Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the admin...Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the administration of several consecutive standard therapies.Although antibiotic resistance reports describe alarming results,the outcome of therapeutic regimens does not seem to parallel this scenario in most cases,since a successful performance is often reached in more than 80%of cases.However,the phenomenon of increasing antibiotic resistance is being closely studied,and the results show controversial aspects even in the same geographic area.For the continents of Europe,America,Asia,Africa,and Oceania,minimal and maximal values of resistance to the main antibiotics(clarithromycin,amoxicillin,metronidazole,and levofloxacin)feature wide ranges in different countries.The real enigma is therefore linked to the several different therapeutic regimens,which show results that often do not parallel the in vitro findings even in the same areas.A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts.Moreover,not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome.The additional use of probiotics may help to reduce adverse events,but their therapeutic impact is doubtful.In conclusion,the"ideal therapy",paradoxically,appears to be a"utopia",despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H.pylori.The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide.On these bases,one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances.In this context,geography must be considered a relevant matter.展开更多
Helicobacter pylori(H.pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide.H.pylori treatment sti...Helicobacter pylori(H.pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide.H.pylori treatment still remains a challenge,since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance,mucosal drug concentration,patient compliance,side-effect profile and cost.While no new drug has been developed,current therapy still relies on different mixture of known antibiotics and anti-secretory agents.A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen.Bismuthcontaining quadruple treatment,sequential treatment or a non-bismuth quadruple treatment(concomitant) are also an alternative therapy.Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H.pylori after defeat of first-line therapy.The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies.Therefore,adding probiotic to the medications,developing anti-H.pylori photodynamic or phytomedicine therapy,and achieving a successful H.pylori vaccine may have the promising to present synergistic or additive consequence against H.pylori,because each of them exert different effects.展开更多
Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bl...Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bleeding ulcers recommend a continuous infusion of proton pump inhibitors (PPI). However, studies comparing intermittent dosing of PPI therapy show that this regimen achieves similar clinical benefits. If the clinical efficacy remains equivalent, intermittent dosing will be more cost-effective for patients and the health care system. Our research study aims to analyze the comparative effectiveness of intermittent versus continuous PPI therapy after endoscopic treatment in patients with UGIB, focusing on such endpoints as rebleeding risk at 3-and 7-day mortality rates. Methods: Resources searched included MEDLINE, EMBASE, PUBMED, and the Cochrane Central Register of Controlled Trials databases from January 2010 through December 2023 with the inclusion of meta-analysis, systematic review, review, or ACG guideline recommendations. Results of the analysis show how recommendations regarding high vs. low PPI regimen changed over time: from no difference in regimen in 2010 to recommending continuous regimen in 2012 to declaring insufficient evidence between choosing one regimen over another in 2013 to determine that both regimens were comparable to each other in 2014-2018 and finally to recommending both regimens in 2021. To conclude, our review shows that in patients with bleeding ulcers and high-risk endoscopic findings, intermittent PPI therapy is non-inferior to continuous PPI infusion for three days, seven days bleeding risk or mortality rates;however, it remains challenging to determine the most optimal intermittent regimen due to heterogeneity of RCTs included in meta-analyses, and further trials will need to be performed.展开更多
Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is o...Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment 展开更多
Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,nega...Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.展开更多
Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(i...Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database.Methods:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database.The entire course of real-world pancreatic cancer management was analyzed.Results:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this cohort.Serum carbohydrate antigen(CA)19-9 is one of the most common tumor markers.In the present study,2562 patients underwent first-line therapy.The median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 months.The major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS rates.Conclusion:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in China.Results revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported data.Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.展开更多
Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of ...Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.展开更多
Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known abou...Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with展开更多
BACKGROUND Highly active antiretroviral therapy (HAART) is provided free of charge to all human immunodeficiency virus (HIV) positive residents in Italy. As fixed dose coformulations (FDCs) are often more expensive in...BACKGROUND Highly active antiretroviral therapy (HAART) is provided free of charge to all human immunodeficiency virus (HIV) positive residents in Italy. As fixed dose coformulations (FDCs) are often more expensive in comparison to the same drugs administered separately in a multi-tablet regimen (MTR), we considered a costeffective strategy involving patients in the switch from their FDCs to corresponding MTRs including generic antiretrovirals. AIM To verify if this would affect the virological and immunological response in comparison to maintaining the FDC regimens. METHODS From January 2012 to December 2013, we assessed the eligibility of all the HIV-1 positive adults on stable HAART being treated at our hospital-based outpatient clinic in Treviso, Italy. Participants who accepted to switch from their FDC regimen to the corresponding MTR joined the MTR group, while those who maintained a FDC regimen joined the FDC group. Clinical data, including changes in HAART regimens, respective reasons why and adverse effects, were recorded at baseline and at follow-up visits occurring at weeks 24, 48 and 96. All participants were assessed for virological and immunological responses at baseline and at weeks 24, 48 and 96. RESULTS Two hundred and forty-three eligible HIV-1 adults on HAART were enrolled: 163 (67%) accepted to switch to a MTR, joining the MTR group, while 80 (33%) maintained their FDCs, joining the FDC group. In a parallel analysis, there were no significant differences in linear trend of distribution of HIV-RNA levels between the two groups and there were no significant odds in favour of a higher level of HIV-RNA in either group at any follow-up and on the overall three strata analysis. In a before-after analysis, both FDC and MTR groups presented no significant differences in distribution of HIV-RNA levels at either weeks 48 vs 24 and weeks 96 vs 24 cross tabulations. A steady increase of mean CD4 count was observed in the MTR group only, while in the FDC group we observed a slight decrease (-23 cells per m展开更多
