Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Single-cell profiling of the pig cecum at various developmental stages

The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.

Novel method for identifying the stages of discharge underwater based on impedance change characteristic

It is difficult to determine the discharge stages in a fixed time of repetitive discharge underwater due to the arc formation process being susceptible to external environmental influences. This paper proposes a novel underwater discharge stage identification method based on the Strong Tracking Filter(STF) and impedance change characteristics. The time-varying equivalent circuit model of the discharge underwater is established based on the plasma theory analysis of the impedance change characteristics and mechanism of the discharge process. The STF is used to reduce the randomness of the impedance of repeated discharges underwater, and then the universal identification resistance data is obtained. Based on the resistance variation characteristics of the discriminating resistance of the pre-breakdown, main, and oscillatory discharge stages, the threshold values for determining the discharge stage are obtained. These include the threshold values for the resistance variation rate(K) and the moment(t).Experimental and error analysis results demonstrate the efficacy of this innovative method in discharge stage determination, with a maximum mean square deviation of Scrless than 1.761.

Understanding changes in volatile compounds and fatty acids of Jincheng orange peel oil at different growth stages using GC-MS

Jincheng orange(Citrus sinensis Osbeck)is widely grown in Chongqing,China,and is commonly consumed because of its characteristic aroma contributed by the presence of diverse volatile compounds.The changes in aroma during the development and maturation of fruit are indicators for ripening and harvest time.However,the influence of growth stages on the volatile compounds in Jincheng orange remains unclear.In addition,volatiles originate from fatty acids,most of which are the precursors of volatile substances.On this basis,gas chromatography-mass spectrometry(GC-MS)was performed to elaborate the changes in volatile constituents and fatty acids as precursors.This study tested proximately 60 volatiles and 8 fatty acids at 9 growth and development stages(AF1-AF9).Of those compounds,more than 92.00%of total volatiles and 87.50%of fatty acids were terpenoid and saturated fatty acids,respectively.As shown in the PCA plot,the AF5,AF6,and AF9 stages were confirmed as completely segregated and appeared different.In addition,most of the volatiles and fatty acids first increased at the beginning of the development stage,then decreased from the AF6 development stage,and finally increased at the AF9 maturity stage.Moreover,the highest contents of terpenoid,alcohols,aldehydes,ketones,and saturated fatty acids in Jincheng orange peel oil were d-limonene,linalool,octanal,cyclohexanone,and stearic acid during development stages,respectively.Our results found that the growth stages significantly affected the volatile constituents and precursors in Jincheng orange peel oil.

Mid-term results of sub-trochanteric valgus osteotomy for symptomatic late stages Legg-Calvé-Perthes disease

BACKGROUND The treatment of late stages of Legg-Calvé-Perthes disease(LCPD)is controversial.Although the concept of femoral head containment is a well-established technique of treatment,its use remains debatable in the late stages of the disease,as it does not improve symptoms in terms of limb length discrepancy and gait.AIM To assess the results of subtrochanteric valgus osteotomy in symptomatic patients with late-stage Perthes disease.METHODS From 2000 to 2007,36 symptomatic patients with late stage of Perthes disease were surgically treated with subtrochanteric valgus osteotomy and followed-up for 8 to 11 years using the IOWA score and range of motion(ROM)variables.The Mose classification was also assessed at the last follow-up to reflect possible remodeling.The patients were 8 years old or older at the time of surgery,in the post-fragmentation stage,and complaining of pain,limited ROM,Trendelenburg gait,and/or abductor weakness.RESULTS The preoperative IOWA score(average:53.3)markedly improved at the 1-year post follow-up period(average:85.41)and then slightly improved at the last follow-up(average:89.4)(P value<0.05).ROM improved,with internal rotation increased on average by 22°(from 10°preoperatively to 32°postoperatively)and abduction increased on average by 15.9°(from 25°preoperatively to 41°postoperatively).The mean Mose deviation of femoral heads was 4.1 mm at the end of the follow-up period.The tests used were the paired t-test and Pearson correlation test,where the level of significance was a P value less than 0.05.CONCLUSION Subtrochanteric valgus osteotomy can be a good option for symptomatic relief in patients with late-stage of LCPD.

