AIM: To analyze,retrospectively in a population-based study,the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorecta...AIM: To analyze,retrospectively in a population-based study,the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision (TME). METHODS: All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection (632 patients) were selected from the Amsterdam Cancer Registry. For patients with recurrent disease,information on treatment of the recurrence was collected from the medical records. RESULTS: Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients (10%). Thirty-two patients had an isolated local recurrence. Ten of these 32 patients (31%) underwent radical re-resection and experienced the highest survival (three quarters survived for at least 3 years). Eight patients (25%) underwent non-radical surgery (median survival 24 mo),seven patients (22%) were treated with radio-and/or chemotherapy without surgery (median survival 15 mo) and seven patients (22%) only received best supportive care (median survival 5 mo). Distant dissemination occurred in 124 patients (20%) of whom 30 patients also had a local recurrence. The majority (54%) of these patients were treated with radio-and/or chemotherapy without surgery (median survival 15 mo). Twenty-seven percent of these patients only received best supportive care (median survival 6 mo),while 16% underwent surgery for their recurrence. Survival was best in the latter group (median survival 32 mo). CONCLUSION: Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME,patients can benefit from additional treatment,especially if a radical resection is feasible.展开更多
Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is lim...Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating pathologies.Despite the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical practice.Therefore,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly desired.This specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell therapies.Research efforts in this field are increasing exponentially,with thousands of publications in the last few years.展开更多
Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of cells.This is in particular the case for cells like neurons that cannot self-renew and acquire unique functional p...Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of cells.This is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their lifetime.Cellular proteostatic stress responses are in place to protect cells from damage in case of proteostatic challenges.The integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.展开更多
Background: International research and innovation efforts for neglected tropical diseases have increased in recent decades due to disparities in overall health research funding in relation to global burden of disease....Background: International research and innovation efforts for neglected tropical diseases have increased in recent decades due to disparities in overall health research funding in relation to global burden of disease. However, within the field of neglected tropical diseases some seem far more neglected than others. In this research the aim is to investigate the distribution of resources and efforts, as well as the mechanisms that underpin funding allocation for neglected tropical diseases. Methodology: A systematic literature review was conducted to establish a comprehensive overview of known indicators for innovation efforts related to a wide range of neglected tropical diseases. Articles were selected based on a subjective evaluation of their relevance, the presence of original data, and the breadth of their scope. This was followed by thirteen in-depth open-ended interviews with representatives of private, public and philanthropic funding organizations, concerning evaluation criteria for funding research proposals. Results: The findings reveal a large difference in the extent to which the individual diseases are neglected with notable differences between absolute and relative efforts. Criteria used in the evaluation of research proposals relate to potential impact, the probability of success and strategic fit. Private organizations prioritize strategic fit and economic impact;philanthropic organizations prioritize short-term societal impact;and public generally prioritize the probability of success by accounting for follow-up funding and involvement of industry. Funding decisions of different types of organizations are highly interrelated. Conclusions: This study shows that the evaluation of funding proposals introduces and retains unequal funding distribution, reinforcing the relative neglect of diseases. Societal impact is the primary rationale for funding but application of it as a funding criterion is associated with significant challenges. Furthermore, current application of evaluation criteria leads to a primary focus on short-term impact. Through current practice, the relatively most neglected diseases will remain so, and a long-term strategy is needed to resolve this.展开更多
To the editor:In the USA alone,there were 1.7 million suicide attempts in 2021.1 Although the majority of suicide attempts are not fatal,immediate medical attention is often necessary,especially when violent methods a...To the editor:In the USA alone,there were 1.7 million suicide attempts in 2021.1 Although the majority of suicide attempts are not fatal,immediate medical attention is often necessary,especially when violent methods are used.2 These methods include jumping from heights,using a firearm,crashing a motor vehicle,and lying down or jumping in front of a moving object.展开更多
BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to...BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.展开更多
Concurrent extreme weather events in geographically distant areas potentially cause high-end risks for societies.By using network analysis,the present study managed to identify significant nearly-simultaneous occurren...Concurrent extreme weather events in geographically distant areas potentially cause high-end risks for societies.By using network analysis,the present study managed to identify significant nearly-simultaneous occurrences of heatwaves between the grid cells in East Asia and Eastern Europe,even though they are geographically far away from each other.By further composite analysis,this study revealed that hot events first occurred in Eastern Europe,typically with a time lag of3-4 days before the East Asian heatwave events.An eastward propagating atmospheric wave train,known as the circumglobal teleconnection(CGT)pattern,bridged the sequent occurrences of extreme events in these two remote regions.Atmospheric blockings,amplified by surface warming over Eastern Europe,not only enhanced local heat extremes but also excited a CGT-like pattern characterized by alternative anomalies of high and low pressures.Subsequent downstream anticyclones in the middle and upper troposphere reduced local cloud cover and increased downward solar radiation,thereby facilitating the formation of heatwaves over East Asia.Nearly half of East Asian heatwave events were preceded by Eastern European heatwave events in the 10-day time range before East Asian heatwave events.This investigation of heatwave teleconnection in the two distant regions exhibits strong potential to improve the prediction accuracy of East Asian heatwaves.展开更多
BACKGROUND Lateral ankle sprains are the most common traumatic musculoskeletal injuries of the lower extremity,with an incidence rate of 15%-20%.The high incidence and prevalence highlights the economic impact of this...BACKGROUND Lateral ankle sprains are the most common traumatic musculoskeletal injuries of the lower extremity,with an incidence rate of 15%-20%.The high incidence and prevalence highlights the economic impact of this injury.Ankle sprains lead to a high socioeconomic burden due to the combination of the high injury incidence and high medical expenses.Up to 40%of patients who suffer from an ankle sprain develop chronic ankle instability.Chronic instability can lead to prolonged periods of pain,immobility and injury recurrence.Identification of factors that influence return to work(RTW)and return to sports(RTS)after a lateral ankle sprain(LAS)may help seriously reduce healthcare costs.AIM To explore which factors may potentially affect RTW and RTS after sustaining an LAS.METHODS EMBASE and PubMed were systematically searched for relevant studies published until June 2023.Inclusion criteria were as follows:(1)Injury including LAS or chronic ankle instability;(2)Described any form of treatment;(3)Assessment of RTW or RTS;(4)Studies published in English;and(5)Study designs including randomized controlled clinical trials,clinical trials or cohort studies.Exclusion criteria were:(1)Studies involving children(age<16 year);or(2)Patients with concomitant ankle injury besides lateral ankle ligament damage.A quality assessment was performed for each of the included studies using established risk of bias tools.Additionally quality of evidence was assessed using the GRADEpro tool in cases where outcomes were included in the quantitative analysis.A best evidence synthesis was performed in cases of qualitative outcome analysis.For all studied outcomes suitable for quantitative analysis a forest plot was created to calculate the effect on RTW and RTS.RESULTS A total of 8904 patients were included in 21 studies,10 randomized controlled trials,7 retrospective cohort studies and 4 prospective cohort studies.Fifteen studies were eligible for meta-analysis.The overall RTS rate ranged were 80%and 83%in the all treatments pool and surgical treatments pool,respectively.The pooled mean days to RTS ranged from 23-93 d.The overall RTW rate was 89%.The pooled mean time to RTW ranged from 5.8-8.1 d.For patients with chronic ankle instability,higher preoperative motivation was the sole factor significantly and independently(P=0.001)associated with the rate of and time to RTS following ligament repair or reconstruction.Higher body mass index was identified as a significant factor(P=0.04)linked to not resuming sports or returning at a lower level(median 24,range 20-37),compared to those who resumed at the same or higher level(median 23,range 17-38).Patients with a history of psychological illness or brain injury,experienced a delay in their rehabilitation process for sprains with fractures and unspecified sprains.The extent of the delayed rehabilitation was directly proportional to the increased likelihood of experiencing a recurrence of the ankle sprain and the number of ankle-related medical visits.We also observed that 10%of athletes who did return to sport after lateral ankle sprain without fractures described non-ankle-related reasons for not returning.CONCLUSION All treatments yielded comparable results,with each treatment potentially offering unique advantages or benefits.Preoperative motivation may influence rehabilitation after LAS.Grading which factor had a greater impact was not possible due to the lack of comparability among the included patients.展开更多
