Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01.

Next-generation sequencing of AML has identified specific genetic mutations in AML patients. Hematologic Malignancies (HM)-SCREEN-Japan 01 is a multicenter study to detect actionable mutations using paraffin-embedded bone marrow (BM) clot specimens rather than BM fluid in AML patients for whom standard treatment has not been established. The purpose of this study is to evaluate the presence of potentially therapeutic target gene mutations in patients with newly diagnosed unfit AML and relapsed/refractory AML (R/R-AML) using BM clot specimens. In this study, 188 patients were enrolled and targeted sequencing was undertaken on DNA from 437 genes and RNA from 265 genes. High-quality DNA and RNA were obtained using BM clot specimens, with genetic alterations successfully detected in 177 patients (97.3%), and fusion transcripts in 41 patients (23.2%). The median turnaround time was 13 days. In the detection of fusion genes, not only common fusion products such as RUNX1-RUX1T1 and KMT2A rearrangements, but also NUP98 rearrangements and rare fusion genes were observed. Among 177 patients (72 with unfit AML, 105 with R/R-AML), mutations in KIT and WT1 were independent factors for overall survival (hazard ratio = 12.6 and 8.88, respectively), and patients with high variant allele frequency (≥40%) of TP53 mutations had a poor prognosis. As for the detection of actionable mutations, 38% (n = 69) of patients had useful genetic mutation (FLT3-ITD/TKD, IDH1/2, and DNMT3AR822 ) for treatment selection. Comprehensive genomic profiling using paraffin-embedded BM clot specimens successfully identified leukemic-associated genes that can be used as therapeutic targets.

Imaging flow cytometry-based multiplex FISH for three IGH translocations in multiple myeloma.

Three types of chromosomal translocations, t(4;14)(p16;q32), t(14;16)(q32;q23), and t(11;14)(q13;q32), are associated with prognosis and the decision making of therapeutic strategy for multiple myeloma (MM). In this study, we developed a new diagnostic modality of the multiplex FISH in immunophenotyped cells in suspension (Immunophenotyped-Suspension-Multiplex (ISM)-FISH). For the ISM-FISH, we first subject cells in suspension to the immunostaining by anti-CD138 antibody and, then, to the hybridization with four different FISH probes for genes of IGH, FGFR3, MAF, and CCND1 tagged by different fluorescence in suspension. Then, cells are analyzed by the imaging flow cytometry MI-1000 combined with the FISH spot counting tool. By this system of the ISM-FISH, we can simultaneously examine the three chromosomal translocations, i.e, t(4;14), t(14;16), and t(11;14), in CD138-positive tumor cells in more than 2.5 × 104 nucleated cells with the sensitivity at least up to 1%, possibly up to 0.1%. The experiments on bone marrow nucleated cells (BMNCs) from 70 patients with MM or monoclonal gammopathy of undetermined significance demonstrated the promising qualitative diagnostic ability in detecting t(11;14), t(4;14), and t(14;16) of our ISM-FISH, which was more sensitive compared with standard double-color (DC) FISH examining 200 interphase cells with its best sensitivity up to 1.0%. Moreover, the ISM-FISH showed a positive concordance of 96.6% and negative concordance of 98.8% with standard DC-FISH examining 1000 interphase cells. In conclusion, the ISM-FISH is a rapid and reliable diagnostic tool for the simultaneous examination of three critically important IGH translocations, which may promote risk-adapted individualized therapy in MM.

Prognostic value of the Kyoto Prognostic Index in higher-risk diffuse large B-cell lymphomas treated by upfront autologous stem cell transplantation in JCOG0908 trial.

BACKGROUND: There is currently no standard prognostic model optimized for the patients with diffuse large B-cell lymphoma (DLBCL) treated with upfront intensive immunochemotherapy including autologous stem cell transplantation (ASCT). The Kyoto Prognostic Index (KPI) has been proposed as a novel prognostic model for DLBCL, which can accurately identify especially high-risk patients. In this study, we investigated the prognostic value of the KPI in JCOG0908 trial in which higher-risk DLBCL patients defined by the conventional International Prognostic Index (IPI) were treated with upfront high dose therapy followed by ASCT. METHODS: Fifty-eight patients with DLBCL, not otherwise specified, enrolled in JCOG0908 and confirmed by the central pathological review were analyzed. The Kaplan-Meier method was used to estimate the probabilities of overall survival (OS) and progression-free survival (PFS). We compared the discrimination ability of the KPI with that of the IPI. RESULTS: According to KPI, 3-year OS and PFS rates were 86.7% and 76.7% in low-intermediate, 73.3% and 60.0% in high-intermediate, and 61.5% and 46.2% in high-risk group. According to IPI, 3-year OS and PFS rates were 75.0% and 50.0% in low-intermediate, 82.9% and 74.3% in high-intermediate, and 63.6% and 54.5% in high-risk group. The concordance-indices of KPI and IPI were 0.642 and 0.580 for OS and 0.606 and 0.606 for PFS. CONCLUSIONS: The KPI may be a suitable predictor of outcome than the IPI for patients with higher-risk DLBCL treated with upfront intensive immunochemotherapy including ASCT.

