Introduction： The department of emergency medicine （DEM） has a high-risk environment due to its unique and complex workflow. Many high-risk medications are ordered and administered at patients’ bedsides without be...Introduction： The department of emergency medicine （DEM） has a high-risk environment due to its unique and complex workflow. Many high-risk medications are ordered and administered at patients’ bedsides without being checked by a pharmacist first, which may lead to an increase in the incidence of patient medication errors （MEs）. Objective： The current study evaluated the needs of the clinical pharmacy service in the DEM at King Saud University Medical City （KSUMC）, Riyadh, Saudi Arabia. Methods： A cross-sectional retrospective study was conducted between Jan 2016 to Dec 2017 and the documentation of clinical pharmacist interventions was extracted from Esihi database. Results： A total of 2,255 interventions for 862 patients were documented. The recommended interventions were as follows： 645 （dose adjustments）, 108 （therapeutic substitutions）, and 354 interventions （initiating drug therapy）. Adverse drug reactions （ADRs） were reported in 16 patients, and drug interactions were managed in 26 patients. The DEM responded to 713 information inquires and 290 pharmacokinetic consultations. Drug discontinuations included 39 incidents （where unjustified drug prescription occurred）, 37 （where contraindications were involved）, and 19 （where duplicate therapy was involved）. The most common interventions were related to the following drugs： antibiotics （34%）, anticoagulants （15%）, and anticonvulsants （10%）. The acceptance rates for the EM clinical pharmacist recommendations increased from 93.9% in 2016 to 99% in 2017. The most common outcome for interventions was to optimize the therapeutic effects of the drugs that were administered （73%）. Reconciliation was done in 796 patients. Conclusions： The clinical pharmacy service plays a critical role in the management of patients in the emergency department （ED）.展开更多
Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-cateni...Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.展开更多
Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic...Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.展开更多
BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth fac...BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.展开更多
BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle fact...BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle factors,and diseases.Obstructive jaundice is one of the most common pathophysiological changes in patients needing hepatobiliary or pancreatic operations that can adversely affect the tissue and organ function throughout the human body.However,the effects of obstructive jaundice on the occurrence of sarcopenia remain unclear.AIM To investigate the incidence of sarcopenia in patients with surgical obstructive jaundice and the association of sarcopenia with postoperative outcome.METHODS This cross-sectional study was conducted from December 2019 to January 2024.Data retrieved included patient demographics,disease entities,sarcopenia-related parameters(including grip strength,6-m walking time,and limb skeletal muscle mass index),postoperative complications,and length of hospital stay.Sarcopenia was confirmed using Asian Working Group standards.Logistic regression was used to analyze the relationship between total bilirubin level and sarcopenia.The factors influencing sarcopenia in patients with surgical obstructive jaundice and association of sarcopenia with postoperative complications were also investigated.RESULTS Overall,1708 patients met the inclusion criteria,with a mean age of 60.09±13.52 years(sex:52.28%male).There were 383 patients(22.42%)with obstructive jaundice and 1325(77.58%)without jaundice.Sarcopenia,low walking speed,low grip strength,and low limb skeletal muscle index were more prevalent in patients with obstructive jaundice than nonobstructive jaundice.The odds ratio(OR)for sarcopenia in patients with obstructive jaundice was 1.689[95%confidence interval(CI):1.295-2.203,P<0.001],indicating that jaundice is a significant risk factor for sarcopenia.The occurrence of sarcopenia was higher in patients with severe obstructive jaundice than mild obstructive jaundice(39.3%vs 22.8%,P<0.05).Obstructive jaundice was positively correlated with reduced walking speed(OR=1.627,95%CI:1.185-2.234,P=0.003)and decreased grip strength(OR=1.669,95%CI:1.212-2.300,P=0.002).Age(OR=1.077,95%CI:1.040-1.114,P<0.001)and body mass index(OR=0.703,95%CI:0.630-0.784,P<0.001)were independent risk factors of sarcopenia in patients with obstructive jaundice.Patients with obstructive jaundice and sarcopenia had a higher rate of postoperative complications(46.3%vs 33.1%,P=0.032),longer postoperative hospital stays(11.33±6.75 days vs 9.19±7.32 days,P=0.016),and longer total hospital stays(17.10±7.69 days vs 15.98±8.55 days,P=0.032)than those without sarcopenia.CONCLUSION Sarcopenia is more prevalent in patients with obstructive jaundice and is positively correlated with the degree of jaundice.Sarcopenia prolongs hospital stays and is associate with postoperative complications.展开更多
BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on th...BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.展开更多
Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for ...Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.展开更多
BACKGROUND Clinical studies using Trabecular Titanium™acetabular cups have shown promising short and medium-term results.This material,due to its macro and micro surface roughness,provides a substrate for osseointegra...BACKGROUND Clinical studies using Trabecular Titanium™acetabular cups have shown promising short and medium-term results.This material,due to its macro and micro surface roughness,provides a substrate for osseointegration and enhances implant stability.However,there is a lack of evidence in the literature on the use of this material in patients with femoral neck fracture.AIM To evaluate the short-term clinical-functional and radiographic outcomes in patients with femoral neck fractures undergoing total hip arthroplasty(THA)with Trabecular Titanium™acetabular cup implants.METHODS The study included 104 patients with medial femoral neck fractures who underwent THA between January 2020 and December 2020 with the Delta TT acetabular cup(Lima Corporate,Villanova di San Daniele del Friuli,Italy).The mean age of the patients was 69.57±10.16 years(range:36-85 years).The followup period ranged from a minimum of 3 to a maximum of 4 years.Three questionnaires(Harris Hip Score,Oxford Hip Score,and EQ5D)were administered along with radiographic evaluations.Statistical methods included the Student's t-test and one-way analysis of variance for comparisons(with significance set at 0.05),and the Kaplan-Meier curve for prosthetic implant survival.RESULTS The mean follow-up was 41.5 months.The Harris Hip Score(HHS)showed a mean increase of 2.74 points(mean HHS 88.52 at 6 months postoperatively and mean HHS 91.26 at the last follow-up)with statistical significance.Similarly,the Oxford Hip Score demonstrated a statistically significant difference between follow-up groups.However,the EQ5D did not show statistically significant differences among the three groups(preoperative,6-month follow-up,and last follow-up).Revision surgery was required in 6 patients.According to Moore's criteria,96%of the acetabular components were radiographically stable and well-integrated at the last follow-up.The Kaplan-Meier curve showed a 96%survival rate.CONCLUSION The clinical and radiographic results obtained in the short to medium term confirm the excellent performance of the Delta TT acetabular cup in terms of osseointegration,providing an optimal solution both for young patients with high functional recovery demands and for fragile patients requiring optimal stability of the acetabular component to reduce the risk of implant failure.