Background: Infertility affects 8% - 12% of couples globally, with approximately half of the cases reported in males. Oxidative stress is a common factor increased in the varicocele condition and particularly affects ...Background: Infertility affects 8% - 12% of couples globally, with approximately half of the cases reported in males. Oxidative stress is a common factor increased in the varicocele condition and particularly affects spermatozoa, due to their sensitivity to oxidative signals and testicular hypotrophy. The objective of this clinical trial is to study the effectiveness of Spermotrend in the improvement of sperm parameters in male infertility. Methods: A total of 170 males aged > 18 years with a diagnosis of infertility and varicocele were consecutively enrolled in a Phase II, open-label clinical trial. Spermotrend was administered 1 capsule (450 mg) orally every 8 hours for 6 months and was evaluated through semen analysis at 4 and 6 months of follow-up. Results: The trial results show a significant improvement following the administration of Spermotrend over 6 months in sperm concentration (44.1% at baseline vs. 64.1% at 6 months), sperm survival (28.2% with sperm survival ≥ 2 hours vs.56.5%), normalization of sperm morphology (31.2% vs. 72.9%). Varicocele condition decreased in all patients and, by the end of the study, 55.3% of patients had normal venous flow and dilation. Only 5.9% of the patients showed grade 2 varicocele at the end of the study, while 38.8% showed grade 1 varicocele, with no patients showing grade 3 varicocele. Regarding testicular hypotrophy, 90.6% of the patients completed the study with normalized testicular volume by recovering normal venous flow. Conclusion: A short-term course of Spermotrend may significantly improve sperm parameters associated with male infertility. Clinical Trial Registration: The clinical trial protocol was registered in the international clinical trial registry, ClinicalTrials.gov, with the code: NCT05222841 on 15/06/2021.展开更多
BACKGROUND Varicocele embolization,a minimally invasive treatment for symptomatic varicoceles,carries a rare risk of complications like ureteral obstruction and hydronephrosis.This case report documents such a case to...BACKGROUND Varicocele embolization,a minimally invasive treatment for symptomatic varicoceles,carries a rare risk of complications like ureteral obstruction and hydronephrosis.This case report documents such a case to raise awareness of these potential complications and showcase minimally invasive surgical management as a successful solution.CASE SUMMARY A 35-year-old male presented with flank pain and hematuria following varicocele embolization.Imaging confirmed left ureteral obstruction and hydronephrosis.Laparoscopic ureterolysis successfully removed the embolization coil and repaired the ureter,resolving the patient's symptoms.Follow-up at six months and two years showed sustained improvement.CONCLUSION Minimally invasive surgery offers an effective treatment option for rare complications like ureteral obstruction arising from varicocele embolization.展开更多
Introduction: Varicocele is one of the most frequent causes of infertility. There are several therapeutic modalities, namely surgery (open and laparoscopic) and conventional radiology. The aim of our study was to eval...Introduction: Varicocele is one of the most frequent causes of infertility. There are several therapeutic modalities, namely surgery (open and laparoscopic) and conventional radiology. The aim of our study was to evaluate the impact of a varicocele cure under local anaesthesia on spermogram quality. Material and Methods: We conducted a retrospective descriptive study from 1 January 2022 to 31 December 2023 in the urology department of the Hôpital Militaire de Ouakam (HMO). The parameters studied were age, reasons for consultation, time to urology consultation, grade of varicocele, Doppler ultrasound and spermogram data before treatment and 3 months after treatment. Treatment consisted of bilateral subinguinal varicocelectomy under local anaesthetic. Data were entered and analysed using Excel software version 2021. Results: We studied 41 patients. The mean age of the patients was 35.3 ± 6.9 years, with extremes of 22 and 50 years. Thirty-eight of our patients (88.37%) were married. The most frequent reason for consultation was primary infertility (72.09%). 28 patients (68.3%) had a bilateral varicocele on ultrasound. Varicocele was associated with bilateral testicular hypotrophy in 13 patients (31.7%) and unilateral left testicular hypotrophy in 11 patients (26.8%). All patients underwent subinguinal varicocelectomy under local anaesthetic. Mean follow-up was 4.5 months. A clear statistically significant improvement was noted in sperm motility and concentration in postoperative spermograms, with normalisation of the spermogram in 15 (36.5%) of patients. Conclusion: The impact of varicocele on sperm parameters has been clearly established. There are various therapeutic methods for curing varicocele, including varicocelectomy under local anaesthetic, which, in addition to its undeniable economic advantages, can significantly improve sperm parameters in patients with varicocele and prevent their deterioration over time.展开更多
