BACKGROUND Ovarian cancer is the most common malignant tumor of the female reproductive system,and the survival rate of patients with relapsed and refractory ovarian cancer is very low.CASE SUMMARY Here,we report a ca...BACKGROUND Ovarian cancer is the most common malignant tumor of the female reproductive system,and the survival rate of patients with relapsed and refractory ovarian cancer is very low.CASE SUMMARY Here,we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy.Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful;however,her tumor relapsed.Subsequent second-line chemotherapy,targeted agents,and other treatments were ineffective,as the tumor continued to recur and metastasize.Anti-programmed cell death-1(PD-1)monotherapy(tislelizumab)completely alleviated the tumor,and the multiple metastatic tumors disappeared.To date,the patient has used anti-PD-1 for 32 months,experiencing no disease progression and maintaining good health without additional treatment.CONCLUSION This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors.Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.展开更多
Background: Neglected clubfoot in this series is defined as untreated equino-cavo-adducto-varus in older children or adults. Relapsed clubfoot is the residual deformity that remains after single or multiple surgical i...Background: Neglected clubfoot in this series is defined as untreated equino-cavo-adducto-varus in older children or adults. Relapsed clubfoot is the residual deformity that remains after single or multiple surgical interventions. Severely neglected clubfoot rarely exists today in developed countries, except in some emigrants from low- and middle-income countries. Acute surgical management with corrective mid-foot osteotomy and elongation of the Achilles tendon has an excellent functional outcome. Objective: To assess the functional outcome of acute correction of neglected Talipes-quinoa-varus deformity in adults. Methods: This is a cross-sectional, hospital–based multi-centric study. Forty patients were included in this study. Midfoot osteotomy and elongation of the Achilles tendon were performed on all patients. Data was collected using a questionnaire and the functional outcome has been assessed using the American Orthopedic Foot and Ankle Society Score (AOFAS). This score was measured before surgery and one year after surgery. Results: the mean age was 19.9 ± 4.7 years. Males were 25 (62.5%) and females were 15 (37.5%). The mean preoperative AOFAS score was 37.7 ± 7.1 (poor). This score improved to 80.7 ± 13.7 (good to excellent), two years after surgery. However, this indicates a significant change in the functional outcome after the operation (p value Conclusion: acute correction of neglected and relapsed TEV with elongation of the Achilles tendon and single midfoot osteotomy has excellent functional outcome as assessed by AOFAS Score. The satisfaction with this procedure is impressive. The younger age population showed better outcomes with this procedure.展开更多
BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we repo...BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient,which is very rare.CASE SUMMARY Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient.The patient had a giant cystic-solid mass in the right hepatic lobe that was evident on ultrasound and computed tomography.Postoperative pathology and immunohistochemistry of the mass,which was surgically removed,suggested fibroblastic osteosarcoma.Hepatic osteosarcoma reoccurred 48 d after surgery,resulting in significant compression and narrowing of the hepatic segment of the inferior vena cava.Consequently,the patient underwent stent implantation in the inferior vena cava and transcatheter arterial chemoembolization.Unfortunately,the patient died of multiple organ failure postoperatively.CONCLUSION ESOS is a rare mesenchymal tumor with a short course and a high likelihood of metastasis and recurrence.The combination of surgical resection and chemotherapy may be the best treatment.展开更多
Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In ...Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.展开更多
Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy...Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.展开更多
BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2...BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.展开更多
BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clini...BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clinical outcome.Although L-asparaginase-based chemotherapy has improved the response rates of relapsed/refractory(R/R) ENKL,relapse occurs in up to 50% of patients with disseminated disease.CASE SUMMARY Immune evasion has emerged as a critical pathway for survival in ENKL and may be effectuated via STAT3-driven upregulation of programmed cell death ligand 1(PD-L1) or other molecular pathways.Anti-PD-1 is effective for R/R ENKL with EBV-driven upregulation of PD-L1 expression.Anti-PD-1 combined with decitabine showed positive preliminary results in a patient with R/R ENKL and resistance to anti-PD-1.CONCLUSION The treatment experience,in this case,demonstrated the potential ability of decitabine combined with PD-1 inhibitor to treat R/R ENKL,thus providing a new treatment strategy for this tumor.展开更多