Rectal Cancer Stages T2 and T3 Identification Based on Asymptotic Hybrid Feature Maps

Many existing intelligent recognition technologies require huge datasets for model learning.However,it is not easy to collect rectal cancer images,so the performance is usually low with limited training samples.In addition,traditional rectal cancer staging is time-consuming,error-prone,and susceptible to physicians’subjective awareness as well as professional expertise.To settle these deficiencies,we propose a novel deep-learning model to classify the rectal cancer stages of T2 and T3.First,a novel deep learning model(RectalNet)is constructed based on residual learning,which combines the squeeze-excitation with the asymptotic output layer and new cross-convolution layer links in the residual block group.Furthermore,a two-stage data augmentation is designed to increase the number of images and reduce deep learning’s dependence on the volume of data.The experiment results demonstrate that the proposed method is superior to many existing ones,with an overall accuracy of 0.8583.Oppositely,other traditional techniques,such as VGG16,DenseNet121,EL,and DERNet,have an average accuracy of 0.6981,0.7032,0.7500,and 0.7685,respectively.

RT-qPCR normalization of reference genes in different lifehistory stages of Gracilaria vermiculophylla(Rhodophyta)

The quantitative realtime polymerase chain reaction(RT-qPCR)is a powerful and sensitive method to measure expression of targeted gene but it highly relies on the use of suitable reference genes for data normalization.We evaluated the expressions of 8 housekeeping genes:18S ribosomal rDNA(18S rDNA),28S ribosomal r DNA(28S rDNA),rubisco large subunit(rbc-L),β-actin(ACT),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),elongation factor 1(EF1),β-tubulin(Tub B),and P-phycoerythrin B(PEB),to select the suitable reference genes for different life-history stages(tetrasporophyte,carposporophyte,and male/female gametophyte)of Gracilaria vermiculophylla by absolute quantitative method.Softwares geNorm and BestKeeper were used to verify the results acquired from copy number analysis.Results show that the expression of identified reference genes varied in comparing groups composed of different type of life stages.It is suggested that 18S rDNA and TubB could be used for highly complex samples composed of mixed ploidy and phases.18S rDNA and 28S rDNA were also preferred for using among the matured isomorphic samples.But for samples with different maturities,TubB and ACT were recommended for tetrasporophytes and gametophytes respectively.

Deformation Mechanism of Bimodal Structured 2205 Duplex Stainless Steel in Two Yield Stages

A kind of micro/nanostructured 2205 duplex stainless steel(DSS)with uniform distribution of nanocrystals was prepared via aluminothermic reaction method.The analysis of stress-strain curve showed that the fracture strength and elongation of the specimen were 946 MPa and 24.7%,respectively.At present,the research on microstructure of bimodal 2205 DSS at room temperature(RT)mainly depended on scanning electron microscope(SEM)observation after loading experiments.The test result indicates that there are two different yield stages in stress-strain curve of specimen during tensile process.The microstructure of duplex bimodal structured stainless steel consists of two pairs of soft hard regions and phases.By studying deformation mechanism of bimodal structured stainless steel,the interaction between soft phase and hard phase are discussed.The principle of composition design and microstructure control of typical duplex stainless steel is obtained,which provides an important research basis for designing of advanced duplex stainless steel.

Ecological network analysis reveals complex responses of tree species life stage interactions to stand variables

Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16 LSINs in the mountainous forests of northwest Hebei,China based on crown overlap from four mixed forests with two dominant tree species.Our results show that LSINs decrease the complexity of stand densities and basal areas due to the interaction cluster differentiation.In addition,we found that mature trees and saplings play different roles,the first acting as“hub”life stages with high connectivity and the second,as“bridges”controlling information flow with high centrality.Across the forests,life stages with higher importance showed better parameter stability within LSINs.These results reveal that the structure of tree interactions among life stages is highly related to stand variables.Our efforts contribute to the understanding of LSIN complexity and provide a basis for further research on tree interactions in complex forest communities.

