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Chronic inflammation induced by infection, autoimmune disorders, and immune reaction against foreign bodies are recognized as causative factors for the development of lymphoma. Here, a case of B cell lymphoma arising after augmentation rhinoplasty with filler injection is reported. A 48-year-old Japanese woman underwent rhinoplasty with filler injection at a cosmetic clinic 10 years ago. She, presently, came with complaints of a nodule at the nasal root. Histologic examination of the biopsy specimen revealed diffuse infiltration of centrocyte-like cells with plasmacytic differentiation in the subcutis and procerus muscle. Immunohistochemistry showed that the tumor cells were CD3−, CD5−, CD10−, CD20+, CD79+, bcl-2+, bcl-10+, IgG+, IgA−, and IgM−. In situ hybridization for Epstein-Barr virus small RNAs was negative. The final diagnosis was extranodal marginal zone lymphoma. This is a case of foreign body-induced carcinogenesis. Various aspects of chronic inflammation that propel lymphoma development are discussed with their morphology, immunophenotype, and viral association.

Isatuximab, an anti‐CD38 monoclonal antibody, targets cells that strongly express CD38 including malignant plasma cells. This open‐label, single‐arm, multicenter, phase 1/2 trial investigated the tolerability/safety and efficacy of isatuximab monotherapy in Japanese patients with heavily pretreated, relapsed/refractory multiple myeloma (RRMM). In Phase 1, patients were sequentially assigned to receive isatuximab once weekly (QW) in cycle 1 (4 weeks) and every 2 weeks (Q2W) in subsequent cycles. Cohort 1 (n = 3) received 10 mg/kg QW/Q2W; cohort 2 (n = 5) received 20 mg/kg QW/Q2W. No dose‐limiting toxicities occurred; the recommended dose for the single‐arm phase 2 study (n = 28) was 20 mg/kg QW/Q2W. The overall safety profile was consistent with the current knowledge of isatuximab. The most common adverse events were infusion reactions (42.9%; 12/28); all were grade 1/2 and generally occurred during the first infusion. The overall response rate with 20 mg/kg QW/Q2W isatuximab was 36.4% (12/33); patients with high‐risk cytogenetic abnormalities had comparable results. In phase 2, the median progression‐free survival was 4.7 (95% confidence interval, 3.75 to not reached) months. Median overall survival was not reached. Isatuximab monotherapy was well tolerated and effective in patients with heavily pretreated RRMM including high‐risk cytogenetic patients. This trial is registered at ClinicalTrials.gov as NCT02812706., This open‐label, single‐arm, multicenter phase 1/2 trial investigated the tolerability/safety and efficacy of isatuximab monotherapy in Japanese patients with heavily pretreated, relapsed/refractory multiple myeloma (RRMM). The results demonstrated that isatuximab monotherapy was well tolerated and effective in patients with heavily pretreated RRMM, including high‐risk cytogenetic patients.

We retrospectively analyzed the clinical features and outcomes in a real-world cohort of adolescents and the young adult (AYA) patients (age between 16 and 39 years) with symptomatic multiple myeloma (MM) registered with the Kansai Myeloma Forum. 26 patients had been diagnosed as symptomatic MM out of 3284 patients. The prevalence of AYA-MM was 0.8% in this cohort. 81% of the patients was received stem cell transplantation, which may improve outcome. Anemia and hypercalcemia might be prognostic factors, however International Staging System failed to predict overall survival. Five patients developed late-onset adverse events which were serious and life-threatening. The 5-year overall survival was 71.0%. We need to develop the new strategy to overcome AYA-MM.

We retrospectively analyzed 51 patients with solitary plasmacytoma diagnosed from October 2002 to September 2018 from a cohort of 3575 patients with plasma cell dyscrasias registered in the Kansai Myeloma Forum. Twenty-seven patients had solitary bone plasmacytoma (SBP) and 24 had extramedullary plasmacytoma (EMP), with prevalence of 0.8% and 0.7%, respectively. The most frequent M protein was IgG (40%) in SBP, whereas non-secretory proteins were most frequent (50%) in EMP. Five-year overall survival was 78.2% in SBP and 80.8% in EMP (P = 0.894). Among patients with SBP, 44% progressed to MM with a median time of 10.5 months (2.4–93.3 months), whereas 8% of EMP patients progressed to MM with a median time of 18.6 months (13.0–24.2 months). The most frequent treatment was radiotherapy (41%) or observation (41%) in SBP, and chemotherapy (54%) in EMP. No statistically significant difference was observed upon univariate analysis of prognostic factors including age, sex, performance status, and IgG M protein. Our results suggest that there are biological differences between SBP and EMP in real-world settings.