In this work the effects of nutrients starvations on Chlorella vulgaris were investigated in different trophic regimens. For all the tested conditions, the cellular response to nutrient starvation and trophic regimen ...In this work the effects of nutrients starvations on Chlorella vulgaris were investigated in different trophic regimens. For all the tested conditions, the cellular response to nutrient starvation and trophic regimen was evaluated on specific growth rate, biomass and lipids productivity, lipids content and quality. These parameters are all crucial for microalgae biodiesel production, but in literature the lipids quality, in terms of polar and nonpolar lipids, is often neglected. Thus the typical high content of polar lipids, a class of molecules that negatively affects the biodiesel production process, of microalgae crude oil is generally not analyzed. In the tested conditions the triggering effect of nitrogen starvation on total lipids productivity is confirmed only in autotrophic regimen, while in mixotrophic and heterotrophic conditions the total lipids productivity is reduced, as a consequence of the lowered biomass productivity, but with an evident compositional shift towards nonpolar lipids production (from 0.5 mg/Ld to 41.6 mg/Ld in mixotrophic regimen). Nitrogen and phosphorus co-starvation induced the highest nonpolar lipids productivity in all trophic regimens. Maximum nonpolar lipids productivity was obtained in nitrogen limited and phosphorus deprived condition during mixotrophic growth, equal to 118.2 mg/Ld, representing the 80% of produced lipids. On the basis of the obtained results, the possibility of a short pre-harvesting cultural step to maximize the nonpolar lipids yield of the crop could be envisaged.展开更多
Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuv...Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.展开更多
Primary immunodeficiency disorders (PIDs) result from inborn errors in immunity.Susceptibility to infections and oftentimes severe autoimmunity pose life-threatening risks to patients with these disorders.Hematopoieti...Primary immunodeficiency disorders (PIDs) result from inborn errors in immunity.Susceptibility to infections and oftentimes severe autoimmunity pose life-threatening risks to patients with these disorders.Hematopoietic cell transplant (HCT) remains the only curative option for many.Severe combined immunodeficiency disorders (SCID) most commonly present at the time of birth and typically require emergent HCT in the first few weeks of life.HCT poses an unusual challenge for PIDs.Donor source and conditioning regimen often impact the outcome of immune reconstitution after HCT in PIDs.The use of matched or unmatched, as well as related versus unrelated donor has resulted in variable outcomes for different subsets of PIDs.Additionally, there is significant variability in the success of engraftment even for a single patient’s lymphocyte subpopulations.While certain cell lines do well without a conditioning regimen, others will not reconstitute unless conditioning is used.The decision to proceed with a conditioning regimen in an already immunocompromised host is further complicated by the fact that alkylating agents should be avoided in radiosensitive PIDs.This manuscript reviews some of the unique elements of HCT in PIDs and evidence-based approaches to transplant in patients with these rare and challenging disorders.展开更多
Background Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein （LDL） cholesterol. However, few studies...Background Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein （LDL） cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration.展开更多
Helicobacter pylori （H. pylori ） is a very common bacterium that infects about 50% of the world population in urban areas and over 90% of people living in rural and developing countries. Fluoroquinolones, a class o...Helicobacter pylori （H. pylori ） is a very common bacterium that infects about 50% of the world population in urban areas and over 90% of people living in rural and developing countries. Fluoroquinolones, a class of antimicrobials, have been extensively used in eradic-ation regimens for H. pylori . Levofloxacin is the most commonly used, and in second-line regimens, is one of the most effective options. However, an increasing resistance rate of H. pylori to fuoroquinolones is being observed, that will likely affect their effectiveness in the near future. Other novel fluoroquinolone molecules, such as moxifoxacin, sitafoxacin, gatifoxacin and gemif-loxacin, have been proposed and showed encouraging results in vitro, although data on their clinical use are still limited. Further studies in large sample trials are needed to confirm their safety and efficacy profile in clinical practice.展开更多
文摘Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the administration of several consecutive standard therapies.Although antibiotic resistance reports describe alarming results,the outcome of therapeutic regimens does not seem to parallel this scenario in most cases,since a successful performance is often reached in more than 80%of cases.However,the phenomenon of increasing antibiotic resistance is being closely studied,and the results show controversial aspects even in the same geographic area.For the continents of Europe,America,Asia,Africa,and Oceania,minimal and maximal values of resistance to the main antibiotics(clarithromycin,amoxicillin,metronidazole,and levofloxacin)feature wide ranges in different countries.The real enigma is therefore linked to the several different therapeutic regimens,which show results that often do not parallel the in vitro findings even in the same areas.A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts.Moreover,not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome.The additional use of probiotics may help to reduce adverse events,but their therapeutic impact is doubtful.In conclusion,the"ideal therapy",paradoxically,appears to be a"utopia",despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H.pylori.The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide.On these bases,one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances.In this context,geography must be considered a relevant matter.