Feedback linearization and equivalent-disturbance compensation control strategy for piezoelectric stage

Piezoelectric stages use piezoelectric actuators and flexure hinges as driving and amplifying mechanisms,respectively.These systems have high positioning accuracy and high-frequency responses,and they are widely used in various precision/ultra-precision positioning fields.However,the main challenge with these devices is the inherent hysteresis nonlinearity of piezoelectric actuators,which seriously affects the tracking accuracy of a piezoelectric stage.Inspired by this challenge,in this work,we developed a Hammerstein model to describe the hysteresis nonlinearity of a piezoelectric stage.In particular,in our proposed scheme,a feedback-linearization algorithm is used to eliminate the static hysteresis nonlinearity.In addition,a composite controller based on equivalent-disturbance compensation was designed to counteract model uncertainties and external disturbances.An analysis of the stability of a closed-loop system based on this feedback-linearization algorithm and composite controller was performed,and this was followed by extensive comparative experiments using a piezoelectric stage developed in the laboratory.The experimental results confirmed that the feedback-linearization algorithm and the composite controller offer improved linearization and trajectory-tracking performance.

An Elite-Class Teaching-Learning-Based Optimization for Reentrant Hybrid Flow Shop Scheduling with Bottleneck Stage

Bottleneck stage and reentrance often exist in real-life manufacturing processes;however,the previous research rarely addresses these two processing conditions in a scheduling problem.In this study,a reentrant hybrid flow shop scheduling problem(RHFSP)with a bottleneck stage is considered,and an elite-class teaching-learning-based optimization(ETLBO)algorithm is proposed to minimize maximum completion time.To produce high-quality solutions,teachers are divided into formal ones and substitute ones,and multiple classes are formed.The teacher phase is composed of teacher competition and teacher teaching.The learner phase is replaced with a reinforcement search of the elite class.Adaptive adjustment on teachers and classes is established based on class quality,which is determined by the number of elite solutions in class.Numerous experimental results demonstrate the effectiveness of new strategies,and ETLBO has a significant advantage in solving the considered RHFSP.

Dry eye rate and its relationship with disease stage in patients with primary hypertension:a cross-sectional study in Vietnam

AIM:To determine the dry eye(DE)rate and its relationship with disease stage in patients with primary hypertension.METHODS:A cross-sectional study included 432 patients with primary hypertension(with an equal number of patients in each group:144 in stage Ⅰ,Ⅱ,and Ⅲ hypertension)and 144 healthy subjects as a control group.The Ocular Surface Disease Index(OSDI)and Schirmer Ⅰ test without anesthetics were conducted on all 576 subjects.Subjects with OSDI scores<13 and Schirmer Ⅰ values equal to or under 10 mm were diagnosed with DE.RESULTS:The ratio of DE in hypertension patients was higher than in the control group(41.7%versus 18.8%;P<0.001).The proportion of patients with DE increased gradually according to the hypertension stage:27.1% in stage Ⅰ,40.3% in stage Ⅱ,and 57.6% in stage Ⅲ,P<0.001.Age,duration of hypertension,plasma urea,creatinine,and high-sensitivity C-reactive protein(CRP-hs)levels in hypertension patients with DE were higher than those without DE,P<0.001.Advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma creatinine,and CRP-hs levels were independent factors associated with DE in primary hypertension patients,P<0.001.CONCLUSION:DE is a common disorder associated with advanced age,a long duration of hypertension,diabetes mellitus,elevated plasma CRP-hs,and creatinine levels in patients with primary hypertension.

CmMYB3-like negatively regulates anthocyanin biosynthesis and flower color formation during the post-flowering stage in Chrysanthemum morifolium

Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease:A meta-analysis

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.

Functional assessment and influencing factors after staged functional training in patients with ankle fractures