Objective: The aim of our study was to analyze the long-term results of rituximab combined with temozolomide in treatment of elderly patients (> 60 years) with relapsed primary central nervous system lymphoma (PCNS...Objective: The aim of our study was to analyze the long-term results of rituximab combined with temozolomide in treatment of elderly patients (> 60 years) with relapsed primary central nervous system lymphoma (PCNSL). Methods: Twelve postoperative elderly patients (> 60 years) were treated between August 2004 and October 2009. Temozolomide 100 mg/m2 to 200 mg/m2 days 1 to 7 and 15 to 21 and rituximab 375 mg/m2 days 1, 5, 8, 22. The maximum number of rituximab cycles was two. After one or two cycles of this combination, patients with an objective response and an acceptable level of toxicity continued treatment with single agent temozolomide (days 1 to 5, every 28 days). The overall survival was analyzed by using Kaplan-Meier. Results: The overall survival was 9 months. Toxicity was very mild with no grade 3-4 neurotoxicity toxic events. Conclusion: Rituximab combined with temozolomide seems to yields substantial long-term survival with moderate toxicity for the treatment of elderly relapsed PCNSL.展开更多
BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high...BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes.Despite the administration of immunotherapeutic agents,in particular bortezomib and daratumumab,which have improved the outcomes of AL amyloidosis,antiplasma cell therapy remains suboptimal for some patients.CASE SUMMARY We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy.He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen.The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion,in which flow cytometry analysis showed abnormal plasma cells.After two cycles of this regimen,the pleural effusion was controlled effectively with no recurrence.CONCLUSION This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.展开更多
BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)...BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.展开更多
Purpose: To assess the response rate, duration of response and prognostic factors affecting response after low-dose involved-field radiotherapy in patients with relapsed low-grade B-cell non-Hodgkin lymphoma. Patients...Purpose: To assess the response rate, duration of response and prognostic factors affecting response after low-dose involved-field radiotherapy in patients with relapsed low-grade B-cell non-Hodgkin lymphoma. Patients and Methods: Forty-four patients were included. Patients were treated with a total dose of 4 Gy (2 × 2 Gy) using 6 - 15 Mv photon or electron beam. Results: most patients were above age of 60 years (59%) with male predominance. Follicular lymphoma was the most common pathological type;bulky disease (>5 cm) was presented in 61.4%. Patients who received only 2 regimens were 63.7% and 31.8% had >2 involved sites. No treatment related toxicity was observed. The overall response rate was 88.7%;complete response was reached in 59.1% and stable disease in 6.8%, progressive disease in 4.5%. Median time to local progression was 33 months (95% CI 23.70 - 42.29);2-year local progression free survival was 78%. Response rate was found to be dependent on age, number of involved sites and lymph node size but independent on sex, pathological type, number of prior regimens, LDH level and time since diagnosis. Conclusion: Short-course-low dose palliative radiotherapy (2 × 2 Gy) affords an attractive option for treatment of relapsed low-grade non-Hodgkin’s lymphoma due to high response rates. However, these results had to be confirmed in a larger number of patients.展开更多
Summary Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation. The development of non-myeloa...Summary Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation. The development of non-myeloablative conditioning regimens allows utilization of allogeneic effects in patients usually not suitable for myeloablative allogeneic transplantation, such as older and heavily pretreated patients. In a small series of 11 patients with multiple myeloma relapsing after autologous transplantation, we show that conditioning with low-dose total body irradiation in combination with fludarabine allows stable engraftment after matched unrelated donor transplantation and is tolerated with acceptable transplant-related morbidity and mortality. With a short median follow-up of 225 days, disease control was achieved only for patients responding to conventional treatment prior to allografting. Future studies with longer follow-up have to define the role of non-myeloablative allogeneic transplantation from unrelated donors as consolidation for patients responding to salvage therapy.展开更多