BACKGROUND Over the years,strides in colon cancer detection and treatment have boosted survival rates;yet,post-colon cancer survival entails cardiovascular disease(CVD)risks.Research on CVD risks and acute cardiovascu...BACKGROUND Over the years,strides in colon cancer detection and treatment have boosted survival rates;yet,post-colon cancer survival entails cardiovascular disease(CVD)risks.Research on CVD risks and acute cardiovascular events in colorectal cancer survivors has been limited.AIM To compare the CVD risk and adverse cardiovascular outcomes in current colon cancer survivors compared to a decade ago.METHODS We analyzed 2007 and 2017 hospitalization data from the National Inpatient Sample,studying two colon cancer survivor groups for CVD risk factors,mortality rates,and major adverse events like pulmonary embolism,arrhythmia,cardiac arrest,and stroke,adjusting for confounders via multivariable regression analysis.RESULTS Of total colon cancer survivors hospitalized in 2007(n=177542)and 2017(n=178325),the 2017 cohort often consisted of younger(76 vs 77 years),male,African-American,and Hispanic patients admitted non-electively vs the 2007 cohort.Furthermore,the 2017 cohort had higher rates of smoking,alcohol abuse,drug abuse,coagulopathy,liver disease,weight loss,and renal failure.Patients in the 2017 cohort also had higher rates of cardiovascular comorbidities,including hypertension,hyperlipidemia,diabetes,obesity,peripheral vascular disease,congestive heart failure,and at least one traditional CVD(P<0.001)vs the 2007 cohort.On adjusted multivariable analysis,the 2017 cohort had a significantly higher risk of pulmonary embolism(PE)(OR:1.47,95%CI:1.37-1.48),arrhythmia(OR:1.41,95%CI:1.38-1.43),atrial fibrillation/flutter(OR:1.61,95%CI:1.58-1.64),cardiac arrest including ventricular tachyarrhythmia(OR:1.63,95%CI:1.46-1.82),and stroke(OR:1.28,95%CI:1.22-1.34)with comparable all-cause mortality and fewer routine discharges(48.4%vs 55.0%)(P<0.001)vs the 2007 cohort.CONCLUSION Colon cancer survivors hospitalized 10 years apart in the United States showed an increased CVD risk with an increased risk of acute cardiovascular events(stroke 28%,PE 47%,arrhythmia 41%,and cardiac arrest 63%).It is vital to regularly screen colon cancer survivors with concomitant CVD risk factors to curtail long-term cardiovascular complications.展开更多
Foam is utilized in enhanced oil recovery and CO_(2) sequestration.Surfactant-alternating-gas(SAG)is a preferred approach for placing foam into reservoirs,due to it enhances gas injection and minimizes corrosion in fa...Foam is utilized in enhanced oil recovery and CO_(2) sequestration.Surfactant-alternating-gas(SAG)is a preferred approach for placing foam into reservoirs,due to it enhances gas injection and minimizes corrosion in facilities.Our previous studies with similar permeability cores show that during SAG injection,several banks occupy the area near the well where fluid exhibits distinct behaviour.However,underground reservoirs are heterogeneous,often layered.It is crucial to understand the effect of permeability on fluid behaviour and injectivity in a SAG process.In this work,coreflood experiments are conducted in cores with permeabilities ranging from 16 to 2300 mD.We observe the same sequence of banks in cores with different permeabilities.However,the speed at which banks propagate and their overall mobility can vary depending on permeability.At higher permeabilities,the gas-dissolution bank and the forced-imbibition bank progress more rapidly during liquid injection.The total mobilities of both banks decrease with permeability.By utilizing a bank-propagation model,we scale up our experimental findings and compare them to results obtained using the Peaceman equation.Our findings reveal that the liquid injectivity in a SAG foam process is misestimated by conventional simulators based on the Peaceman equation.The lower the formation permeability,the greater the error.展开更多
This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis ...This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.展开更多
Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) u...Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.展开更多
文摘AIM: To analyze,retrospectively in a population-based study,the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision (TME). METHODS: All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection (632 patients) were selected from the Amsterdam Cancer Registry. For patients with recurrent disease,information on treatment of the recurrence was collected from the medical records. RESULTS: Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients (10%). Thirty-two patients had an isolated local recurrence. Ten of these 32 patients (31%) underwent radical re-resection and experienced the highest survival (three quarters survived for at least 3 years). Eight patients (25%) underwent non-radical surgery (median survival 24 mo),seven patients (22%) were treated with radio-and/or chemotherapy without surgery (median survival 15 mo) and seven patients (22%) only received best supportive care (median survival 5 mo). Distant dissemination occurred in 124 patients (20%) of whom 30 patients also had a local recurrence. The majority (54%) of these patients were treated with radio-and/or chemotherapy without surgery (median survival 15 mo). Twenty-seven percent of these patients only received best supportive care (median survival 6 mo),while 16% underwent surgery for their recurrence. Survival was best in the latter group (median survival 32 mo). CONCLUSION: Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME,patients can benefit from additional treatment,especially if a radical resection is feasible.