BACKGROUND The recovery of limb function after ankle fracture surgery is a gradual process.The main purpose of implementing early functional exercise,joint mobility,muscle contraction function,passive ankle flexion and extension exercises,or physical factor therapy techniques is to achieve the rapid recovery of normal physiological limb function.However,currently the most effective rehabilitation training method is staged limb functional exercise,which promotes rapid recovery of limb function while preventing adverse consequences caused by overwork or insufficient training.Staged limb functional exercise divides the rehabilitation process into multiple stages,each of which has specific training objectives and contents.This method helps patients gradually restore limb function.Nevertheless,some patients still exhibit poor limb function after standardized exercise.Therefore,a functional evaluation should be performed to analyze the impact of staged functional training after ankle fracture surgery.AIM To perform a functional evaluation and determine the influencing factors of staged functional training in patients with ankle fracture.METHODS A retrospective study enrolled 150 patients who underwent surgical treatment for ankle fracture from May 2020 to May 2022 at our hospital.Univariate and multivariate linear regression analyses were performed on general data,functional exercise compliance scale for orthopedic patients,Social Support Rating Scale(SSRS),American Orthopedic Foot and Ankle Score(AOFAS)Ankle-Hindfoot Score,and pain factors[serum bradykinin(BK),prostaglandin E2(PGE2),5-hydroxytryptamine(5-HT)].RESULTS Based on the AOFAS Ankle-Hindfoot Scale,the cases were divided into the excellent function(n=111)and ordinary function(n=39)groups.Univariate analysis revealed that monthly family income,education level,diabetes mellitus,functional exercise compliance scale of orthopedic patients score,SSRS,BK,PGE2,and 5-HT significantly influenced limb function after ankle fracture(P<0.05);Multiple linear regression analysis showed that the functional exercise compliance scale score,SSRS,BK,PGE2,and 5-HT were independent risk factors affecting functional performance after staged functional exercise(P<0.05).CONCLUSION Exercise compliance,SSRS,and pain level are the independent risk factors affecting functional performance after staged functional training following ankle surgery.Clinical nursing care after ankle surgery should include analgesic and health education measures to ensure optimal recovery of limb function.

Is there sufficient evidence to support the use of antibiotic holiday just before the second stage of an infected total hip or knee arthroplasty revision surgery?

The practice of implementing an antibiotic holiday before the second stage of hip or knee arthroplasty is currently controversial due to limited evidence for this approach,as per the International Consensus Meeting 2018 on Musculoskeletal Infection.A greater understanding of this issue could augment the quality of Alrayes and Sukeik’s mini-review(2023)on diagnosing,managing,and treating periprosthetic knee infections.However,a significant lack of literature exists concerning the optimal duration for the antibiotic holiday,calling for more research before establishing any clinical guidelines.

Computed tomography-based radiomics diagnostic approach for differential diagnosis between early-and late-stage pancreatic ductal adenocarcinoma

BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages.METHODS A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the study.Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system.Radiomics features were extracted from the region of interest(ROI)for each patient using Analysis Kit software.The most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)method.Random forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the model.RESULTS A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit software.Nine most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR method.RF method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive value.The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models.CONCLUSION The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

Subsequent total joint arthroplasty: Are we learning from the first stage?

BACKGROUND With the increasing incidence of total joint arthroplasty(TJA),there is a desire to reduce peri-operative complications and resource utilization.As degenerative conditions progress in multiple joints,many patients undergo multiple proce-dures.AIM To determine if both physicians and patients learn from the patient’s initial arth-roplasty,resulting in improved outcomes following the second procedure.METHODS The institutional database was retrospectively queried for primary total hip arth-roplasty(THA)and total knee arthroplasty(TKA).Patients with only unilateral THA or TKA,and patients undergoing same-day bilateral TJA,were excluded.Patient demographics,comorbidities,and implant sizes were collected at the time of each procedure and patients were stratified by first vs second surgery.Outcome metrics evaluated included operative time,length of stay(LOS),disposition,90-d readmissions and emergency department(ED)visits.RESULTS A total of 642 patients,including 364 undergoing staged bilateral TKA and 278 undergoing bilateral THA,were analyzed.There was no significant difference in demographics or comorbidities between the first and second procedure,which were separated by a mean of 285 d.For THA and TKA,LOS was significantly less for the second surgery,with 66%of patients having a shorter hospitalization(P<0.001).THA patients had significantly decreased operative time only when the same sized implant was utilized(P=0.025).The vast majority(93.3%)of patients were discharged to the same type of location following their second surgery.However,when a change in disposition was present from the first surgery,patients were significantly more likely to be discharged to home after the second procedure(P=0.033).There was no difference between procedures for post-operative readmissions(P=0.438)or ED visits(P=0.915).CONCLUSION After gaining valuable experience recovering from the initial surgery,a patient’s perioperative outcomes are improved for their second TJA.This may be the result of increased confidence and decreased anxiety,and it supports the theory that enhanced patient education pre-operatively may improve outcomes.For the surgical team,the second procedure of a staged THA is more efficient,although this finding did not hold for TKA.