In the pivotal phase III, randomized, multicenter ICARIA-MM study (NCT02990338), isatuximab plus pomalidomide and dexamethasone (Isa-Pd) improved progression-free survival and overall response rate versus pomalidomide and dexamethasone (Pd) in the overall population of patients with relapsed/refractory multiple myeloma.In this predefined subgroup analysis, efficacy, and safety between East Asian patients and the overall population were assessed.In total, 36 East Asian patients were included (Japanese, n = 13; Korean, n = 9; Taiwanese, n = 14). At a median follow-up of 11.6 months, median progression-free survival was not reached (95% confidence interval [CI] 5.80-not calculable) in the Isa-Pd arm and was 7.9 months (95% CI 2.90-not calculable) in the Pd arm. The hazard ratio for the between-group difference was 0.52 (95% CI 0.19-1.39), which was similar to the overall population (hazard ratio, 0.60; 95% CI 0.44-0.82). No new safety signals were observed, except that a higher proportion of patients in the East Asian population experienced Grade ≥ 3 neutropenia compared with the overall population.These results confirm the efficacy of Isa-Pd in East Asian patients with relapsed/refractory multiple myeloma, and the related safety data are consistent with those observed in the overall population and are manageable.

A total of 129 symptomatic patients with multiple myeloma (MM) who underwent high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) were analyzed. The 4-year overall survival (OS) of patients with maintenance (

Objectives This study aimed to investigate real-world data of ixazomib plus lenalidomide and dexamethasone (IRd) therapy for patients with relapsed and refractory multiple myeloma (RRMM). Methods We retrospectively analyzed 122 patients treated with IRd at 16 centers from May 2017 to January 2019 by using the Kansai Myeloma Forum database. Result At the start of IRd, the median age was 72 years, 66.7% of patients had IgG type, and the median number of prior therapies was 4, comprising bortezomib (85.4%) and lenalidomide (89.3%)-based regimens. Disease progression and adverse events accounted for treatment discontinuation in 46 and 32 patients, respectively. The median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 11.9 months. Sensitivity to bortezomib did not affect the PFS, whereas lenalidomide-refractory patients had significantly lower PFS than lenalidomide-sensitive patients, who were comparable to TOURMALINE-MM1 study. The patients with IgG type had significantly better PFS and OS than those with non-IgG type. Conclusion This study presents the largest real-world data of patients treated with IRd in Asia. However, in real clinical practice, the patient background is different from the TOURMALINE-MM1 study, and IRd showed poor efficacy, especially in the non-IgG type and lenalidomide-refractory patients with RRMM.

We retrospectively analyzed 51 patients with solitary plasmacytoma diagnosed from October 2002 to September 2018 from a cohort of 3575 patients with plasma cell dyscrasias registered in the Kansai Myeloma Forum. Twenty-seven patients had solitary bone plasmacytoma (SBP) and 24 had extramedullary plasmacytoma (EMP), with prevalence of 0.8% and 0.7%, respectively. The most frequent M protein was IgG (40%) in SBP, whereas non-secretory proteins were most frequent (50%) in EMP. Five-year overall survival was 78.2% in SBP and 80.8% in EMP (P = 0.894). Among patients with SBP, 44% progressed to MM with a median time of 10.5 months (2.4-93.3 months), whereas 8% of EMP patients progressed to MM with a median time of 18.6 months (13.0-24.2 months). The most frequent treatment was radiotherapy (41%) or observation (41%) in SBP, and chemotherapy (54%) in EMP. No statistically significant difference was observed upon univariate analysis of prognostic factors including age, sex, performance status, and IgG M protein. Our results suggest that there are biological differences between SBP and EMP in real-world settings.