文摘Helicobacter pylori(H.pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide.H.pylori treatment still remains a challenge,since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance,mucosal drug concentration,patient compliance,side-effect profile and cost.While no new drug has been developed,current therapy still relies on different mixture of known antibiotics and anti-secretory agents.A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen.Bismuthcontaining quadruple treatment,sequential treatment or a non-bismuth quadruple treatment(concomitant) are also an alternative therapy.Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H.pylori after defeat of first-line therapy.The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies.Therefore,adding probiotic to the medications,developing anti-H.pylori photodynamic or phytomedicine therapy,and achieving a successful H.pylori vaccine may have the promising to present synergistic or additive consequence against H.pylori,because each of them exert different effects.
文摘Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bleeding ulcers recommend a continuous infusion of proton pump inhibitors (PPI). However, studies comparing intermittent dosing of PPI therapy show that this regimen achieves similar clinical benefits. If the clinical efficacy remains equivalent, intermittent dosing will be more cost-effective for patients and the health care system. Our research study aims to analyze the comparative effectiveness of intermittent versus continuous PPI therapy after endoscopic treatment in patients with UGIB, focusing on such endpoints as rebleeding risk at 3-and 7-day mortality rates. Methods: Resources searched included MEDLINE, EMBASE, PUBMED, and the Cochrane Central Register of Controlled Trials databases from January 2010 through December 2023 with the inclusion of meta-analysis, systematic review, review, or ACG guideline recommendations. Results of the analysis show how recommendations regarding high vs. low PPI regimen changed over time: from no difference in regimen in 2010 to recommending continuous regimen in 2012 to declaring insufficient evidence between choosing one regimen over another in 2013 to determine that both regimens were comparable to each other in 2014-2018 and finally to recommending both regimens in 2021. To conclude, our review shows that in patients with bleeding ulcers and high-risk endoscopic findings, intermittent PPI therapy is non-inferior to continuous PPI infusion for three days, seven days bleeding risk or mortality rates;however, it remains challenging to determine the most optimal intermittent regimen due to heterogeneity of RCTs included in meta-analyses, and further trials will need to be performed.
文摘Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment
文摘Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.
基金funded by the National Natural Science Foundation of China(Grant nos.81874048,82171824,82272906)Shanghai Municipal Commission of Health and Family Planning Grant 2018ZHYL0223+6 种基金Shanghai Municipal Education Commission—Gao Feng Clinical Medicine Grant Support(Grant no.20161312)Scientific and Technological Innovation Project of Science and Technology Commission of Shanghai Municipality(Grant no.21JC1404300)Clinical Research Plan of SHDC(Grant no.SHDC2020CR1035B)Innovation Group Project of Shanghai Municipal Health Commission(Grant no.2019CXJQ03)National Key R&D Program of China(Grant no.2019YFC1315900)Project from CSCO Clinical Oncology Research Foundation(Grant no.Y-2019AZZD-0513)the Innovative Research Team of High-Level Local Universities in Shanghai(Grant no.SHSMU-ZDCX20210802).
文摘Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database.Methods:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database.The entire course of real-world pancreatic cancer management was analyzed.Results:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this cohort.Serum carbohydrate antigen(CA)19-9 is one of the most common tumor markers.In the present study,2562 patients underwent first-line therapy.The median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 months.The major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS rates.Conclusion:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in China.Results revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported data.Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.
文摘Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.
