BACKGROUND Intraoperative fluid management is an important aspect of anesthesia mana-gement in gastrointestinal surgery.Intraoperative goal-directed fluid therapy(GDFT)is a method for optimizing a patient's physio...BACKGROUND Intraoperative fluid management is an important aspect of anesthesia mana-gement in gastrointestinal surgery.Intraoperative goal-directed fluid therapy(GDFT)is a method for optimizing a patient's physiological state by monitoring and regulating fluid input in real-time.AIM To evaluate the efficacy of intraoperative GDFT in patients under anesthesia for gastrointestinal surgery.METHODS This study utilized a retrospective comparative study design and included 60 patients who underwent gastrointestinal surgery at a hospital.The experimental group(GDFT group)and the control group,each comprising 30 patients,received intraoperative GDFT and traditional fluid management strategies,respectively.The effect of GDFT was evaluated by comparing postoperative recovery,com-plication rates,hospitalization time,and other indicators between the two patient groups.RESULTS Intraoperative blood loss in the experimental and control groups was 296.64±46.71 mL and 470.05±73.26 mL(P<0.001),and urine volume was 415.13±96.72 mL and 239.15±94.69 mL(P<0.001),respectively.The postoperative recovery time was 5.44±1.1 days for the experimental group compared to 7.59±1.45 days(P<0.001)for the control group.Hospitalization time for the experimental group was 10.87±2.36 days vs 13.65±3 days for the control group(P<0.001).The visual analogue scale scores of the experimental and control groups at 24 h and 48 h INTRODUCTION Gastrointestinal surgery is one of the most common procedures in the field of general surgery[1],involving the stomach,intestines,liver,pancreas,spleen,and other internal abdominal organs[2,3].With advancements in surgical technology and anesthesia methods,the safety and success rates of surgery have significantly improved[4,5].However,intraop-erative fluid management remains a critical challenge[6].Traditional fluid management strategies often rely on experience and basic physiological parameters,which may lead to excessive or insufficient fluid input,thereby affecting postoperative recovery and complication rates.Intraoperative goal-directed fluid therapy(GDFT)is an emerging fluid management strategy that dynamically adjusts fluid input volume by monitoring the patient's hemodynamic parameters in real-time to optimize the patient's physiological state[7,8].GDFT has shown superiority in many surgical fields;however,its application in gastrointestinal surgery requires further research and verification[9,10].The application of intraoperative GDFT in clinical settings has gradually increased in recent years[11,12].Studies have demonstrated that GDFT can optimize tissue perfusion and oxygenation by precisely controlling fluid input and reducing the occurrence of postoperative complications[13,14].For example,in cardiac and major vascular surgeries,GDFT significantly reduced the incidence of postoperative acute kidney injury and cardiovascular events[15,16].Similarly,in abdominal surgery,GDFT effectively reduced postoperative infections and expedited recovery[17].However,studies on the utilization of GDFT in gastrointestinal surgery are relatively limited and they are confounded by contradictory findings[18].Traditional fluid management strategies typically rely on estimating fluid input volume based on the patient's weight,preoperative status,and basic physiological parameters[19].However,this method lacks real-time dynamic adjustment,which may result in either insufficient or excessive fluid input,consequently affecting postoperative recovery.Insufficient fluid input can lead to hypovolemia and inadequate tissue perfusion,whereas excessive fluid input can cause tissue edema and postoperative complications,such as pulmonary edema and heart failure.GDFT involves dynamically adjusting fluid input volume by monitoring the patient's hemodynamic parameters in real-time,such as cardiac output,pulse pressure variability,and central venous pressure.Commonly used monitoring equipment include esophageal Doppler and pulse wave profile analyzers[20].These devices provide real-time hemo-dynamic data to assist anesthesiologists in tailoring fluid therapy to a patient's specific condition.Firstly,the patient's volume responsiveness is assessed by preloading fluid;secondly,fluid input volume is dynamically adjusted based on real-time monitoring data;finally,vasoactive and inotropic drugs are administered in combination to further optimize the patient’s hemodynamic status.Through personalized fluid management,GDFT can more accurately maintain intraop-erative hemodynamic stability and reduce complications[21].Gastrointestinal surgery involves procedures on multiple organs,often requiring prolonged operative times and extensive tissue trauma,which presents challenges for intraop-erative fluid management.Surgical procedures can lead to significant bleeding and fluid loss,requiring prompt and effective fluid replenishment.In addition,the slow recovery of gastrointestinal function after surgery and susceptibility to complications such as intestinal obstruction and delayed gastric emptying elevate the necessity for postoperative fluid management.展开更多