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver cancer,with high mortality at advanced stages.Loco-regional treatment including:Radiofrequency(RF)or transarterial chemoembolization(TACE)is dec...BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver cancer,with high mortality at advanced stages.Loco-regional treatment including:Radiofrequency(RF)or transarterial chemoembolization(TACE)is decided according to the size,and the site of the tumor,according to practice guidelines.Alpha fetoprotein(AFP),the most used biomarker in the guidelines,although specific,lacks sensitivity.New biomarkers are needed to understand the underlying pathophysiology,and to be used in clinical practice.AIM To study the effect of loco-regional treatment on telomere length,as a diagnostic and short-term(3 months)prognostic marker.METHODS This is a prospective cohort study,and includes 60 patients visiting Ain Shams University Hospitals.The patients were divided into 2 groups:30 patients with liver cirrhosis(group 1)and 30 HCC patients undergoing RF or TACE(group 2).Laboratory investigations for all patients included:Telomere length in peripheral leukocytes by polymerase chain reaction,AFP,and liver function.In the HCC group,the aforementioned laboratory investigations with abdominal triphasic computed tomography with contrast were performed at baseline,and after 3 months.RESULTS With regard to age,Child-Pugh and Model for End-Stage Liver Disease scores,there was no statistically significant correlation with telomere length.However,there was a correlation between telomere length and age,and both scores before and after 3 months of treatment among HCC patients.On dividing the HCC group according to tumor size with a cutoff of 5 cm,and performing the Mann-Whitney test we found that at baseline telomere length was significantly lower among cases with tumor size≥5 cm than in those with tumor size<5 cm(30 patients;P=0.03).In addition,we found a positive Spearman's rank correlation between telomere length and tumor size in the≥5 cm only group(28 samples from the before and after intervention data;P=0.025).CONCLUSION Telomere length in leukocytes is a potential marker in HCC tumor prognosis.Further research using telomerase activity and telomerase reverse transcriptase promoter gene mutation in a larger cohort is recommended.展开更多
Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October ...Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.展开更多
Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within...Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within hospitals in the city of Yaoundé in 2023. Methods: This was a descriptive cross-sectional study with prospective data collection in the maternity wards of the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, and the Yaoundé Central Hospital for 7 months, from the 1st of November 2022 to the 31st of May 2023. The variables studied were demographic and clinical characteristics, means of recourse and post-abortion contraception. The frequency of abortions was calculated as the ratio of the number of abortions to the number of deliveries. The calculation of numbers and frequencies was used to describe the study population, and to highlight the sociodemographic and clinical characteristics of the patients recruited. Quantitative variables were expressed as mean ± standard deviation. Data were collected numerically and classified according to type, then analyzed using Epi-info version 7.2 software. Microsoft Office Excel 2013 was used to produce figures and tables. Results: During the study period, 169 patients were selected out of 1882 patients who had consulted for gynaecological emergencies;but only 164 of them accepted to participate. The frequency of abortions was 9.6% (169/1882). The age group of 25 to 29 years was the most represented, with 29.3% (48/164). They were mainly single 76.2% (125/164), and housewives 33.5% (55/164). The notion of previous abortion was found in 30.5% (50/164) of them. Approximately 19.5% of patients (32/164) reported to have conceived while using contraception, 56.2% of whom (18/32) used male condoms. At the time of admission to the emergency unit, the predominant symptom was bleeding in 70.7% of cases. The abortions were mainly spontaneous, in 75% of cases (123/164). In cases of induced abortions, 24.4% (10/41) of them took place after 14 weeks. Unexpected pregnancy was the main reason for termination in 46.3% of cases (19/41). Regarding induced abortion, 58.54% (24/41) of them resorted to voluntary medical termination. The mortality rate was 1.2%. The acceptability rate of a modern contraceptive method before discharge was 31.7%. Conclusion: Although frequent in our environment, data relating to abortion remain under-evaluated. Abortions occur mainly among young, single women, with a still very high proportion of induced abortions. The acceptability of post-abortion contraception remains poor. Prevention of unwanted pregnancies and risk factors is necessary to reduce the burden of abortions in low-income countries.展开更多
Recent data suggest that vascular endothelial growth factor receptor inhibitor(VEGFRi)can enhance the anti-tumor activity of the anti-programmed cell death-1(anti-PD-1)antibody in colorectal cancer(CRC)with microsatel...Recent data suggest that vascular endothelial growth factor receptor inhibitor(VEGFRi)can enhance the anti-tumor activity of the anti-programmed cell death-1(anti-PD-1)antibody in colorectal cancer(CRC)with microsatellite stability(MSS).However,the comparison between this combination and standard third-line VEGFRi treatment is not performed,and reliable biomarkers are still lacking.We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi(combination group,n=54)or VEGFRi alone(VEGFRi group,n=32),and their efficacy and safety were evaluated.We additionally examined the immune characteristics of the MSS CRC tumor microenvironment(TME)through single-cell and spatial transcriptomic data,and an MSS CRC immune cell-related signature(MCICRS)that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort.Compared with VEGFRi alone,the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit(median progression-free survival:4.4 vs.2.0 months,P=0.0024;median overall survival:10.2 vs.5.2 months,P=0.0038)and a similar adverse event incidence.Through single-cell and spatial transcriptomic analysis,we determined ten MSS CRC-enriched immune cell types and their spatial distribution,including naive CD4+T,regulatory CD4+T,CD4+Th17,exhausted CD8+T,cytotoxic CD8+T,proliferated CD8+T,natural killer(NK)cells,plasma,and classical and intermediate monocytes.Based on a systemic meta-analysis and ten machine learning algorithms,we obtained MCICRS,an independent risk factor for the prognosis of MSS CRC patients.Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation,and hence a significant relation with the superior efficacy of pan-cancer immunotherapy.More importantly,the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort.Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity.MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.展开更多
Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression....Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.展开更多
BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly lead...BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear.Clarifying this relationship may help deter-mine the prognostic significance of colonization in these patients.AIM To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis.METHODS This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center(2018-2024).Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission.Outcomes analyzed included MDRO infection during ICU stay,concordance between colonizing and infecting strains,organ support requirements,and 28-day transplant free survival.Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality.RESULTS Nearly one-third(29.9%)of patients were colonized with MDROs on admission,more commonly in the acute-onchronic liver failure phenotype than those with acute decompensation(34.5 vs 10.0%,P=0.033).Although infections were established in the majority(85%)of cases,of which 17.6%due to MDROs,colonization alone did not independently predict these infections[odds ratio(OR)=2.18,P=0.383]nor influenced short-term mortality(OR=1.14,P=0.813).However,once MDRO infection occurred,an 82%concordance was observed between colonizing and infecting strains.MDRO infections,unlike colonization,significantly increased the need for organsupport interventions,including mechanical ventilation and vasopressor therapy and prolonged ICU stays.Only severity of organ dysfunction,quantified by the Sequential Organ Failure Assessment score,independently predicted 28-day mortality(OR=1.38,P=0.024).CONCLUSION MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis,particularly those with acute-on-chronic liver failure.While colonization alone does not predict infection or early mortality,its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected.Ultimately,short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.展开更多
In their retrospective study of 298 diabetic patients with renal/ureteral calculi,Zhou et al identified critical predictors for urosepsis using multivariate logisticregression.Key findings revealed female gender(OR=2....In their retrospective study of 298 diabetic patients with renal/ureteral calculi,Zhou et al identified critical predictors for urosepsis using multivariate logisticregression.Key findings revealed female gender(OR=2.237,P=0.03),advancedage(OR=1.05/year,P=0.002),fever(OR=2.999,P=0.015),severe hydronephrosis(OR=6.129,P=0.011),and elevated urinary markers-particularly urineleukocytes(U-LEU+++:OR=66.0,P<0.001)and glucose(U-GLU+++:OR=7.248,P=0.005)as independent risk factors.These readily accessible clinicalparameters offer significant potential for early risk stratification in high-riskpopulations.While this STROBE-adherent study provides actionable insights,limitations include its single-center design and unaddressed antibiotic protocols.Future multicenter validation should assess residual stone impacts and optimizeintervention thresholds.This work establishes a foundation for targeted surveillanceprotocols in diabetic urolithiasis management.展开更多
BACKGROUND The topography between the common carotid artery(CA),internal CA,and external CA(ECA)with the greater horn of the hyoid bone(GHHB)is of particular importance for anatomists,radiologists and neck surgeons.AI...BACKGROUND The topography between the common carotid artery(CA),internal CA,and external CA(ECA)with the greater horn of the hyoid bone(GHHB)is of particular importance for anatomists,radiologists and neck surgeons.AIM To investigate these topographical relationships emphasizing anatomical classification,sexual dimorphism,and clinical significance.METHODS A retrospective study was performed on 224 computed tomography angiographies from a cohort comprising 161 male and 63 female patients,with a mean age of 63.2 years.Multiplanar and three-dimensional reconstructions were executed utilizing Horos software.The spatial relationships between the CA and hyoid bone were categorized based on the 12-type classification system delineated by Manta et al in 2023.The data were subsequently stratified by sex and laterality.RESULTS Type 0(no arterial contact with the GHHB)was the most common configuration(46.9%),followed by type VI(ECA lateral to GHHB,23.9%)and type VIII(internal CA and ECA lateral to GHHB,13.2%).Bilateral symmetry was present in 54.02%of cases,mainly in males.Statistically significant sex-based differences were found(P=0.012),while laterality was not significant(P=0.779).CONCLUSION Carotid–hyoid topography displays significant anatomical variation with clinically essential patterns.Non-null variants,such as types VI and VIII,may increase the risk of dynamic carotid compression,especially in younger patients with cryptogenic cerebrovascular symptoms.Recognizing these variants during preoperative imaging is crucial to minimize surgical risk and inform patient care.展开更多
Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodi...Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.展开更多
BACKGROUND Antithrombotic strategies after percutaneous coronary interventions(PCI)in elderly patients on oral anticoagulant therapy(OAT)are debated due to the balance between ischemic and bleeding risks.Recent guidel...BACKGROUND Antithrombotic strategies after percutaneous coronary interventions(PCI)in elderly patients on oral anticoagulant therapy(OAT)are debated due to the balance between ischemic and bleeding risks.Recent guidelines recommend early transitioning from triple antithrombotic therapy to dual antithrombotic therapy,but there are limited data on elderly patients.METHODS We performed a post-hoc age-specific analysis of the PERSEO Registry population aimed to compare clinical features,therapeutic strategies,and outcomes of individuals aged≥80 years and<80 years who were on OAT and underwent PCI with stent.The primary endpoint was net adverse clinical events at 1-year follow-up.Secondary endpoints included major adverse cardiac and cerebral events(MACCE),major bleeding[Bleeding Academic Research Consortium(BARC)type 3–5],and clinically relevant bleeding(BARC type 2-5).RESULTS Among the 1234 patients enrolled,31%of patients were aged≥80 years(84±3 years,76% males).Compared to younger patients,elderly patients had higher rates of comorbidities such as hypertension,anaemia or chronic kidney disease,and atrial fibrillation was the leading indication for OAT.Elderly patients were more often discharged on dual antithrombotic therapy(23%)compared to younger patients(13%)(P<0.0001).They experienced higher net adverse clinical events(38%vs.21%,P<0.001),MACCE(24%vs.12%,P<0.001),as well as higher bleeding rates.Specifically,rates of major bleeding(9%vs.6%,P=0.026),and clinically relevant bleeding(21%vs.12%,P<0.001)were significantly higher in elderly patients.CONCLUSIONS Elderly patients on OAT undergoing PCI are a particular frail population with higher risk of MACCE and bleeding compared to younger patients despite a less aggressive antithrombotic therapy.展开更多
Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabol...Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.展开更多
Background:Fat loss mainly conveys the benefits of caloric restriction for people living with type 2 diabetes.The literature is equivocal regarding whether exercise facilitates fat loss during caloric restriction.This...Background:Fat loss mainly conveys the benefits of caloric restriction for people living with type 2 diabetes.The literature is equivocal regarding whether exercise facilitates fat loss during caloric restriction.This analysis aimed to assess the dose-response effects of exercise in combination with a caloric restriction on fat mass(FM)and FM percentage(FM%)in persons with diagnosed type 2 diabetes.Methods:In this secondary analysis of a 4-armed randomized trial,82 persons living with type 2 diabetes were randomly allocated to the control group(CON)(n=21),diet control(DCON)(25%caloric restriction;n=20),diet control and exercise 3 times per week(MED)(n=20),or diet control and exercise 6 times per week(HED)(n=21)for 16 weeks.The primary analysis was the change in FM%points.Secondary analyses included fat-free mass and visceral adipose tissue(VAT)volume(cm^(3)).Results:FM%decreased compared to CON by a mean difference of-3.5%(95%confidence interval(95%CI):-5.6%to-1.4%),-6.3%(95%CI:-8.4%to-4.1%),and-8.0%(95%CI:-10.2%to-5.8%)for DCON,MED,and HED,respectively.Compared to DCON,MED,and HED decreased FM%by-2.8%(95%CI:-4.9%to-0.7%)and-4.5%(95%CI:-6.6%to-2.4%),respectively.The difference in FM%between HED and MED was-1.8%(95%CI:-3.9%to 0.4%).DCON and MED decreased fat-free mass compared to CON,whereas HED preserved fat-free mass(-0.2%;95%CI:-2.0%to 1.7%).Compared to CON,VAT volume decreased by-666.0 cm^(3)(95%CI:-912.8 cm^(3) to-385.1 cm^(3)),-1264.0 cm^(3)(95%CI:-1679.6 cm^(3) to-655.9 cm^(3)),and-1786.4 cm^(3)(95%CI:-2264.6 cm^(3) to-1321.2 cm^(3))more for DCON,MED,and HED,respectively.HED decreased VAT volume more than DCON(-1120.4 cm^(3);95%CI:-1746.6 cm^(3) to-639.4 cm^(3))while the remaining comparisons did not reveal any differences.Conclusion:All interventions were superior in reducing FM%compared to standard care.Adding exercise to a caloric restriction was superior in reducing FM%compared to a caloric restriction alone.展开更多
文摘Introduction： The department of emergency medicine （DEM） has a high-risk environment due to its unique and complex workflow. Many high-risk medications are ordered and administered at patients’ bedsides without being checked by a pharmacist first, which may lead to an increase in the incidence of patient medication errors （MEs）. Objective： The current study evaluated the needs of the clinical pharmacy service in the DEM at King Saud University Medical City （KSUMC）, Riyadh, Saudi Arabia. Methods： A cross-sectional retrospective study was conducted between Jan 2016 to Dec 2017 and the documentation of clinical pharmacist interventions was extracted from Esihi database. Results： A total of 2,255 interventions for 862 patients were documented. The recommended interventions were as follows： 645 （dose adjustments）, 108 （therapeutic substitutions）, and 354 interventions （initiating drug therapy）. Adverse drug reactions （ADRs） were reported in 16 patients, and drug interactions were managed in 26 patients. The DEM responded to 713 information inquires and 290 pharmacokinetic consultations. Drug discontinuations included 39 incidents （where unjustified drug prescription occurred）, 37 （where contraindications were involved）, and 19 （where duplicate therapy was involved）. The most common interventions were related to the following drugs： antibiotics （34%）, anticoagulants （15%）, and anticonvulsants （10%）. The acceptance rates for the EM clinical pharmacist recommendations increased from 93.9% in 2016 to 99% in 2017. The most common outcome for interventions was to optimize the therapeutic effects of the drugs that were administered （73%）. Reconciliation was done in 796 patients. Conclusions： The clinical pharmacy service plays a critical role in the management of patients in the emergency department （ED）.
基金financially supporting this work through the Large Research Group Project under Grant no.R.G.P.2/509/45
文摘Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.
文摘Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.
文摘BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.
基金Supported by Shandong Province Biliary Pancreatic Cancer Clinical Quality Specialty Construction Fund,No.SLCZDZK-2401.
文摘BACKGROUND Sarcopenia is a clinical syndrome presented with progressive and generalized skeletal muscle loss and function dysfunction.Usually,it is considered an agerelated process influenced by genetic,lifestyle factors,and diseases.Obstructive jaundice is one of the most common pathophysiological changes in patients needing hepatobiliary or pancreatic operations that can adversely affect the tissue and organ function throughout the human body.However,the effects of obstructive jaundice on the occurrence of sarcopenia remain unclear.AIM To investigate the incidence of sarcopenia in patients with surgical obstructive jaundice and the association of sarcopenia with postoperative outcome.METHODS This cross-sectional study was conducted from December 2019 to January 2024.Data retrieved included patient demographics,disease entities,sarcopenia-related parameters(including grip strength,6-m walking time,and limb skeletal muscle mass index),postoperative complications,and length of hospital stay.Sarcopenia was confirmed using Asian Working Group standards.Logistic regression was used to analyze the relationship between total bilirubin level and sarcopenia.The factors influencing sarcopenia in patients with surgical obstructive jaundice and association of sarcopenia with postoperative complications were also investigated.RESULTS Overall,1708 patients met the inclusion criteria,with a mean age of 60.09±13.52 years(sex:52.28%male).There were 383 patients(22.42%)with obstructive jaundice and 1325(77.58%)without jaundice.Sarcopenia,low walking speed,low grip strength,and low limb skeletal muscle index were more prevalent in patients with obstructive jaundice than nonobstructive jaundice.The odds ratio(OR)for sarcopenia in patients with obstructive jaundice was 1.689[95%confidence interval(CI):1.295-2.203,P<0.001],indicating that jaundice is a significant risk factor for sarcopenia.The occurrence of sarcopenia was higher in patients with severe obstructive jaundice than mild obstructive jaundice(39.3%vs 22.8%,P<0.05).Obstructive jaundice was positively correlated with reduced walking speed(OR=1.627,95%CI:1.185-2.234,P=0.003)and decreased grip strength(OR=1.669,95%CI:1.212-2.300,P=0.002).Age(OR=1.077,95%CI:1.040-1.114,P<0.001)and body mass index(OR=0.703,95%CI:0.630-0.784,P<0.001)were independent risk factors of sarcopenia in patients with obstructive jaundice.Patients with obstructive jaundice and sarcopenia had a higher rate of postoperative complications(46.3%vs 33.1%,P=0.032),longer postoperative hospital stays(11.33±6.75 days vs 9.19±7.32 days,P=0.016),and longer total hospital stays(17.10±7.69 days vs 15.98±8.55 days,P=0.032)than those without sarcopenia.CONCLUSION Sarcopenia is more prevalent in patients with obstructive jaundice and is positively correlated with the degree of jaundice.Sarcopenia prolongs hospital stays and is associate with postoperative complications.