文摘Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with
文摘BACKGROUND Highly active antiretroviral therapy (HAART) is provided free of charge to all human immunodeficiency virus (HIV) positive residents in Italy. As fixed dose coformulations (FDCs) are often more expensive in comparison to the same drugs administered separately in a multi-tablet regimen (MTR), we considered a costeffective strategy involving patients in the switch from their FDCs to corresponding MTRs including generic antiretrovirals. AIM To verify if this would affect the virological and immunological response in comparison to maintaining the FDC regimens. METHODS From January 2012 to December 2013, we assessed the eligibility of all the HIV-1 positive adults on stable HAART being treated at our hospital-based outpatient clinic in Treviso, Italy. Participants who accepted to switch from their FDC regimen to the corresponding MTR joined the MTR group, while those who maintained a FDC regimen joined the FDC group. Clinical data, including changes in HAART regimens, respective reasons why and adverse effects, were recorded at baseline and at follow-up visits occurring at weeks 24, 48 and 96. All participants were assessed for virological and immunological responses at baseline and at weeks 24, 48 and 96. RESULTS Two hundred and forty-three eligible HIV-1 adults on HAART were enrolled: 163 (67%) accepted to switch to a MTR, joining the MTR group, while 80 (33%) maintained their FDCs, joining the FDC group. In a parallel analysis, there were no significant differences in linear trend of distribution of HIV-RNA levels between the two groups and there were no significant odds in favour of a higher level of HIV-RNA in either group at any follow-up and on the overall three strata analysis. In a before-after analysis, both FDC and MTR groups presented no significant differences in distribution of HIV-RNA levels at either weeks 48 vs 24 and weeks 96 vs 24 cross tabulations. A steady increase of mean CD4 count was observed in the MTR group only, while in the FDC group we observed a slight decrease (-23 cells per m
文摘In this work the effects of nutrients starvations on Chlorella vulgaris were investigated in different trophic regimens. For all the tested conditions, the cellular response to nutrient starvation and trophic regimen was evaluated on specific growth rate, biomass and lipids productivity, lipids content and quality. These parameters are all crucial for microalgae biodiesel production, but in literature the lipids quality, in terms of polar and nonpolar lipids, is often neglected. Thus the typical high content of polar lipids, a class of molecules that negatively affects the biodiesel production process, of microalgae crude oil is generally not analyzed. In the tested conditions the triggering effect of nitrogen starvation on total lipids productivity is confirmed only in autotrophic regimen, while in mixotrophic and heterotrophic conditions the total lipids productivity is reduced, as a consequence of the lowered biomass productivity, but with an evident compositional shift towards nonpolar lipids production (from 0.5 mg/Ld to 41.6 mg/Ld in mixotrophic regimen). Nitrogen and phosphorus co-starvation induced the highest nonpolar lipids productivity in all trophic regimens. Maximum nonpolar lipids productivity was obtained in nitrogen limited and phosphorus deprived condition during mixotrophic growth, equal to 118.2 mg/Ld, representing the 80% of produced lipids. On the basis of the obtained results, the possibility of a short pre-harvesting cultural step to maximize the nonpolar lipids yield of the crop could be envisaged.
基金supported by Shenzhen Sanming Project(No.SZSM201612051)。
文摘Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.
文摘Primary immunodeficiency disorders (PIDs) result from inborn errors in immunity.Susceptibility to infections and oftentimes severe autoimmunity pose life-threatening risks to patients with these disorders.Hematopoietic cell transplant (HCT) remains the only curative option for many.Severe combined immunodeficiency disorders (SCID) most commonly present at the time of birth and typically require emergent HCT in the first few weeks of life.HCT poses an unusual challenge for PIDs.Donor source and conditioning regimen often impact the outcome of immune reconstitution after HCT in PIDs.The use of matched or unmatched, as well as related versus unrelated donor has resulted in variable outcomes for different subsets of PIDs.Additionally, there is significant variability in the success of engraftment even for a single patient’s lymphocyte subpopulations.While certain cell lines do well without a conditioning regimen, others will not reconstitute unless conditioning is used.The decision to proceed with a conditioning regimen in an already immunocompromised host is further complicated by the fact that alkylating agents should be avoided in radiosensitive PIDs.This manuscript reviews some of the unique elements of HCT in PIDs and evidence-based approaches to transplant in patients with these rare and challenging disorders.
文摘Background Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein （LDL） cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration.
文摘Helicobacter pylori （H. pylori ） is a very common bacterium that infects about 50% of the world population in urban areas and over 90% of people living in rural and developing countries. Fluoroquinolones, a class of antimicrobials, have been extensively used in eradic-ation regimens for H. pylori . Levofloxacin is the most commonly used, and in second-line regimens, is one of the most effective options. However, an increasing resistance rate of H. pylori to fuoroquinolones is being observed, that will likely affect their effectiveness in the near future. Other novel fluoroquinolone molecules, such as moxifoxacin, sitafoxacin, gatifoxacin and gemif-loxacin, have been proposed and showed encouraging results in vitro, although data on their clinical use are still limited. Further studies in large sample trials are needed to confirm their safety and efficacy profile in clinical practice.
