Objective:two new cases of temporal bone squamous cell carcinoma(TBSCC)with a bilateral occurrence are presented.Furthermore,a review of the literature was performed and the yearly incidence was calculated.Methods:A s...Objective:two new cases of temporal bone squamous cell carcinoma(TBSCC)with a bilateral occurrence are presented.Furthermore,a review of the literature was performed and the yearly incidence was calculated.Methods:A systematic review of the literature was conducted using PRISMA guidelines.Results:Twenty-two more cases were found in literature.With a total of 24 cases,the calculated yearly incidence of bilateral TBSCC is 49:10^12 A history of chronic otitis or regional radiotherapy was found in respectively 50%and 12%of patients.In nine patients,the tumors developed synchronously(within 6 months)and in 13 metachronously.Conclusions:The calculated incidence is 89 times higher than mathematically expected considering the incidence of unilateral cases.An explanation might be a history of chronic otitis or prior radiotherapy.The tumor staging of both the first tumor group and the contralateral tumor group are similar to unilateral temporal bone squamous cell carcinoma series.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 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
BACKGROUND Despite the emerging knowledge about colorectal anastomotic leakage(CAL)through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the w...BACKGROUND Despite the emerging knowledge about colorectal anastomotic leakage(CAL)through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the wide variety of definitions used in literature, comparison of study outcomes and quality of care is complicated.AIM To reach consensus on the definition of CAL using a modified Delphi method.METHODS The RAND/UCLA appropriateness method was used. The expert panel consisted of international colorectal surgeons and researchers who had published three or more articles about CAL. The consensus process consisted of two online distributed questionnaires and a third round with a recommendation. In the questionnaires participants were asked to rate the appropriateness of statements using a 1-9 Likert scale. Consensus was defined as a panel median between 1-3 or 7-9 without disagreement. In the final round a recommendation was formed regarding the definition of CAL and the expert panel was asked if they agreed or disagreed.RESULTSTwenty-three authors participated in the first round and twenty-one finished the second round. After two rounds consensus was reached on 37 items(80%) in nine different categories. The International Study Group of Rectal Cancer definition is the most frequently advised general definition by our panel. Consensus was reached regarding the clinical symptoms of CAL, which serum markers contributes to the suspicion of CAL, which radiological and perioperative findings should be considered as CAL, which grading system is appropriate and if there should be a range of postoperative days in the definition. Eventually, 19 experts completed all three rounds of which 16(84%) agreed with our final recommendations for the definition of CAL.CONCLUSION A consensus-based recommendation for the definition of CAL was formed using our modified Delphi method that can be widely incorporated in the field.展开更多
BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into...BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.展开更多
AIM To determine which of the common used incision techniques has the lowest chance of iatrogenic damage to the nerves which at risk are the superficial branch of the radial nerve(SBRN) and the Lateral Antebrachial Cu...AIM To determine which of the common used incision techniques has the lowest chance of iatrogenic damage to the nerves which at risk are the superficial branch of the radial nerve(SBRN) and the Lateral Antebrachial Cutaneous Nerve(LABCN).METHODS Twenty embalmed arms were dissected and the course of the SBRN and the LABCN in each individual arm was marked and the distance between the two branches of the SBRN at the location of the First Extensor Compartment(FEC) was measured. This data was used as input in a visualization tool called Computer Assisted Anatomy Mapping(CASAM) to map the course of the nerves in each individual arm. RESULTS This image visualizes that in 90% of the arms, one branch of the SBRN crosses the FEC and one branch runs volar to the compartment. The distance between the two branches was 7.8 mm at the beginning of the FEC and 10.2 mm at the end. Finally the angle of incision at which the chance of damage to the nerves is lowest, is 19.4 degrees volar to the radius.CONCLUSION CASAM shows the complexity of the course of the SBRN over the FEC. None of the four widely used incision techniques has a significantly lower chance of iatrogenic nerve damage. Surgical skills are paramount to prevent iatrogenic nerve damage.展开更多
Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few spe...Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer,which do not seem to support it.However,these studies are affected by several limitations and,therefore,a link between AIP(and,specifically,type 1 AIP)and pancreatic cancer cannot be ruled out definitively on this basis.Moreover,several immunopathological aspects of type 1 AIP and,in general,immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression.In detail,Th2 immunological dominance,type 2 macrophage polarization and basophil infiltration observed in type 1 AIP,may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis,in addition to the immunosuppressive therapies that can be used in these patients.展开更多