基金Supported by National Natural Science Foundation of China,No.82160762Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Scientific Research Project,No.GXZYA20230267+2 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598060XChina Undergraduate Innovation and Entrepreneurship Training Program,No.X202410598360Future Academic Star of Guangxi Medical University,No.WLXSZX24074.
文摘BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.
文摘Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.
文摘BACKGROUND Clinical studies using Trabecular Titanium™acetabular cups have shown promising short and medium-term results.This material,due to its macro and micro surface roughness,provides a substrate for osseointegration and enhances implant stability.However,there is a lack of evidence in the literature on the use of this material in patients with femoral neck fracture.AIM To evaluate the short-term clinical-functional and radiographic outcomes in patients with femoral neck fractures undergoing total hip arthroplasty(THA)with Trabecular Titanium™acetabular cup implants.METHODS The study included 104 patients with medial femoral neck fractures who underwent THA between January 2020 and December 2020 with the Delta TT acetabular cup(Lima Corporate,Villanova di San Daniele del Friuli,Italy).The mean age of the patients was 69.57±10.16 years(range:36-85 years).The followup period ranged from a minimum of 3 to a maximum of 4 years.Three questionnaires(Harris Hip Score,Oxford Hip Score,and EQ5D)were administered along with radiographic evaluations.Statistical methods included the Student's t-test and one-way analysis of variance for comparisons(with significance set at 0.05),and the Kaplan-Meier curve for prosthetic implant survival.RESULTS The mean follow-up was 41.5 months.The Harris Hip Score(HHS)showed a mean increase of 2.74 points(mean HHS 88.52 at 6 months postoperatively and mean HHS 91.26 at the last follow-up)with statistical significance.Similarly,the Oxford Hip Score demonstrated a statistically significant difference between follow-up groups.However,the EQ5D did not show statistically significant differences among the three groups(preoperative,6-month follow-up,and last follow-up).Revision surgery was required in 6 patients.According to Moore's criteria,96%of the acetabular components were radiographically stable and well-integrated at the last follow-up.The Kaplan-Meier curve showed a 96%survival rate.CONCLUSION The clinical and radiographic results obtained in the short to medium term confirm the excellent performance of the Delta TT acetabular cup in terms of osseointegration,providing an optimal solution both for young patients with high functional recovery demands and for fragile patients requiring optimal stability of the acetabular component to reduce the risk of implant failure.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common primary liver cancer,with high mortality at advanced stages.Loco-regional treatment including:Radiofrequency(RF)or transarterial chemoembolization(TACE)is decided according to the size,and the site of the tumor,according to practice guidelines.Alpha fetoprotein(AFP),the most used biomarker in the guidelines,although specific,lacks sensitivity.New biomarkers are needed to understand the underlying pathophysiology,and to be used in clinical practice.AIM To study the effect of loco-regional treatment on telomere length,as a diagnostic and short-term(3 months)prognostic marker.METHODS This is a prospective cohort study,and includes 60 patients visiting Ain Shams University Hospitals.The patients were divided into 2 groups:30 patients with liver cirrhosis(group 1)and 30 HCC patients undergoing RF or TACE(group 2).Laboratory investigations for all patients included:Telomere length in peripheral leukocytes by polymerase chain reaction,AFP,and liver function.In the HCC group,the aforementioned laboratory investigations with abdominal triphasic computed tomography with contrast were performed at baseline,and after 3 months.RESULTS With regard to age,Child-Pugh and Model for End-Stage Liver Disease scores,there was no statistically significant correlation with telomere length.However,there was a correlation between telomere length and age,and both scores before and after 3 months of treatment among HCC patients.On dividing the HCC group according to tumor size with a cutoff of 5 cm,and performing the Mann-Whitney test we found that at baseline telomere length was significantly lower among cases with tumor size≥5 cm than in those with tumor size<5 cm(30 patients;P=0.03).In addition,we found a positive Spearman's rank correlation between telomere length and tumor size in the≥5 cm only group(28 samples from the before and after intervention data;P=0.025).CONCLUSION Telomere length in leukocytes is a potential marker in HCC tumor prognosis.Further research using telomerase activity and telomerase reverse transcriptase promoter gene mutation in a larger cohort is recommended.
文摘Background:Chiglitazar is a novel pan-agonist that can activate all three subtypes of peroxisome proliferator-activated receptor.It was approved for the treatment of type 2 diabetes mellitus as monotherapy on October 19,2021,and as combination therapy with metformin when using metformin alone failed in blood glucose control on July 16,2024,by the National Medical Products Administration(NMPA)in China.However,pharmacokinetic(PK)study of this product in patients with renal impairment have not yet been conducted.The purpose of this study is to evaluate the effects of renal impairment on the PK and safety after a single oral dose of Chiglitazar.Methods:This multicenter,open-label,parallel-controlled,single-dose Phase I clinical trial(NCT 05515458)enrolled 24 participants(12/group)with severe renal impairment(SRI)or normal renal function(NRF).All participants received a single oral dose of 48 mg chiglitazar after breakfast and the PK and safety was evaluated.Results:The median Tmax was similar in both SRI and NRF groups(5.01 vs.5.02 hours).The geometric mean ratios(GMR)for Cmax,AUC0-t,and AUC0-∞were 0.807(90%confidence interval[CI]:0.697–0.935),0.853(90%CI:0.713–1.02),and 0.855(90%CI:0.716–1.02),respectively,indicating that SRI did not significantly affect the exposure of chiglitazar.The Cmax was weakly positively correlated with eGFR(r=0.4798,P=0.0177)and creatinine clearance rate(r=0.4667,P=0.0215).Urinary excretion of chiglitazar was negligible in the SRI group,with average values of Ae0-t=2,900 ng,Fe0-t=0.0060%,and CLR=0.323 mL/h within 0–72 hours post-dose.The treatment-emergent adverse event(TEAE)incidence in the SRI group(16.7%,2/12)was comparable to that in the NRF group(25%,3/12).All TEAEs were of mild severity and were adjudicated by the investigators to be unrelated to chiglitazar.No serious AE were reported.Chiglitazar exhibits a favorable safety profile.Conclusion:Severe renal impairment does not significantly affect the PK and safety of chiglitazar,and no dose adjustment for mild,moderate,and severe renal impairments is required.