Objective Although goal-directed fluid therapy(GDFT)has been proven to be effective in reducing the incidence of postoperative complications,the underlying mechanisms remain unknown.The aim of this study was to examin...Objective Although goal-directed fluid therapy(GDFT)has been proven to be effective in reducing the incidence of postoperative complications,the underlying mechanisms remain unknown.The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications.We further tested the role of this mediation effect using mean arterial pressure,a hemodynamic indicator.Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis.We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications.We conducted mediation analysis using the mediation package in R(version 3.1.2),based on 5,000 bootstrapped samples,adjusting for covariates.Results Among the 300 patients in the study,40%(120/300)developed postoperative complications within 30 days.GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders(odds ratio:0.460,95%CI:0.278,0.761;P=0.003).The total effect of GDFT on postoperative complications was-0.18(95%CI:-0.28,-0.07;P<0.01).The average causal mediation effect was-0.08(95%CI:-0.15,-0.04;P<0.01).The average direct effect was-0.09(95%CI:-0.20,0.03;P=0.17).The proportion mediated was 49.9%(95%CI:18.3%,140.0%).Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications.Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.展开更多
Intraoperative fluid management is pivotal to the outcome and success of surgery, especially in high-risk proce- dures. Empirical formula and invasive static monitoring have been traditionally used to guide intraopera...Intraoperative fluid management is pivotal to the outcome and success of surgery, especially in high-risk proce- dures. Empirical formula and invasive static monitoring have been traditionally used to guide intraoperative fluid management and assess volume status. With the awareness of the potential complications of invasive procedures and the poor reliability of these methods as indicators of volume status, we present a case scenario of a patient who underwent major abdominal surgery as an example to discuss how the use of minimally invasive dynamic monitoring may guide intraoperative fluid therapy.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.展开更多
<b><span style="font-family:Verdana;">Background: </span></b></span><span><span><span style="font-family:""><span style="font-family:Ver...<b><span style="font-family:Verdana;">Background: </span></b></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Scoliosis is among interventions with high postoperative com</span><span><span style="font-family:Verdana;">plication rates due to the characteristics of the surgery, where blood los</span><span style="font-family:Verdana;"></span><span style="font-family:Verdana;">s,</span></span><span style="font-family:Verdana;"> transfusion and fluid requirements can be increased. A monocentric retrospective observational study was undertaken earlier to determine predictors of intraoperative and postoperative outcomes in surgical patients. In this initial cohort, there were patients who underwent scoliosis surgery, and a secondary </span><span style="font-family:Verdana;">analysis to describe outcomes in these patients was realized and presented</span> <span><span style="font-family:Verdana;">here. </span><b><span style="font-family:Verdana;">Objective:</span></b><span style="font-family:Verdana;"> To describe intraoperative and postoperative outcomes in</span></span><span style="font-family:Verdana;"> patients under 18 years old in scoliosis surgery included in the initial study and </span><span style="font-family:Verdana;">to propose improvement </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">implementation measures. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A sec</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ondary analysis of patients undergoing scoliosis surgery </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">from</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> 1 January 2014 to </span><span style="font-family:Verdana;">17 May 2017 was undertaken in our institution—Necker Enfants Malades</span> <span style="font-family:Verdana;">uni</span><span style="font-family:Verdana;">ver</span><span><span style="font-family:Verdana;">sity hospital. The study was approved by the Ethics Committee. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> There </span></span><span style="font-family:Verdana;">were 116 patients with a mean age of 147.5 ± 40.2 months. Twenty-eight pa</span><span style="font-family:Verdana;">tients </span><span style="font-family:Verdana;">(24.1%) presented intraoperative and/or postoperative complications. The most</span> <span style="font-family:Verdana;">common intraoperative complication was hemorrhagic shock in 3 patients </span><span style="font-family:Verdana;">(2.6%). The most common postoperative organ failure was neuro</span><span style="font-family:Verdana;">logic in seven patients (6%), respiratory in 3 patients (2.6%), car</span><span style="font-family:Verdana;">dio-circulatory in 2 patients (1.7%) and renal failure in </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">1</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> patient (0.9%). The most common postoperative infection was surgical wound sepsis in 8 patients (6.9%), urinary sepsis in </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">3</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> patients (2.6%), and abdominal sepsis and septicemia in </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">2</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> patients (1.7%). </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">12</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> patients (10.3%) had reoperations. Fif</span><span style="font-family:Verdana;">ty-six patients (48.3%) had </span><span><span style="font-family:Verdana;">intraoperative transfusion. There was no in-hospital mortality. </span><b><span style="font-family:Verdana;">Conclusion:</span></b></span><span style="font-family:Verdana;"> The </span><span style="font-family:Verdana;">portion of patients with intraoperative and or postoperative complications </span><span style="font-family:Verdana;">was 24.1%, integrating goal-directed therapies in this surgical setting could improve postoperative outcomes.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monocl...Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.展开更多
Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Not...Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative res...Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.展开更多
Since the outbreak of COVID-19,tourists have been increasingly concerned over various risks of international travel,while knowledge of the pandemic appears to vary significantly.In addition,as travel restrictions cont...Since the outbreak of COVID-19,tourists have been increasingly concerned over various risks of international travel,while knowledge of the pandemic appears to vary significantly.In addition,as travel restrictions continue to impact adversely on international tourism,tourism efforts should be placed more on the domestic markets.Via structural equation modeling,this study unearthed different risk factors impacting Korean travelers’choices of alternative local destinations in the post-pandemic era.In addition,this study extended the goal-directed behavior framework with the acquisition of perceived risk and knowledge of COVID-19,which was proven to hold a sig-nificantly superior explanatory power of tourists’decisions of local alternatives over foreign countries during the COVID-19 pandemic.Furthermore,desire was found to play an imminent mediating role in the conceptual mod-el,maximizing the impact of perceived risk on travel intentions.Henceforth,this research offers meaningful the-oretical implication as thefirst empirical study to deepen the goal-directed behaviour framework with perceived risk and knowledge in the context of post-COVID-19 era.It also serves as insightful knowledge for Korean tour-ism authorities and practitioners to understand local tourists’decision-making processes and tailor effective recovery strategy for domestic tourism.展开更多
<span style="font-family:Verdana;"> <strong>Background: </strong></span><span><span><span style="font-family:;" "=""><span style=&qu...<span style="font-family:Verdana;"> <strong>Background: </strong></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">Femoral and pelvic osteotomies are potential hemorrhagic interventions where transfusion requirements can be necessary. </span><b><span style="font-family:Verdana;">Objective: </span></b><span style="font-family:Verdana;">We undertook a secondary analysis of patients who underwent femoral and pelvic osteotomy in the initial cohort. The objective of this secondary analysis was to describe intraoperative and postoperative outcomes and to describe intraoperative management in these patients in terms of blood product management and fluid and hemodynamic therapy with the aim of implementing optimization management protocols for postoperative outcome improvement. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A secondary analysis of patients who underwent femoral and pelvic osteotomy surgery was included in the initial retrospective study. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">There were eighteen patients with a mean age of 104 ± 47.1 months. Four (22.2%) patients had intraoperative and/or postoperative complications. One patient (5.6%) had an intraoperative hemorrhagic shock, two patients (11.1%) had postoperative neurologic failure, and one patient (5.6%) had postoperative wound sepsis. The transfusion rate was 50% in nine patients. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Femoral and pelvic osteotomies are interventions where blood, transfusion and fluid requirements can be increased;thus, this implies the necessity of a global patient blood management protocol with point-of-care tests and fluid- and hemodynamic-guided protocols with validated tools in children for intraoperative and postoperative outcome optimization.</span></span></span></span>展开更多
Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safet...Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.展开更多
BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential thera...BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.展开更多
Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id...Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.展开更多
Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helico...Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.展开更多
In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients...In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.展开更多
BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effec...BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effects of hormone replacement therapy in menopausal female patients.METHODS A total of 152 menopausal female patients admitted to the Gynecology Department of the Ganzhou Maternal and Child Health Hospital between January 2021 and December 2023 were divided into the observation group(n=76,conventional treatment+hormone replacement therapy)and the control group(n=76,conventional treatment only)via random casting.The improvement observed in the following items were compared between the groups:Kupperman menopausal index(KMI),emotional state[The Positive and Negative Affect Scale(PANAS)],sleep quality[Self-Rating Scale of Sleep(SRSS)],treatment effectiveness,and treatment safety.RESULTS The modified KMI and SRSS scores of the observation group were lower than those of the control group after three rounds of treatment.The improvement in the PANAS score observed in the observation group was greater than that observed in the control group(P<0.05).The total treatment effectivity rate in the observation group was higher than that in the control group(86.84%vs 96.05%,χ2=4.121,P=0.042).The incidence rate of adverse reactions in the two groups was comparable(6.58%vs 9.21%,χ2=0.361,P=0.547).CONCLUSION Hormone replacement therapy effectively improved the clinical symptoms,actively channeled negative emotions,and improved the quality of sleep in menopausal patients,indicating its effectiveness and safety.展开更多
Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM ...Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.展开更多
文摘BACKGROUND Intraoperative fluid management is an important aspect of anesthesia mana-gement in gastrointestinal surgery.Intraoperative goal-directed fluid therapy(GDFT)is a method for optimizing a patient's physiological state by monitoring and regulating fluid input in real-time.AIM To evaluate the efficacy of intraoperative GDFT in patients under anesthesia for gastrointestinal surgery.METHODS This study utilized a retrospective comparative study design and included 60 patients who underwent gastrointestinal surgery at a hospital.The experimental group(GDFT group)and the control group,each comprising 30 patients,received intraoperative GDFT and traditional fluid management strategies,respectively.The effect of GDFT was evaluated by comparing postoperative recovery,com-plication rates,hospitalization time,and other indicators between the two patient groups.RESULTS Intraoperative blood loss in the experimental and control groups was 296.64±46.71 mL and 470.05±73.26 mL(P<0.001),and urine volume was 415.13±96.72 mL and 239.15±94.69 mL(P<0.001),respectively.The postoperative recovery time was 5.44±1.1 days for the experimental group compared to 7.59±1.45 days(P<0.001)for the control group.Hospitalization time for the experimental group was 10.87±2.36 days vs 13.65±3 days for the control group(P<0.001).The visual analogue scale scores of the experimental and control groups at 24 h and 48 h INTRODUCTION Gastrointestinal surgery is one of the most common procedures in the field of general surgery[1],involving the stomach,intestines,liver,pancreas,spleen,and other internal abdominal organs[2,3].With advancements in surgical technology and anesthesia methods,the safety and success rates of surgery have significantly improved[4,5].However,intraop-erative fluid management remains a critical challenge[6].Traditional fluid management strategies often rely on experience and basic physiological parameters,which may lead to excessive or insufficient fluid input,thereby affecting postoperative recovery and