Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.

A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma:A retrospective study

Intravesical Bacillus Calmette Guerin(BCG)is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer(NMIBC).However,the response rate is~60%,and 50%of non-responders will progress to muscle-invasive disease.BCG induces massive local infiltration of inflammatory cells(Th1)and ultimately cytotoxic tumor elimination.We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte(TIL)polarization in the tumor microenvironment(TME)in pre-treatment biopsies.Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG(n=32)were evaluated retrospectively by immunohistochemistry.TME polarization was assessed by quantifying the T-Bet+(Th1)and GATA-3+(Th2)lymphocyte ratio(G/T),and the density and degranulation of EPX+eosinophils.In addition,PD-1/PD-L1 staining was quantified.The results correlated with BCG response.In most non-responders,Th1/Th2 markers were compared in pre-and post-BCG biopsies.ORR was 65.6%in the study population.BCG responders had a higher G/T ratio and a greater number of degranulated EPX+cells.Variables combined into a Th2-score showed a significant association with higher scores in responders(p=0.027).A Th2-score cut-off value>48.1 allowed discrimination of responders with 91%sensitivity but lower specificity.Relapse-free survival was significantly associated with the Th2-score(p=0.007).In post-BCG biopsies from recurring patients,TILs increased Th2-polarization,probably reflecting BCG failure to induce a pro-inflammatory status and,thus,a lack of response.PD-L1/PD-1 expression was not associated with the response to BCG.Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG,assuming a reversion to Th1 polarization and antitumor activity.

Intravesical bacillus Calmette-Guerin(BCG)in treating non-muscle invasive bladder cancer—analysis of adverse effects and effectiveness of two strains of BCG(Danish 1331 and Moscow-I)

Objective:To compare the differences in adverse effects and efficacy profile between bacillus Calmette-Guerin(BCG)Danish 1331 and BCG Moscow-I strain in management of non-muscle invasive bladder cancer.Methods:Clinical data of 188 cases of non-muscle invasive bladder cancer treated with BCG between January 2008 and December 2018 in our institute were collected prospectively and analysed retrospectively,and 114 patients who completed a minimum of 12 months of follow-up were analysed.Patient and tumor characteristics,strain of BCG,adverse effects,and tumor progression were included for analysis.Intravesical BCG was instilled in intermediate-and high-risk patients.Six weeks of induction BCG,followed by three weekly maintenance BCG at 3,6,12,18,and 24 months was advised in high-risk patients.Results:Overall 68 patients received BCG Danish 1331 strain and 46 patients received Moscow-I strain.Patient and tumor characteristics were well balanced between the two groups.The median follow-up period was 42.5 months and 34.5 months in Danish 1331 and Moscow-I groups,respectively.Adverse events like dropout rate,antitubercular treatment requirement,and need of cystectomy were higher in Moscow-I group(n=31,67.4%)when compared to Danish 1331 strain(n=33,48.5%)(p=0.046).On direct comparison between Danish 1331 and Moscow-I strain,there was similar 3-year recurrence-free survival(80.0%vs.72.9%)and 3-year progression-free survival(96.5%vs.97.8%).Conclusion:Study results suggest no significant differences between Danish 1331 and Moscow-I strain in recurrence-free survival and progression-free survival,but a significantly higher incidence of moderate to severe adverse events in BCG Moscow-I strain.

Molecular mechanisms and novel therapeutic strategies of BCG-unresponsive non-muscle invasive bladder cancer: Emerging immunotherapy has become a new choice?