The relationship of lacunocanalicular network structure and mechanoresponse has not been well studied. The lacunocanalicular structures differed in the compression and tension sides, in the regions, and in genders in wild-type femoral cortical bone. The overexpression of Sp7 in osteoblasts resulted in thin and porous cortical bone with increased osteoclasts and apoptotic osteocytes, and the number of canaliculi was half of that in the wild-type mice, leading to a markedly impaired lacunocanalicular network. To investigate the response to unloading, we performed tail suspension. Unloading reduced trabecular and cortical bone in the Sp7 transgenic mice due to reduced bone formation. Sost-positive osteocytes increased by unloading on the compression side, but not on the tension side of cortical bone in the wild-type femurs. However, these differential responses were lost in the Sp7 transgenic femurs. Serum Sost increased in the Sp7 transgenic mice, but not in the wild-type mice. Unloading reduced the Col1a1 and Bglap/Bglap2 expression in the Sp7 transgenic mice but not the wild-type mice. Thus, Sp7 transgenic mice with the impaired lacunocanalicular network induced Sost expression by unloading but lost the differential regulation in the compression and tension sides, and the mice failed to restore bone formation during unloading, implicating the relationship of lacunocanalicular network structure and the regulation of bone formation in mechanoresponse.

Highlights • The prevalence of pPCL was 1.2%. • Treatment with novel agents and transplantation may yield a better prognosis. • Hypercalcemia at diagnosis was suggested to predict worse outcomes., We retrospectively analyzed twenty-six patients with primary plasma cell leukemia (pPCL) registered from May 2005 until April 2015 by the Kansai Myeloma Forum. Twenty patients received novel agents (bortezomib or lenalidomide), and their median survival of was 34 months. The median survival of patients who underwent autologous stem cell transplantation (SCT) was 40 months, those undergoing allogeneic SCT 55 months, and those undergoing both types of SCT (auto–allo) 61 months; whereas for those who did not undergo SCT it was 28 months (p = 0.845). The only statistically significant risk factor identified by multivariate analysis was hypercalcemia.

Chondrocytes proliferate and mature into hypertrophic chondrocytes. Vascular invasion into the cartilage occurs in the terminal hypertrophic chondrocyte layer, and terminal hypertrophic chondrocytes die by apoptosis or transdifferentiate into osteoblasts. Runx2 is essential for osteoblast differentiation and chondrocyte maturation. Runx2-deficient mice are composed of cartilaginous skeletons and lack the vascular invasion into the cartilage. However, the requirement of Runx2 in the vascular invasion into the cartilage, mechanism of chondrocyte transdifferentiation to osteoblasts, and its significance in bone development remain to be elucidated. To investigate these points, we generated Runx2fl/flCre mice, in which Runx2 was deleted in hypertrophic chondrocytes using Col10a1 Cre. Vascular invasion into the cartilage was similarly observed in Runx2fl/fl and Runx2fl/flCre mice. Vegfa expression was reduced in the terminal hypertrophic chondrocytes in Runx2fl/flCre mice, but Vegfa was strongly expressed in osteoblasts in the bone collar, suggesting that Vegfa expression in bone collar osteoblasts is sufficient for vascular invasion into the cartilage. The apoptosis of terminal hypertrophic chondrocytes was increased and their transdifferentiation was interrupted in Runx2fl/flCre mice, leading to lack of primary spongiosa and osteoblasts in the region at E16.5. The osteoblasts appeared in this region at E17.5 in the absence of transdifferentiation, and the number of osteoblasts and the formation of primary spongiosa, but not secondary spongiosa, reached to levels similar those in Runx2fl/fl mice at birth. The bone structure and volume and all bone histomophometric parameters were similar between Runx2fl/fl and Runx2fl/flCre mice after 6 weeks of age. These findings indicate that Runx2 expression in terminal hypertrophic chondrocytes is not required for vascular invasion into the cartilage, but is for their survival and transdifferentiation into osteoblasts, and that the transdifferentiation is necessary for trabecular bone formation in embryonic and neonatal stages, but not for acquiring normal bone structure and volume in young and adult mice., PLoS Genetics, 16(11), art.no.1009169; 2020

Primary central nervous system lymphoma (PCNSL) is more difficult to treat than other lymphomas. Recently, it has been suggested that high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is effective for treating PCNSL. In the present study, we retrospectively analyzed 12 patients with PCNSL at our hospital. Five young patients with good performance status (PS) received upfront ASCT. The conditioning regimen prior to ASCT with busulfan ＋ cyclophosphamide ＋ etoposide showed good prognosis (complete remission rate of 100%). In addition, the PS improved in patients treated with high-dose chemotherapy followed by ASCT, while it worsened in those treated without ASCT. Further investigations are needed to clarify inclusion/exclusion criteria and optimize conditioning regimens for ASCT.

