Safety and efficacy of transpapillary bridged bilateral side-by-side stenting for unresectable malignant hilar biliary obstruction

To the Editor:Biliary drainage is most frequently performed among endoscopic procedures using pancreatobiliary endoscopy.A large-diameter metallic stent can significantly extend the patency period rather than a plastic stent for extrahepatic biliary stricture.;However,the optimal drainage for the hilar biliary obstruction is still controversial.

Safety and efficacy of trimodality therapy in patients undergoing extrapleural pneumonectomy

Malignant pleural mesothelioma （MPM） is a rare but rapidly deadly disease （1）. Macroscopic complete resection （MCR） is the goal of surgery （2）. MCR seems to have the most significant impact on survival in patients undergoing multimodality treatment for MPM. The role of surgical resection in the management of MPM remains controversial. The selection criterion to perform either extrapleural pneumonectomy （EPP） or extended/radical pleurectomy/ decortication （PD） rely not only on the cardio-pulmonary status of the patient, tumor stage and intraoperative findings but is strongly dependent also on surgeons＇ decision and philosophy. This is reflected by a recent survey of opinions and beliefs among 802 thoracic surgeons, in which EPP was believed to be more effective than PD （3）. Nonetheless, either surgery might achieve MCR.

Safety and efficacy of the SeparGateTM balloon-guiding catheter in neurointerventional surgery:A prospective,multicenter,single-arm clinical trial

Objective:To evaluate the safety and efficacy of the SeparGateballoon-guiding catheter(BGC)for blocking flow and delivering devices in neurointerventional surgery.Method:This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy.The primary endpoint was immediate procedural success rate in flow arrest,device delivery,and withdrawal.The efficacy endpoints were intraoperative product performance,including rigidity,smoothness,fracture resistance of the catheter wall,catheter push performance,compatibility and radiopaque display,integrity,adhesion thrombus after withdrawal and balloon rupture.The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration.Result:A total of 129 patients were included;of them,128 were analyzed in the full analysis set(FAS)and per protocol set(PPS).Immediate procedural success was achieved in 97.7%of patients with FAS and PPS.The lower bound of the 95%confidence interval was 94.6%,higher than the preset efficacy margin of 94%.Device-related adverse events occurred in 2(1.6%)cases.One was mild adverse event of vasospasm,which resolved spontaneously.The other was serious adverse event of dissection aggravation,which was treated with stenting angioplasty.No device defects were observed.Conclusion:In neurointerventional surgery,the SeparGateBGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position.

Safety and efficacy of acute normovolemic hemodilution during liver surgery: a Meta-analysis

Objective The aim of this study was to evaluate the safety and efficacy of acute normovolemic hemodilution(ANH) during liver surgery.Methods Structured searches of the Pub Med,Chinese Biological Medicine Database,and Cochrane Library electronic databases were performed,followed by a meta-analysis of outcomes,including intraoperative blood transfusion(s),intraoperative bleeding,postoperative hematocrit(Hct) levels,postoperative prothrombin time(PT),and number of patients who underwent transfusions during liver surgery.Results In total,14 eligible studies were included in the meta-analysis,which revealed that ANH for liver resection was associated with a reduction in intraoperative blood transfusions [weighted mean difference(WMD)-1.99;95% confidence interval(CI)-2.82 to -1.16;P<0.00001].The ANH group experienced less intraoperative bleeding(WMD -72.81;95% CI -136.12 to -9.50;P<0.00001) and exhibited a lower postoperative Hct level(WMD -3.38;95% CI -7.14 to -0.67;P<0.00001) than the control group.Moreover,meta-analysis revealed that postoperative prothrombin time was not affected by ANH(WMD -0.02;95% CI -0.18 to -0.32;P=0.65).Finally,the number of patients requiring allogeneic transfusion was significantly smaller in the ANH group than in the control group(odds ratio 0.13;95% CI 0.09 to 0.18;P=0.24).Conclusion Results of the present meta-analysis indicated that ANH can reduce intraoperative bleeding and the need for blood transfusions.In addition,ANH did not negatively affect the coagulation system after surgery;therefore,ANH appears to be safe and effective during liver surgery.

Comparison of safety,efficacy,and long-term follow-up between“one-step”and“step-up”approaches for infected pancreatic necrosis

