Neurological signs and segmcntal demyelination in a cervical nerve were observed in rats treated orally with permethrin (300 mg/kg/day) for 5 days. Inflammatory and degenerative signals were recorded in the diaphragm ...Neurological signs and segmcntal demyelination in a cervical nerve were observed in rats treated orally with permethrin (300 mg/kg/day) for 5 days. Inflammatory and degenerative signals were recorded in the diaphragm muscle. These effects were more intense with the trade grade than with the technical grade product. The possible influence of the percentage of cisitrans isomers on the intensity of the observed effects is discussed. 5 imi Academic Press.Inc.展开更多
BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resi...BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.展开更多
Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early....Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.展开更多
In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients....In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.展开更多
Objective:To analyze the clinical effect of high-dose citrate in segmental extracorporeal anticoagulation for high-throughput hemodialysis.Methods:The subjects included in this study were admitted to the hospital for ...Objective:To analyze the clinical effect of high-dose citrate in segmental extracorporeal anticoagulation for high-throughput hemodialysis.Methods:The subjects included in this study were admitted to the hospital for maintenance hemodialysis treatment from January 2021 to January 2023.All patients had a high risk of bleeding and received 4%trisodium citrate anticoagulant treatment,administered at a rate of 200 mL/h before and after the dialyzer.The anticoagulant effects achieved by the patients were observed and analyzed.Results:The total number of patients who received high-dose segmented citrate extracorporeal anticoagulation dialysis treatment was 50,with each patient undergoing 100 treatments.During the treatment,2 patients had to end the treatment early due to transmembrane pressure exceeding 30 mmHg and an increase in venous pressure exceeding 250 mmHg;the treatment times for these patients were 20 minutes and 200 minutes,respectively.The remaining patients successfully completed the 4-hour treatment.Blood pH and calcium ion concentration in the venous pot were monitored.It was observed that before dialysis,after 2 hours of dialysis,and at the end of dialysis,the blood pH of the patients remained within a relatively normal range.Although some patient levels changed after dialysis,they remained within the normal range.No adverse reactions(such as numbness of the limbs or convulsions)were observed during the anticoagulant treatment.Conclusion:Administering 4%trisodium citrate at a rate of 200 mL/h before and after the dialyzer achieves a good anticoagulant effect,maintains the patient’s blood gas levels within the normal range at the end of dialysis,and causes no adverse reactions.展开更多
AIM:To determine the feasibility and safety of high dose rate intraluminal brachytherapy(HDR-ILBT) boost during preoperative chemoradiation for rectal cancer.METHODS:Between 2008 and 2009,thirty-six patients with loca...AIM:To determine the feasibility and safety of high dose rate intraluminal brachytherapy(HDR-ILBT) boost during preoperative chemoradiation for rectal cancer.METHODS:Between 2008 and 2009,thirty-six patients with locally advanced rectal cancer(≥ T3 or N+),were treated initially with concurrent capecitabine(825 mg/m2 oral twice daily) and pelvic external beam radiotherapy(EBRT)(45 Gy in 25 fractions),then were randomized to group A;HDR-ILBT group(n = 17) to receive 5.5-7 Gy×2 to gross tumor volume(GTV) and group B;EBRT group(n = 19) to receive 5.4 Gy×3 fractions to GTV with EBRT.All patients underwent total mesorectal excision.RESULTS:Grade 3 acute toxicities were registered in 12 patients(70.6%) in group A and in 8(42.1%) in group B.Complete pathologic response of T stage(ypT0) in group A was registered in 10 patients(58.8%) and in group B,3 patients(15.8%) had ypT0(P < 0.0001).Sphincter preservation was reported in 6/9 patients(66.7%) in group A and in 5/10 patients(50%) in group B(P < 0.01).Overall radiological response was 68.15% and 66.04% in Group A and B,respectively.During a median follow up of 18 mo,late grade 1 and 2 sequelae were registered in 3 patients(17.6%) and 4 patients(21.1%) in the groups A and B,respectively.CONCLUSION:HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers,with higher response rates,downstaging and with manageable acute toxicities.展开更多
In this paper, toxicity and safety of high-dose irradiated chicken-breast meat were evaluated. For assays of acute toxicity, genetic toxicity, and sub-chronic toxicity, ames test, mice bone marrow erythrocyte micronuc...In this paper, toxicity and safety of high-dose irradiated chicken-breast meat were evaluated. For assays of acute toxicity, genetic toxicity, and sub-chronic toxicity, ames test, mice bone marrow erythrocyte micronucleus, and mice sperm abnormality were performed. The results showed that, in the acute oral toxicity tests, median lethal dose (more than 10 000 mg kg-~) in male and female ICR mice showed no toxicological signs. For subacute 30-d oral toxicology of irradiated chicken-breast meat with dose of 10, 15 and 25 kGy in both male and female SD rats, no noticeable toxicological effects were observed. It is concluded that chicken-breast meat with high-dose irradiation has no acute toxicity and no genotoxicity, nor harmful effects on the animal body at the tested dosage range. Therefore, high-dose irradiated chicken-breast meat is safe for pet consumption.展开更多