Multicentric Castleman's disease is a systemic inflammatory disorder characterized by lymphadenopathy and excessive interleukin-6 production. A unique clinicopathologic variant of multicentric Castleman's disease, TAFRO (i.e., thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly) syndrome, was recently proposed in Japan. Despite the successful use of anti-interleukin-6 therapy in some patients with TAFRO syndrome, not all patients achieve remission. The pathophysiological etiology of and suitable therapeutic strategies for this variant have not been established. Here, we present our experience of a unique case of TAFRO syndrome in a 78-year-old woman whose symptoms responded differently to several therapies. Tocilizumab, an anti-interleukin-6 receptor antibody, successfully induced remission of fever and lymphadenopathy. However, severe thrombocytopenia persisted and she developed anasarca, ascites, and pleural effusion shortly thereafter. Rituximab, an anti-CD20 antibody, and glucocorticoid therapy provided no symptom relief. In contrast, cyclosporine A, an immunosuppressive agent that blocks T cell function by inhibiting interleukin-2, yielded immediate improvements in systemic fluid retention and a gradual increase in platelet count, with complete resolution of disease symptoms. Excessive serum interleukin-2, when used as an anti-cancer agent, has been reported to cause side effects such as fluid retention, thrombocytopenia, and renal failure. Our case was unique because the anti-interleukin-2 therapy successfully improved symptoms that were not relieved with anti-interleukin-6 therapy. The present report therefore provides insight into the possible role of interleukin-2, in addition to interleukin-6, in TAFRO syndrome. This report will certainly help to clarify the pathogenesis of and optimal treatment strategies for TAFRO syndrome.

Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma (RRMM) were examined retrospectively in a real-world clinical practice setting in Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum, who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58 (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and LEN, respectively. The median overall survival (OS) was not reached. The median time to treatment failure (TTF) was 4.4 months. The best response was recorded in 96 patients, with a 31% overall response rate (ORR) and a 79% rate of achieving at least stable disease. Number of pre-POM regimens ≥ 5, non-IgG-type M-protein, and time from initial therapy to POM or POM/DEX therapy 2 years were associated with shorter TTF and OS. Frequent ( 10%) severe adverse events included neutropenia (55.1%), thrombocytopenia (33.7%), anemia (30.6%), febrile neutropenia (12.2%), fatigue (11.2%), and anorexia (10.2%). In conclusion, POM and POM/DEX showed substantial efficacy against RRMM, but new combination therapies with POM are needed to improve efficacy further without causing hematologic toxicities.

We retrospectively investigated the prognostic factor of lenalidomide plus low-dose dexamethasone (Rd) in Japanese patients with refractory or relapsed multiple myeloma (RRMM) registered in the Kansai Myeloma Forum from January 2006 to December 2013. A total of 140 patients were analyzed. The median age was 66 years. The overall response rate was 68.6 %, including 33.1 % with a better than very good partial response. At 13.0 months median follow-up, the median overall survival (OS) and progression-free survival (PFS) were 34.2 and 17.0 months, respectively. In univariate analyses, patients with one or two prior therapies had significantly longer OS (41.2 vs. 21.5 months; P = 0.002) and PFS (29.0 vs. 13.0 months; P = 0.006) than patients treated with three or more prior therapies. Prior use of thalidomide was associated with significantly shorter PFS (19.0 vs. 16.0 months; P = 0.045). The prior use of bortezomib or high-dose therapy with stem cell transplantation, and the International Staging System had no impact on long-term outcome. Multivariate analysis showed that only the number of prior therapies was a significant predictor of both OS and PFS. Our findings suggest that greater benefit may occur when Rd therapy is used at the first or second relapse in RRMM.