【正】Dear Sir,We hereby report two cases of methanol optic neuropathy with relapsed vision disturbance.Methanol intoxication appears after accidental or suicidal oral ingestion of industrial solvents or cleaning and ...【正】Dear Sir,We hereby report two cases of methanol optic neuropathy with relapsed vision disturbance.Methanol intoxication appears after accidental or suicidal oral ingestion of industrial solvents or cleaning and antifreeze liquids or occasionally is due to fraudulent adulteration of wine or other alcoholic beverages.Its ingestion can cause severe visual disturbances and the outcomes of visual disturbances vary diffusively.Some completely or partially recovered,and some suffered展开更多
Objective:To investigate the clinical efficacy and safety of ixazomib in the treatment of relapsed/refractory multiple myeloma(RRMM).Methods:The clinical data of 20 patients with RRMM admitted to the hospital from Jan...Objective:To investigate the clinical efficacy and safety of ixazomib in the treatment of relapsed/refractory multiple myeloma(RRMM).Methods:The clinical data of 20 patients with RRMM admitted to the hospital from January 2020 to January 2022 were analyzed retrospectively.All patients were treated with ixazomib-based chemotherapy regimen(IRD regimen 13 cases;ID regimen 7 cases).The objective response rate(ORR)and adverse events(AEs)were observed.Results:All 20 patients received two to seven courses of treatment,in which the median was three courses.One patient had CR,four patients had VGPR,seven patients had PR,two patients had SD,and six patients had PD.The ORR was 60.00%(12/20),and 25.00%(5/20)of them had VGPR or more.The ORR of patients with previous treatment lines≥3,ISS stage III,and high-risk cytogenetic was lower than that of patients with previous treatment lines<3,ISS stage I/II,and low-risk cytogenetics.The main AEs include anemia,thrombocytopenia,neutropenia,nausea and vomiting,diarrhea,constipation,and respiratory tract infection,most of which are grade I/II.Conclusion:Ixazomib is effective in the treatment of RRMM in some patients,and the AEs are controllable.Patients who had received less than 3 lines of treatment in the past,with ISS stage I to II and low-risk cytogenetics had better treatment effect.展开更多
Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocyti...Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.展开更多
Acute myeloid leukemia （AML） is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AM...Acute myeloid leukemia （AML） is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair （MMR） function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease Datho8enesis.展开更多
AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received ...AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received treatment at our institution were queried.Analysis was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF.RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determined by Fibroscan or MRI. Seven(87.5%) patients had genotype 1a HCV. Seven(87.5%) patients had over 1 million IU/m L HCV RNA at the time of re-treatment.CONCLUSION: This study identifies factors associated with SMV/SOF treatment failure and provides evidence that twleve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titer genotype 1a HCV.展开更多
Dynamic supination of the foot is a common residual deformity in children with clubfeet treated with the Ponseti method. Transfer of the anterior tibialis tendon (ATT) to the lateral cuneiform is an effective method f...Dynamic supination of the foot is a common residual deformity in children with clubfeet treated with the Ponseti method. Transfer of the anterior tibialis tendon (ATT) to the lateral cuneiform is an effective method for correcting this deformity when the cuneiform is ossified in children who are 3 to 5 years of age. We describe two cases of a previously unreported method of ATT transposition for correction of bilateral residual dynamic supination in a 26-month-old and a 19-month-old patient. Both patients presented shortly after birth with bilateral congenital idiopathic clubfoot and were initially treated with the Ponseti method. Both had residual deformity following initial treatment that included posterior contracture and metatarsus adductus with dynamic forefoot supination. This was surgically corrected with a posterior release and medial release of the 1st metatarsal/1st cuneiform joint. To correct dynamic supination, the ATT was transplanted laterally into the released midfoot joint. These two patients were followed post-operatively for 7.5 years and have correction of their residual deformity in both feet based on subjective functioning, appearance, range of motion, strength, and gait. Both have excellent lateral pull of their ATT, which functions as a strong foot dorsiflexor. No residual supination is present. This is the first report of lateral transposition of the ATT as an interposition graft at the released 1st metatarsal/1st cuneiform joint in patients with relapsed clubfoot. We suggest that this method should provide a high level of functioning in children with relapsed supination deformity and whose 3rd cuneiform has not yet ossified.展开更多