Objective: A pilot study to test the feasibility and efficacy of high dose IFO and standard dose ADR and DTIC with G-CSF support in treatment of advanced soft tissue sarcoma (STS). Methods: 35 patients of no prior che...Objective: A pilot study to test the feasibility and efficacy of high dose IFO and standard dose ADR and DTIC with G-CSF support in treatment of advanced soft tissue sarcoma (STS). Methods: 35 patients of no prior chemotherapy with metastatic or locally advanced unresectable STS were treated by this regimen, including 18 rhabdomyosarcomas, 7 malignant fibrous histiocytomas, 2 neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2 synoviosarcomas, and 2 malignant hemangiopericytomas. IFO dose was 2 g/m2 on day 1–5 (with mesna uroprotection), ADR 50mg/m2 on day 1 and DTIC 250 mg/m2 on day 1–5. G-CSF (2 μg/kg/d) was administered on day 6 to 15 or until recovery of leukocytes account. The cycles were repeated every 3 weeks. Result: There were five complete responses (CR including pathologic CR) and eleven partial responses for overall 46% objective response rate. Most responses were observed within two cycles. The median survival was 15 months. Following CR, two patients remain disease free at 45 and 28 months, respectively. 6/120 (5%) cycles were complicated by grade IV neutropenia, 46/120 (38%) cycles had grade III neutropenia. No patients had treatment-related deaths. Nonhematologic toxicity consisted predominantly of anorexia and vomiting. No other severe toxicities were seen, especially no severe cardiotoxicity. Conclusion: This regimen is well tolerated and has substantial benefits for patients with advanced soft tissue sarcomas.展开更多
In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid ...In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.展开更多
Dear Editor,Sildenafil citrate(Viagra;Pfizer Pharmaceuticals,New York,NY,USA),a selective inhibitor of phosphodiesterase type 5(PDE-5),is widely used for erectile dysfunction.Its clinical recommended dosage is 25 ...Dear Editor,Sildenafil citrate(Viagra;Pfizer Pharmaceuticals,New York,NY,USA),a selective inhibitor of phosphodiesterase type 5(PDE-5),is widely used for erectile dysfunction.Its clinical recommended dosage is 25 to 100 mg per day.展开更多
Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from A...Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.展开更多
Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order...Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods: A total of 60 rats were divided into 5 groups: blank control, 10^-6 mol/L dexamethasone (DEX) group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group (10^-2mol/L RU486). All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy (LCSM); CRH mRNA level was explored by in situ hybridization. Results: 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion : High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.展开更多
Objective: High dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT) has become one of the important salvage treatments for the Hodgkin抯 Lymphoma patients with relapsed or resistant disea...Objective: High dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT) has become one of the important salvage treatments for the Hodgkin抯 Lymphoma patients with relapsed or resistant disease, but its role as the primary treatment remains indefinite. This study was designed to further evaluate its status in the combined modality treatment, especially, to discuss its value in the primary treatment of the patients who had advanced disease with poor prognostic factors. Methods: Eleven patients who had advanced or relapsed disease with poor prognostic factors were enrolled in this study. Among them, 9 cases had primary treatment, and 2 cases had secondary treatment; one patient received autologous bone marrow transplantation (ABMT), and 10 patients received autologous peripheral blood stem cell transplantation (APBSCT). After induction treatment 4 cases achieved complete response (CR) and 7 cases achieved partial response (PR). High dose chemotherapy combined with total body irradiation (TBI) or total lymph node irradiation (TLI)/subtotal lymph node irradiation (STLI) were adopted in 7 cases and only high dose chemotherapy were adopted in 4 cases as the transplant preparative regimens. 5 cases received complementary irradiation in the primary sites after transplant. Results: The patients who had CR before transplantation were given consolidative therapy. Among the rest with PR, 2 cases achieved CR, 1 case PR, and 4 cases SD. Furthermore all these patients who maintained SD had bone involvement. With a median follow-up for all patients of 13(1-80) months, all of them are alive currently. Four cases are event-free survival (EFS); 4 cases with bone involvement are progression-free survival (PFS); 3 cases experienced relapse after transplant, one of them is EFS for 42 months again after a local relapsed site irradiation; the other two cases are being given further salvaged treatment now. According to the Life Tables method, the cumulative probability of 6-year PFS and OS is 55.68% and 100% respectively. The dominating transplant- related toxicity was bone marrow suppression in grades IV. No obvious cardiac, hepatic, and nephritic toxicity was found. No transplant related mortality. Conclusion: HDT combined with ASCT is a method worthwhile to further study for the treatment of the patients with advanced or relapsed Hodgkin抯 Lymphoma with poor prognostic factors.展开更多