Background The phase 3 ICARIA study demonstrated that isatuximab (Isa) plus pomalidomide and dexamethasone (Pd) significantly improved progression free survival (PFS) compared with Pd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) (HR = 0.596, 95%CI 0.44-0.81, P = 0.001). We evaluated the efficacy/safety of Isa-Pd in the East Asian pts (13 Japanese, 9 Korean and 14 Taiwanese pts) of ICARIA. Methods RRMM pts who had received ≥2 prior lines of therapies, including lenalidomide (len) and at least a proteasome inhibitor (PI), and were refractory to their last therapy were enrolled. Pts were randomized into either Isa-Pd arm who received Isa 10 mg/kg IV weekly for the first 4 weeks (wks) followed by biweekly or Pd arm, and all pts received Pom (4mg PO days 1-21) and dex (40mg [20mg if older than 75 yrs] PO or IV weekly) in 28 day cycle until disease progression or unacceptable toxicity. Results Data from 36 East Asian pts (21 Isa-Pd, 15 Pd) including Japanese pts (9 Isa-Pd, 4 Pd) were analyzed. Patient’s characteristics were similar in the East Asian subgroup and the entire population of ICARIA study (n = 307). Of these pts, median age: 65 (range, 41-85) yrs; median prior lines of therapy: 3 (range, 2-7); 91.7% and 69.4% were refractory to len and PI, respectively; and 13.9% had high-risk cytogenetics. After median follow-up of 11.6 months, median PFS was not reached yet in Isa-Pd arm and was 7.9 months in Pd arm (HR 0.517 [95% CI 0.19-1.39]). ORR (≥PR) was 71.4% in Isa-Pd arm 60% in Pd arm. The VGPR rate or better was 61.9% and 13.3% in Isa-Pd and Pd arm, respectively. Median time to first response was 32 days and 59 days for Isa-Pd and Pd arm, respectively. Grade ≥3 AEs were observed in 90.5% and 73.3% pts in Isa-Pd and Pd arm, respectively and which caused 9.5% pts in the Isa-Pd arm and 0 % in Pd arm to discontinue their treatment. Infusion associated reactions were reported in 57.1% pts receiving Isa-Pd but none of them were grade 3-4. Conclusions This subgroup analysis of ICARIA demonstrates that the efficacy and safety of Isa-Pd in East Asian population, including Japanese pts, are comparable with the entire population of ICARIA. Isa-Pd is a novel treatment option for East Asian pts with RRMM. Clinical trial identification Clinical trial information: NCT02990338. Legal entity responsible for the study Sanofi. Funding Sanofi. Disclosure K. Sunami: Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: GlaxoSmithKline; Speaker Bureau / Expert testimony: Janssen Pharmaceutical. M. Matsumoto: Speaker Bureau / Expert testimony: Celgene Co., LTD; Speaker Bureau / Expert testimony: Janssen Pharmaceutical Co., LTD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb K.K.; Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., LTD. C. Shimazaki: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co. Ltd.; Speaker Bureau / Expert testimony: Celgen Co. Ltd.; Speaker Bureau / Expert testimony: Fujimoto Pharmaceutical Co. Ltd. F. Campana: Full / Part-time employment: Sanofi. K. Tada: Full / Part-time employment: Sanofi. S. Iida: Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Celgene; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Daiichi-Sankyo; Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Kyowa Hakko Kirin; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Gilead; Speaker Bureau / Expert testimony: AbbVie. K. Suzuki: Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Celgene; Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: Fujimoto; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Sumitomo Dainippon ; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Sanofi. All other authors have declared no conflicts of interest.

A 49-year-old female from China was referred to our hospital after endocervical polypectomy. Twenty years before admission, after the birth of her first child, an intrauterine device (IUD) had been inserted due to the one-child policy in China. She had noticed abnormal vaginal bleeding with a foul smell 3 years before admission. Then the IUD was removed and a polyp was found at the IUD contact site. Two months before admission, endocervical polypectomy was performed. Lymphoma was suspected by histological examination and she was referred to our hospital. Further examination confirmed the diagnosis of primary uterine diffuse large B-cell lymphoma (DLBCL). Subsequently, a combination of three cycles of R-CHOP regimen and involved-field radiation therapy was performed, followed by maintenance therapy with five cycles of rituximab. She has remained in complete remission for over 1 year. This case suggests that chronic inflammation induced by prolonged IUD insertion may contribute to the development of primary uterine lymphoma. To the best of our knowledge, this is the first reported case of DLBCL associated with prolonged IUD insertion.