complication rates.Intraoperative goal-directed fluid therapy(GDFT)is an emerging fluid management strategy that dynamically adjusts fluid input volume by monitoring the patient's hemodynamic parameters in real-time to optimize the patient's physiological state[7,8].GDFT has shown superiority in many surgical fields;however,its application in gastrointestinal surgery requires further research and verification[9,10].The application of intraoperative GDFT in clinical settings has gradually increased in recent years[11,12].Studies have demonstrated that GDFT can optimize tissue perfusion and oxygenation by precisely controlling fluid input and reducing the occurrence of postoperative complications[13,14].For example,in cardiac and major vascular surgeries,GDFT significantly reduced the incidence of postoperative acute kidney injury and cardiovascular events[15,16].Similarly,in abdominal surgery,GDFT effectively reduced postoperative infections and expedited recovery[17].However,studies on the utilization of GDFT in gastrointestinal surgery are relatively limited and they are confounded by contradictory findings[18].Traditional fluid management strategies typically rely on estimating fluid input volume based on the patient's weight,preoperative status,and basic physiological parameters[19].However,this method lacks real-time dynamic adjustment,which may result in either insufficient or excessive fluid input,consequently affecting postoperative recovery.Insufficient fluid input can lead to hypovolemia and inadequate tissue perfusion,whereas excessive fluid input can cause tissue edema and postoperative complications,such as pulmonary edema and heart failure.GDFT involves dynamically adjusting fluid input volume by monitoring the patient's hemodynamic parameters in real-time,such as cardiac output,pulse pressure variability,and central venous pressure.Commonly used monitoring equipment include esophageal Doppler and pulse wave profile analyzers[20].These devices provide real-time hemo-dynamic data to assist anesthesiologists in tailoring fluid therapy to a patient's specific condition.Firstly,the patient's volume responsiveness is assessed by preloading fluid;secondly,fluid input volume is dynamically adjusted based on real-time monitoring data;finally,vasoactive and inotropic drugs are administered in combination to further optimize the patient’s hemodynamic status.Through personalized fluid management,GDFT can more accurately maintain intraop-erative hemodynamic stability and reduce complications[21].Gastrointestinal surgery involves procedures on multiple organs,often requiring prolonged operative times and extensive tissue trauma,which presents challenges for intraop-erative fluid management.Surgical procedures can lead to significant bleeding and fluid loss,requiring prompt and effective fluid replenishment.In addition,the slow recovery of gastrointestinal function after surgery and susceptibility to complications such as intestinal obstruction and delayed gastric emptying elevate the necessity for postoperative fluid management.
基金supported by the National High Level Hospital Clinical Research Funding(2022-PUMCHB-119).
文摘Objective Although goal-directed fluid therapy(GDFT)has been proven to be effective in reducing the incidence of postoperative complications,the underlying mechanisms remain unknown.The aim of this study was to examine the mediating role of intraoperative hemodynamic lability in the association between GDFT and the incidence of postoperative complications.We further tested the role of this mediation effect using mean arterial pressure,a hemodynamic indicator.Methods This secondary analysis used the dataset of a completed nonrandomized controlled study to investigate the effect of GDFT on the incidence of postoperative complications in patients undergoing posterior spine arthrodesis.We used a simple mediation model to test whether there was a mediation effect of average real variability between the association of GDFT and postoperative complications.We conducted mediation analysis using the mediation package in R(version 3.1.2),based on 5,000 bootstrapped samples,adjusting for covariates.Results Among the 300 patients in the study,40%(120/300)developed postoperative complications within 30 days.GDFT was associated with fewer 30-day postoperative complications after adjustment for confounders(odds ratio:0.460,95%CI:0.278,0.761;P=0.003).The total effect of GDFT on postoperative complications was-0.18(95%CI:-0.28,-0.07;P<0.01).The average causal mediation effect was-0.08(95%CI:-0.15,-0.04;P<0.01).The average direct effect was-0.09(95%CI:-0.20,0.03;P=0.17).The proportion mediated was 49.9%(95%CI:18.3%,140.0%).Conclusions The intraoperative blood pressure lability mediates the relationship between GDFT and the incidence of postoperative complications.Future research is needed to clarify whether actively reducing intraoperative blood pressure lability can prevent postoperative complications.