文摘Abortion is one of the leading causes of maternal death in Cameroon, despite numerous policies and strategies put in place to reduce it by 2030.This study aims to describe the epidemiologic aspects of abortions within hospitals in the city of Yaoundé in 2023. Methods: This was a descriptive cross-sectional study with prospective data collection in the maternity wards of the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, and the Yaoundé Central Hospital for 7 months, from the 1st of November 2022 to the 31st of May 2023. The variables studied were demographic and clinical characteristics, means of recourse and post-abortion contraception. The frequency of abortions was calculated as the ratio of the number of abortions to the number of deliveries. The calculation of numbers and frequencies was used to describe the study population, and to highlight the sociodemographic and clinical characteristics of the patients recruited. Quantitative variables were expressed as mean ± standard deviation. Data were collected numerically and classified according to type, then analyzed using Epi-info version 7.2 software. Microsoft Office Excel 2013 was used to produce figures and tables. Results: During the study period, 169 patients were selected out of 1882 patients who had consulted for gynaecological emergencies;but only 164 of them accepted to participate. The frequency of abortions was 9.6% (169/1882). The age group of 25 to 29 years was the most represented, with 29.3% (48/164). They were mainly single 76.2% (125/164), and housewives 33.5% (55/164). The notion of previous abortion was found in 30.5% (50/164) of them. Approximately 19.5% of patients (32/164) reported to have conceived while using contraception, 56.2% of whom (18/32) used male condoms. At the time of admission to the emergency unit, the predominant symptom was bleeding in 70.7% of cases. The abortions were mainly spontaneous, in 75% of cases (123/164). In cases of induced abortions, 24.4% (10/41) of them took place after 14 weeks. Unexpected pregnancy was the main reason for termination in 46.3% of cases (19/41). Regarding induced abortion, 58.54% (24/41) of them resorted to voluntary medical termination. The mortality rate was 1.2%. The acceptability rate of a modern contraceptive method before discharge was 31.7%. Conclusion: Although frequent in our environment, data relating to abortion remain under-evaluated. Abortions occur mainly among young, single women, with a still very high proportion of induced abortions. The acceptability of post-abortion contraception remains poor. Prevention of unwanted pregnancies and risk factors is necessary to reduce the burden of abortions in low-income countries.
基金supported by the National Natural Science Foundation of China(No.81972012).
文摘Recent data suggest that vascular endothelial growth factor receptor inhibitor(VEGFRi)can enhance the anti-tumor activity of the anti-programmed cell death-1(anti-PD-1)antibody in colorectal cancer(CRC)with microsatellite stability(MSS).However,the comparison between this combination and standard third-line VEGFRi treatment is not performed,and reliable biomarkers are still lacking.We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi(combination group,n=54)or VEGFRi alone(VEGFRi group,n=32),and their efficacy and safety were evaluated.We additionally examined the immune characteristics of the MSS CRC tumor microenvironment(TME)through single-cell and spatial transcriptomic data,and an MSS CRC immune cell-related signature(MCICRS)that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort.Compared with VEGFRi alone,the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit(median progression-free survival:4.4 vs.2.0 months,P=0.0024;median overall survival:10.2 vs.5.2 months,P=0.0038)and a similar adverse event incidence.Through single-cell and spatial transcriptomic analysis,we determined ten MSS CRC-enriched immune cell types and their spatial distribution,including naive CD4+T,regulatory CD4+T,CD4+Th17,exhausted CD8+T,cytotoxic CD8+T,proliferated CD8+T,natural killer(NK)cells,plasma,and classical and intermediate monocytes.Based on a systemic meta-analysis and ten machine learning algorithms,we obtained MCICRS,an independent risk factor for the prognosis of MSS CRC patients.Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation,and hence a significant relation with the superior efficacy of pan-cancer immunotherapy.More importantly,the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort.Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity.MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
基金partially supported by the Construction Fund of Key Medical Disciplines of Hangzhou(No.OO2020491)the National Key Research and Development Program of China(No.2023YFC2506200)+4 种基金the Zhejiang Provincial Key Research and Development Program(No.2021C03107)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(No.JNL-2023001B)the Leading Talent of Scientific and Technological Innovation-“Ten Thousand Talents Program”of Zhejiang Province(No.2021R52016)the Innovation Team for Precision Diagnosis and Treatment of Major Brain Diseases(No.2020R01001)the Chinese Medical Education Association(No.2022KTZ004).
文摘Objective:Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial.This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.Methods:Patients with bipolarⅡdepression were enrolled in this prospective,two-center,randomized,12-week pilot trial.The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale(MADRS)of≥50%.All eligible patients initially received four weeks of lurasidone monotherapy.Patients who responded well continued to receive this kind of monotherapy.However,no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks.By comprehensively comparing the results of MADRS over a period of 4-12 weeks,a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.Results:Thirty-seven patients responded to lurasidone monotherapy,and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks.After two weeks of combined valproate or vortioxetine treatment,the MADRS score in the vortioxetine group was significantly lower than that in the valproate group.There was no difference in the MADRS scores between the two groups at 8 and 12 weeks.The incidence of side effects did not significantly differ between the valproate and vortioxetine groups.Importantly,three patients in the vortioxetine group appeared to switch to mania or hypomania.Conclusions:This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage,while disease progression should be monitored closely for the risk of switching to mania.
基金approved by the Institutional Review Board of the University Hospital Centre Zagreb(Approval No:02/013 AG).