Background The immunomodulatory agent pomalidomide in combination with low-dose dexamethasone has demonstrated efficacy and safety for the treatment of relapsed and refractory multiple myeloma (RRMM) in phase 2 and 3 trials. However, these trials enrolled very few Asian patients. Methods This phase 2 study investigated pomalidomide plus low-dose dexamethasone in 36 Japanese patients with RRMM after ≥2 prior therapies. Results Patients enrolled in the study had a relatively high disease burden (81 % Durie–Salmon stage II or III) and were heavily pretreated (median, 6.5 prior antimyeloma regimens). The overall response rate was 42 % (1 patient with complete response and 14 with partial response), with an additional 44 % (16 patients) achieving stable disease (SD). Response rates in patients aged ≤65 years and >65 years were 47 and 35 %, respectively. None of the five patients with extramedullary disease achieved a response, with three of them maintaining SD of short duration. Median progression-free survival was 10.1 months after a 7.7-month median follow-up, and the median overall survival was not reached. The most frequent grade ≥3 adverse events (AEs) were neutropenia (64 %), anemia (42 %), and thrombocytopenia (31 %). The most frequent nonhematologic grade ≥3 AEs were pneumonia and decreased appetite (8 % each). Adverse events in patients aged >65 years were similar to those in patients aged ≤65 years, except for a higher rate of grade ≥3 pneumonia. Conclusions Collectively, the results of this study demonstrate that pomalidomide plus low-dose dexamethasone is an effective and safe treatment for Japanese patients with RRMM, although careful attention needs to be paid to serious infections. Trial registration: Clinicaltrials.gov NCT02011113

Background Dietary habits are associated with obesity, and both are important contributing factors to lifestyle-related diseases. The STYLIST study examined the effects of dietary counseling by registered dietitians and the delivery of proper calorie-controlled meals (UMIN Registration No: 000006582). Methods and results Two-hundred adult patients with hypertension and/or diabetes mellitus were randomly divided into 2 groups with/without dietary counseling and consumed an ordinary diet for 4 weeks. Each group was then subdivided into 2 groups with/without dietary counseling and received calorie-controlled lunch and dinner boxes for the next 4 weeks. The calories in the delivered meals were based on the subject's ideal body weight (BW) and physical activity level. BW, waist circumference, blood pressure, and laboratory data, including glycoalbumin, were measured at 0, 4, and 8 weeks. BW and the other parameters were significantly reduced during the study period in patients who received diet counseling in the ordinary diet period and/or delivered meal period but not in patients without dietary counseling, as assessed by linear mixed models for longitudinal data. Conclusions The combination of dietary counseling by dietitians and delivery of calorie-controlled meals was effective in reducing BW, as well as blood pressure and glycoalbumin, in patients with hypertension and/or diabetes mellitus.

Splenic abscess is a rare clinical condition with a high mortality rate. Multiple splenic abscesses, rather than a solitary abscess, are present in immunocompromised states including hematological malignancies. As symptoms of splenic abscesses, fever and abdominal pain, are non-specific, timely and adequate use of imaging studies is crucial for early diagnosis. We report the cases of 2 patients with myelodysplastic syndrome and multiple splenic abscesses. Notwithstanding the higher mortality rate of patients with multiple splenic abscesses as compared with those with a solitary splenic abscess, we successfully treated the 2 patients by using antibiotic therapy and fine needle aspiration.

A 62-year-old female suffering from rheumatoid arthritis(RA) for 16 years was referred to our hospital with out ofbreath on slight exertion. She had been prescribed withmethotrexate (MTX; 4 mg per week) and prednisolone for10 years for the treatment of RA. Upon physical exami-nation, tender liver and spleen that extended below thexiphoid were palpable with a protuberant abdomen. Com-puted tomography (CT) showed hepatosplenomegaly,bilateral pleural effusions and ascites in the absence of lungfield abnormalities or lymphadenopathy. Bone marrowexamination was performed to demonstrate an infiltrationof clonal B cells confirmed by immunocytological analysiswith flow cytometry. She was diagnosed as having MTX-associated lymphoproliferative disorder (LPD). The effu-sions in the body cavities and hepatosplenomegaly weredramatically improved only with the withdrawal of MTX.She had been asymptomatic for 2 years until the currenthospitalization. She presented herself in the outpatientdepartmentwithacomplaintofheadache,vertigoandlossofvisionandthenshewasreadmittedbecauseofextensivefluidretention in the chest, abdomen and lower extremities. A CTscan showed recurrence of the massive effusions in the bodycavities and hepatosplenomegaly (Fig. 1a). Histologicalanalysis for the liver specimen obtained by an ultrasound-guided needle biopsy showed a typical relatively monoto-nousappearanceoflymphocytes,plasmacytoidlymphocytesand plasma cells (Fig. 1b). Proliferating cells were stronglyexpressedwithCD20(Fig. 1c).Immunocytologicalanalysiswith flow cytometry demonstrated that the atypical lym-phocytes were positive for CD19, CD20 surface moleculeswith jlight chain-restricted surface immunoglobulin (Ig)-Mand negative for CD5, CD10 and CD23 surface molecules.Bone marrow examination showed a lymphoplasmacyticinfiltrate composed of lymphocytes with basophilic cyto-plasm and plasmacytoid cells (Fig. 1d). Laboratory studieswere remarkable for a white blood cell (WBC) of 2.8 910