AIM： To assess the efficacy of different schedules of consensus interferon （CIFN） plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon （rIFN） monotherapy. METHODS： ...AIM： To assess the efficacy of different schedules of consensus interferon （CIFN） plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon （rIFN） monotherapy. METHODS： Forty-five patients （34 males and 11 females） with chronic hepatitis due to hepatitis C virus （HCV） genotype 1 who relapsed after a previous course of rIFN monotherapy were randomized to receive 9 μg CIFN three times per week for 52 wk （group A, n = 22） or 18 μg CIFN three times per week for 52 wk （group B, n = 23） in combination with ribavirin 800 to 1200 mg daily for 52 wk （according to body weight）. Virological response was evaluated at week 24 （ERR）, at the end of treatment （ETR） and at 76 wk （SVR）. RESULTS： By intention-to-treat analysis, subjects in group A had an EVR in 35% of cases, an ETR in 35% and a SVR in 27.3% of cases. Subjects in group B had an EVR in 32% of cases, an ETR in 35% and a SVR in 26.1% of cases. Treatment was stopped because of adverse effects （mostly intolerance） in 15 patients （6 in group A and 9 in group B）. IFN dose reduction was needed in 2 patients （1 in group A and 1 in group B）. Ribavirin dose was reduced in 2 patients in group A and 1 in group B respectively. Among the 15 subjects who received at least 80% of the intended schedule, the rate of SVR was 80% （6 in group A and 6 in group B）. CONCLUSION： CIFN in combination with ribavirin when given to HCV genotype 1 relapsers after rIFN monotherapy obtains an unsatisfactory rate of sustained viral clearance independently of dosage of the drug. This may be due to its scarce tolerability.展开更多
文摘BACKGROUND Ovarian cancer is the most common malignant tumor of the female reproductive system,and the survival rate of patients with relapsed and refractory ovarian cancer is very low.CASE SUMMARY Here,we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy.Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful;however,her tumor relapsed.Subsequent second-line chemotherapy,targeted agents,and other treatments were ineffective,as the tumor continued to recur and metastasize.Anti-programmed cell death-1(PD-1)monotherapy(tislelizumab)completely alleviated the tumor,and the multiple metastatic tumors disappeared.To date,the patient has used anti-PD-1 for 32 months,experiencing no disease progression and maintaining good health without additional treatment.CONCLUSION This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors.Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.
文摘Background: Neglected clubfoot in this series is defined as untreated equino-cavo-adducto-varus in older children or adults. Relapsed clubfoot is the residual deformity that remains after single or multiple surgical interventions. Severely neglected clubfoot rarely exists today in developed countries, except in some emigrants from low- and middle-income countries. Acute surgical management with corrective mid-foot osteotomy and elongation of the Achilles tendon has an excellent functional outcome. Objective: To assess the functional outcome of acute correction of neglected Talipes-quinoa-varus deformity in adults. Methods: This is a cross-sectional, hospital–based multi-centric study. Forty patients were included in this study. Midfoot osteotomy and elongation of the Achilles tendon were performed on all patients. Data was collected using a questionnaire and the functional outcome has been assessed using the American Orthopedic Foot and Ankle Society Score (AOFAS). This score was measured before surgery and one year after surgery. Results: the mean age was 19.9 ± 4.7 years. Males were 25 (62.5%) and females were 15 (37.5%). The mean preoperative AOFAS score was 37.7 ± 7.1 (poor). This score improved to 80.7 ± 13.7 (good to excellent), two years after surgery. However, this indicates a significant change in the functional outcome after the operation (p value Conclusion: acute correction of neglected and relapsed TEV with elongation of the Achilles tendon and single midfoot osteotomy has excellent functional outcome as assessed by AOFAS Score. The satisfaction with this procedure is impressive. The younger age population showed better outcomes with this procedure.
