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Mental illnesses commonly occur in the reproductive age. This study aimed to identify the issues that exist within the perinatal mental health care system. A cross-sectional survey was conducted in Aichi Prefecture in central Japan. Questionnaires on the situation between 2016 and 2018 were mailed to the head physicians of 128 maternity care units, 21 neonatal intensive care units (NICUs), and 40 assisted reproductive technology (ART) units. A total of 82 (52.6 per 100,000 births) women were admitted to mental health care units during the perinatal period, and 158 (1.0 per 1000 births) neonates born to mothers with mental illness were admitted to NICUs. Approximately 40% of patients were hospitalized in psychiatric hospitals without maternity care units. Eighty-four (71.1%) and 76 (64.4%) maternity care units did not have psychiatrists or social workers, respectively. Moreover, 20–35% of the head physicians in private clinics, general hospitals, and ART units endorsed the discontinuation of psychotropic drug use during pregnancy. However, the corresponding figures were only 5% among those in maternal-fetal centers. Resources for perinatal mental illness might be limited. Perspectives on psychotropic drug use differed based on the type of facilities where the doctors were working.

Despite the importance of a prompt diagnosis to improve cancer patients' survival, little has been reported on diagnostic delay in diffuse large B-cell lymphoma (DLBCL). A single-centre, retrospective study was conducted to examine the association between diagnostic wait time (DWT), the interval from the initial hospital visit to diagnosis, and survival in patients with DLBCL. A total of 193 patients were enrolled from 2007 to 2017 in our institution. A covariate-adjusted Cox proportional hazards model with restricted cubic spline was used to evaluate the impact of DWT on survival, with a subgroup analysis according to the International Prognostic Index (IPI). DWT was not associated with survival in the entire DLBCL population, but the impact of DWT on survival differed between IPI < 3 and ≥ 3; prolongation of DWT steadily exacerbated the prognosis in patients with IPI ≥ 3, whereas there was a patient population with IPI < 3 who had a high mortality rate despite rather early diagnosis. The opposite trend in the effect of DWT on survival between patients with IPI < 3 and ≥ 3 offset survival in all DLBCL patients. DWT had no observable impact on outcomes in the entire DLBCL population, but longer DWT worsened the prognosis, particularly in patients with IPI ≥ 3.

The controlling nutritional status (CONUT) is a simplified nutritional index calculated from serum albumin, total cholesterol, and the total lymphocyte count. Although the CONUT score is an independent prognostic factor in several hematological malignancies, the prognostic impact of the CONUT score in peripheral T-cell lymphoma (PTCL) is unclear. This study evaluated the prognostic impact of the CONUT score on overall survival (OS) in patients with PTCL. A multicentre, retrospective, cohort study including 99 patients with PTCL was conducted. The CONUT score was significantly higher in the non-survivor group (median 5, range 0-12) than in the survivor group (median 3, range 0-11) (P = 0.026). The CONUT score was an independent prognostic factor in a multivariable Cox proportional hazards model (hazard ratio 1.118, 95% confidence interval 1.020-1.225, P = 0.017). The Cox proportional hazards model with restricted cubic spline showed an S-shaped relationship between the CONUT score and OS. No significant effect-modification by the International Prognostic Index (IPI) was observed, and the CONUT score affected the prognosis of PTCL regardless of the IPI (P for interaction = 0.208). In conclusion, the CONUT score is an independent prognostic factor in patients with PTCL irrespective of IPI categories.

Background The management of severe adverse events (AEs) is important in safely and effectively providing chemotherapy to older adults with diffuse large B-cell lymphoma (DLBCL). However, reports on simple and DLBCL-specific predictive models for treatment-related toxicity in elderly individuals are scarce. The aim of this study was to examine the usefulness of Geriatric 8 (G8) in predicting treatment-related severe AEs, nonhematological toxicity, and febrile neutropenia in older adults with DLBCL in real-world practice. Materials and Methods We conducted a multicenter, retrospective study on 398 consecutive patients with DLBCL (aged ≥65 years) who received standard therapy at three centers in Japan (University of Fukui Hospital, the Fukui Prefectural Hospital, and the Japanese Red Cross Fukui Hospital), between 2007 and 2017. Result Multivariate logistic analysis demonstrated that the G8 score was an independent predictive factor for severe AEs. Moreover, a logistic regression model with restricted cubic spline showed a nonlinear association between the incidence of severe AEs and the G8 score. According to receiver operating characteristic analysis, the most discriminative cutoff value of the G8 for the incidence of severe AEs was 11, with an area under the curve value of 0.670. AEs occurred most often in the first course of chemotherapy and decreased as the course progressed. Conclusion The G8 score, an easy-to-use geriatric assessment tool, can be a useful prediction model of treatment-related severe AEs during standard therapy in older adults with DLBCL. Implications for Practice In older patients with diffuse large B-cell lymphoma (DLBCL), to accurately predict the risk of severe adverse events (AEs) in advance is essential for safe and effective treatment. This study demonstrated that the Geriatric 8 score, a simple and established geriatric assessment tool, indicated a high predictive ability for occurrence of therapy-related severe AEs in elderly patients with DLBCL who were treated with standard treatment.