咀嚼・嚥下機能低下者に対応する食品の基礎的研究として，固体分散ペーストの摂食量が咽頭部通過時の食塊の移動速度に与える影響について超音波パルスドップラ法，嚥下造影法および官能評価により検討し，以下の結果を得た．機器測定においてはキサンタンガムペースト添加を除く他の試料において摂食量が増加すると硬さは高くなる傾向がみられた．官能評価においてはグアーガム，キサンタンガムペースト添加試料は摂食量の影響を受けにくかったが，摂食量が増加すると付着しやすさの評価は高くなった．食塊の最大移動速度は5回咀嚼，30回咀嚼ともに，水添加，澱粉ペースト添加は，摂食量が増加するに従って速くなる傾向がみられ，摂食量の影響を受けやすい試料であったが，グアーガム，キサンタンガムペースト添加試料は，摂食量に影響を受けず，ほぼ一定の速度であった．通過時間においては，食塊が液体的な場合は摂食量の増加に伴い通過時間が長くなる傾向がみられたが，食塊が固体的で粘稠な場合は，液体的試料よりも摂食量増加の影響を受けにくかった．固体分散ペーストの摂食量の影響は，添加するペーストの力学特性値が関与する可能性が高いと推察された．

Image quality of halftone print is significantly influenced by optical characteristics of paper. Light scattering in paper produces optical dot gain, which has a significant influence on the tone and color reproductions of halftone print. The light scattering can be quantified by the Modulation Transfer Function (MTF) of paper. Several methods have been proposed to measure the MTF of paper. However, these methods have problems in efficiency or accuracy in the measurement. In this article, a new method is proposed to measure the MTF of paper efficiently and accurately, and the dot gain effect on halftone print is analyzed. The MTF is calculated from the ratio in spatial frequency domain between the responses of incident pencil light to paper and the perfect specular reflector. Since the spatial frequency characteristic of input pencil light can be obtained from the response of perfect specular reflector, it does not need to produce the input illuminant having “ideal” impulse characteristic. Our method is experimentally efficient since only two images need to be measured. Besides it can measure accurately since the data can be approximated by the conventional MTF model. Next, we predict the reflectance distribution of halftone print using the measured MTF in microscopy in order to analyze the dot gain effect since it can clearly be observed in halftone micro-structure. Finally, a simulation is carried out to remove the light scattering effect from the predicted image. Since the simulated image is not affected by the optical dot gain, it can be applied to analyze the real dot coverage. key words: MTF, paper, halftone print, dot gain

We investigated the utility of Near Infrared Spectroscopy as a means to quantify the diet of seals via analysis of feces. A pilot study showed that we could accurately determine the proportion of each species in a mixture of flesh of two species of fish and one squid. Having done so, we then assessed whether the same capacity existed for fecal material. Again we used two species of fish and one squid as the diet components offered to two captive seals (a California sea lion and an Australian fur seal). Five of the six calibrations could accurately and precisely quantify how much of a given diet component the seal had eaten the previous day from an NIR scan of the feces. NIR spectroscopy is theoretically a viable way to quantify seal diets. We discuss the logistical requirements for development of calibration equations for application to a field study. These may be prohibitive in many cases, but in others may be offset by the particular circumstances or objectives of the study. Adoption of NIRS may confer significant benefits in these circumstances.

We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of >30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents.