 01 mutation in the 23 S r RNA gene was noticed. In fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. D91 N mutation was observed in 34.8%(23/66),D91 G in 18.1%(12/66),N87 K in 16.6%(11/66) and D91 Y in 13.6%(9/66) of cases. Among fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. CONCLUSION The H. pylori clarithromycin resistance rate in Brazil is at the borderline(15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate(13.5%) is equally concerning.

Medical management of connector pin thrombosis with the Amplatzer cardiac plug left atrial closure device

Transcatheter closure of the left atrial appendage with the Amplatzer cardiac plug device and double antiplatelet treatment for 3 mo has become an alternative treatment for patients with atrial fibrillation at high embolism risk and contraindications for chronic oral anticoagulation.The inadequate implantation of the left atrial appendage closure device and the discontinuation of double antiplatelet therapy are well-known as factors related to device thrombosis.Nevertheless,device thrombosis after adequate implantation requiring surgical treatment or restarting chronic oral anticoagulation has been reported and can reach 15% of patients.The connector pin thrombosis of the Amplatzer cardiac plug,despite a good adherence to antiplatelet treatment,has been recently described as a potential mechanism for device thrombosis.Our clinical case reports the management of this condition for the first time,showing that the early detection of thrombotic complications by transesophageal echocardiography permits solving this serious complication with medical treatment only.

Proton nuclear magnetic resonance-based metabonomic models for non-invasive diagnosis of liver fibrosis in chronic hepatitis C:Optimizing the classification of intermediate fibrosis

AIM To develop metabonomic models(MMs), using 1 H nuclear magnetic resonance(NMR) spectra of serum, to predict significant liver fibrosis(SF: Metavir ≥ F2), advanced liver fibrosis(AF: METAVIR ≥ F3) and cirrhosis(C: METAVIR = F4 or clinical cirrhosis) in chronic hepatitis C(CHC) patients. Additionally, to compare the accuracy of the MMs with the aspartate aminotransferase to platelet ratio index(APRI) and fibrosis index based on four factors(FIB-4). METHODS Sixty-nine patients who had undergone biopsy in the previous 12 mo or had clinical cirrhosis were included. The presence of any other liver disease was a criterion for exclusion. The MMs, constructed using partial least squares discriminant analysis and linear discriminant analysis formalisms, were tested by cross-validation, considering SF, AF and C. RESULTS Results showed that forty-two patients(61%) presented SF, 28(40%) AF and 18(26%) C. The MMs showed sensitivity and specificity of 97.6% and 92.6% to predict SF; 96.4% and 95.1% to predict AF; and 100% and 98.0% to predict C. Besides that, the MMs correctly classified all 27(39.7%) and 25(38.8%) patients with intermediate values of APRI and FIB-4, respectively. CONCLUSION The metabonomic strategy performed excellently in predicting significant and advanced liver fibrosis in CHC patients, including those in the gray zone of APRI and FIB-4, which may contribute to reducing the need for these patients to undergo liver biopsy.

Hepatocellular carcinoma staging systems: Hong Kong liver cancer vs Barcelona clinic liver cancer in a Western population

BACKGROUND Despite being the world’s most widely used system for staging and therapeutic guidance in hepatocellular carcinoma(HCC)treatment,the Barcelona clinic liver cancer(BCLC)system has limitations,especially regarding intermediate-grade(BCLC-B)tumors.The recently proposed Hong Kong liver cancer(HKLC)staging system appears useful but requires validation in Western populations.AIM To evaluate the agreement between BCLC and HKLC staging on the management of HCC in a Western population,estimating the overall patient survival.METHODS This was a retrospective study of HCC patients treated at a university hospital in southern Brazil between 2011 and 2016.Demographic,clinical,and laboratory data were collected.HCC staging was carried out according to the HKLC and BCLC systems to assess treatment agreement.Overall survival was estimated based on the treatment proposed in each system.RESULTS A total of 519 HCC patients were assessed.Of these,178(34.3%)were HKLC-I;95(18.3%)HKLC-IIA;47(9.1%)HKLC-IIB;29(5.6%)HKLC-IIIA;30(5.8%)HKLCIIIB;75(14.4%)HKLC-IV;and 65(12.5%)HKLC-V.According to the BCLC,25(4.9%)were BCLC-0;246(47.4%)BCLC-A;107(20.6%)BCLC-B;76(14.6%)BCLCC;and 65(12.5%)BCLC-D.The general agreement between the two systems was 80.0%-BCLC-0 and HKLC-I(100%);BCLC-A and HKLC-I/HKLC-II(96.7%);BCLC-B and HKLC-III(46.7%);BCLC-C and HKLC-IV(98.7%);BCLC-D and HKLC-V(41.5%).When sub-classifying BCLC-A,HKLC-IIB,HKLC-IIIA and HKLC-IIIB stages according to the up-to-7 in/out criterion,13.4,66.0,100 and 36.7%,respectively,of the cases were classified as up-to-7 out.CONCLUSION In a Western population,the general agreement between the two systems was 80.0%,although in BCLC-B cases the agreement was low,suggesting that some individuals could be candidates for the curative treatment recommended by the HKLC.The authors suggest that the BCLC system should be routinely employed,although for BCLC-B cases it should be associated with the HKLC system.

Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

Clinicopathological differences,risk factors and prognostic scores for western patients with intestinal and diffuse-type gastric cancer

BACKGROUND In the molecular era,the Laurén system is still a cost-effective and widely implemented classification for gastric cancer(GC)and it has been recently associated with clinical,histological and molecular features of these tumors.Despite recent advances in the understanding of the molecular biology of GC,there is a need to develop new prognostic tools for patient stratification in clinical practice.Thus,the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in GC.AIM To identify clinicopathological differences,risk factors,and to develop costeffective prognostic scores for patients with intestinal and diffuse-type GC.METHODS Retrospective study of all patients undergoing surgery for GC at a tertiary referral center from 2001 to 2019.286 cases met inclusion criteria(intestinal:190,diffuse:96).Clinical data and gross findings were collected.All specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was followed.Five tissue microarrays(TMAs)were constructed and sections of the TMA block were immunostained for HERCEPTEST,MSH2,MSH6,MLH1 and PMS2.Statistical analyses were performed and prognostic scores were developed based on hazard ratios.RESULTS Intestinal and diffuse-type GC showed different epidemiological,clinicopathological and prognostic features.Diffuse tumors were significantly associated with younger age,less symptomatology,flat morphology,deeper invasion,perineural infiltration,advanced stage at diagnosis,administration of adjuvant therapy and poorer prognosis.Intestinal lesions were fungoid or polypoid,showed necrosis,desmoplasia,microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier stages.Tumor depth,desmoplasia,macroscopic type and lymph node involvement were independently related to the Laurén subtype.Furthermore,intestinal and diffuse GC were associated with different risk factors for progression and death.Vascular invasion,perineural infiltration and growth pattern were important prognostic factors in intestinal-type GC.On the contrary,tumor size and necrosis were significant prognosticators in diffuse-type GC.Our recurrence and cancer-specific death scores for patients with intestinal and diffuse-type GC showed an excellent patient stratification into three(diffuse GC)or four(intestinal)prognostic groups.CONCLUSION Our findings support that Laurén subtypes represent different clinicopathological and biological entities.The development of specific prognostic scores is a useful and cost-effective strategy to improve risk assessment in GC.