基金supported by Amsterdam Neuroscience(project number NDIS-2019-03,to AEW and EVB).
文摘Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating pathologies.Despite the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical practice.Therefore,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly desired.This specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell therapies.Research efforts in this field are increasing exponentially,with thousands of publications in the last few years.
基金supported by ZonMW and Stichting Proefdiervrij (#114022506)PPP Allo wance made available by Health~Holland,Top Sector Life Sciences&Health,to stimulate public-private partnerships (#LSHM17014 and LSHM18024)+3 种基金Alzheimer Nederland (grant WE.03-2017-10)European Commission (Joint Programming Initiative Neurodegenerative Diseases/JPco-fuND (ZonMW#733051062)Weston Brain Institute (#NR1 60014)ZonMW Memorabel/Alzheimer Nederland (#733050101)(to WS)
文摘Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of cells.This is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their lifetime.Cellular proteostatic stress responses are in place to protect cells from damage in case of proteostatic challenges.The integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.
文摘Background: International research and innovation efforts for neglected tropical diseases have increased in recent decades due to disparities in overall health research funding in relation to global burden of disease. However, within the field of neglected tropical diseases some seem far more neglected than others. In this research the aim is to investigate the distribution of resources and efforts, as well as the mechanisms that underpin funding allocation for neglected tropical diseases. Methodology: A systematic literature review was conducted to establish a comprehensive overview of known indicators for innovation efforts related to a wide range of neglected tropical diseases. Articles were selected based on a subjective evaluation of their relevance, the presence of original data, and the breadth of their scope. This was followed by thirteen in-depth open-ended interviews with representatives of private, public and philanthropic funding organizations, concerning evaluation criteria for funding research proposals. Results: The findings reveal a large difference in the extent to which the individual diseases are neglected with notable differences between absolute and relative efforts. Criteria used in the evaluation of research proposals relate to potential impact, the probability of success and strategic fit. Private organizations prioritize strategic fit and economic impact;philanthropic organizations prioritize short-term societal impact;and public generally prioritize the probability of success by accounting for follow-up funding and involvement of industry. Funding decisions of different types of organizations are highly interrelated. Conclusions: This study shows that the evaluation of funding proposals introduces and retains unequal funding distribution, reinforcing the relative neglect of diseases. Societal impact is the primary rationale for funding but application of it as a funding criterion is associated with significant challenges. Furthermore, current application of evaluation criteria leads to a primary focus on short-term impact. Through current practice, the relatively most neglected diseases will remain so, and a long-term strategy is needed to resolve this.
文摘To the editor:In the USA alone,there were 1.7 million suicide attempts in 2021.1 Although the majority of suicide attempts are not fatal,immediate medical attention is often necessary,especially when violent methods are used.2 These methods include jumping from heights,using a firearm,crashing a motor vehicle,and lying down or jumping in front of a moving object.