Aim: To evaluate the treatment outcome of antegrade internal spermatic vein sclerotherapy in men with non-obstructive azoospermia or severe oligoteratoasthenospermia (OTA) as a result of varicocele. Methods: Betwe...Aim: To evaluate the treatment outcome of antegrade internal spermatic vein sclerotherapy in men with non-obstructive azoospermia or severe oligoteratoasthenospermia (OTA) as a result of varicocele. Methods: Between September 1995 and January 2004, 47 patients (mean age 33.8 ± 6.3 years) underwent antegrade internal spermatic vein sclerotherapy for the treatment of varicocele with azoospermia (14 patients) or severe OTA (33 patients). Testicular core biopsy was also performed in complete azoospermic patients who provided informed consent. The outcome was assessed in terms of improvement in semen parameters and conception rate. Results: Forty-two (89.4%) of 47 patients had bilateral varicocele. Serum follicle stimulating hormone (FSH) did not differ between patients with azoospermia and severe OTA. After the follow-up of 24.8 ± 9.2 months, significant improvement was noted in mean sperm concentration, motility and morphology in 35 patients (74.5%). Comparison between groups during the follow-up revealed significantly higher values of sperm concentration, motility and normal morphology in the severe OTA group. Pregnancy was achieved in 14 cases (29.8%). Testicular histopathology of the azoospermic patients with postoperative induction of spermatogenesis revealed maturation arrest at spermatid stage, Sertoli-cell-only (SCO) with focal spermatogenesis or hypospermatogenesis. None of the patients with pure SCO pattern or maturation arrest at spermatocyte stage achieved spermatogenesis after the treatment. Preoperative serum FSH levels didn't relate to treatment outcome. Conclusion: Antegrade internal spermatic vein sclerotherapy is an easy and effective treatment for symptomatic varicocele. It can significantly reverse testicular dysfunction and improve spermatogenesis in men with severe OTA, as well as induce sperm production in men with azoospermia, improving pregnancy rates in subfertile couples.展开更多
Antegrade scrotal sclerotherapy is a simple and easy technique for the treatment of varicocele. The success rate varies between 87% and 95%. The initial reflux grade and the number of collateral vessels of the spermat...Antegrade scrotal sclerotherapy is a simple and easy technique for the treatment of varicocele. The success rate varies between 87% and 95%. The initial reflux grade and the number of collateral vessels of the spermatic vein are the most important factors to predict the outcome of the technique. The postoperative complication rate is about 7% and the common ones are scrotal hematoma and epididymo-orchitis of slight severity. Testicular athrophy is a rare event (0.6%). This technique offers a considerable cost reduction compared to other therapeutic options currently available for varicocele.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
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
The aim of this study was to verify the role of antegrade scrotal sclerotherapy for the treatment of varicoceles in infertile men with severe oligo-astheno-teratozoospermia (OAT). The 59 patients with severe OAT in ...The aim of this study was to verify the role of antegrade scrotal sclerotherapy for the treatment of varicoceles in infertile men with severe oligo-astheno-teratozoospermia (OAT). The 59 patients with severe OAT in this study underwent antegrade scrotal sclerotherapy for the treatment of varicoceles. The outcome was assessed in terms of improvement in semen parameters and spontaneous conception rate. Semen parameters and reproductive hormones were evaluated before antegrade sclerotherapy (AS) and 6 months after AS. After an average follow-up time of 34.8_+3.2 months, significant improvement was noted in the mean sperm concentration, motility and morphology in 36 patients (61%). Spontaneous pregnancy occurred in nine couples (15%). Six months after treatment, inhibin B levels were significantly higher (P〉0.04), whereas follicle-stimulating hormone (FSH) levels were significantly lower (P〈0.001) than before treatment. Antegrade internal spermatic vein sclerotherapy can significantly improve seminal parameters and hormonal parameters in men with severe OAT and may even result in spontaneous pregnancy in couples who would otherwise be candidates for intracytoplasmic sperm injection (ICSI).展开更多
Objective:The clinical grading system for varicoceles is subjective and dependent on clinician experience.Color Doppler ultrasound(US)has not been standardized in the diagnosis of varicoceles.We aimed to determine if ...Objective:The clinical grading system for varicoceles is subjective and dependent on clinician experience.Color Doppler ultrasound(US)has not been standardized in the diagnosis of varicoceles.We aimed to determine if US measurement of varicocele could be predictive of World Health Organization(WHO)varicocele grade.Methods:Men who presented for either scrotal pain or infertility to a tertiary men’s health clinic underwent physical examination,and varicoceles were graded following WHO criteria(0Zsubclinical,1,2,3).US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver.Receiver operator characteristic curve analysis was used to determine if resting diameter,diameter during Valsalva,or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade.Threshold values for diameter were determined from these receiver operator characteristic curves.Results:A total of 102 men(50 with clinical varicocele and 52 with subclinical varicocele)were included.Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles(area under the curve[AUC]Z0.67)with a diameter threshold of 3.0 mm(sensitivity 79%,specificity 42%).Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2(AUCZ0.57)with diameter threshold of 5.7 mm(sensitivity 71%,specificity 33%).For differentiating between Grades 2 and 3,diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm(sensitivity 71%,specificity 58%).Conclusion:Our results corroborate other studies that have shown a weak correlation between US and clinical grading.The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele.A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making.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