Risk factors for shoulder osteoarthritis with rotator cuff tear in the elderly general population.

HYPOTHESIS AND/OR BACKGROUND: The relationship between shoulder osteoarthritis (OA) and rotator cuff tear (RCT) is unclear. We hypothesized that there is a difference between the pathogenesis of OA complicating RCT and that of RCT complicating OA. In this study, our primary objective was to determine the prevalence of shoulder OA without RCT, RCT without OA, and OA with RCT in the general older population. Our secondary objective was to identify risk factors for the association with OA+RCT in shoulder OA alone or RCT alone, respectively. METHODS: We enrolled patients from the public health checkup conducted in Gunma prefecture (Japan) in 2014. Subjects' shoulder pain at rest, during motion, and at night was evaluated using a questionnaire. Moreover, active and passive range of motions (ROMs) in flexion, abduction, and external rotation were measured. For RCT parameters, we evaluated as no tear, partial-thickness supraspinatus (SSP) tear, full-thickness SSP tear, and SSP-infraspinatus tears. For further analysis, the shoulders were divided into three groups according to the presence of RCT and/or OA: OA, RCT, and OA + RCT groups. Risk factors for OA + RCT were identified in a logistic regression analysis. RESULTS: Overall, 944 of 1148 shoulders were eligible for inclusion. The prevalence rates of shoulder OA, RCT, and OA + RCT were 5.8%, 21.1%, and 4.2%, respectively. Furthermore, 650 shoulders were excluded, and 55, 199, and 40 shoulders had OA, RCT, and OA + RCT, respectively. There were significant differences for age, ROM of active external rotation, strength of abduction, external rotation, and morphology of the rotator tears. However, there were no significant differences for pain visual analog scale score, passive ROM, Simple Shoulder Test, and grades of OA. Older age decreased active ROM in external rotation, and the presence of both subscapularis and SSP-infraspinatus tears was a risk factor for the association of OA with an RCT shoulder. Older age, weaker power in external rotation, and affected dominant side were risk factors for the association of RCT with an OA shoulder. DISCUSSION AND/OR CONCLUSION: This study is the first to report risk factors by considering both shoulder OA and RCT in the general population. Our findings will be useful for the treatment and management of OA and RCT as well as for the prevention of these conditions in the older adults.

Hematopoietic stem cell transplantation for diffuse large B-cell lymphoma having 8q24/MYC rearrangement in Japan.

The prognosis of diffuse large B-cell lymphoma (DLBCL) having MYC rearrangement (MYC-R), including double hit lymphoma (DHL), is poor by standard immunochemotherapy. To evaluate the significance of hematopoietic stem cell transplantation (SCT) for DLBCL with MYC-R, we retrospectively analyzed Japanese SCT registry data. In total, 54 patients with DLBCL with MYC-R were identified from 4336 registered adult DLBCL patients. Detailed clinical and cytogenetic information was obtained for 48 patients. The median age at diagnosis of the 48 patients was 54.5 (range 21-67) years. Twenty-six (54%) patients had MYC-R only (single hit), and 22 (46%) had MYC-R and BCL2, and/or BCL6 rearrangement (double/triple hit). In 12 patients who received auto-SCT during the first complete response (CR), both the 2-year overall survival (OS) and progression-free survival (PFS) rates were 75.0% (95% confidence interval [CI], 40.8%-91.2%). In 20 patients who received auto-SCT after relapsed or refractory state, the 2-year OS and PFS rates were 68.2% (95% CI, 41.9%-84.5%) and 59.6% (95% CI, 35.1%-77.4%), respectively. In 17 patients who received allo-SCT, only 4 patients underwent SCT in CR. The 2-year OS and PFS rates were 29.4% (95% CI, 10.7%-51.1%) and 17.6% (95% CI, 4.3%-38.3%), respectively. The rate of non-relapse mortality at 1 year was 41.2% (95% CI, 17.1%-64.0%) in this group. The outcomes of single hit and double or triple hit were not different. These findings suggest that auto-SCT may be effective for MYC-R DLBCL, including DHL patients of chemosensitive relapsed or refractory state. Since most patients received allo-SCT not in CR, the outcome of allo-SCT was unsatisfactory due to high non-relapse mortality and early relapse. To clarify the role of allo-SCT for MYC-R DLBCL, further accumulation of patients is necessary.

Durable Remission of Chemotherapy-Refractory Myeloid Sarcoma by Azacitidine.