文摘BACKGROUND Colonization with multidrug-resistant organisms(MDROs)is frequently observed in critically ill patients with liver cirrhosis admitted to intensive care units(ICUs).However,whether colonization directly leads to infections or adversely impacts clinical outcomes remains unclear.Clarifying this relationship may help deter-mine the prognostic significance of colonization in these patients.AIM To evaluate the clinical relevance of MDRO colonization and infection at ICU admission in patients with cirrhosis.METHODS This retrospective single-center cohort study included 107 ICU admissions of patients with liver cirrhosis at a tertiary care center(2018-2024).Colonization was assessed by rectal and nasal/pharyngeal swabs within 48 hours of ICU admission.Outcomes analyzed included MDRO infection during ICU stay,concordance between colonizing and infecting strains,organ support requirements,and 28-day transplant free survival.Multivariable logistic regression and Kaplan-Meier analyses were used to evaluate predictors of infection and mortality.RESULTS Nearly one-third(29.9%)of patients were colonized with MDROs on admission,more commonly in the acute-onchronic liver failure phenotype than those with acute decompensation(34.5 vs 10.0%,P=0.033).Although infections were established in the majority(85%)of cases,of which 17.6%due to MDROs,colonization alone did not independently predict these infections[odds ratio(OR)=2.18,P=0.383]nor influenced short-term mortality(OR=1.14,P=0.813).However,once MDRO infection occurred,an 82%concordance was observed between colonizing and infecting strains.MDRO infections,unlike colonization,significantly increased the need for organsupport interventions,including mechanical ventilation and vasopressor therapy and prolonged ICU stays.Only severity of organ dysfunction,quantified by the Sequential Organ Failure Assessment score,independently predicted 28-day mortality(OR=1.38,P=0.024).CONCLUSION MDRO colonization at ICU admission is frequent among critically ill patients with cirrhosis,particularly those with acute-on-chronic liver failure.While colonization alone does not predict infection or early mortality,its clinical value emerges in guiding empirical antibiotic treatment once infection is suspected.Ultimately,short-term survival appears to be more strongly influenced by the severity of organ failure than by either MDRO colonization or infection.
基金Supported by National Natural Science Foundation of China,No.82300780Natural Science Foundation of Jiangsu Province,No.BK20220306Yancheng Key Research and Development Plan(Social Development)Project,No.YCBE202214.
文摘In their retrospective study of 298 diabetic patients with renal/ureteral calculi,Zhou et al identified critical predictors for urosepsis using multivariate logisticregression.Key findings revealed female gender(OR=2.237,P=0.03),advancedage(OR=1.05/year,P=0.002),fever(OR=2.999,P=0.015),severe hydronephrosis(OR=6.129,P=0.011),and elevated urinary markers-particularly urineleukocytes(U-LEU+++:OR=66.0,P<0.001)and glucose(U-GLU+++:OR=7.248,P=0.005)as independent risk factors.These readily accessible clinicalparameters offer significant potential for early risk stratification in high-riskpopulations.While this STROBE-adherent study provides actionable insights,limitations include its single-center design and unaddressed antibiotic protocols.Future multicenter validation should assess residual stone impacts and optimizeintervention thresholds.This work establishes a foundation for targeted surveillanceprotocols in diabetic urolithiasis management.
文摘BACKGROUND The topography between the common carotid artery(CA),internal CA,and external CA(ECA)with the greater horn of the hyoid bone(GHHB)is of particular importance for anatomists,radiologists and neck surgeons.AIM To investigate these topographical relationships emphasizing anatomical classification,sexual dimorphism,and clinical significance.METHODS A retrospective study was performed on 224 computed tomography angiographies from a cohort comprising 161 male and 63 female patients,with a mean age of 63.2 years.Multiplanar and three-dimensional reconstructions were executed utilizing Horos software.The spatial relationships between the CA and hyoid bone were categorized based on the 12-type classification system delineated by Manta et al in 2023.The data were subsequently stratified by sex and laterality.RESULTS Type 0(no arterial contact with the GHHB)was the most common configuration(46.9%),followed by type VI(ECA lateral to GHHB,23.9%)and type VIII(internal CA and ECA lateral to GHHB,13.2%).Bilateral symmetry was present in 54.02%of cases,mainly in males.Statistically significant sex-based differences were found(P=0.012),while laterality was not significant(P=0.779).CONCLUSION Carotid–hyoid topography displays significant anatomical variation with clinically essential patterns.Non-null variants,such as types VI and VIII,may increase the risk of dynamic carotid compression,especially in younger patients with cryptogenic cerebrovascular symptoms.Recognizing these variants during preoperative imaging is crucial to minimize surgical risk and inform patient care.
基金Supported by Fondazione di Sardegna,No.2020.2284.
文摘Celiac disease(CD)is a systemic autoimmune disorder triggered by gluten ingestion ingenetically predisposed individuals.It is characterized by intestinal histological damage and the production of specific autoantibodies.The latest European Society for Paediatric Gastroenterology,Hepatology,and Nutrition(ESPGHAN)2020 guidelines have excluded human leukocyte antigen(HLA)genotyping from the no-biopsy diagnostic approach due to its weak positive predictive value,limited availability,and high cost in some countries.However,HLA genetic testing remains valuable in certain clinical contexts.This study provided practical indications for when to request and how to interpret HLA genotyping,emphasizing its continued relevance for CD diagnosis in specific cases.We also proposed a strategy for monitoring the risk of developing type 1 diabetes(T1D)in patients with CD,based on the risk stratification carried by different HLA genotypes.A retrospective analysis of 746 patients with CD and 627 controls was conducted at our hospital starting in2012,when HLA genotyping became mandatory for the diagnosis of CD.We identified key clinical scenarios where HLA testing remains useful.Several high risk HLA-DQ genotypes strongly associated with CD were highlighted,including HLA-DQ2.5/HLA-DQ2.2and HLA-DQ2.5/HLA-DQ2.5.Notably,while the HLA-DQ2.5/HLA-DQ2.2 genotype is linked to CD,it appears to confer protection against T1D.To support clinical practice,we presented a table clarifying commonly used HLA terminology,and another summarized the main clinical situations in which HLAgenotyping should still be considered.These findings underscore the dual role of HLA testing:Not only can it help rule out CD in selected cases,but it also identifies patients with CD at risk for T1D,guiding personalized monitoring strategies.