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
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 With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concent...BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.展开更多
文摘Background: Infertility affects 8% - 12% of couples globally, with approximately half of the cases reported in males. Oxidative stress is a common factor increased in the varicocele condition and particularly affects spermatozoa, due to their sensitivity to oxidative signals and testicular hypotrophy. The objective of this clinical trial is to study the effectiveness of Spermotrend in the improvement of sperm parameters in male infertility. Methods: A total of 170 males aged > 18 years with a diagnosis of infertility and varicocele were consecutively enrolled in a Phase II, open-label clinical trial. Spermotrend was administered 1 capsule (450 mg) orally every 8 hours for 6 months and was evaluated through semen analysis at 4 and 6 months of follow-up. Results: The trial results show a significant improvement following the administration of Spermotrend over 6 months in sperm concentration (44.1% at baseline vs. 64.1% at 6 months), sperm survival (28.2% with sperm survival ≥ 2 hours vs.56.5%), normalization of sperm morphology (31.2% vs. 72.9%). Varicocele condition decreased in all patients and, by the end of the study, 55.3% of patients had normal venous flow and dilation. Only 5.9% of the patients showed grade 2 varicocele at the end of the study, while 38.8% showed grade 1 varicocele, with no patients showing grade 3 varicocele. Regarding testicular hypotrophy, 90.6% of the patients completed the study with normalized testicular volume by recovering normal venous flow. Conclusion: A short-term course of Spermotrend may significantly improve sperm parameters associated with male infertility. Clinical Trial Registration: The clinical trial protocol was registered in the international clinical trial registry, ClinicalTrials.gov, with the code: NCT05222841 on 15/06/2021.
文摘BACKGROUND Varicocele embolization,a minimally invasive treatment for symptomatic varicoceles,carries a rare risk of complications like ureteral obstruction and hydronephrosis.This case report documents such a case to raise awareness of these potential complications and showcase minimally invasive surgical management as a successful solution.CASE SUMMARY A 35-year-old male presented with flank pain and hematuria following varicocele embolization.Imaging confirmed left ureteral obstruction and hydronephrosis.Laparoscopic ureterolysis successfully removed the embolization coil and repaired the ureter,resolving the patient's symptoms.Follow-up at six months and two years showed sustained improvement.CONCLUSION Minimally invasive surgery offers an effective treatment option for rare complications like ureteral obstruction arising from varicocele embolization.
文摘Introduction: Varicocele is one of the most frequent causes of infertility. There are several therapeutic modalities, namely surgery (open and laparoscopic) and conventional radiology. The aim of our study was to evaluate the impact of a varicocele cure under local anaesthesia on spermogram quality. Material and Methods: We conducted a retrospective descriptive study from 1 January 2022 to 31 December 2023 in the urology department of the Hôpital Militaire de Ouakam (HMO). The parameters studied were age, reasons for consultation, time to urology consultation, grade of varicocele, Doppler ultrasound and spermogram data before treatment and 3 months after treatment. Treatment consisted of bilateral subinguinal varicocelectomy under local anaesthetic. Data were entered and analysed using Excel software version 2021. Results: We studied 41 patients. The mean age of the patients was 35.3 ± 6.9 years, with extremes of 22 and 50 years. Thirty-eight of our patients (88.37%) were married. The most frequent reason for consultation was primary infertility (72.09%). 28 patients (68.3%) had a bilateral varicocele on ultrasound. Varicocele was associated with bilateral testicular hypotrophy in 13 patients (31.7%) and unilateral left testicular hypotrophy in 11 patients (26.8%). All patients underwent subinguinal varicocelectomy under local anaesthetic. Mean follow-up was 4.5 months. A clear statistically significant improvement was noted in sperm motility and concentration in postoperative spermograms, with normalisation of the spermogram in 15 (36.5%) of patients. Conclusion: The impact of varicocele on sperm parameters has been clearly established. There are various therapeutic methods for curing varicocele, including varicocelectomy under local anaesthetic, which, in addition to its undeniable economic advantages, can significantly improve sperm parameters in patients with varicocele and prevent their deterioration over time.