基金supported by the Department of Anesthesiologyand Pain MedicineUniversity of California Davis Health System+1 种基金SacramentoCA 95617 and NIH Grant(#UL1 TR000002)
文摘Intraoperative fluid management is pivotal to the outcome and success of surgery, especially in high-risk proce- dures. Empirical formula and invasive static monitoring have been traditionally used to guide intraoperative fluid management and assess volume status. With the awareness of the potential complications of invasive procedures and the poor reliability of these methods as indicators of volume status, we present a case scenario of a patient who underwent major abdominal surgery as an example to discuss how the use of minimally invasive dynamic monitoring may guide intraoperative fluid therapy.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金Supported by Shanghai Hospital Development Center Foundation,No.SHDC2022CRS033.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.
文摘<b><span style="font-family:Verdana;">Background: </span></b></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Scoliosis is among interventions with high postoperative com</span><span><span style="font-family:Verdana;">plication rates due to the characteristics of the surgery, where blood los</span><span style="font-family:Verdana;"></span><span style="font-family:Verdana;">s,</span></span><span style="font-family:Verdana;"> transfusion and fluid requirements can be increased. A monocentric retrospective observational study was undertaken earlier to determine predictors of intraoperative and postoperative outcomes in surgical patients. In this initial cohort, there were patients who underwent scoliosis surgery, and a secondary </span><span style="font-family:Verdana;">analysis to describe outcomes in these patients was realized and presented</span> <span><span style="font-family:Verdana;">here. </span><b><span style="font-family:Verdana;">Objective:</span></b><span style="font-family:Verdana;"> To describe intraoperative and postoperative outcomes in</span></span><span style="font-family:Verdana;"> patients under 18 years old in scoliosis surgery included in the initial study and </span><span style="font-family:Verdana;">to propose improvement </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">implementation measures. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A sec</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ondary analysis of patients undergoing scoliosis surgery </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">from</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> 1 January 2014 to </span><span style="font-family:Verdana;">17 May 2017 was undertaken in our institution—Necker Enfants Malades</span> <span style="font-family:Verdana;">uni</span><span style="font-family:Verdana;">ver</span><span><span style="font-family:Verdana;">sity hospital. The study was approved by the Ethics Committee. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> There </span></span><span style="font-family:Verdana;">were 116 patients with a mean age of 147.5 ± 40.2 months. Twenty-eight pa</span><span style="font-family:Verdana;">tients </span><span style="font-family:Verdana;">(24.1%) presented intraoperative and/or postoperative complications. The most</span> <span style="font-family:Verdana;">common intraoperative complication was hemorrhagic shock in 3 patients </span><span style="font-family:Verdana;">(2.6%). The most common postoperative organ failure was neuro</span><span style="font-family:Verdana;">logic in seven patients (6%), respiratory in 3 patients (2.6%), car</span><span style="font-family:Verdana;">dio-circulatory in 2 patients (1.7%) and renal failure in </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">1</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> patient (0.9%). The most common postoperative infection was surgical wound sepsis in 8 patients (6.9%), urinary sepsis in </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">3</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> patients (2.6%), and abdominal sepsis and septicemia in </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">2</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> patients (1.7%). </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">12</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> patients (10.3%) had reoperations. Fif</span><span style="font-family:Verdana;">ty-six patients (48.3%) had </span><span><span style="font-family:Verdana;">intraoperative transfusion. There was no in-hospital mortality. </span><b><span style="font-family:Verdana;">Conclusion:</span></b></span><span style="font-family:Verdana;"> The </span><span style="font-family:Verdana;">portion of patients with intraoperative and or postoperative complications </span><span style="font-family:Verdana;">was 24.1%, integrating goal-directed therapies in this surgical setting could improve postoperative outcomes.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.
文摘Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
基金the Specific Research Project of Guangxi for Research Bases and Talents,No.GuiKe AD22035057the National Natural Science Foundation of China,No.82060510 and No.82260569.
文摘Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.
基金supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea(NRF-2020S1A5A2A01046684).
文摘Since the outbreak of COVID-19,tourists have been increasingly concerned over various risks of international travel,while knowledge of the pandemic appears to vary significantly.In addition,as travel restrictions continue to impact adversely on international tourism,tourism efforts should be placed more on the domestic markets.Via structural equation modeling,this study unearthed different risk factors impacting Korean travelers’choices of alternative local destinations in the post-pandemic era.In addition,this study extended the goal-directed behavior framework with the acquisition of perceived risk and knowledge of COVID-19,which was proven to hold a sig-nificantly superior explanatory power of tourists’decisions of local alternatives over foreign countries during the COVID-19 pandemic.Furthermore,desire was found to play an imminent mediating role in the conceptual mod-el,maximizing the impact of perceived risk on travel intentions.Henceforth,this research offers meaningful the-oretical implication as thefirst empirical study to deepen the goal-directed behaviour framework with perceived risk and knowledge in the context of post-COVID-19 era.It also serves as insightful knowledge for Korean tour-ism authorities and practitioners to understand local tourists’decision-making processes and tailor effective recovery strategy for domestic tourism.
文摘<span style="font-family:Verdana;"> <strong>Background: </strong></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">Femoral and pelvic osteotomies are potential hemorrhagic interventions where transfusion requirements can be necessary. </span><b><span style="font-family:Verdana;">Objective: </span></b><span style="font-family:Verdana;">We undertook a secondary analysis of patients who underwent femoral and pelvic osteotomy in the initial cohort. The objective of this secondary analysis was to describe intraoperative and postoperative outcomes and to describe intraoperative management in these patients in terms of blood product management and fluid and hemodynamic therapy with the aim of implementing optimization management protocols for postoperative outcome improvement. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A secondary analysis of patients who underwent femoral and pelvic osteotomy surgery was included in the initial retrospective study. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">There were eighteen patients with a mean age of 104 ± 47.1 months. Four (22.2%) patients had intraoperative and/or postoperative complications. One patient (5.6%) had an intraoperative hemorrhagic shock, two patients (11.1%) had postoperative neurologic failure, and one patient (5.6%) had postoperative wound sepsis. The transfusion rate was 50% in nine patients. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Femoral and pelvic osteotomies are interventions where blood, transfusion and fluid requirements can be increased;thus, this implies the necessity of a global patient blood management protocol with point-of-care tests and fluid- and hemodynamic-guided protocols with validated tools in children for intraoperative and postoperative outcome optimization.</span></span></span></span>
基金The work was financially supported by the National Natural Science Foundation of China(No.52173135,22207024)Jiangsu Specially Appointed Professorship,Leading Talents of Innovation and Entrepreneurship of Gusu(ZXL2022496)the Suzhou Science and Technology Program(SKY2022039).
文摘Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.
文摘BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.
基金the Huzhou Science and Technology Bureau,Zhejiang Province,China(2020GZ41).
文摘Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
文摘Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.
文摘In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.
文摘BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effects of hormone replacement therapy in menopausal female patients.METHODS A total of 152 menopausal female patients admitted to the Gynecology Department of the Ganzhou Maternal and Child Health Hospital between January 2021 and December 2023 were divided into the observation group(n=76,conventional treatment+hormone replacement therapy)and the control group(n=76,conventional treatment only)via random casting.The improvement observed in the following items were compared between the groups:Kupperman menopausal index(KMI),emotional state[The Positive and Negative Affect Scale(PANAS)],sleep quality[Self-Rating Scale of Sleep(SRSS)],treatment effectiveness,and treatment safety.RESULTS The modified KMI and SRSS scores of the observation group were lower than those of the control group after three rounds of treatment.The improvement in the PANAS score observed in the observation group was greater than that observed in the control group(P<0.05).The total treatment effectivity rate in the observation group was higher than that in the control group(86.84%vs 96.05%,χ2=4.121,P=0.042).The incidence rate of adverse reactions in the two groups was comparable(6.58%vs 9.21%,χ2=0.361,P=0.547).CONCLUSION Hormone replacement therapy effectively improved the clinical symptoms,actively channeled negative emotions,and improved the quality of sleep in menopausal patients,indicating its effectiveness and safety.
基金from CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-002)National Key Clinical Specialty Construction Project(ZK108000)+1 种基金National High-Level Hospital Clinical Research Funding(2022-PUMCH-B-024)National Natural Science Foundation of China,Joint Fund Project(U20A600).
文摘Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.