Reflecting the increasing risk in elderly patients with diffuse large B cell lymphoma (DLBCL), prognostic predictors other than the International Prognostic Index have attracted more attention. This study presents the first analysis of the prognostic utility of the Geriatric Nutritional Risk Index (GNRI) in combination with the Charlson Comorbidity Index (CCI) for overall survival (OS) in elderly DLBCL patients. A multicentre retrospective was conducted on a cohort of 451 patients (≥65 years). The GNRI and CCI were independent predictors in a multivariate Cox proportional hazard model. There was a nonlinear correlation between the GNRI and OS in a Cox model with restricted cubic spline. Multivariate receiver operating characteristic curves showed a significant improvement in prediction accuracy when the GNRI was added to CCI. Adding the GNRI to CCI yielded a significant category-free net reclassification improvement (0·556; 95% CI: 0·378-0·736, P < 0·001) and integrated discrimination improvement (0·094; 95% CI: 0·067-0·122, P < 0·001). The decision curve analysis demonstrated the clinical net benefit associated with the adoption of the GNRI. The GNRI was not only a predictor of OS but also remarkably improved the prognosis prediction accuracy when incorporated with the CCI, having the ability to stratify the prognosis of elderly DLBCL patients.

Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, in which control of serum uric acid (S-UA) levels is important. S-UA-lowering efficacy of a new xanthine oxidase inhibitor, febuxostat, was retrospectively evaluated in seven patients with hematological malignancies who were at an intermediate risk of developing TLS. A 10-mg dose of febuxostat was initiated and chemotherapy was started within 24 h of administering the first dose of febuxostat. Febuxostat was continued until at least day 7 of chemotherapy treatment. The UA-lowering treatment was considered effective if febuxostat reduced S-UA levels to ≤7.5 mg/dl by day 5. The mean S-UA level at base line was 6.4±2.6 mg/dl and, on day 5, the mean S-UA level was 4.7±1.8 mg/dl. All the patients achieved S-UA levels ≤7.5 mg/dl. Serum creatinine levels decreased from 0.93±0.25 to 0.85±0.25 mg/dl. The estimated glomerular filtration rate values increased from 69.7±24.5 to 76.9±26.2 ml/min. No adverse reactions were noted during the study period and no patients experienced progressive TLS. Successful control of S-UA and improved renal function were obtained in response to febuxostat treatment in cancer patients at a risk of TLS.

Background Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL featured by rapid progression. Given its rapid progression, prompt diagnosis and treatment are essential for achieving long-term survival in DLBCL. In solid cancers, it is known that prolonging diagnostic wait time (DWT), interval from diagnosis to initiation of treatment, could result in stage progression and a worse survival. In DLBCL patients, a prolonged DWT is also expected to be associated with a worse survival, however, little is known about this issue. The purpose of this investigation was to verify the impact of DWT on survival in DLBCL patients using a Cox hazards model with restricted cubic spline (RCS) because this model was more suitable to reflect real-world clinical practice than the linear model. It has been reported a possible association between the International Prognostic Index (IPI) and prognosis, hence the Cox hazards model with RCS was used to examine the differential effects of IPI on survival in association with DWT. Methods We conducted a single center, retrospective study of all consecutive patients seen from 2007 to 2017 at our Hospital. The inclusion criteria were newly diagnosed de novo DLBCL, aged 18 years and older, and treated with standard therapies. We define the standard regimens as R-CHOP [rituximab (RTX), cyclophosphamide (CPA), adriamycin, vincristine (VCR), and prednisolone (PSL)] and R-THP-COP (RTX, CPA, tetrahydropyranyl adriamycin, VCR, and PSL). The primary outcome was overall survival (OS). Exclusion criteria were central nerve system involvement, transformed DLBCL, and receiving non-standard therapies. Furthermore, the subgroup analysis according to IPI was performed. Results Among 179 patients, the median age was 72 (27 - 91) years, the median DWT was 39.5 (0 - 223) days and 53.9% patients had IPI ≥3, the median follow-up time was 29.2 (0.03 - 137.6) months, and 59 (31.3%) patients died during the follow-up period. A multivariate Cox proportional hazards model for OS showed DWT was not associated with worse OS in the entire study population. However, the Cox hazards model with RCS in the all study population revealed that there was nearly U-shaped association between DWT and OS. The Cox hazards model with RCS for each group depending on IPI score (0-5) showed the effect between DWT and OS differed by IPI. The mortality risk increased proportionally as DWT was prolonged in three groups with IPI 3 to 5, but rather negative correlations were seen between in three groups with IPI 0 to 2. Opposite tendencies between IPI ≥3 and Discussion These results demonstrated that the impact of DWT on OS differed depending on the IPI, while DWT did not affect OS of the entire DLBCL patients. DWT steadily increased the risk of mortality in IPI ≥3 group. On the other hand, in IPI 3 at the initial visit should be expedited the diagnosis if there was suspicious of DLBCL, because DWT is a critical predictor determining prognosis in such patients. Moreover, in suspected DLBCL cases, computed tomography, positron emission tomography contributing to identify the IPI, and bone marrow biopsy might be needed immediately when the definitive IPI is uncertain at the initial visit. Conclusions In conclusion, DWT did not associate with survival of entire DLBCL patients who treated with standard therapies, but the impact of DWT on survival differed depending on IPI. Especially in patients with IPI ≥3 at the diagnosis, steadily increased mortality risk was observed. Disclosures Yamauchi: Astellas, AbbVie: Consultancy; Pfizer, Chugai, Teijin, Solasia: Research Funding.