<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of meta...<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of metastatic breast cancer (MBC) is still challenging.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Many studies documented the efficacy of</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">pegylated liposomal doxorubicin (PLD) in patients with MBC, but there is a limited data about the cardiac safety with high cumulative dose (HCD) of PLD. </span><b><span style="font-family:Verdana;">Aim of the work:</span></b></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">We conducted this trial to outline the cardiac safety of HCD of PLD in patients </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">with MBC who previously received conventional anthracyclines. </span><b><span style="font-family:Verdana;">Methods:</span></b> <span style="font-family:Verdana;">During the period of nine years (January 2011 to December 2019). We extracted</span><span style="font-family:Verdana;"> the data of the patients with MBC receiving PLD at Medical Oncology Department, South Egypt Cancer Institute, Assiut University. These included patients’ demographics and therapeutic data including the full data of PLD, prior conventional anthracyclines, prior trastuzumab, and prior radiotherapy. Also, data about comorbidities as well as cardiac and other toxicities of PLD were obtained. The data was analysed using SPSS v. 21. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> For all 81 eligible patients, the mean age was 43.9 years (±standard deviation (SD) 13.2). The mean cumulative dose of PLD was 378.4 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> (± SD of 250.2) and a range of 100</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">1200 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;">. About thirty-one (38.3%) patients received high </span><span><span style="font-family:Verdana;">cumulative dose (400 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> or more), while the remaining 50 patients did not.</span></span></span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">The decline in </span><a name="_Hlk36276945"></a><span style="font-family:Verdana;">left ventricular ejection fraction (LVEF) was relatively rare;and</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> of low grade. Grade 2 decline in LVEF occurred in only two patients who received high cumulative dose of PLD, and only one patient who did not reach HCD (p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">= </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">.555). Grade 3 or 4 decline in LVEF did not occur in patients either with or without HCD. Regarding other toxicities, there was a significant increase in incidence of all grades palmar plantar erythrodysesthesia (PPE) in </span><span style="font-family:Verdana;">patients </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">received HCD of PLD when compared to those </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">did not reach</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> the HCD (38.7% versus 16% respectively;p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">=</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 0</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.021).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Our </span><span style="font-family:Verdana;">study concluded that the use of PLD seems to be a justified agent in the treatment</span><span style="font-family:Verdana;"> of MBC who previously treated by</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.</span></span></span>展开更多
Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues pu...Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.展开更多
Objective: High dose chemotherapy supported by autologous hematopoietic stem cells transplantation (AHSCT) has developed dramaticly in recent years and become the most effective approach to improve radical treatment f...Objective: High dose chemotherapy supported by autologous hematopoietic stem cells transplantation (AHSCT) has developed dramaticly in recent years and become the most effective approach to improve radical treatment for the chemo-sensitive lymphoma. The purposes of this study was to evaluate the efficacy and tolerance of preparative regimen BEAC and hematopoietic reconsti- tution after high dose chemotherapy in Chinese patients with advanced and recurrent lymphoma. Methods: After confirmed complete or partial remission from conventional chemotherapy, 24 patients with advanced or recurrent lymphoma including 1 recurrent HD and 23 NHL, 16 male and 8 female with median age of 29 (13-50) years, were enrolled into this study and treated by BEAC regimen (CTX 3600-4000 mg/m2, VP-16 1200 mg/m2. BCNU 300 mg/m2 and Ara-C 1500-2000 mg/m2). 3 patients were supported by ABMT and 21 by APBSCT. Mobilization regimen for APBSCT was CTX 3500 mg/m2 + G-CSF 3.5-5 mg/kg + Dexamethasone 10 mg. Autologous hematopoietic stem cells was re-infused 24-48 h after completion of high dose chemotherapy. Results: MNC 1.3 (1.0-1.7) 108/kg and MNC 1.8 (1.0-4.4) 108, CFU-GM 5.1 (1.9-9.6) 105/kg plus CD34 + cells 2.9 (1.9-8.7) 106/kg were re-infused in the ABMT group and APBSCT group respectively. All patients obtained prompt and sustained hematopoietic reconstitution. ANC 0.5 109/L and Pt 2.0 109/L were at day 9 (6-17) and day 10 (0-31) respectively. 16 patients were alive with median 21 (2-69) months follow-up till end of May, 2001. 1, 2 and 3 years survival rate were 60.5%, 50.1% and 50.1%, respectively. Non-hematologic toxicity was mild and tolerable. Conclusions: High dose chemotherapy supported by AHSCT in the treatment of previously-untreated poor- prognostic and recurrent lymphoma was a safe and effective modality. Further investigation was warranted.展开更多
Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and pla...Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and planned range of irradiation field,remains unclear.This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields.Methods:This trial compared two aspects of radiation treatment,total dose and field,using a two-by-two factorial design.The high-dose(HD)group received 59.4 Gy radiation,and the standard-dose(SD)group received 50.4 Gy.The involved field irradiation(IFI)group and elective nodal irradiation(ENI)group adopted different irradiation ranges.The participants were assigned to one of the four groups(HD+ENI,HD+IFI,SD+ENI and SD+IFI).The primary endpoint was overall survival(OS),and the secondary endpoints included progressionfree survival(PFS).The synergy indexwas used to measure the interaction effect between dose and field.Results:The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field.In comparison to the target field,patients in IFI or ENI showed similar OS(hazard ratio[HR]=0.99,95%CI:0.80-1.23,p=0.930)and PFS(HR=1.02,95%CI:0.82–1.25).TheHDtreatment did not show significantly prolonged OS compared with SD(HR=0.90,95%CI:0.72–1.11,p=0.318),but it suggested improved PFS(25.2 months to 18.0 months).Among the four groups,the HD+IFI group presented the best survival,while the SD+IFI group had the worst prognosis.No significant difference in the occurrence of severe adverse events was found in dose or field comparisons.Conclusions:IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC.The HD demonstrated improved PFS,but did not significantly improve OS.The dose escalation based on IFI(HD+IFI)showed better therapeutic efficacy than the current recommendation(SD+ENI)and is worth further validation.展开更多