文摘BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.
基金Guangdong Major Project of Basic and Applied Basic Research (2020B0301030004)National Natural Science Foundation of China (42275020)+1 种基金Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) (311021001)Guangdong Province Key Laboratory for Climate Change and Natural Disaster Studies (2020B1212060025)。
文摘Concurrent extreme weather events in geographically distant areas potentially cause high-end risks for societies.By using network analysis,the present study managed to identify significant nearly-simultaneous occurrences of heatwaves between the grid cells in East Asia and Eastern Europe,even though they are geographically far away from each other.By further composite analysis,this study revealed that hot events first occurred in Eastern Europe,typically with a time lag of3-4 days before the East Asian heatwave events.An eastward propagating atmospheric wave train,known as the circumglobal teleconnection(CGT)pattern,bridged the sequent occurrences of extreme events in these two remote regions.Atmospheric blockings,amplified by surface warming over Eastern Europe,not only enhanced local heat extremes but also excited a CGT-like pattern characterized by alternative anomalies of high and low pressures.Subsequent downstream anticyclones in the middle and upper troposphere reduced local cloud cover and increased downward solar radiation,thereby facilitating the formation of heatwaves over East Asia.Nearly half of East Asian heatwave events were preceded by Eastern European heatwave events in the 10-day time range before East Asian heatwave events.This investigation of heatwave teleconnection in the two distant regions exhibits strong potential to improve the prediction accuracy of East Asian heatwaves.
文摘BACKGROUND Lateral ankle sprains are the most common traumatic musculoskeletal injuries of the lower extremity,with an incidence rate of 15%-20%.The high incidence and prevalence highlights the economic impact of this injury.Ankle sprains lead to a high socioeconomic burden due to the combination of the high injury incidence and high medical expenses.Up to 40%of patients who suffer from an ankle sprain develop chronic ankle instability.Chronic instability can lead to prolonged periods of pain,immobility and injury recurrence.Identification of factors that influence return to work(RTW)and return to sports(RTS)after a lateral ankle sprain(LAS)may help seriously reduce healthcare costs.AIM To explore which factors may potentially affect RTW and RTS after sustaining an LAS.METHODS EMBASE and PubMed were systematically searched for relevant studies published until June 2023.Inclusion criteria were as follows:(1)Injury including LAS or chronic ankle instability;(2)Described any form of treatment;(3)Assessment of RTW or RTS;(4)Studies published in English;and(5)Study designs including randomized controlled clinical trials,clinical trials or cohort studies.Exclusion criteria were:(1)Studies involving children(age<16 year);or(2)Patients with concomitant ankle injury besides lateral ankle ligament damage.A quality assessment was performed for each of the included studies using established risk of bias tools.Additionally quality of evidence was assessed using the GRADEpro tool in cases where outcomes were included in the quantitative analysis.A best evidence synthesis was performed in cases of qualitative outcome analysis.For all studied outcomes suitable for quantitative analysis a forest plot was created to calculate the effect on RTW and RTS.RESULTS A total of 8904 patients were included in 21 studies,10 randomized controlled trials,7 retrospective cohort studies and 4 prospective cohort studies.Fifteen studies were eligible for meta-analysis.The overall RTS rate ranged were 80%and 83%in the all treatments pool and surgical treatments pool,respectively.The pooled mean days to RTS ranged from 23-93 d.The overall RTW rate was 89%.The pooled mean time to RTW ranged from 5.8-8.1 d.For patients with chronic ankle instability,higher preoperative motivation was the sole factor significantly and independently(P=0.001)associated with the rate of and time to RTS following ligament repair or reconstruction.Higher body mass index was identified as a significant factor(P=0.04)linked to not resuming sports or returning at a lower level(median 24,range 20-37),compared to those who resumed at the same or higher level(median 23,range 17-38).Patients with a history of psychological illness or brain injury,experienced a delay in their rehabilitation process for sprains with fractures and unspecified sprains.The extent of the delayed rehabilitation was directly proportional to the increased likelihood of experiencing a recurrence of the ankle sprain and the number of ankle-related medical visits.We also observed that 10%of athletes who did return to sport after lateral ankle sprain without fractures described non-ankle-related reasons for not returning.CONCLUSION All treatments yielded comparable results,with each treatment potentially offering unique advantages or benefits.Preoperative motivation may influence rehabilitation after LAS.Grading which factor had a greater impact was not possible due to the lack of comparability among the included patients.