Background In a three-month report from the CGA-TAVI registry, we found the Multidimensional Prognostic Index (MPI) and Short Physical Performance Battery (SPPB) to be of value for predicting short-term outcomes in el...Background In a three-month report from the CGA-TAVI registry, we found the Multidimensional Prognostic Index (MPI) and Short Physical Performance Battery (SPPB) to be of value for predicting short-term outcomes in elderly patients undergoing transcatheter aortic valve implantation (TAVI). In the present analysis, we examined the association of these tools with outcomes up to one year post-TAVI. Methods CGA-TAVI is an international, observational registry of geriatric patients undergoing TAVI. Patients were assessed using the MPI and SPPB. Efficacy of baseline values and any postoperative change for predicting outcome were established using logistic regression. Kaplan- Meier analysis was carried out for each comprehensive geriatric assessment tool, with survival stratified by risk category. Results One year after TAVI, 14.1% of patients deceased, while 17.4% met the combined endpoint of death and/or non-fatal stroke, and 37.7% the combined endpoint of death and/or hospitalisation and/or non-fatal stroke. A high-risk MPI score was associated with an increased risk of all-cause mortality (aOR = 36.13, 95% CI: 2.77–470.78, P = 0.006) and death and/or non-fatal stroke (aOR = 10.10, 95% CI: 1.48–68.75, P = 0.018). No significant associations were found between a high-risk SPPB score and mortality or two main combined endpoints. In contrast to a worsening SPPB, an aggravating MPI score at three months post-TAVI was associated with an increased risk of death and/or non-fatal stoke at one year (aOR = 95.16, 95% CI: 3.41–2657.01). Conclusions The MPI showed value for predicting the likelihood of death and a combination of death and/or non-fatal stroke by one year after TAVI in elderly patients.展开更多
Metastatic prostate cancer patients present in two waysdwith already disseminated disease at the time of presentation or with disease recurrence after definitive local therapy.Androgen deprivation therapy is given as ...Metastatic prostate cancer patients present in two waysdwith already disseminated disease at the time of presentation or with disease recurrence after definitive local therapy.Androgen deprivation therapy is given as the most effective initial treatment to patients.However,after the initial response,almost all patients will eventually progress despite the low levels of testosterone.Disease at this stage is termed castration resistant prostate cancer(CRPC).Before 2010,the taxane docetaxel was the first and only life prolonging agent for metastatic CRPC(mCRPC).The last decade has witnessed robust progress in CRPC therapeutics development.Abiraterone,enzalutamide,apalutamide and sipuleucel-T have been evaluated as first-and second-line agents in mCRPC patients,while cabazitaxel was approved as a second-line treatment.Radium-223 dichloride was approved in symptomatic patients with bone metastases and no known visceral metastases pre-and post-docetaxel.However,despite significant advances,mCRPC remains a lethal disease.Both primary and acquired resistance have been observed in CRPC patients treated by these new agents.It could be solely cell intrinsic or it is possible that the clonal heterogeneity in treated tumors may result from the adaptive responses to the selective pressures within the tumor microenvironment.The aim of this review is to list current treatment agents of CRPC and summarize recent findings in therapeutic resistance mechanisms.展开更多
Acute acalculous cholecystitis(AAC) is the inflammatory disease of the gallbladder in the absence of gallstones. AAC is estimated to represent at least 50% to 70% of all cases of acute cholecystitis during childhood. ...Acute acalculous cholecystitis(AAC) is the inflammatory disease of the gallbladder in the absence of gallstones. AAC is estimated to represent at least 50% to 70% of all cases of acute cholecystitis during childhood. Although this pathology was originally described in critically ill or post-surgical patients, most pediatric cases have been observed during several infectious diseases. In addition to cases caused by bacterial and parasitic infections, most pediatric reports after 2000 described children developing AAC during viral illnesses(such as Epstein-Barr virus and hepatitis A virus infections). Moreover, some pediatric cases have been associated with several underlying chronic diseases and, in particular, with immune-mediated disorders. Here, we review the epidemiological aspects of pediatric AAC, and we discuss etiology, pathophysiology and clinical management, according to the cases reported in the medical literature.展开更多