Since the middle of 1990 s autologous stem cell trans-plantation has been the cornerstone for the treatment of young patients with multiple myeloma(MM). In the last decade the introduction of novel agents such as immu...Since the middle of 1990 s autologous stem cell trans-plantation has been the cornerstone for the treatment of young patients with multiple myeloma(MM). In the last decade the introduction of novel agents such as immunomodulatory drugs(IMi Ds) and proteasome inhibitors(PI), has dramatically changed the therapeutic scenario of this yet incurable disease. Due to the impressive results achieved with IMi Ds and PI both in terms of response rates and in terms of progression free and overall survival, and to the toxicity linked to high dose therapy and autologous stem cell transplantation(ASCT), a burning question nowadays is whether all young patients should be offered autotransplanta-tion up front or if this should be reserved for the time of relapse. This article provides a review of the data available regarding ASCT in MM and of the current opinion of the scientific community regarding its optimal timing.展开更多
The essential objective of radiation dosimetry is to develop suitable sensitive materials for different measurements in radiation fields. Our exploration is to find potentially suitable high gamma radiation dosimeters...The essential objective of radiation dosimetry is to develop suitable sensitive materials for different measurements in radiation fields. Our exploration is to find potentially suitable high gamma radiation dosimeters in the range from 0.5E4 to 1.5E4 Gy. Gamma rays source (<sup>60</sup>Co, 136 Gy/min) has been used. Many compound semiconductor materials were prepared and investigated. Thermoluminescence (TL) glow curve was analyzed into its component by analytical segregation program using computerized glow curve deconvolution (CGCD). Three zero dose readings for non-irradiated powders of the materials have been taken as lower limit of detection. The results indicated that some of the tested materials have exhibited TL linearly with respect to dose. In addition, dose response of these materials was found to be useful for high radiation dosimetry. Glow curve structures exhibited several peaks corresponding to the various energies of the emptied traps. Variation in the standard deviation for reusability cycles has been ten readout. The fading at ambient temperature was studied up to 60 days which reached a relative stability (~1.5% for all), 10 days after irradiation. A typical glow curve of CoPa which irradiated with 1.5E4 Gy was analyzed. Characterizations of tested materials indicated that crystals of ZnLa:Li, ZnLa:Cd, and ZnLa:Cr have stable and increasing thermoluminescent responses with high gamma radiation dose range. Special glow peaks can be used as estimators for absorbed doses as well as re-estimation for time elapsed exposures.展开更多
The single high-dose application of biochar to increase rice yield has been well reported.However,limited information is available about the long-term effects of increasing rice yield and soil fertility.This study was...The single high-dose application of biochar to increase rice yield has been well reported.However,limited information is available about the long-term effects of increasing rice yield and soil fertility.This study was designed to perform a 6-year field experiment to unveil the rice yield with time due to various biochar application strategies.Moreover,an alternative strategy of the Annual Low dose biochar application(AL,8×35%=2.8 t ha^(−1))was also conducted to make a comparison with the High Single dose(HS,22.5 t ha^(−1)),and annual Rice Straw(RS,8 t ha^(−1))amendment to investigate the effects on annual rice yield attributes and soil nutrient concentrations.Results showed that the rice yield in AL with a lower biochar application exceeded that of HS significantly(p<0.05)in the 6th experimental year.The rice yield increased by 14.3%in RS,10.9%in AL,and 4.2%in HS.The unexpectedly higher rice yield in AL than HS resulted from enhanced soil total carbon(TC),pH,and available Ca.However,compared to AL,liable carbon fraction increased by 33.7%in HS,while refractory carbon fraction dropped by 22.3%.Likewise,biochar characterization showed that more oxygen functional groups existed in HS than in AL.Decreasing inert organic carbon pools due to the constant degradation of the aromatic part of biochar in HS led to a lower soil TC than AL,even with a higher amount of biochar application.Likewise,the annual depletion lowered the soil pH and available Ca declination in HS.Based on the obtained results,this study suggested AL as a promising strategy to enhance rice productivity,soil nutrient enrichment,and carbon sequestration in the paddy ecosystem.展开更多
文摘Neurological signs and segmcntal demyelination in a cervical nerve were observed in rats treated orally with permethrin (300 mg/kg/day) for 5 days. Inflammatory and degenerative signals were recorded in the diaphragm muscle. These effects were more intense with the trade grade than with the technical grade product. The possible influence of the percentage of cisitrans isomers on the intensity of the observed effects is discussed. 5 imi Academic Press.Inc.
