Impact of HIV Infection on Transplant Outcomes after Autologous Peripheral Blood Stem Cell Transplantation: A Retrospective Study of Japanese Registry Data

Autologous stem cell transplantation (ASCT) is a treatment option for HIV-positive patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). However, the prognosis after ASCT in HIV-positive Japanese patients remains unclear. The aim of this study was to evaluate the impact of HIV infection on transplant outcomes after ASCT in Japan. Using the national database of the Japan Society for Hematopoietic Cell Transplantation, we retrospectively evaluated patients with NHL (n?=?3862) and MM (n?=?2670) who underwent their first ASCT between 2001 and 2014. The presence of HIV antibody was used to diagnose HIV infection. Fifty-six patients with NHL (1.4%) and 23 with MM (.8%) were positive for HIV antibody. Among patients with NHL overall survival (OS) was lower in HIV-positive patients than in HIV-negative patients (5-year OS: HIV-positive patients, 44% versus HIV-negative patients, 65%; P?<?.001). In a multivariate analysis HIV infection was significantly associated with an increased risk of overall mortality (hazard ratio, 2.30; P?<?.001). The incidence of relapse was higher in HIV-positive patients (P?=?.036), whereas there was a similar incidence of nonrelapse mortality (P?=?.879). OS in patients with MM was similar between those with/without HIV infection (5-year OS: HIV-positive patients, 61% versus HIV-negative patients, 63%; P?=?.988). HIV infection was associated with a higher risk of overall mortality and relapse after ASCT for NHL in a Japanese population.     

Identification of novel helper epitope peptides of Survivin cancer-associated antigen applicable to developing helper/killer-hybrid epitope long peptide cancer vaccine

We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01. The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02. This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4⁺ and CD8⁺ T cells though it contained both helper and killer epitopes. To enhance the vaccine efficacy, we synthesized a long peptide by conjugating SU18 peptide and another DR53-restricted helper epitope peptide (SU22; 12 amino-acids) using glycine-linker. We designated this artificial 40 amino-acids long peptide containing two helper and three killer epitopes as Survivin-helper/killer-hybrid epitope long peptide (Survivin-H/K-HELP). Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4⁺ Th1 cells and CD8⁺ Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC). Survivin-H/K-HELP-pulsed Mo-DC pretreated with OK-432 also exhibited sustained antigen-presentation capability of stimulating Survivin-specific Th1 cells compared with Mo-DC pulsed with a mixture of SU18 and SU22 short peptides. Moreover, we demonstrated that Survivin-H/K-HELP induced a complete response in a breast cancer patient with the induction of cellular and humoral immune responses. Thus, we believe that an artificially synthesized Survivin-H/K-HELP will become an innovative cancer vaccine.     

Lung miliary micro‐nodules in human T‐cell leukemia virus type I carriers

Human T‐cell leukemia virus type 1 (HTLV‐1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well‐known complication, adult T‐cell leukemia/lymphoma (ATLL). HTLV‐1 associated bronchiolo‐alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV‐1 carriers. The reported clinico‐pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP). We here report three cases of HTLV‐1 carriers showing miliary micro‐nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro‐nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA.     

Cause-of-death ascertainment for deaths that occur outside hospitals in Thailand: application of verbal autopsy methods

Background  

Ascertainment of cause for deaths that occur in the absence of medical attention is a significant problem in many countries, including Thailand, where more than 50% of such deaths are registered with ill-defined causes. Routine implementation of standardized, rigorous verbal autopsy methods is a potential solution. This paper reports findings from field research conducted to develop, test, and validate the use of verbal autopsy (VA) methods in Thailand.     

Evaluation of the Efficacy and Safety of Hyaluronic Acid Vaginal Gel to Ease Vaginal Dryness: A Multicenter,Randomized, Controlled,Open‐Label,Parallel‐Group,Clinical Trial

IntroductionAtrophic vaginitis is a common occurrence, particularly among postmenopausal women; however, few seek or receive treatment. One therapeutic solution is topically applied products. Estrogen‐based treatments have been shown to be effective; however, many patients are reluctant to use such formulations due to health concerns, hence the need to assess the efficacy of acceptable alternatives.AimThis multicenter, randomized, controlled, open‐label, parallel‐group clinical trial set out to evaluate the efficacy and safety of hyaluronic acid vaginal gel to treat vaginal dryness compared with estriol cream in postmenopausal women.MethodsOne hundred forty‐four subjects were randomized, 72 to the test group treated with hyaluronic acid vaginal gel (Hyalofemme) and 72 to the control group treated with estriol cream (Ovestin). Treatment in both groups was applied by means of a device once every 3 days for a total of 10 applications over 30 days.Main Outcome MeasuresEfficacy was measured by grading vaginal dryness and three other vaginal symptoms on a visual analog scale. Safety assessments included vital signs, laboratory examinations of the vaginal microecosystem, vaginal pH value, vaginal B ultrasound, and incidence of adverse events. Assessments were performed at baseline, by telephone after the third application, and at the final visit.ResultsBoth hyaluronic acid vaginal gel and estriol cream can significantly improve the clinical symptoms of vaginal dryness in postmenopausal women, with improvement rate of 84.44% and 89.42%, respectively, after 10 applications, without statistically significant difference between them.ConclusionBoth hyaluronic acid vaginal gel and estriol cream are effective in the treatment of vaginal dryness. Hyaluronic acid vaginal gel may be considered as a valid alternative to estrogen‐based treatments in relieving the symptoms of vaginal dryness.     

Prospective assessment of time-dependent changes in quality of life of Japanese patients with prostate cancer following robot-assisted radical prostatectomy

The objective of this study was to characterize changes in the quality of life (QOL) of Japanese patients following robot-assisted radical prostatectomy (RARP). This study included 298 consecutive localized prostate cancer (PC) patients undergoing RARP. The health-related QOL and disease-specific QOL were assessed using The Medical Outcomes Study 8-Item Short Form (SF-8) and The Extended Prostate Cancer Index Composite (EPIC), respectively, before and 1, 3, 6, 12 and 24 months after RARP. At 1 month after RARP, four (physical function, role limitations because of physical health problems, social function and role limitations because of emotional problems) of the eight scores in SF-8 were significantly impaired compared with those of baseline scores. However, all eight scores on all postoperative assessments, except for at 1 month after RARP, showed no significant differences from baseline scores. Although there were no significant differences in the bowel function, bowel bother, sexual bother, hormonal function or hormonal bother between baseline and postoperative assessments of EPIC at all time points, the urinary function, urinary incontinence and sexual function scores at 1, 3 and 6 months after RARP were significantly inferior to those of baseline scores, and urinary bother and urinary irritation/obstruction scores at 1 month after RARP were significantly impaired compared with those of baseline scores. These findings suggest that the health-related QOL of Japanese PC patients undergoing RARP may not be markedly deteriorated following RARP; however, as for the disease-specific QOL, urinary and sexual functions, particularly those early after RARP, appeared to be significantly impaired.