文摘BACKGROUND Over the years,strides in colon cancer detection and treatment have boosted survival rates;yet,post-colon cancer survival entails cardiovascular disease(CVD)risks.Research on CVD risks and acute cardiovascular events in colorectal cancer survivors has been limited.AIM To compare the CVD risk and adverse cardiovascular outcomes in current colon cancer survivors compared to a decade ago.METHODS We analyzed 2007 and 2017 hospitalization data from the National Inpatient Sample,studying two colon cancer survivor groups for CVD risk factors,mortality rates,and major adverse events like pulmonary embolism,arrhythmia,cardiac arrest,and stroke,adjusting for confounders via multivariable regression analysis.RESULTS Of total colon cancer survivors hospitalized in 2007(n=177542)and 2017(n=178325),the 2017 cohort often consisted of younger(76 vs 77 years),male,African-American,and Hispanic patients admitted non-electively vs the 2007 cohort.Furthermore,the 2017 cohort had higher rates of smoking,alcohol abuse,drug abuse,coagulopathy,liver disease,weight loss,and renal failure.Patients in the 2017 cohort also had higher rates of cardiovascular comorbidities,including hypertension,hyperlipidemia,diabetes,obesity,peripheral vascular disease,congestive heart failure,and at least one traditional CVD(P<0.001)vs the 2007 cohort.On adjusted multivariable analysis,the 2017 cohort had a significantly higher risk of pulmonary embolism(PE)(OR:1.47,95%CI:1.37-1.48),arrhythmia(OR:1.41,95%CI:1.38-1.43),atrial fibrillation/flutter(OR:1.61,95%CI:1.58-1.64),cardiac arrest including ventricular tachyarrhythmia(OR:1.63,95%CI:1.46-1.82),and stroke(OR:1.28,95%CI:1.22-1.34)with comparable all-cause mortality and fewer routine discharges(48.4%vs 55.0%)(P<0.001)vs the 2007 cohort.CONCLUSION Colon cancer survivors hospitalized 10 years apart in the United States showed an increased CVD risk with an increased risk of acute cardiovascular events(stroke 28%,PE 47%,arrhythmia 41%,and cardiac arrest 63%).It is vital to regularly screen colon cancer survivors with concomitant CVD risk factors to curtail long-term cardiovascular complications.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.U2240210,52279098)the Natural Science Foundation of Jiangsu Province(Grant No.BK20200525)the Fundamental Research Funds for the Central Universities(Grant No.B230201021).We express our gratitude to PETRONAS and Shell Global Solution International B.V.for their support of this work.
文摘Foam is utilized in enhanced oil recovery and CO_(2) sequestration.Surfactant-alternating-gas(SAG)is a preferred approach for placing foam into reservoirs,due to it enhances gas injection and minimizes corrosion in facilities.Our previous studies with similar permeability cores show that during SAG injection,several banks occupy the area near the well where fluid exhibits distinct behaviour.However,underground reservoirs are heterogeneous,often layered.It is crucial to understand the effect of permeability on fluid behaviour and injectivity in a SAG process.In this work,coreflood experiments are conducted in cores with permeabilities ranging from 16 to 2300 mD.We observe the same sequence of banks in cores with different permeabilities.However,the speed at which banks propagate and their overall mobility can vary depending on permeability.At higher permeabilities,the gas-dissolution bank and the forced-imbibition bank progress more rapidly during liquid injection.The total mobilities of both banks decrease with permeability.By utilizing a bank-propagation model,we scale up our experimental findings and compare them to results obtained using the Peaceman equation.Our findings reveal that the liquid injectivity in a SAG foam process is misestimated by conventional simulators based on the Peaceman equation.The lower the formation permeability,the greater the error.
文摘This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.
文摘Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.