文摘BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.
文摘Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.
文摘In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.
文摘Objective:To analyze the clinical effect of high-dose citrate in segmental extracorporeal anticoagulation for high-throughput hemodialysis.Methods:The subjects included in this study were admitted to the hospital for maintenance hemodialysis treatment from January 2021 to January 2023.All patients had a high risk of bleeding and received 4%trisodium citrate anticoagulant treatment,administered at a rate of 200 mL/h before and after the dialyzer.The anticoagulant effects achieved by the patients were observed and analyzed.Results:The total number of patients who received high-dose segmented citrate extracorporeal anticoagulation dialysis treatment was 50,with each patient undergoing 100 treatments.During the treatment,2 patients had to end the treatment early due to transmembrane pressure exceeding 30 mmHg and an increase in venous pressure exceeding 250 mmHg;the treatment times for these patients were 20 minutes and 200 minutes,respectively.The remaining patients successfully completed the 4-hour treatment.Blood pH and calcium ion concentration in the venous pot were monitored.It was observed that before dialysis,after 2 hours of dialysis,and at the end of dialysis,the blood pH of the patients remained within a relatively normal range.Although some patient levels changed after dialysis,they remained within the normal range.No adverse reactions(such as numbness of the limbs or convulsions)were observed during the anticoagulant treatment.Conclusion:Administering 4%trisodium citrate at a rate of 200 mL/h before and after the dialyzer achieves a good anticoagulant effect,maintains the patient’s blood gas levels within the normal range at the end of dialysis,and causes no adverse reactions.
文摘AIM:To determine the feasibility and safety of high dose rate intraluminal brachytherapy(HDR-ILBT) boost during preoperative chemoradiation for rectal cancer.METHODS:Between 2008 and 2009,thirty-six patients with locally advanced rectal cancer(≥ T3 or N+),were treated initially with concurrent capecitabine(825 mg/m2 oral twice daily) and pelvic external beam radiotherapy(EBRT)(45 Gy in 25 fractions),then were randomized to group A;HDR-ILBT group(n = 17) to receive 5.5-7 Gy×2 to gross tumor volume(GTV) and group B;EBRT group(n = 19) to receive 5.4 Gy×3 fractions to GTV with EBRT.All patients underwent total mesorectal excision.RESULTS:Grade 3 acute toxicities were registered in 12 patients(70.6%) in group A and in 8(42.1%) in group B.Complete pathologic response of T stage(ypT0) in group A was registered in 10 patients(58.8%) and in group B,3 patients(15.8%) had ypT0(P < 0.0001).Sphincter preservation was reported in 6/9 patients(66.7%) in group A and in 5/10 patients(50%) in group B(P < 0.01).Overall radiological response was 68.15% and 66.04% in Group A and B,respectively.During a median follow up of 18 mo,late grade 1 and 2 sequelae were registered in 3 patients(17.6%) and 4 patients(21.1%) in the groups A and B,respectively.CONCLUSION:HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers,with higher response rates,downstaging and with manageable acute toxicities.
基金supported by the Special Fund for Agro-Scientific Research in the Public Interest, China(201103007)
文摘In this paper, toxicity and safety of high-dose irradiated chicken-breast meat were evaluated. For assays of acute toxicity, genetic toxicity, and sub-chronic toxicity, ames test, mice bone marrow erythrocyte micronucleus, and mice sperm abnormality were performed. The results showed that, in the acute oral toxicity tests, median lethal dose (more than 10 000 mg kg-~) in male and female ICR mice showed no toxicological signs. For subacute 30-d oral toxicology of irradiated chicken-breast meat with dose of 10, 15 and 25 kGy in both male and female SD rats, no noticeable toxicological effects were observed. It is concluded that chicken-breast meat with high-dose irradiation has no acute toxicity and no genotoxicity, nor harmful effects on the animal body at the tested dosage range. Therefore, high-dose irradiated chicken-breast meat is safe for pet consumption.