Objective:THigh-risk non-invasive bladder cancer(NMIBC)has a high rate of recurrence and disease progression.At present,there are still insufficient effective prevention and treatment methods,especially for patients who have failed BCG treatment.This article reviews the research progress of the molecular mechanism of BCG unresponsive NMIBC,and summarizes the current status and prospects of emerging therapeutic strategies represented by immunotherapy,providing a theoretical basis for the immunotherapy of BCG non-reactive NMIBC.Methods:We searched the PubMed and CNKI journal full-text database search system for keywords"non-muscle invasive bladder cancer,BCG unresponsive,disease recurrence,disease progression,and immunotherapy"with 126 English and 538 Chinese articles.The literature,as well as the relevant clinical research in ClinicalTrials.gov,were integrated together to obtain the results.Results:Immunotherapy was performed in various types of tumors,and the use of immunotherapeutic drugs with different oncotargets administered alone,sequentially or in combination for the treatment of BCG-unresponsive NMIBC have achieved favorable effects,and more Clinical research is still ongoing.Conclusion:Immunotherapy is currently the most promising treatment for cancer,and it is indispensable for patients with NMIBC,both biologically and clinically.We look forward to more laboratory and clinical research in immunotherapy in the future.

Did the Scientific Innovations in the Management of Non-Muscle Invasive Bladder Cancer Patients Improve the Outcome during the Last 2 Decades?

Objectives: Previous reviews reported the outcome of each scientific modality in the management of T1 high-grade bladder cancer. The objective of this review is to assess and evaluate the available scientific modalities used during the last two decades and determine whether they were able to improve the clinical outcome. Literature Search Methodology: A systematic literature review was conducted from 2000-2020 using PubMed, Medline, Embase, and other database sites looking at randomized controlled trials (RCTs), clinical trials, research, review articles, and original articles addressing the different scientific modalities used to diagnose and manage patients with non-muscle invasive Bladder cancer (NMIBC)during the last 2 decades. More than 573 studies were retrieved following the preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and PICOS criteria (Population, Intervention, Comparators, Outcomes, and Study design). Only 85 articles were selected for review including 19 prospective trials, 44 RCTs, original articles, research articles, one review article, and clinical trials—Retrospective studies were excluded to limit bias as much as possible in the analysis. Results: Randomized controlled trials (RCTs) have become the gold standard for evaluating the efficacy of new treatments. They are considered the highest standard of evidence-based medicine and are the method of choice. Overall, we selected 85 studies for review, among them 63 prospective trials and RCTs, with a total of 21,895 patients, published between 2000 and 2020. Previously conducted studies have shown that identifying rare histological types with poor prognoses can help improve outcomes, mainly the plasmacytoid type. Many articles addressed the role of biomarkers in the early identification of patients with NMIBC for recurrence and progression—P-cadherin expression and others were used to predict recurrence and/or progression with promising results. Despite the need for modifications, risk stratification is an important tool that should be used to improve the outcome of patients with NMIBC. Some found that fluorescence diagnostic cystoscopy (FDC) and Photodynamic diagnosis (PDD) improved recurrence-free survival but not progression and outcome. All authors agree that intravesical BCG is the most effective therapy that changes the course of high-grade T1 mainly progression. Re-TURBT has become one of the recommendations of international societies, but its potential effect on survival improvement is debatable. Most of the articles showed the advantages of early cystectomy in NMIBC but all agree that the selection criteria must be clearly defined. Conclusions: This review analyzed the outcomes provided by the scientific advances in the field of management of NMIBC patients in the last two decades. Patients with T1 bladder cancer have variable outcomes because of tumor heterogeneity and clinical staging. Despite the great development in the field of diagnosis, risk stratification, and management, further large studies are mostly needed to better elucidate this subset of patients and avoid over and under-treatment.

Molecular Assessment of Non-Muscle Invasive and Muscle Invasive Bladder Tumors: Mapping of Putative Urothelial Stem Cells and Toll-Like Receptors (TLR) Signaling