BACKGROUND Bedside needle arthroscopy of the ankle under local anesthesia has been proposed for intra-articular delivery of injectable agents.Accuracy and tolerability of this approach in the clinical setting–includi...BACKGROUND Bedside needle arthroscopy of the ankle under local anesthesia has been proposed for intra-articular delivery of injectable agents.Accuracy and tolerability of this approach in the clinical setting–including patients with end-stage ankle pathology and/or a history of prior surgery–is not known.AIM To assess clinical accuracy and tolerability of bedside needle arthroscopy as a delivery system for injectable agents into the tibiotalar joint.METHODS This was a prospective study that included adult patients who were scheduled for an injection with hyaluronic acid to the tibiotalar joint.In our center,these injections are used as a last resort prior to extensive surgery.The primary outcome was injection accuracy,which was defined as injecting through the arthroscopic cannula with intra-articular positioning confirmed by a clear arthroscopic view of the joint space.Secondary outcome measures included a patientreported numeric rating scale(NRS,0-10)of pain during the procedure and willingness of patients to return for the same procedure.NRS of ankle pain at rest and during walking was collected at baseline and at 2-wk follow-up.Complications were monitored from inclusion up to a 2-wk control visit.RESULTS We performed 24 inspection-injections.Eleven(46%)participants were male,and mean age was 46.8±14.5 years.Osteoarthritis was the indication for injection in 20(83%)cases,of which 8(33%)patients suffered from osteoarthritis Kellgren-Lawrence grade IV,and 10(42%)patients from Kellgren-Lawrence grade III.An osteochondral defect was the indication for injection in 4(17%)cases.A history of ankle surgery was present in 14(58%)participants and a history of multiple ankle surgeries in 11(46%)participants.It was possible to confirm accuracy in 21(88%)procedures.The 3(12%)participants where needle arthroscopy did not reach a clear view of the joint space all suffered from Kellgren-Lawrence grade IV osteoarthritis.Pain during the procedure was reported with a median of 1[interquartile ranges(IQR):0–2].Willingness to return was 100%.Pain in rest decreased from a median NRS of 4(IQR:2–7)at baseline to a median of 3(IQR:1–5)at follow-up(P<0.01).Pain during walking decreased from a median NRS of 8(IQR:6–9)to a median of 7(IQR:4–8)(P<0.01).Infections or other complications were not encountered.CONCLUSION Clinical accuracy and tolerability of bedside needle arthroscopy of the ankle as a delivery system for injectable agents are excellent.Accuracy was 100%in patients without total ventral joint obliteration.展开更多
文摘Objective:two new cases of temporal bone squamous cell carcinoma(TBSCC)with a bilateral occurrence are presented.Furthermore,a review of the literature was performed and the yearly incidence was calculated.Methods:A systematic review of the literature was conducted using PRISMA guidelines.Results:Twenty-two more cases were found in literature.With a total of 24 cases,the calculated yearly incidence of bilateral TBSCC is 49:10^12 A history of chronic otitis or regional radiotherapy was found in respectively 50%and 12%of patients.In nine patients,the tumors developed synchronously(within 6 months)and in 13 metachronously.Conclusions:The calculated incidence is 89 times higher than mathematically expected considering the incidence of unilateral cases.An explanation might be a history of chronic otitis or prior radiotherapy.The tumor staging of both the first tumor group and the contralateral tumor group are similar to unilateral temporal bone squamous cell carcinoma series.
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 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Supported by the Dutch Research Council(NWO)research programme Vidi project,No.91719343。
文摘BACKGROUND Despite the emerging knowledge about colorectal anastomotic leakage(CAL)through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the wide variety of definitions used in literature, comparison of study outcomes and quality of care is complicated.AIM To reach consensus on the definition of CAL using a modified Delphi method.METHODS The RAND/UCLA appropriateness method was used. The expert panel consisted of international colorectal surgeons and researchers who had published three or more articles about CAL. The consensus process consisted of two online distributed questionnaires and a third round with a recommendation. In the questionnaires participants were asked to rate the appropriateness of statements using a 1-9 Likert scale. Consensus was defined as a panel median between 1-3 or 7-9 without disagreement. In the final round a recommendation was formed regarding the definition of CAL and the expert panel was asked if they agreed or disagreed.RESULTSTwenty-three authors participated in the first round and twenty-one finished the second round. After two rounds consensus was reached on 37 items(80%) in nine different categories. The International Study Group of Rectal Cancer definition is the most frequently advised general definition by our panel. Consensus was reached regarding the clinical symptoms of CAL, which serum markers contributes to the suspicion of CAL, which radiological and perioperative findings should be considered as CAL, which grading system is appropriate and if there should be a range of postoperative days in the definition. Eventually, 19 experts completed all three rounds of which 16(84%) agreed with our final recommendations for the definition of CAL.CONCLUSION A consensus-based recommendation for the definition of CAL was formed using our modified Delphi method that can be widely incorporated in the field.
