Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Background: Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in surgical treatment. Although the benefits of preoperative rehabilitation (prehabilitation) in hip arthroplasty have been reported, pain management remains a challenge. The pericapsular nerve group (PENG) block, known for its exceptional analgesic effect and motor function preservation, may be a promising intervention during prehabilitation in these patients. Case: We enrolled ten patients with Garden classification 3–4 femoral neck fractures scheduled for hip arthroplasty. After receiving a PENG block with 20 ml of 0.375% ropivacaine, all patients underwent initial prehabilitation sessions comprising 9 mobility levels, ranging from bed-sitting to walking. One patient was excluded due to experiencing high blood pressure during prehabilitation. Six of the nine remaining patients (66.7%) were successfully transferred from bed to wheelchair. Conclusions The PENG block enhanced prehabilitation for patients with femoral neck fractures undergoing hip arthroplasty.

Objective: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. Results: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. Conclusion Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.

Objective: In this study we sought to investigate the clinical factors that affect postprogression survival (PPS) in patients with recurrent or persistent clear cell carcinoma (CCC).We utilized the JGOG3017/Gynecological Cancer InterGroup data to compare paclitaxel plus carboplatin (TC) and irinotecan plus cisplatin (CPT-P) in the treatment of stages I to IV CCC. Methods: We enrolled 166 patients with recurrent or persistent CCC and assessed the impact of variables, including platinum sensitivity, treatment arm, crossover chemotherapy, primary stage, residual tumor at primary surgery, performance status, ethnicity, and tumor reduction surgery at recurrence on the median of PPS in patients with recurrent or persistent CCC. Results: A total of 77 patients received TC, and 89 patients received CPT-P. The median PPS for patients with platinum-resistant disease was 10.9 months, compared with 18.8 months for patients with platinum-sensitive disease (hazard ratio [HR]=1.88; 95% confidence interval [CI]=1.30–2.72; log-rank p<0.001). In the multivariate analysis, the platinum sensitivity (resistant vs. sensitivity; HR=1.60; p=0.027) and primary stage (p=0.009) were identified as independent predictors of prognosis factors for PPS in recurrent or persistent CCC. Conclusions Our findings revealed that platinum sensitivity and primary stage are clinical factors that significantly affect PPS in patients with recurrent or persistent CCC as wellas other histologic subtypes of ovarian cancer. PPS in patients with recurrent CCC should establish the basis for future clinical trials in this population.

PURPOSE: To evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC).METHODS: The study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test.RESULTS: A total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P<0.0001). The median recurrence-free time for the first HD/FUL was 10.1 months, while that for the second HD/FUL plus maintenance DMSO therapy has yet to be reached. The recurrence-free rate for the first HD/FUL was 81.0% at 6 months, 38.1% at 1 year, 9.5% at 2 years, and 4.8% at 3 years. In contrast, the rate for the second HD/FUL plus maintenance DMSO therapy was 100% at 6 months, 94.7% at 1 year, 82.6% at 2 years, and 82.6% at 3 years. There were no significant differences in efficacy between the first and second HD/FUL.CONCLUSIONS: HD/FUL plus maintenance DMSO therapy clearly prolongs the recurrence-free time compared with HD/FUL alone in Hunner type IC.
Cystitis, Interstitial ; Dimethyl Sulfoxide ; Humans ; Methods ; Pilot Projects ; Recurrence

The production of red blood cells, termed erythropoiesis, occurs in two waves in the developing mouse embryo: first primitive erythropoiesis followed by definitive erythropoiesis. In the mouse embryo, both primitive and definitive erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave then migrates to the fetal liver, fetal spleen and fetal bone marrow as these organs form. The fetal liver serves as the major organ for hematopoietic cell expansion and erythroid maturation after mid-gestation. The erythropoietic niche, which expresses critical cytokines such as stem cell factor (SCF), thrombopoietin (TPO) and the insulin-like growth factors IGF1 and IGF2, supports hematopoietic expansion in the fetal liver. Previously, our group demonstrated that DLK1⁺ hepatoblasts support fetal liver hematopoiesis through erythropoietin and SCF release as well as extracellular matrix deposition. Loss of DLK1⁺ hepatoblasts in Map2k4(−/−) mouse embryos resulted in decreased numbers of hematopoietic cells in fetal liver. Genes encoding proteinases and peptidases were found to be highly expressed in DLK1⁺ hepatoblasts. Capitalizing on this knowledge, and working on the assumption that these proteinases and peptidases are generating small, potentially biologically active peptides, we assessed a range of peptides for their ability to support erythropoiesis in vitro. We identified KS-13 (PCT/JP2010/067011) as an erythropoietic peptide-a peptide which enhances the production of red blood cells from progenitor cells. Here, we discuss the elements regulating embryonic erythropoiesis with special attention to niche cells, and demonstrate how this knowledge can be applied in the identification of niche-derived peptides with potential therapeutic capability.
Animals ; Bone Marrow ; Cytokines ; Embryonic Structures ; Erythrocytes ; Erythropoiesis ; Erythropoietin ; Extracellular Matrix ; Hematopoiesis ; In Vitro Techniques ; Liver ; Mice ; Peptide Hydrolases ; Peptides ; Somatomedins ; Spleen ; Stem Cell Factor ; Stem Cells ; Thrombopoietin ; Yolk Sac

Although numerous studies have shown that each neuropsychological test is effective for diagnosing mild cognitive impairment (MCI) or Alzheimer’s disease (AD), studies comparing diagnostic accuracies of various neuropsychological tests are relatively rare and practical cutoff values are not available. The present study aimed to investigate the validity of neuropsychological tests and develop cutoff values for each in differentiating healthy control (HC), MCI and AD groups. A total of 84 HC, 187 with MCI and 195 with AD were evaluated by the selected seven neuropsychological tests using receiver operating characteristic (ROC) curve analysis. Logical Memory (LM) delayed recall (cutoff, 7) and Rey Auditory Verbal Learning Test (RAVLT) delayed recall (cutoff, 6) were effective for differentiating HC from MCI. To distinguish MCI and AD, Rey Osterrieth Complex Figure Test (ROCFT) 3 mindelayed recall (cutoff, 6) and LM immediate recall (cutoff, 4) were excellent. Delayed recall of verbal materials, as indexed by LM and RAVLT was sensitive for discriminating MCI from HC. Handling visual memory traces, as indexed by ROCFT and immediate verbal information by LM were sensitive for differentiating MCI and AD.
Alzheimer Disease ; Dementia ; Neuropsychological Tests