文摘Objective: A pilot study to test the feasibility and efficacy of high dose IFO and standard dose ADR and DTIC with G-CSF support in treatment of advanced soft tissue sarcoma (STS). Methods: 35 patients of no prior chemotherapy with metastatic or locally advanced unresectable STS were treated by this regimen, including 18 rhabdomyosarcomas, 7 malignant fibrous histiocytomas, 2 neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2 synoviosarcomas, and 2 malignant hemangiopericytomas. IFO dose was 2 g/m2 on day 1–5 (with mesna uroprotection), ADR 50mg/m2 on day 1 and DTIC 250 mg/m2 on day 1–5. G-CSF (2 μg/kg/d) was administered on day 6 to 15 or until recovery of leukocytes account. The cycles were repeated every 3 weeks. Result: There were five complete responses (CR including pathologic CR) and eleven partial responses for overall 46% objective response rate. Most responses were observed within two cycles. The median survival was 15 months. Following CR, two patients remain disease free at 45 and 28 months, respectively. 6/120 (5%) cycles were complicated by grade IV neutropenia, 46/120 (38%) cycles had grade III neutropenia. No patients had treatment-related deaths. Nonhematologic toxicity consisted predominantly of anorexia and vomiting. No other severe toxicities were seen, especially no severe cardiotoxicity. Conclusion: This regimen is well tolerated and has substantial benefits for patients with advanced soft tissue sarcomas.
文摘In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.
文摘Dear Editor,Sildenafil citrate(Viagra;Pfizer Pharmaceuticals,New York,NY,USA),a selective inhibitor of phosphodiesterase type 5(PDE-5),is widely used for erectile dysfunction.Its clinical recommended dosage is 25 to 100 mg per day.
文摘Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.
文摘Objective: To explore the effect of high dose of glucocorticoid (GC) on the synthesis of corticotropin releasing hormone (CRH) and transcription of its mRNA in hypothalamus paraventricular nuclei (PVN) in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods: A total of 60 rats were divided into 5 groups: blank control, 10^-6 mol/L dexamethasone (DEX) group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group (10^-2mol/L RU486). All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy (LCSM); CRH mRNA level was explored by in situ hybridization. Results: 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion : High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.
基金supported by a grant f rom National“95”Key Program of China(No.96-906-01-12)Huo Ying-dong Foundation for the Young Teacher of Academy and College
文摘Objective: High dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT) has become one of the important salvage treatments for the Hodgkin抯 Lymphoma patients with relapsed or resistant disease, but its role as the primary treatment remains indefinite. This study was designed to further evaluate its status in the combined modality treatment, especially, to discuss its value in the primary treatment of the patients who had advanced disease with poor prognostic factors. Methods: Eleven patients who had advanced or relapsed disease with poor prognostic factors were enrolled in this study. Among them, 9 cases had primary treatment, and 2 cases had secondary treatment; one patient received autologous bone marrow transplantation (ABMT), and 10 patients received autologous peripheral blood stem cell transplantation (APBSCT). After induction treatment 4 cases achieved complete response (CR) and 7 cases achieved partial response (PR). High dose chemotherapy combined with total body irradiation (TBI) or total lymph node irradiation (TLI)/subtotal lymph node irradiation (STLI) were adopted in 7 cases and only high dose chemotherapy were adopted in 4 cases as the transplant preparative regimens. 5 cases received complementary irradiation in the primary sites after transplant. Results: The patients who had CR before transplantation were given consolidative therapy. Among the rest with PR, 2 cases achieved CR, 1 case PR, and 4 cases SD. Furthermore all these patients who maintained SD had bone involvement. With a median follow-up for all patients of 13(1-80) months, all of them are alive currently. Four cases are event-free survival (EFS); 4 cases with bone involvement are progression-free survival (PFS); 3 cases experienced relapse after transplant, one of them is EFS for 42 months again after a local relapsed site irradiation; the other two cases are being given further salvaged treatment now. According to the Life Tables method, the cumulative probability of 6-year PFS and OS is 55.68% and 100% respectively. The dominating transplant- related toxicity was bone marrow suppression in grades IV. No obvious cardiac, hepatic, and nephritic toxicity was found. No transplant related mortality. Conclusion: HDT combined with ASCT is a method worthwhile to further study for the treatment of the patients with advanced or relapsed Hodgkin抯 Lymphoma with poor prognostic factors.