Purpose: The main objectives of this study were to characterize and compare the urothelial stem cells (healthy and cancer cells) and TLRs features in the urinary bladder of men without lesionsand with non-muscle-invasive and muscle invasive urothelial tumors. Materials and Methods: Thirty samples of the urinary bladder of 50 to 80-year-old men, with and without diagnosis of malignant urothelial lesions were used. The 30 samples were divided into 3 groups (n = 10 per group): Normal Group;Non-Muscle Invasive Bladder Cancer Group;Muscle Invasive Bladder Cancer Group. The samples were histopathologically and immunohistochemically analyzed. The study was conducted at teaching Hospital of the University of Campinas (UNICAMP). Results: The CD44 and CD133 immunoreactivities were significantly intense in the muscle-invasive cancer group when compared to the other groups. The ABCG2 biomarker demonstrated intense immunoreactivities in both non-muscle and muscle invasive groups, and absent immunoreactivity in the normal group. All groups showed weak CD117 immunoreactivity. Putative Healthy Stem Cells (CD44/CD133/ CD117+) occurred in all groups. Putative Cancer Stem Cells (CD44/CD133/ABCG2+) only occurred in the non-muscle and muscle invasive cancer groups. TLR2 immunoreactivity was significantly lower in the non-muscle invasive cancer group and absent in the muscle invasive cancer group. TLR4 immunoreactivity was significantly lower in both cancer groups. Conclusions: This study leads us to the conclusion that putative cancer stem cell occurrence was sensitive to the decreased in TLR2 and TLR4 immunoreactivities. Also, TLR2 and TLR4 demonstrated their involvement in the regulation of the different biomarkers for putative healthy and cancer urothelial stem cells, probably acting as negative regulators of urothelial carcinogenesis. Taken together data obtained suggest that use of TLRs agonists could be a promising alternative for the treatment of non-muscle and muscle invasive bladder tumors.

Recirculating chemohyperthermia as a treatment for non-muscle invasive bladder cancer:Current and future perspectives

About 75% of all bladder cancer diagnosed are non-muscle invasive bladder cancer(NMIBC), recurring over 50% of them after transurethral resection of the bladder tumor. In order to prevent recurrences, adjuvant intravesical chemotherapy with mitomycin C and immunotherapy with bacillus Calmette-Gu-érin(BCG) is traditionally used. Unfortunately, many patients relapse after receiving these treatments and a significant proportion of them require surgery. After a one-to-three years BCG maintenance, the risk for progression at 5 years was 19.3% for T1G3 tumors. Many new treatment approaches are being investigated to increase the effectiveness of adjuvant intravesical therapy. One of the developing treatments for intermediate and high-risk NMIBC is the combination of intravesical chemotherapy and hyperthermia, called chemohyperthermia. This article provides a review of the mechanism of action, current status and indications, results and future perspectives.

Treatment and surveillance for non-muscle-invasive bladder cancer:a clinical practice guideline(2021 edition)

Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.

Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with non-muscle invasive bladder cancer？ An update and cumulative meta-analysis

Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer （NMIBC）. NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guerin （BCG） instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

New direction for surgery:Super minimally invasive surgery

The top goal of modern medicine is treating disease without destroying organ structures and making patients as healthy as they were before their sickness.Minimally invasive surgery(MIS)has dominated the surgical realm because of its lesser invasiveness.However,changes in anatomical structures of the body and reconstruction of internal organs or different organs are common after traditional surgery or MIS,decreasing the quality of life of patients post-operation.Thus,I propose a new treatment mode,super MIS(SMIS),which is defined as“curing a disease or lesion which used to be treated by MIS while preserving the integrity of the organs”.In this study,I describe the origin,definition,operative channels,advantages,and future perspectives of SMIS.

Toward less invasive coloproctology: The future is out there

Medical care has undergone remarkable improvements over the past few decades.One of the most important innovative breakthroughs in modern medicine is the advent of minimally and less invasive treatments.The trend towards employing less invasive treatment has been vividly shown in the field of gastroenterology,particularly coloproctology.Parallel to foregut interventions,colorectal surgery has shifted towards a minimally invasive approach.Coloproctology,including both medical and surgical management of colorectal diseases,has undergone a remarkable paradigm shift.The treatment of both benign and malignant colorectal conditions has gradually transitioned towards more conservative and less inva-sive approaches.An interesting paradigm shift was the trend to avoid the need for radical resection of rectal cancer altogether in patients who showed complete response to neoadjuvant treatment.The trend of adopting less invasive appro-aches to treat various colorectal conditions does not seem to be stopping soon as further research on novel,more effective and safer methods is ongoing.