文摘BACKGROUND A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery.Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis,a potential life-threatening condition.Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIM To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODS A systematic review and meta-analysis was done by searching PubMed,EMBASE and the Cochrane Library,using entry terms related to:(1)Hirschsprung disease;and(2)Botulinum toxin injections.14 studies representing 278 patients met eligibility criteria.Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection,proportion of patients with adverse effects and data on type botulinum toxin,mean dose,average age at first injection and patients with associated syndromes.Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTS Botulinum toxin injections are effective in treating obstructive symptoms in on average 66%of patients[event rate(ER)=0.66,P=0.004,I2=49.5,n=278 patients].Type of botulinum toxin,average dose,average age at first injections and proportion of patients with associated syndromes were not predictive for this effect.Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures.There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections(ER=0.79,vs ER=0.46,Q=19.37,P<0.001).Botulinum toxin injections were not effective in treating enterocolitis(ER 0.58,P=0.65,I2=71.0,n=52 patients).There were adverse effects in on average 17%of patients(ER=0.17,P<0.001,I2=52.1,n=187 patients),varying from temporary incontinence to mild anal pain.CONCLUSION Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present,but mild and temporary.
文摘AIM To determine which of the common used incision techniques has the lowest chance of iatrogenic damage to the nerves which at risk are the superficial branch of the radial nerve(SBRN) and the Lateral Antebrachial Cutaneous Nerve(LABCN).METHODS Twenty embalmed arms were dissected and the course of the SBRN and the LABCN in each individual arm was marked and the distance between the two branches of the SBRN at the location of the First Extensor Compartment(FEC) was measured. This data was used as input in a visualization tool called Computer Assisted Anatomy Mapping(CASAM) to map the course of the nerves in each individual arm. RESULTS This image visualizes that in 90% of the arms, one branch of the SBRN crosses the FEC and one branch runs volar to the compartment. The distance between the two branches was 7.8 mm at the beginning of the FEC and 10.2 mm at the end. Finally the angle of incision at which the chance of damage to the nerves is lowest, is 19.4 degrees volar to the radius.CONCLUSION CASAM shows the complexity of the course of the SBRN over the FEC. None of the four widely used incision techniques has a significantly lower chance of iatrogenic nerve damage. Surgical skills are paramount to prevent iatrogenic nerve damage.
文摘Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer,which do not seem to support it.However,these studies are affected by several limitations and,therefore,a link between AIP(and,specifically,type 1 AIP)and pancreatic cancer cannot be ruled out definitively on this basis.Moreover,several immunopathological aspects of type 1 AIP and,in general,immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression.In detail,Th2 immunological dominance,type 2 macrophage polarization and basophil infiltration observed in type 1 AIP,may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis,in addition to the immunosuppressive therapies that can be used in these patients.
基金provided by Edwards Lifesciences (Nyon, Switzerland) to the Sponsor IPPMed (Cloppenburg, Germany)funding from Edwards Lifesciences as did Andrea Ungar
文摘Background In a three-month report from the CGA-TAVI registry, we found the Multidimensional Prognostic Index (MPI) and Short Physical Performance Battery (SPPB) to be of value for predicting short-term outcomes in elderly patients undergoing transcatheter aortic valve implantation (TAVI). In the present analysis, we examined the association of these tools with outcomes up to one year post-TAVI. Methods CGA-TAVI is an international, observational registry of geriatric patients undergoing TAVI. Patients were assessed using the MPI and SPPB. Efficacy of baseline values and any postoperative change for predicting outcome were established using logistic regression. Kaplan- Meier analysis was carried out for each comprehensive geriatric assessment tool, with survival stratified by risk category. Results One year after TAVI, 14.1% of patients deceased, while 17.4% met the combined endpoint of death and/or non-fatal stroke, and 37.7% the combined endpoint of death and/or hospitalisation and/or non-fatal stroke. A high-risk MPI score was associated with an increased risk of all-cause mortality (aOR = 36.13, 95% CI: 2.77–470.78, P = 0.006) and death and/or non-fatal stroke (aOR = 10.10, 95% CI: 1.48–68.75, P = 0.018). No significant associations were found between a high-risk SPPB score and mortality or two main combined endpoints. In contrast to a worsening SPPB, an aggravating MPI score at three months post-TAVI was associated with an increased risk of death and/or non-fatal stoke at one year (aOR = 95.16, 95% CI: 3.41–2657.01). Conclusions The MPI showed value for predicting the likelihood of death and a combination of death and/or non-fatal stroke by one year after TAVI in elderly patients.