文摘<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of metastatic breast cancer (MBC) is still challenging.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Many studies documented the efficacy of</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">pegylated liposomal doxorubicin (PLD) in patients with MBC, but there is a limited data about the cardiac safety with high cumulative dose (HCD) of PLD. </span><b><span style="font-family:Verdana;">Aim of the work:</span></b></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">We conducted this trial to outline the cardiac safety of HCD of PLD in patients </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">with MBC who previously received conventional anthracyclines. </span><b><span style="font-family:Verdana;">Methods:</span></b> <span style="font-family:Verdana;">During the period of nine years (January 2011 to December 2019). We extracted</span><span style="font-family:Verdana;"> the data of the patients with MBC receiving PLD at Medical Oncology Department, South Egypt Cancer Institute, Assiut University. These included patients’ demographics and therapeutic data including the full data of PLD, prior conventional anthracyclines, prior trastuzumab, and prior radiotherapy. Also, data about comorbidities as well as cardiac and other toxicities of PLD were obtained. The data was analysed using SPSS v. 21. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> For all 81 eligible patients, the mean age was 43.9 years (±standard deviation (SD) 13.2). The mean cumulative dose of PLD was 378.4 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> (± SD of 250.2) and a range of 100</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">1200 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;">. About thirty-one (38.3%) patients received high </span><span><span style="font-family:Verdana;">cumulative dose (400 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> or more), while the remaining 50 patients did not.</span></span></span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">The decline in </span><a name="_Hlk36276945"></a><span style="font-family:Verdana;">left ventricular ejection fraction (LVEF) was relatively rare;and</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> of low grade. Grade 2 decline in LVEF occurred in only two patients who received high cumulative dose of PLD, and only one patient who did not reach HCD (p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">= </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">.555). Grade 3 or 4 decline in LVEF did not occur in patients either with or without HCD. Regarding other toxicities, there was a significant increase in incidence of all grades palmar plantar erythrodysesthesia (PPE) in </span><span style="font-family:Verdana;">patients </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">received HCD of PLD when compared to those </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">did not reach</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> the HCD (38.7% versus 16% respectively;p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">=</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 0</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.021).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Our </span><span style="font-family:Verdana;">study concluded that the use of PLD seems to be a justified agent in the treatment</span><span style="font-family:Verdana;"> of MBC who previously treated by</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.</span></span></span>
文摘Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.
基金This work was supported by a grant from the National 9th Five-Year Program of China (No. 96-906-12).
文摘Objective: High dose chemotherapy supported by autologous hematopoietic stem cells transplantation (AHSCT) has developed dramaticly in recent years and become the most effective approach to improve radical treatment for the chemo-sensitive lymphoma. The purposes of this study was to evaluate the efficacy and tolerance of preparative regimen BEAC and hematopoietic reconsti- tution after high dose chemotherapy in Chinese patients with advanced and recurrent lymphoma. Methods: After confirmed complete or partial remission from conventional chemotherapy, 24 patients with advanced or recurrent lymphoma including 1 recurrent HD and 23 NHL, 16 male and 8 female with median age of 29 (13-50) years, were enrolled into this study and treated by BEAC regimen (CTX 3600-4000 mg/m2, VP-16 1200 mg/m2. BCNU 300 mg/m2 and Ara-C 1500-2000 mg/m2). 3 patients were supported by ABMT and 21 by APBSCT. Mobilization regimen for APBSCT was CTX 3500 mg/m2 + G-CSF 3.5-5 mg/kg + Dexamethasone 10 mg. Autologous hematopoietic stem cells was re-infused 24-48 h after completion of high dose chemotherapy. Results: MNC 1.3 (1.0-1.7) 108/kg and MNC 1.8 (1.0-4.4) 108, CFU-GM 5.1 (1.9-9.6) 105/kg plus CD34 + cells 2.9 (1.9-8.7) 106/kg were re-infused in the ABMT group and APBSCT group respectively. All patients obtained prompt and sustained hematopoietic reconstitution. ANC 0.5 109/L and Pt 2.0 109/L were at day 9 (6-17) and day 10 (0-31) respectively. 16 patients were alive with median 21 (2-69) months follow-up till end of May, 2001. 1, 2 and 3 years survival rate were 60.5%, 50.1% and 50.1%, respectively. Non-hematologic toxicity was mild and tolerable. Conclusions: High dose chemotherapy supported by AHSCT in the treatment of previously-untreated poor- prognostic and recurrent lymphoma was a safe and effective modality. Further investigation was warranted.
基金Key Research and Development Program of Shandong Province of China,Grant/Award Number:2017CXZC1206National Natural Science Foundation of China,Grant/Award Number:81874224+1 种基金Academic promotion program of Shandong First Medical University,China,Grant/Award Number:2019LJ004Key Research and Development Program of Shandong Province,Grant/Award Numbers:2021LCZX04,2021SFGC0501。
文摘Background:Concurrent chemoradiotherapy(CCRT)is the standard treatment for locally advanced esophageal squamous cell carcinoma(ESCC).However,the optimal radiotherapy regimen,particularly in terms of total dose and planned range of irradiation field,remains unclear.This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields.Methods:This trial compared two aspects of radiation treatment,total dose and field,using a two-by-two factorial design.The high-dose(HD)group received 59.4 Gy radiation,and the standard-dose(SD)group received 50.4 Gy.The involved field irradiation(IFI)group and elective nodal irradiation(ENI)group adopted different irradiation ranges.The participants were assigned to one of the four groups(HD+ENI,HD+IFI,SD+ENI and SD+IFI).The primary endpoint was overall survival(OS),and the secondary endpoints included progressionfree survival(PFS).The synergy indexwas used to measure the interaction effect between dose and field.Results:The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field.In comparison to the target field,patients in IFI or ENI showed similar OS(hazard ratio[HR]=0.99,95%CI:0.80-1.23,p=0.930)and PFS(HR=1.02,95%CI:0.82–1.25).TheHDtreatment did not show significantly prolonged OS compared with SD(HR=0.90,95%CI:0.72–1.11,p=0.318),but it suggested improved PFS(25.2 months to 18.0 months).Among the four groups,the HD+IFI group presented the best survival,while the SD+IFI group had the worst prognosis.No significant difference in the occurrence of severe adverse events was found in dose or field comparisons.Conclusions:IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC.The HD demonstrated improved PFS,but did not significantly improve OS.The dose escalation based on IFI(HD+IFI)showed better therapeutic efficacy than the current recommendation(SD+ENI)and is worth further validation.