Feasibility and safety of minimally invasive multivisceral resection for T4b rectal cancer:A 9-year review

BACKGROUND Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality worldwide.About 5%-10%of patients are diagnosed with locally advanced rectal cancer(LARC)on presentation.For LARC invading into other structures(i.e.T4b),multivisceral resection(MVR)and/or pelvic ex-enteration(PE)remains the only potential curative surgical treatment.MVR and/or PE is a major and complex surgery with high post-operative morbidity.Minimally invasive surgery(MIS)has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies,but there is little evi-dence on its use in MVR,especially so for robotic MVR.This is a single-center retrospective cohort study from 1st January 2015 to 31st March 2023.Inclusion criteria were patients diagnosed with cT4b rectal cancer and underwent MVR,or stage 4 disease with resectable systemic metastases.Pa-tients who underwent curative MVR for locally recurrent rectal cancer,or me-tachronous rectal cancer were also included.Exclusion criteria were patients with systemic metastases with non-resectable disease.All patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal surgery.Complex sur-gery was defined based on technical difficulty of surgery(i.e.total PE,bladder-sparing prostatectomy,pelvic lymph node dissection or need for flap creation).Our primary outcomes were the margin status,and complication rates.Cate-gorical values were described as percentages and analysed by the chi-square test.Continuous variables were expressed as median(range)and analysed by Mann-Whitney U test.Cumulative overall survival(OS)and recurrence-free survival(RFS)were analysed using Kaplan-Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.Meier estimates with life table analysis.Log-rank test was performed to determine statistical significance between cumulative estimates.Statistical significance was defined as P<0.05.RESULTS A total of 46 patients were included in this study[open MVR(oMVR):12(26.1%),miMVR:36(73.9%)].Patients’American Society of Anesthesiologists score,body mass index and co-morbidities were comparable between oMVR and miMVR.There is an increasing trend towards robotic MVR from 2015 to 2023.MiMVR was associated with lower estimated blood loss(EBL)(median 450 vs 1200 mL,P=0.008),major morbidity(14.7%vs 50.0%,P=0.014),post-operative intra-abdominal collections(11.8%vs 50.0%,P=0.006),post-operative ileus(32.4%vs 66.7%,P=0.04)and surgical site infection(11.8%vs 50.0%,P=0.006)compared with oMVR.Length of stay was also shorter for miMVR compared with oMVR(median 10 vs 30 d,P=0.001).Oncological outcomes-R0 resection,recurrence,OS and RFS were comparable between miMVR and oMVR.There was no 30-d mortality.More patients underwent robotic compared with laparoscopic MVR for complex cases(robotic 57.1%vs laparoscopic 7.7%,P=0.004).The operating time was longer for robotic compared with laparoscopic MVR[robotic:602(400-900)min,laparoscopic:Median 455(275-675)min,P<0.001].Incidence of R0 resection was similar(laparoscopic:84.6%vs robotic:76.2%,P=0.555).Overall complication rates,major morbidity rates and 30-d readmission rates were similar between la-paroscopic and robotic MVR.Interestingly,3-year OS(robotic 83.1%vs 58.6%,P=0.008)and RFS(robotic 72.9%vs 34.3%,P=0.002)was superior for robotic compared with laparoscopic MVR.CONCLUSION MiMVR had lower post-operative complications compared to oMVR.Robotic MVR was also safe,with acceptable post-operative complication rates.Prospective studies should be conducted to compare short-term and long-term outcomes between robotic vs laparoscopic MVR.