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.

Systemic and focal cerebral acidosis is considered deleterious to cell metabolism and neuronal recovery. We investigated the immediate effect of tris-(hydroxymethyl)-aminomethane (THAM), an alkalizing agent, on focal cerebral ischemia produced by occlusion of the left middle cerebral artery (MCA) in cats with systemic acidosis. Occlusion of MCA resulted in prompt decreases in local cerebral blood flow of the ipsilateral marginal and ectosylvian gyri from 47.7 ml/100 g per minute in control to 32.3 ml/100 g per minute and 8.3 ml/100 g per minute, respectively. In the control group, physiological saline was infused continuously and the treated group received 0.3 M THAM to normalize systemic and focal cerebral acidosis. There were no significant changes in the systemic arterial pressure, arterial PO2 and PCO2 throughout the experiments in the two groups. Arterial pH decreased from 7.42 to 7.30 in the control, while it remained normal during THAM treatment. Extracellular pH of the marginal gyrus (peri-infarct zone) decreased from 7.39 to 6.87 with 6 h ischemia in the control group. In THAM infusion, extracellular pH was kept between 7.26 and 7.29, which was significantly higher than the control group. THAM significantly decreased infarct volume and lactate and water contents of the gray matter in the marginal gyrus at 6 h after occlusion. It is concluded that THAM infusion immediately after ischemia onset is considered effective in improving acidosis at the site of ischemic penumbra and consequently reduces lactate production, brain edema, and infarct volume.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. The present study assessed retrospectively the clinical significance of the serum soluble interleukin-2 receptor (sIL-2R) level in patients with advanced DLBCL. Twenty-one patients (age; range, 56–87, median, 73-year old, 14 males/7 females) were newly diagnosed as having advanced DLBCL (stages III and IV) based on pathological findings of the biopsy specimen and by using computed tomography and positron emission tomography between 2006 and 2009. All the patients received 6–8 cycles of the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) (R-CHOP) or THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) (R-THP-COP) and attained complete response at the end of the treatment. The follow-up period ranged between 12 and 73 months with the median of 37 months. The serum sIL-2R levels (normal range, 144–518 U/ml) were determined at least before and after the second and the sixth cycles of the chemotherapy were carried out. Although all the patients reached complete remission, six patients experienced the disease relapse within 1 year from the initiation of the treatment. sIL-2R levels before the chemotherapy ranged from 416 to 21300 U/ml (median 2609 U/ml). sIL-2R levels after the second cycle of the chemotherapy ranged from 276 to 1980 U/ml (median 675 U/ml). sIL-2R levels after the sixth cycle of the chemotherapy ranged from 364 to 822 U/ml (median 548 U/ml). The early relapse was significantly associated with the high sIL-2R levels at the sixth cycle of the treatment, while the sIL-2R levels were low in the patients with the durable remission. sIL-2R levels at the disease onset or after the second cycle of the treatment were not correlated to the duration of the remission. Thus, the present study suggested that the sIL-2R levels after the sixth cycle of the chemotherapy might predict the early relapse in patients with advanced DLBCL.

Originally presented as the first author's thesis, (Sc.D.) in the M.I.T. Dept. of Nuclear Engineering, 1978.