文摘Since the middle of 1990 s autologous stem cell trans-plantation has been the cornerstone for the treatment of young patients with multiple myeloma(MM). In the last decade the introduction of novel agents such as immunomodulatory drugs(IMi Ds) and proteasome inhibitors(PI), has dramatically changed the therapeutic scenario of this yet incurable disease. Due to the impressive results achieved with IMi Ds and PI both in terms of response rates and in terms of progression free and overall survival, and to the toxicity linked to high dose therapy and autologous stem cell transplantation(ASCT), a burning question nowadays is whether all young patients should be offered autotransplanta-tion up front or if this should be reserved for the time of relapse. This article provides a review of the data available regarding ASCT in MM and of the current opinion of the scientific community regarding its optimal timing.
文摘The essential objective of radiation dosimetry is to develop suitable sensitive materials for different measurements in radiation fields. Our exploration is to find potentially suitable high gamma radiation dosimeters in the range from 0.5E4 to 1.5E4 Gy. Gamma rays source (<sup>60</sup>Co, 136 Gy/min) has been used. Many compound semiconductor materials were prepared and investigated. Thermoluminescence (TL) glow curve was analyzed into its component by analytical segregation program using computerized glow curve deconvolution (CGCD). Three zero dose readings for non-irradiated powders of the materials have been taken as lower limit of detection. The results indicated that some of the tested materials have exhibited TL linearly with respect to dose. In addition, dose response of these materials was found to be useful for high radiation dosimetry. Glow curve structures exhibited several peaks corresponding to the various energies of the emptied traps. Variation in the standard deviation for reusability cycles has been ten readout. The fading at ambient temperature was studied up to 60 days which reached a relative stability (~1.5% for all), 10 days after irradiation. A typical glow curve of CoPa which irradiated with 1.5E4 Gy was analyzed. Characterizations of tested materials indicated that crystals of ZnLa:Li, ZnLa:Cd, and ZnLa:Cr have stable and increasing thermoluminescent responses with high gamma radiation dose range. Special glow peaks can be used as estimators for absorbed doses as well as re-estimation for time elapsed exposures.
基金National Natural Science Foundation of China[grant numbers 42077032 and 41571241]National Key Technology Research and Development Program of the Ministry of Science and Technology of China[grant number 2015BAC02B01]+1 种基金We gratefully acknowledge the financial support from the China Scholarship Council[grant number 202106320251]Doctoral Rising Star Program of Zhejiang University.
文摘The single high-dose application of biochar to increase rice yield has been well reported.However,limited information is available about the long-term effects of increasing rice yield and soil fertility.This study was designed to perform a 6-year field experiment to unveil the rice yield with time due to various biochar application strategies.Moreover,an alternative strategy of the Annual Low dose biochar application(AL,8×35%=2.8 t ha^(−1))was also conducted to make a comparison with the High Single dose(HS,22.5 t ha^(−1)),and annual Rice Straw(RS,8 t ha^(−1))amendment to investigate the effects on annual rice yield attributes and soil nutrient concentrations.Results showed that the rice yield in AL with a lower biochar application exceeded that of HS significantly(p<0.05)in the 6th experimental year.The rice yield increased by 14.3%in RS,10.9%in AL,and 4.2%in HS.The unexpectedly higher rice yield in AL than HS resulted from enhanced soil total carbon(TC),pH,and available Ca.However,compared to AL,liable carbon fraction increased by 33.7%in HS,while refractory carbon fraction dropped by 22.3%.Likewise,biochar characterization showed that more oxygen functional groups existed in HS than in AL.Decreasing inert organic carbon pools due to the constant degradation of the aromatic part of biochar in HS led to a lower soil TC than AL,even with a higher amount of biochar application.Likewise,the annual depletion lowered the soil pH and available Ca declination in HS.Based on the obtained results,this study suggested AL as a promising strategy to enhance rice productivity,soil nutrient enrichment,and carbon sequestration in the paddy ecosystem.