文摘Aim: To evaluate the treatment outcome of antegrade internal spermatic vein sclerotherapy in men with non-obstructive azoospermia or severe oligoteratoasthenospermia (OTA) as a result of varicocele. Methods: Between September 1995 and January 2004, 47 patients (mean age 33.8 ± 6.3 years) underwent antegrade internal spermatic vein sclerotherapy for the treatment of varicocele with azoospermia (14 patients) or severe OTA (33 patients). Testicular core biopsy was also performed in complete azoospermic patients who provided informed consent. The outcome was assessed in terms of improvement in semen parameters and conception rate. Results: Forty-two (89.4%) of 47 patients had bilateral varicocele. Serum follicle stimulating hormone (FSH) did not differ between patients with azoospermia and severe OTA. After the follow-up of 24.8 ± 9.2 months, significant improvement was noted in mean sperm concentration, motility and morphology in 35 patients (74.5%). Comparison between groups during the follow-up revealed significantly higher values of sperm concentration, motility and normal morphology in the severe OTA group. Pregnancy was achieved in 14 cases (29.8%). Testicular histopathology of the azoospermic patients with postoperative induction of spermatogenesis revealed maturation arrest at spermatid stage, Sertoli-cell-only (SCO) with focal spermatogenesis or hypospermatogenesis. None of the patients with pure SCO pattern or maturation arrest at spermatocyte stage achieved spermatogenesis after the treatment. Preoperative serum FSH levels didn't relate to treatment outcome. Conclusion: Antegrade internal spermatic vein sclerotherapy is an easy and effective treatment for symptomatic varicocele. It can significantly reverse testicular dysfunction and improve spermatogenesis in men with severe OTA, as well as induce sperm production in men with azoospermia, improving pregnancy rates in subfertile couples.
文摘Antegrade scrotal sclerotherapy is a simple and easy technique for the treatment of varicocele. The success rate varies between 87% and 95%. The initial reflux grade and the number of collateral vessels of the spermatic vein are the most important factors to predict the outcome of the technique. The postoperative complication rate is about 7% and the common ones are scrotal hematoma and epididymo-orchitis of slight severity. Testicular athrophy is a rare event (0.6%). This technique offers a considerable cost reduction compared to other therapeutic options currently available for varicocele.
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The aim of this study was to verify the role of antegrade scrotal sclerotherapy for the treatment of varicoceles in infertile men with severe oligo-astheno-teratozoospermia (OAT). The 59 patients with severe OAT in this study underwent antegrade scrotal sclerotherapy for the treatment of varicoceles. The outcome was assessed in terms of improvement in semen parameters and spontaneous conception rate. Semen parameters and reproductive hormones were evaluated before antegrade sclerotherapy (AS) and 6 months after AS. After an average follow-up time of 34.8_+3.2 months, significant improvement was noted in the mean sperm concentration, motility and morphology in 36 patients (61%). Spontaneous pregnancy occurred in nine couples (15%). Six months after treatment, inhibin B levels were significantly higher (P〉0.04), whereas follicle-stimulating hormone (FSH) levels were significantly lower (P〈0.001) than before treatment. Antegrade internal spermatic vein sclerotherapy can significantly improve seminal parameters and hormonal parameters in men with severe OAT and may even result in spontaneous pregnancy in couples who would otherwise be candidates for intracytoplasmic sperm injection (ICSI).
文摘Objective:The clinical grading system for varicoceles is subjective and dependent on clinician experience.Color Doppler ultrasound(US)has not been standardized in the diagnosis of varicoceles.We aimed to determine if US measurement of varicocele could be predictive of World Health Organization(WHO)varicocele grade.Methods:Men who presented for either scrotal pain or infertility to a tertiary men’s health clinic underwent physical examination,and varicoceles were graded following WHO criteria(0Zsubclinical,1,2,3).US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver.Receiver operator characteristic curve analysis was used to determine if resting diameter,diameter during Valsalva,or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade.Threshold values for diameter were determined from these receiver operator characteristic curves.Results:A total of 102 men(50 with clinical varicocele and 52 with subclinical varicocele)were included.Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles(area under the curve[AUC]Z0.67)with a diameter threshold of 3.0 mm(sensitivity 79%,specificity 42%).Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2(AUCZ0.57)with diameter threshold of 5.7 mm(sensitivity 71%,specificity 33%).For differentiating between Grades 2 and 3,diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm(sensitivity 71%,specificity 58%).Conclusion:Our results corroborate other studies that have shown a weak correlation between US and clinical grading.The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele.A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making.
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 With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.