文摘BACKGROUND Extraskeletal osteosarcoma(ESOS)is a highly malignant osteosarcoma that occurs in extraskeletal tissues.It often affects the soft tissues of the limbs.ESOS is classified as primary or secondary.Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient,which is very rare.CASE SUMMARY Here,we report a case of primary hepatic osteosarcoma in a 76-year-old male patient.The patient had a giant cystic-solid mass in the right hepatic lobe that was evident on ultrasound and computed tomography.Postoperative pathology and immunohistochemistry of the mass,which was surgically removed,suggested fibroblastic osteosarcoma.Hepatic osteosarcoma reoccurred 48 d after surgery,resulting in significant compression and narrowing of the hepatic segment of the inferior vena cava.Consequently,the patient underwent stent implantation in the inferior vena cava and transcatheter arterial chemoembolization.Unfortunately,the patient died of multiple organ failure postoperatively.CONCLUSION ESOS is a rare mesenchymal tumor with a short course and a high likelihood of metastasis and recurrence.The combination of surgical resection and chemotherapy may be the best treatment.
基金the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
文摘Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.
基金the National Natural Science Foundation of China(No.81873452)the Clinical Research Program of Huazhong University of Science and Technology Affiliated Tongji Hospital(No.2020003).
文摘Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.
文摘BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.
基金Supported by the Medical Health Science and Technology Project of Zhejiang Province Health Commission,No.2020376298。
文摘BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clinical outcome.Although L-asparaginase-based chemotherapy has improved the response rates of relapsed/refractory(R/R) ENKL,relapse occurs in up to 50% of patients with disseminated disease.CASE SUMMARY Immune evasion has emerged as a critical pathway for survival in ENKL and may be effectuated via STAT3-driven upregulation of programmed cell death ligand 1(PD-L1) or other molecular pathways.Anti-PD-1 is effective for R/R ENKL with EBV-driven upregulation of PD-L1 expression.Anti-PD-1 combined with decitabine showed positive preliminary results in a patient with R/R ENKL and resistance to anti-PD-1.CONCLUSION The treatment experience,in this case,demonstrated the potential ability of decitabine combined with PD-1 inhibitor to treat R/R ENKL,thus providing a new treatment strategy for this tumor.
文摘Objective: The aim of our study was to analyze the long-term results of rituximab combined with temozolomide in treatment of elderly patients (> 60 years) with relapsed primary central nervous system lymphoma (PCNSL). Methods: Twelve postoperative elderly patients (> 60 years) were treated between August 2004 and October 2009. Temozolomide 100 mg/m2 to 200 mg/m2 days 1 to 7 and 15 to 21 and rituximab 375 mg/m2 days 1, 5, 8, 22. The maximum number of rituximab cycles was two. After one or two cycles of this combination, patients with an objective response and an acceptable level of toxicity continued treatment with single agent temozolomide (days 1 to 5, every 28 days). The overall survival was analyzed by using Kaplan-Meier. Results: The overall survival was 9 months. Toxicity was very mild with no grade 3-4 neurotoxicity toxic events. Conclusion: Rituximab combined with temozolomide seems to yields substantial long-term survival with moderate toxicity for the treatment of elderly relapsed PCNSL.
文摘BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes.Despite the administration of immunotherapeutic agents,in particular bortezomib and daratumumab,which have improved the outcomes of AL amyloidosis,antiplasma cell therapy remains suboptimal for some patients.CASE SUMMARY We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy.He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen.The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion,in which flow cytometry analysis showed abnormal plasma cells.After two cycles of this regimen,the pleural effusion was controlled effectively with no recurrence.CONCLUSION This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.
文摘BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.
文摘Purpose: To assess the response rate, duration of response and prognostic factors affecting response after low-dose involved-field radiotherapy in patients with relapsed low-grade B-cell non-Hodgkin lymphoma. Patients and Methods: Forty-four patients were included. Patients were treated with a total dose of 4 Gy (2 × 2 Gy) using 6 - 15 Mv photon or electron beam. Results: most patients were above age of 60 years (59%) with male predominance. Follicular lymphoma was the most common pathological type;bulky disease (>5 cm) was presented in 61.4%. Patients who received only 2 regimens were 63.7% and 31.8% had >2 involved sites. No treatment related toxicity was observed. The overall response rate was 88.7%;complete response was reached in 59.1% and stable disease in 6.8%, progressive disease in 4.5%. Median time to local progression was 33 months (95% CI 23.70 - 42.29);2-year local progression free survival was 78%. Response rate was found to be dependent on age, number of involved sites and lymph node size but independent on sex, pathological type, number of prior regimens, LDH level and time since diagnosis. Conclusion: Short-course-low dose palliative radiotherapy (2 × 2 Gy) affords an attractive option for treatment of relapsed low-grade non-Hodgkin’s lymphoma due to high response rates. However, these results had to be confirmed in a larger number of patients.