BACKGROUND Although the“Step-up”strategy is the primary surgical treatment for infected pancreatic necrosis,it is not suitable for all such patients.The“One-step”strategy represents a novel treatment,but the safety,efficacy,and long-term follow-up have not yet been compared between these two approaches.AIM To compare the safety,efficacy,and long-term follow-up of two surgical approaches to provide a reference for infected pancreatic necrosis treatment.METHODS This was a retrospective analysis of infectious pancreatic necrosis patients who underwent“One-step”or“Step-up”necrosectomy at Xuan Wu Hospital,Capital Medical University,from May 2014 to December 2020.The primary outcome was the composite endpoint of severe complications or death.Patients were followed up every 6 mo after discharge until death or June 30,2021.Statistical analysis was performed using SPSS 21.0 and GraphPad Prism 8.0,and statistical significance was set at P<0.05.RESULTS One-hundred-and-fifty-eight patients were enrolled,of whom 61 patients underwent“One-step”necrosectomy and 97 patients underwent“Step-up”necrosectomy.During the long-term follow-up period,40 patients in the“Onestep”group and 63 patients in the“Step-up”group survived.The time from disease onset to hospital admission(53.69±38.14 vs 32.20±20.75,P<0.001)and to initial surgical treatment was longer in the“Step-up”than in the“One-step”group(54.38±10.46 vs 76.58±17.03,P<0.001).Patients who underwent“Step up”necrosectomy had a longer hospitalization duration(65.41±28.14 vs 52.76±24.71,P=0.02),and more interventions(4.26±1.71 vs 3.18±1.39,P<0.001).Postoperative inflammatory indicator levels were significantly lower than preoperative levels in each group.Although the incisional hernia incidence was higher in the“One-step”group,no significant difference was found in the composite outcomes of severe complications or death,new-onset organ failure,postoperative complications,inflammatory indicators,long-term complications,quality of life,and medical costs between the groups(P>0.05).CONCLUSION Compared with the“Step-up”approach,the“One-step”approach is a safe and effective treatment method with better long-term quality of life and prognosis.It also provides an alternative surgical treatment strategy for patients with infected pancreatic necrosis.

Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients： A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China

Background：High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia,and a domestically developed pacemaker will help lower the burden.This study aimed to evaluate the safety and efficacy ofQinming8631 DR （Qinming Medical,Baoji,China）,the first domestically developed dual-chamber pacemaker of China,compared with a commercially available pacemaker Talos DR （Biotronik,Berlin,Germany） in Chinese patients.Methods：A prospective randomized trial was conducted at 14 centers in China.Participants were randomized into trial （Qinming8631 DR） and control （Talos DR） groups.Parameters of the pacing systems were collected immediately after device implantation and during follow-ups.The effective pacing rate at 6-month follow-up was recorded as the primary end point.Electrical properties,magnet response,single-and double-pole polarity conversion,rate response function,and adverse events of the pacing system were analyzed.The Cochran-Mantel-Haenszel Chi-square test,paired t-test,and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data.Results：A total of 225 patients with a diagnosis ofbradyarrhythmia and eligible for this study were randomly enrolled into the trial （n =113） and control （n =112） groups.They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity.Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set （81.4% vs.79.5%,P =0.712 and 95.4% vs.89.5%,P =0.143,respectively）.In both data sets,noninferiority of the trial group was above the predefined noninferiority limit（-9.5%）.Conclusions：This study established the noninferiority ofQinming8631 DR to Talos DR.The safety and efficacy ofQinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

A PROSPECTIVE STUDY TO EVALUATE THE SAFETY AND EFFICACY USING REMOVING BLOOD STASIS HERBALS FOR PATIENTS WITH INTRACRANIAL HEMORRHAGE OF HYPERACUTE STAGE AND RELATIVE FACTORS OF HEMATOMA ENLARGEMENT(A MULTICENTER PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO

The aim was to investigate whether using a removing blood stasis method in hyperacute intracranial hemorrhage stage can lead to hematoma enlargement and its clinical efficacy.A multicenter retrospective randomized double-blind placebo-controlled clinical study.We recruited patients aged 18 years or older and presenting at less than 6 h from symptom onset in 8 research centers.All the patients

A multi-center clinical observation on safety and efficacy of a plasma derived coagulator factor Ⅷ for treatment of patients with hemophilia A

Objective To evaluate the efficacy and safety of home-made plasma derived coagulation factorⅧin patients with hemophilia A.Methods Patients with congenital hemophilia A who met the inclusive and exclusive criteria were enrolled in the study after informed consent.

Complementary and Alternative Medicine Therapies for Chronic Pain

ABSTRACT Pain afflicts over 50 million people in the US, with 30.7% US adults suffering with chronic pain. Despite advances in therapies, many patients will continue to deal with ongoing symptoms that are not fully addressed by the best conventional medicine has to offer them. The patients frequently turn to therapies outside the usual purview of conventional medicine （herbs, acupuncture, meditation, etc.） called complementary and alternative medicine （CAM）. Academic and governmental groups are also starting to incorporate CAM recommendations into chronic pain management strategies. Thus, for any physician who care for patients with chronic pain, having some familiarity with these therapies--including risks and benefits--will be key to helping guide patients in making evidence-based, well informed decisions about whether or not to use such therapies. On the other hand, if a CAM therapy has evidence of both safety and efficacy then not making it available to a patient who is suffering does not meet the need of the patient. We summarize the current evidence of a wide variety of CAM modalities that have potential for helping patients with chronic pain in this article. The triad of chronic pain symptoms, ready access to information on the internet, and growing patient empowerment suggest that CAM therapies will remain a consistent part of the healthcare of patients dealing with chronic pain.