No effect of invasive tree species on aboveground biomass increments of oaks and pines in temperate forests

Prunus serotina and Robinia pseudoacacia are the most widespread invasive trees in Central Europe.In addition,according to climate models,decreased growth of many economically and ecologically important native trees will likely be observed in the future.We aimed to assess the impact of these two neophytes,which differ in the biomass range and nitrogen-fixing abilities observed in Central European conditions,on the relative aboveground biomass increments of native oaks Qucrcus robur and Q.petraea and Scots pine Pinus sylvestris.We aimed to increase our understanding of the relationship between facilitation and competition between woody alien species and overstory native trees.We established 72 circular plots(0.05 ha)in two different forest habitat types and stands varying in age in western Poland.We chose plots with different abundances of the studied neophytes to determine how effects scaled along the quantitative invasion gradient.Furthermore,we collected growth cores of the studied native species,and we calculated aboveground biomass increments at the tree and stand levels.Then,we used generalized linear mixed-effects models to assess the impact of invasive species abundances on relative aboveground biomass increments of native tree species.We did not find a biologically or statistically significant impact of invasive R.pseudoacacia or P.serotina on the relative aboveground,biomass increments of native oaks and pines along the quantitative gradient of invader biomass or on the proportion of total stand biomass accounted for by invaders.The neophytes did not act as native tree growth stimulators but also did not compete with them for resources,which would escalate the negative impact of climate change on pines and oaks.The neophytes should not significantly modify the carbon sequestration capacity of the native species.Our work combines elements of the per capita effect of invasion with research on mixed forest management.

Efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer

BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditional open surgery is the main treatment for ovarian cancer,but it has the disadvantages of big trauma and slow recovery.With the continuous development of minimally invasive technology,minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery.However,the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.AIM To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.METHODS The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively.According to the different surgical treatment methods,patients were divided into study group and control group(45 cases in each group).The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer,while the control group received traditional open surgery for ovarian cancer.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),clinical efficacy and safety of the two groups were compared.RESULTS The intraoperative blood loss,length of hospital stay,postoperative gas evacuation time,and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group(P<0.05).The incidence of postoperative complications in the study group was significantly lower than in the control group(P<0.05).The two groups had no significant differences in the preoperative adrenocorticotropic hormone(ACTH),androstenedione(AD),cortisol(Cor),cluster of differentiation 3 positive(CD3+),and cluster of differentiation 4 positive(CD4+)indexes(P>0.05).In contrast,postoperatively,the study group's ACTH,AD,and Cor indexes were lower,and the CD3+and CD4+indexes were higher than those in the control group(P<0.05).CONCLUSION Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety,improve the short-term prognosis and quality of life of patients,and is worth popularizing.

Increased dependence on nitrogen-fixation of a native legume in competition with an invasive plant

Suppression of roots and/or their symbiotic microorganisms,such as mycorrhizal fungi and rhizobia,is an effective way for alien plants to outcompete native plants.However,little is known about how invasive and native plants interact with the quantity and activity of nutrient-acquisition agents.Here a pot experiment was conducted with monoculture and mixed plantings of an invasive plant,Xanthium strumarium,and a common native legume,Glycine max.We measured traits related to root and nodule quantity and activity and mycorrhizal colonization.Compared to the monoculture,fine root quantity(biomass,surface area)and activity(root nitrogen(N)concentration,acid phosphatase activity)of G.max decreased in mixed plantings;nodule quantity(biomass)decreased by 45%,while nodule activity in Nfixing via rhizobium increased by 106%;mycorrhizal colonization was unaffected.Contribution of N fixation to leaf N content in G.max increased in the mixed plantings,and this increase was attributed to a decrease in the rhizosphere soil N of G.max in the mixed plantings.Increased root quantity and activity,along with a higher mycorrhizal association was observed in X.strumarium in the mixed compared to monoculture.Together,the invasive plant did not directly scavenge N from nodule-fixed N,but rather depleted the rhizosphere soil N of the legume,thereby stimulating the activity of N-fixation and increasing the dependence of the native legume on this N source.The quantity-activity framework holds promise for future studies on how native legumes respond to alien plant invasions.