基金was given by a 2017 Research Grant of the Italian Society of Interventional Cardiology (SICI-GISE)
文摘BACKGROUND Antithrombotic strategies after percutaneous coronary interventions(PCI)in elderly patients on oral anticoagulant therapy(OAT)are debated due to the balance between ischemic and bleeding risks.Recent guidelines recommend early transitioning from triple antithrombotic therapy to dual antithrombotic therapy,but there are limited data on elderly patients.METHODS We performed a post-hoc age-specific analysis of the PERSEO Registry population aimed to compare clinical features,therapeutic strategies,and outcomes of individuals aged≥80 years and<80 years who were on OAT and underwent PCI with stent.The primary endpoint was net adverse clinical events at 1-year follow-up.Secondary endpoints included major adverse cardiac and cerebral events(MACCE),major bleeding[Bleeding Academic Research Consortium(BARC)type 3–5],and clinically relevant bleeding(BARC type 2-5).RESULTS Among the 1234 patients enrolled,31%of patients were aged≥80 years(84±3 years,76% males).Compared to younger patients,elderly patients had higher rates of comorbidities such as hypertension,anaemia or chronic kidney disease,and atrial fibrillation was the leading indication for OAT.Elderly patients were more often discharged on dual antithrombotic therapy(23%)compared to younger patients(13%)(P<0.0001).They experienced higher net adverse clinical events(38%vs.21%,P<0.001),MACCE(24%vs.12%,P<0.001),as well as higher bleeding rates.Specifically,rates of major bleeding(9%vs.6%,P=0.026),and clinically relevant bleeding(21%vs.12%,P<0.001)were significantly higher in elderly patients.CONCLUSIONS Elderly patients on OAT undergoing PCI are a particular frail population with higher risk of MACCE and bleeding compared to younger patients despite a less aggressive antithrombotic therapy.
文摘Background:Developing a granulomatous liver injury preclinical model may pave the way to understanding hepatic-TB(tuberculosis)and autoimmune granulomatous liver diseases.Antitubercular(ATT)and other drugs'metabolism in the presence of a specific type of liver injury is not well understood.The present study aimed to establish a preclinical model of granulomatous hepatitis by using the BCG(Bacillus CalmetteGuérin)vaccine,further studying it in the presence of ATT dosing,and analyze the pharmacokinetics of isoniazid,rifampicin,and their respective primary metabolites.Methods:We used 56 rats in seven equal groups.Group I functioned as a normal control(NC)receiving normal saline only.Groups II-IV received intravenous injections of low-,medium-,and high-dose BCG vaccine daily for 21 days.Groups V,VI,and VII received isoniazid(H)alone,rifampicin(R)alone,and isoniazid+rifampicin(HR)for a subsequent 15 days in addition to high dose BCG for the first 21 days,respectively.Liver function tests(LFT)were monitored on days 0,21,28,and 36.Rats were sacrificed later for oxidative stress and histopathological examination.Results:The study observed BCG dose-specific LFT derangements in groups II-IV compared to group I on day 21(p<0.05).Isoniazid,rifampicin,and combination intervention groups demonstrated normalization of the BCG-led LFT changes.Histology and oxidative stress parameters confirmed model development and biochemical changes.Isoniazid area under the curve(AUC)showed a reduction of 16.9%in BCG+HR group in comparison to the BCG+H group(p=0.01).Des-acetyl-rifampicin AUC and maximum-concentration value demonstrated a significant rise in BCG+HR group in comparison to the BCG+R group(p=0.001).Conclusion:A novel preclinical model of granulomatous liver injury was developed using the BCG vaccine strain and validated with ATT response.
基金supported by grants from Tryg Fonden(Grant No.123497 and Grant No.124708)Svend Andersen Fonden(this foundation does not use grant numbers,but the filename for the grant was 81-A.15)+2 种基金supported by TrygFonden(Grant No.101390,Grant No.20045,and Grant No.125132)supported by a research grant from the Danish Diabetes Academy(now called Danish Diabetes and Endocrine Academy),which is funded by the Novo Nordisk Foundation(Grant No.NNF17SA0031406)supported by the Canadian Institutes of Health Research(MFE-176582)。
文摘Background:Fat loss mainly conveys the benefits of caloric restriction for people living with type 2 diabetes.The literature is equivocal regarding whether exercise facilitates fat loss during caloric restriction.This analysis aimed to assess the dose-response effects of exercise in combination with a caloric restriction on fat mass(FM)and FM percentage(FM%)in persons with diagnosed type 2 diabetes.Methods:In this secondary analysis of a 4-armed randomized trial,82 persons living with type 2 diabetes were randomly allocated to the control group(CON)(n=21),diet control(DCON)(25%caloric restriction;n=20),diet control and exercise 3 times per week(MED)(n=20),or diet control and exercise 6 times per week(HED)(n=21)for 16 weeks.The primary analysis was the change in FM%points.Secondary analyses included fat-free mass and visceral adipose tissue(VAT)volume(cm^(3)).Results:FM%decreased compared to CON by a mean difference of-3.5%(95%confidence interval(95%CI):-5.6%to-1.4%),-6.3%(95%CI:-8.4%to-4.1%),and-8.0%(95%CI:-10.2%to-5.8%)for DCON,MED,and HED,respectively.Compared to DCON,MED,and HED decreased FM%by-2.8%(95%CI:-4.9%to-0.7%)and-4.5%(95%CI:-6.6%to-2.4%),respectively.The difference in FM%between HED and MED was-1.8%(95%CI:-3.9%to 0.4%).DCON and MED decreased fat-free mass compared to CON,whereas HED preserved fat-free mass(-0.2%;95%CI:-2.0%to 1.7%).Compared to CON,VAT volume decreased by-666.0 cm^(3)(95%CI:-912.8 cm^(3) to-385.1 cm^(3)),-1264.0 cm^(3)(95%CI:-1679.6 cm^(3) to-655.9 cm^(3)),and-1786.4 cm^(3)(95%CI:-2264.6 cm^(3) to-1321.2 cm^(3))more for DCON,MED,and HED,respectively.HED decreased VAT volume more than DCON(-1120.4 cm^(3);95%CI:-1746.6 cm^(3) to-639.4 cm^(3))while the remaining comparisons did not reveal any differences.Conclusion:All interventions were superior in reducing FM%compared to standard care.Adding exercise to a caloric restriction was superior in reducing FM%compared to a caloric restriction alone.