文摘Summary Existence of a graft-versus-myeloma effect has been well documented by responses to donor lymphocyte infusions and long-term survival after allogeneic bone marrow transplantation. The development of non-myeloablative conditioning regimens allows utilization of allogeneic effects in patients usually not suitable for myeloablative allogeneic transplantation, such as older and heavily pretreated patients. In a small series of 11 patients with multiple myeloma relapsing after autologous transplantation, we show that conditioning with low-dose total body irradiation in combination with fludarabine allows stable engraftment after matched unrelated donor transplantation and is tolerated with acceptable transplant-related morbidity and mortality. With a short median follow-up of 225 days, disease control was achieved only for patients responding to conventional treatment prior to allografting. Future studies with longer follow-up have to define the role of non-myeloablative allogeneic transplantation from unrelated donors as consolidation for patients responding to salvage therapy.
基金Supported by Natural Science Foundation of Guangdong ProvinceChina(S2012010008439)
文摘【正】Dear Sir,We hereby report two cases of methanol optic neuropathy with relapsed vision disturbance.Methanol intoxication appears after accidental or suicidal oral ingestion of industrial solvents or cleaning and antifreeze liquids or occasionally is due to fraudulent adulteration of wine or other alcoholic beverages.Its ingestion can cause severe visual disturbances and the outcomes of visual disturbances vary diffusively.Some completely or partially recovered,and some suffered
文摘Objective:To investigate the clinical efficacy and safety of ixazomib in the treatment of relapsed/refractory multiple myeloma(RRMM).Methods:The clinical data of 20 patients with RRMM admitted to the hospital from January 2020 to January 2022 were analyzed retrospectively.All patients were treated with ixazomib-based chemotherapy regimen(IRD regimen 13 cases;ID regimen 7 cases).The objective response rate(ORR)and adverse events(AEs)were observed.Results:All 20 patients received two to seven courses of treatment,in which the median was three courses.One patient had CR,four patients had VGPR,seven patients had PR,two patients had SD,and six patients had PD.The ORR was 60.00%(12/20),and 25.00%(5/20)of them had VGPR or more.The ORR of patients with previous treatment lines≥3,ISS stage III,and high-risk cytogenetic was lower than that of patients with previous treatment lines<3,ISS stage I/II,and low-risk cytogenetics.The main AEs include anemia,thrombocytopenia,neutropenia,nausea and vomiting,diarrhea,constipation,and respiratory tract infection,most of which are grade I/II.Conclusion:Ixazomib is effective in the treatment of RRMM in some patients,and the AEs are controllable.Patients who had received less than 3 lines of treatment in the past,with ISS stage I to II and low-risk cytogenetics had better treatment effect.
基金supported by grants from the National Natural Science Foundation of China(No.81300412 and No.81470333)
文摘Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.
文摘Acute myeloid leukemia （AML） is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair （MMR） function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease Datho8enesis.