Routine invasive strategy and frailty burden in non-ST-segment elevation acute myocardial infarction

Objective To assess the prognostic impact of a routine invasive strategy according to the frailty burden in patients with non-ST-segment elevation myocardial infarction(NSTEMI)from the MOSCA-FRAIL clinical trial.Methods The MOSCA-FRAIL trial randomized 167 frail patients,defined by a Clinical Frailty Scale(CFS)≥4,with NSTEMI to an invasive or conservative strategy.The primary endpoint was the number of days alive and out of hospital(DAOH)one year after discharge.For this subanalysis,we compared the impact of an invasive strategy on the outcomes between vulnerable(CFS=4,n=43)and frail(CFS>4,n=124)patients.Results Compared to vulnerable patients,frail patients presented lower values of DAOH(289.8 vs.320.6,P=0.146),more read-missions(1.03 vs.0.58,P=0.046)and higher number of days spent at the hospital during the first year(10.8 vs.3.8,P=0.014).The cau-ses of readmission were mostly non-cardiac(56%).Among vulnerable patients,DAOH were similar regardless of strategy(invasive vs.conservative:325.7 vs.314.7,P=0.684).Among frailest patients,the invasive group tended to have less DAOH(267.7 vs.311.1,P=0.117).Indeed,patients with CFS>4,invasively managed lived 29 days less than their conservative counterparts.In contrast,the-re were no differences in the subgroup with CFS=4.Conclusions Adult patients with frailty and NSTEMI showed different prognosis according to the degree of frailty.A routine in-vasive strategy does not improve outcomes and might be harmful to the frailest patients.

The evolution and diurnal expression patterns of photosynthetic pathway genes of the invasive alien weed,Mikania micrantha

Mikania micrantha is a fast-growing global invasive weed species that causes severe damage to natural ecosystems and very large economic losses of forest and crop production.It has advantages in photosynthesis,including a similar net photosynthetic rate as C4 plants and a higher carbon fixation capacity.We used a combination of genomics and transcriptomics approaches to study the evolutionary mechanisms and circadian expression patterns of M.micrantha.In M.micrantha,16 positive selection genes focused on photoreaction and utilization of photoassimilates.In different tissues,98.1%of the genes associated with photoresponse had high expression in stems,and more than half of the genes of the C4 cycle had higher expression in stems than in leaves.In stomatal opening and closing,2 genes of carbonic anhydrase(CAs)had higher expression at 18:00 than at 8:00,and the slow anion channel 1(SLAC1)and high-leaf-temperature 1 kinase(HT1)genes were expressed at low levels at 18:00.In addition,genes associated with photosynthesis had higher expression levels at 7:00 and 17:00.We hypothesized that M.micrantha may undergo photosynthesis in the stem and flower organs and that some stomata of the leaves were opening at night by CO_(2)signals.In addition,its evolution may attenuate photoinhibition at high light intensities,and enhance more efficient of photosynthesis during low light intensity.And the tissue-specific photosynthetic types and different diurnal pattern of photosynthetic-related genes may contribute to its rapid colonization of new habitats of M.micrantha.

Education Programs for Invasive Procedures Involving Nurses: A Scoping Review

Background: Implementing invasive procedures is an important part of patient management by clinical nurses;however, there are gaps between nurses’ actual knowledge and skills and expected professional care capacity. Purpose: This scoping review aimed to map the existing literature related to recent institution-provided educational programs for invasive procedures involving clinical nurses. This study seeks to understand the contents of educational programs and the methods for assessing educational effects. Methods: This scoping review was completed using the following four databases: PubMed (MEDLINE), Embase, Cochrane Library, and Emcare for the period 2000-2022. We included studies that used all forms of educational approaches (e.g., didactic lectures, hands-on training, or on-the-job training). This scoping review considered peer-reviewed publications published in English using quantitative, qualitative, or mixed approaches. A total of 83 studies underwent in the final analysis. Results and Conclusion: A combination of didactic lectures and hands-on training was provided as an educational program in most studies. Contrary to our prediction, educational interventions with advanced technologies such as VR are extremely rare, suggesting that the effectiveness of advanced technologies in learning invasive procedures should be examined to facilitate and retain educational effects more efficiently in future studies. Regarding the assessment of educational effects, nurses’ cognitive (i.e., theoretical knowledge about procedures), psychomotor (i.e., implementing procedures), and psychological aspects (e.g., confidence and self-efficacy in procedures) were evaluated using questionnaires and observational methods. While most studies used a one-group pretest-posttest design, the ratio of randomized controlled trials (RCT) was relatively low. Thus, an RCT design should be introduced in future studies to test the validity of the developed educational program more accurately.