Intelligent tunable CAR-T cell therapy leads the new trend

Adoptive transfer of T cells engineered with chimeric antigen receptor(CAR)has been proved to have robust anti-tumor effects against hematological malignancies.However,problems about safety and efficacy,such as cytokine release syndrome(CRS),T cell exhaustion and antigen escape are still raised when patients are treated with CAR-T cells.Moreover,CAR-T therapy has limited applications in treating solid tumors,owing to inefficient infiltration and poor functional persistence of CAR-T cells and diverse immunosuppression in tumor microenvironment.In order to overcome these limitations and broad its applications,multiple controllable CAR-T technologies were exploited.In this article,we review the designs of intelligent controlled CAR-T technologies and the innovations that they bring about in recent years.

The biological effect of recombinant humanized collagen on damaged skin induced by UV-photoaging:An in vivo study

The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field,such as collagen or hyaluronic acid,etc.However,the biosafety and efficacy of these implants are still challenged.In this study,a skin damage animal model was prepared by UV-photoaging and recombinant humanized type Ⅲ collagen(rhCol Ⅲ)was applied as a bioactive material to implant in vivo to study its biological effect,comparing with saline and uncrosslinked hyaluronic acid(HA).Animal skin conditions were non-invasively and dynamically monitored during the 8 weeks experiment.Histological observation,specific gene expression and other molecular biological methods were applied by the end of the animal experiment.The results indicated that rhCol Ⅲ could alleviate the skin photoaging caused by UV radiation,including reduce the thickening of epidermis and dermis,increase the secretion of Collagen Ⅰ(Col Ⅰ)and Collagen Ⅲ(Col Ⅲ)and remodel of extracellular matrix(ECM).Although the cell-material interaction and mechanism need more investigation,the effect of rhCol Ⅲ on damaged skin was discussed from influence on cells,reconstruction of ECM,and stimulus of small biological molecules based on current results.In conclusion,our findings provided rigorous biosafety information of rhCol Ⅲ and approved its potential in skin repair and regeneration.Although enormous efforts still need to be made to achieve successful translation from bench to clinic,the recombinant humanized collagen showed superiorities from both safety and efficacy aspects.

A regulatory perspective on recombinant collagen-based medical devices

As a class of novel biomaterials manufactured by synthetic biology technologies,recombinant collagens are candidates for a variety of medical applications.In this article,a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition,translation,classification and technical review.Recombinant collagens are categorized as recombinant human collagen,recombinant humanized collagen and recombinant collagen-like protein,as differentiated by specific compositions and structures.Based on their intended uses and associated risks,recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China.The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations.Taken together,opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound,which highlights the essential role of regulatory science to provide new tools,standards,guidelines and methods to evaluate the safety and efficacy of medical products.

Translation of a spinal bone cement product from bench to bedside

Spinal acrylic bone cements(ABCs)are used clinically for percutaneous vertebroplasty(PVP)and kyphoplasty(PKP)to treat osteoporotic vertebral compression fractures.Product translation of spinal ABC products followed the design control processes including design verification and validation.The bench to bedside translation of the first Chinese spinal ABC product(Alliment®,namely Alliment Cement)approved by National Medical Products Administration of China was investigated and another commercial product served as the control(Osteopal®V,namely Osteopal V Cement).Results of non-clinical bench performance verification tests of compression,bending and monomer release showed that the newly marketed Alliment Cement is similar to the Osteopal V Cement with properties of both meeting the criteria specified by standards.The Alliment Cement demonstrated good biocompatibility during the 26 weeks’bone implantation test.Porcine cadaver validation tests further revealed that the Alliment Cement satisfied the needs for both PVP and PKP procedures.A post-approval,retrospective clinical investigation further demonstrated the safety and efficacy of the Alliment Cement,with a significant reduction of pain and the improved stability of the fractured vertebral bodies.A successful translation of biomaterial medical products needs close collaborations among academia,industry,healthcare professionals and regulatory agencies.

Regulatory perspectives of combination products

Combination products with a wide range of clinical applications represent a unique class of medical products that are composed of more than a singular medical device or drug/biological product.The product research and development,clinical translation as well as regulatory evaluation of combination products are complex and challenging.This review firstly introduced the origin,definition and designation of combination products.Key areas of systematic regulatory review on the safety and efficacy of device-led/supervised combination products were then presented.Preclinical and clinical evaluation of combination products was discussed.Lastly,the research prospect of regulatory science for combination products was described.New tools of computational modeling and simulation,novel technologies such as artificial intelligence,needs of developing new standards,evidence-based research methods,new approaches including the designation of innovative or breakthrough medical products have been developed and could be used to assess the safety,efficacy,quality and performance of combination products.Taken together,the fast development of combination products with great potentials in healthcare provides new opportunities for the advancement of regulatory review as well as regulatory science.