基金Supported by The Grants No.R01 DK090317 and No.R01 DA031095(in part)
文摘AIM: To determine risk factors associated with hepatitis C virus(HCV) treatment failure after direct acting antivirals in patients with complex treatment histories.METHODS: All HCV mono-infected patients who received treatment at our institution were queried.Analysis was restricted to patients who previously failed treatment with boceprevir(BOC) or telaprevir(TVR) and started simeprevir(SMV) and sofosbuvir(SOF) ± ribavirin(RBV) between December 2013 and June 2014. Patients with human immunodeficiency virus(HIV)/HCV co-infection or patients who received a liver transplant in the past were excluded. Viral loads were recorded while on treatment and after treatment. Data collection continued until December,31 st 2014 when data analysis was initiated. Patients missing virologic outcomes data were not included in the analysis. Analysis of 35 patients who had virologic outcome data available resulted in eight patients who were viral load negative at the end of treatment with SMF/SOF but later relapsed. Data related to patient demographics,HCV infection,and treatment history was collected in order to identify risk factors shared among patients who failed treatment with SMF/SOF.RESULTS: Eight patients who were treated with the first generation HCV protease inhibitors BOC or TVR in combination with pegylated-interferon(PEG) and RBV who failed this triple therapy were subsequently retreated with an off-label all-oral regimen of SMV and SOF for 12 wk,with RBV in seven cases. Treatment was initiated before the Food and Drug Administration approved a 24-wk SMV/SOF regimen for patients with liver cirrhosis. All eight patients had an end of treatment response,but later relapsed. Eight(100%) patients were male. Mean age was 56(range,49-64). Eight(100%) patients had previously failed PEG/RBV dual therapy at least once in addition to prior failure with triple therapy. Total number of times treated ranged from 3-6(mean 3.8). Eight(100%) patients were male had liver cirrhosis as determined by Fibroscan or MRI. Seven(87.5%) patients had genotype 1a HCV. Seven(87.5%) patients had over 1 million IU/m L HCV RNA at the time of re-treatment.CONCLUSION: This study identifies factors associated with SMV/SOF treatment failure and provides evidence that twleve weeks of SMV/SOF/RBV is insufficient in cirrhotics with high-titer genotype 1a HCV.
文摘Dynamic supination of the foot is a common residual deformity in children with clubfeet treated with the Ponseti method. Transfer of the anterior tibialis tendon (ATT) to the lateral cuneiform is an effective method for correcting this deformity when the cuneiform is ossified in children who are 3 to 5 years of age. We describe two cases of a previously unreported method of ATT transposition for correction of bilateral residual dynamic supination in a 26-month-old and a 19-month-old patient. Both patients presented shortly after birth with bilateral congenital idiopathic clubfoot and were initially treated with the Ponseti method. Both had residual deformity following initial treatment that included posterior contracture and metatarsus adductus with dynamic forefoot supination. This was surgically corrected with a posterior release and medial release of the 1st metatarsal/1st cuneiform joint. To correct dynamic supination, the ATT was transplanted laterally into the released midfoot joint. These two patients were followed post-operatively for 7.5 years and have correction of their residual deformity in both feet based on subjective functioning, appearance, range of motion, strength, and gait. Both have excellent lateral pull of their ATT, which functions as a strong foot dorsiflexor. No residual supination is present. This is the first report of lateral transposition of the ATT as an interposition graft at the released 1st metatarsal/1st cuneiform joint in patients with relapsed clubfoot. We suggest that this method should provide a high level of functioning in children with relapsed supination deformity and whose 3rd cuneiform has not yet ossified.
文摘AIM： To assess the efficacy of different schedules of consensus interferon （CIFN） plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon （rIFN） monotherapy. METHODS： Forty-five patients （34 males and 11 females） with chronic hepatitis due to hepatitis C virus （HCV） genotype 1 who relapsed after a previous course of rIFN monotherapy were randomized to receive 9 μg CIFN three times per week for 52 wk （group A, n = 22） or 18 μg CIFN three times per week for 52 wk （group B, n = 23） in combination with ribavirin 800 to 1200 mg daily for 52 wk （according to body weight）. Virological response was evaluated at week 24 （ERR）, at the end of treatment （ETR） and at 76 wk （SVR）. RESULTS： By intention-to-treat analysis, subjects in group A had an EVR in 35% of cases, an ETR in 35% and a SVR in 27.3% of cases. Subjects in group B had an EVR in 32% of cases, an ETR in 35% and a SVR in 26.1% of cases. Treatment was stopped because of adverse effects （mostly intolerance） in 15 patients （6 in group A and 9 in group B）. IFN dose reduction was needed in 2 patients （1 in group A and 1 in group B）. Ribavirin dose was reduced in 2 patients in group A and 1 in group B respectively. Among the 15 subjects who received at least 80% of the intended schedule, the rate of SVR was 80% （6 in group A and 6 in group B）. CONCLUSION： CIFN in combination with ribavirin when given to HCV genotype 1 relapsers after rIFN monotherapy obtains an unsatisfactory rate of sustained viral clearance independently of dosage of the drug. This may be due to its scarce tolerability.