Energy spectrum computed tomography multi-parameter imaging in preoperative assessment of vascular and neuroinvasive status in gastric cancer

BACKGROUND Vascular and nerve infiltration are important indicators for the progression and prognosis of gastric cancer(GC),but traditional imaging methods have some limitations in preoperative evaluation.In recent years,energy spectrum computed tomography(CT)multiparameter imaging technology has been gradually applied in clinical practice because of its advantages in tissue contrast and lesion detail display.AIM To explore and analyze the value of multiparameter energy spectrum CT imaging in the preoperative assessment of vascular invasion(LVI)and nerve invasion(PNI)in GC patients.METHODS Data from 62 patients with GC confirmed by pathology and accompanied by energy spectrum CT scanning at our hospital between September 2022 and September 2023,including 46 males and 16 females aged 36-71(57.5±9.1)years,were retrospectively collected.The patients were divided into a positive group(42 patients)and a negative group(20 patients)according to the presence of LVI/PNI.The CT values(CT40 keV,CT70 keV),iodine concentration(IC),and normalized IC(NIC)of lesions in the upper energy spectrum CT images of the arterial phase,venous phase,and delayed phase 40 and 70 keV were measured,and the slopes of the energy spectrum curves[K(40-70)]from 40 to 70 keV were calculated.Arterial Core Tip:To investigate the application value of multiparameter energy spectrum computed tomography(CT)imaging in the preoperative assessment of vascular and nerve infiltration in patients with gastric cancer(GC).The imaging data of GC patients were retrospectively analyzed to evaluate the accuracy and sensitivity of CT for identifying and quantifying vascular and nerve infiltration and for comparison with postoperative pathological results.The purpose of this study was to verify the clinical feasibility and potential advantages of multiparameter energy spectrum CT imaging in guiding preoperative diagnosis and treatment decision-making and to provide a new imaging basis for improving the diagnostic accuracy and prognosis of GC patients.

Assessing the effect of invasive organisms on forests under information uncertainty: The case of pine wood nematode in continental Europe

Forests worldwide are experiencing increasingly intense biotic disturbances;however,assessing impacts of these disturbances is challenging due to the diverse range of organisms involved and the complex interactions among them.This particularly applies to invasive species,which can greatly alter ecological processes in their invaded territories.Here we focus on the pine wood nematode(PWN,Bursaphelenchus xylophilus),an invasive pathogen that has caused extensive mortality of pines in East Asia and more recently has invaded southern Europe.It is expected to expand its range into continental Europe with heavy impacts possible.Given the unknown dynamics of PWN in continental Europe,we reviewed laboratory and field experiments conducted in Asia and southern Europe to parameterize the main components of PWN biology and host-pathogen interactions in the Biotic Disturbance Engine(BITE),a model designed to implement a variety of forest biotic agents,from fungi to large herbivores.To simulate dynamically changing host availability and conditions,BITE was coupled with the forest landscape model iLand.The potential impacts of introducing PWN were assessed in a Central European forest landscape(40,928ha),likely within PWN’s reach in future decades.A parameter sensitivity analysis indicated a substantial influence of factors related to dispersal,colonization,and vegetation impact,whereas parameters related to population growth manifested a minor effect.Selection of different assumptions about biological processes resulted in differential timing and size of the main mortality wave,eliminating 40%–95%of pine trees within 100 years post-introduction,with a maximum annual carbon loss between 1.3%and 4.2%.PWN-induced tree mortality reduced the Gross Primary Productivity,increased heterotrophic respiration,and generated a distinct legacy sink effect in the recovery period.This assessment has corroborated the ecological plausibility of the simulated dynamics and highlighted the need for new strategies to navigate the substantial uncertainty in the agent’s biology and population dynamics.