基金Liang Dong is supported by Shanghai Natural Science Fund exploration project(17ZR1447400)Shanghai Jiao Tong University medicine-engineering cross project(YG2016QN56)Richard C.Zieren is supported by Stichting Cure for Cancer foundation,Amsterdam,The Netherlands.
文摘Metastatic prostate cancer patients present in two waysdwith already disseminated disease at the time of presentation or with disease recurrence after definitive local therapy.Androgen deprivation therapy is given as the most effective initial treatment to patients.However,after the initial response,almost all patients will eventually progress despite the low levels of testosterone.Disease at this stage is termed castration resistant prostate cancer(CRPC).Before 2010,the taxane docetaxel was the first and only life prolonging agent for metastatic CRPC(mCRPC).The last decade has witnessed robust progress in CRPC therapeutics development.Abiraterone,enzalutamide,apalutamide and sipuleucel-T have been evaluated as first-and second-line agents in mCRPC patients,while cabazitaxel was approved as a second-line treatment.Radium-223 dichloride was approved in symptomatic patients with bone metastases and no known visceral metastases pre-and post-docetaxel.However,despite significant advances,mCRPC remains a lethal disease.Both primary and acquired resistance have been observed in CRPC patients treated by these new agents.It could be solely cell intrinsic or it is possible that the clonal heterogeneity in treated tumors may result from the adaptive responses to the selective pressures within the tumor microenvironment.The aim of this review is to list current treatment agents of CRPC and summarize recent findings in therapeutic resistance mechanisms.
文摘Acute acalculous cholecystitis(AAC) is the inflammatory disease of the gallbladder in the absence of gallstones. AAC is estimated to represent at least 50% to 70% of all cases of acute cholecystitis during childhood. Although this pathology was originally described in critically ill or post-surgical patients, most pediatric cases have been observed during several infectious diseases. In addition to cases caused by bacterial and parasitic infections, most pediatric reports after 2000 described children developing AAC during viral illnesses(such as Epstein-Barr virus and hepatitis A virus infections). Moreover, some pediatric cases have been associated with several underlying chronic diseases and, in particular, with immune-mediated disorders. Here, we review the epidemiological aspects of pediatric AAC, and we discuss etiology, pathophysiology and clinical management, according to the cases reported in the medical literature.
文摘BACKGROUND Bedside needle arthroscopy of the ankle under local anesthesia has been proposed for intra-articular delivery of injectable agents.Accuracy and tolerability of this approach in the clinical setting–including patients with end-stage ankle pathology and/or a history of prior surgery–is not known.AIM To assess clinical accuracy and tolerability of bedside needle arthroscopy as a delivery system for injectable agents into the tibiotalar joint.METHODS This was a prospective study that included adult patients who were scheduled for an injection with hyaluronic acid to the tibiotalar joint.In our center,these injections are used as a last resort prior to extensive surgery.The primary outcome was injection accuracy,which was defined as injecting through the arthroscopic cannula with intra-articular positioning confirmed by a clear arthroscopic view of the joint space.Secondary outcome measures included a patientreported numeric rating scale(NRS,0-10)of pain during the procedure and willingness of patients to return for the same procedure.NRS of ankle pain at rest and during walking was collected at baseline and at 2-wk follow-up.Complications were monitored from inclusion up to a 2-wk control visit.RESULTS We performed 24 inspection-injections.Eleven(46%)participants were male,and mean age was 46.8±14.5 years.Osteoarthritis was the indication for injection in 20(83%)cases,of which 8(33%)patients suffered from osteoarthritis Kellgren-Lawrence grade IV,and 10(42%)patients from Kellgren-Lawrence grade III.An osteochondral defect was the indication for injection in 4(17%)cases.A history of ankle surgery was present in 14(58%)participants and a history of multiple ankle surgeries in 11(46%)participants.It was possible to confirm accuracy in 21(88%)procedures.The 3(12%)participants where needle arthroscopy did not reach a clear view of the joint space all suffered from Kellgren-Lawrence grade IV osteoarthritis.Pain during the procedure was reported with a median of 1[interquartile ranges(IQR):0–2].Willingness to return was 100%.Pain in rest decreased from a median NRS of 4(IQR:2–7)at baseline to a median of 3(IQR:1–5)at follow-up(P<0.01).Pain during walking decreased from a median NRS of 8(IQR:6–9)to a median of 7(IQR:4–8)(P<0.01).Infections or other complications were not encountered.CONCLUSION Clinical accuracy and tolerability of bedside needle arthroscopy of the ankle as a delivery system for injectable agents are excellent.Accuracy was 100%in patients without total ventral joint obliteration.