Myeloid sarcoma is a rare disease entity of extramedullary myeloid neoplasm that can occur both as an initial isolated myeloid sarcoma without leukemic cell invasion in the peripheral blood and bone marrow, and as the secondary lesion of acute and chronic myeloid leukemias, myelodysplastic syndrome and chronic myeloproliferative neoplasms. Due to its rarity and its frequent emergence as the recurrent lesion after intensive systemic therapy, including allogeneic hematopoietic stem cell transplantation, the standard treatment has not been established for myeloid sarcoma. In this report, we presented an 84-year-old female patient with isolated myeloid sarcoma which progressed to myelodysplastic syndrome and systemic myeloid sarcoma despite various types of conventional anti-leukemic chemotherapies. However, the patient got a durable partial response by the monotherapy of azacitidine, a hypomethylating agent. She received thirteen courses of azacitidine therapy without progression. We discuss the possibility that hypomethylating agents are the novel effective and feasible therapeutic options for myeloid sarcoma, even in cases refractory to or relapsed after intensive systemic treatment. We also discuss the possible future development of hypomethylating agent-containing combinatory therapeutic strategy for myeloid sarcoma, given its direct anti-leukemic effect and immunomodulatory effect.

Successful management of acquired hemophilia A onset during pregnancy: A case report.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII. Pregnancy could be associated with AHA in younger women. Because of its rarity, the optimal management for pregnancy-related AHA has not yet been established. Herein, we present the case of a 32-year-old woman with AHA diagnosed during pregnancy because of elevated activated partial prothrombin time, decreased factor VIII activity, and the presence of a factor VIII inhibitor. She was treated with immunosuppressive therapy consisting of corticosteroid and cyclosporine administration. Although complete remission could not be induced in the peripartum period, she gave birth safely by cesarean delivery in combination with prophylactic bypass hemostatic therapy. This work would provide helpful information to guide better recognition and treatment of pregnancy-related AHA cases.

Pronation and palmar pinch improve the stability of the medial elbow joint space in high school baseball pitchers.

HYPOTHESIS: We aimed to investigate the contributions of grip, pronation, and pinch to stabilization of the medial elbow joint space; examine their relationship with muscle strength; and assess the effect of stabilization on the medial elbow joint space in baseball pitchers. METHODS: In this controlled laboratory study, we measured the medial elbow joint space using ultrasound during the following conditions: unloading; loading; and loading with grip, pronation, and pinch. To evaluate changes in the medial elbow joint space as a result of various conditions, 1-way repeated-measures analysis of variance and post hoc analysis for multiple comparisons were performed. To investigate whether strong or weak muscle strength improved the medial elbow joint space during the loaded condition, Pearson correlation analysis was performed. Finally, a post hoc power analysis was performed. RESULTS: We enrolled 121 pitchers. The medial elbow joint space in the loaded condition, loaded condition with full grip, and loaded condition with full pinch was significantly larger than that in the unloaded condition. The medial elbow joint space in the loaded condition with full grip, loaded condition with full pronation, and loaded condition with full palmar pinch was significantly smaller than that in the loaded condition. A post hoc power analysis showed that the power of the 1-way repeated-measures analysis of variance was 100%. The strengths of the full grip and palmar pinch were significantly correlated with a reduced gap distance of the medial elbow joint space (P < .001 for both). CONCLUSION: In high school baseball pitchers, pronation and palmar pinch contraction significantly improved the gap distance of the medial elbow joint space in the loaded condition and during grip contraction. Moreover, the grip and palmar pinch strengths were significantly correlated with stabilizing effects on the medial elbow joint space.

[The current therapeutic landscape for follicular lymphoma].

The prognosis of patients with follicular lymphoma (FL) has improved over the last decades. However, most patients with FL will eventually relapse. The management of FL is mainly determined by clinical stage and tumor burden. For localized-stage patients, an involved-field radiation therapy is recommended. For advanced-stage low tumor burden patients, watchful waiting remains the standard treatment, whereas rituximab monotherapy may be an alternative option. Immuno-chemotherapy combined with rituximab maintenance has been the standard care for patients with high tumor burden. Recently, the novel anti-CD20 monoclonal antibody obinutuzumab was approved for the treatment of FL. Obinutuzumab with chemotherapy followed by obinutuzumab maintenance is considered one of the standard therapeutic options. After relapse or progression, it is necessary to consider a treatment strategy based on several disease-related, treatment-related, and patient-related factors. During the last decade, the development of biological knowledge and use of molecularly targeted agents offer new therapeutic perspectives with chemo-free strategies. This review highlights the current standards for the treatment of FL.

Lenalidomide and pomalidomide potently interfere with induction of myeloid-derived suppressor cells in multiple myeloma.

An increase in immunosuppressive myeloid-derived suppressor cells (MDSCs) is associated with disease progression and treatment resistance in multiple myeloma (MM). We investigated the mechanisms underlying MDSC induction, and sought to discover a strategy for prevention of MDSC induction in MM. Using a transwell co-culture system, four of nine examined human myeloma-derived cell lines (HMCLs) were potent in inducing monocytic (M)-MDSCs from normal peripheral blood mononuclear cells (PBMCs). As the results, we identified that secretion of C-C motif chemokine ligand 5 (CCL5) and macrophage migration inhibitory factor (MIF) by myeloma cells is a prerequisite for induction of MDSCs in MM. The immunomodulatory drug (IMiD) compounds, such as lenalidomide (LEN) and pomalidomide (POM), were identified as potent inhibitors of MDSC induction through bidirectional molecular effects of cereblon (CRBN)-dependent and -independent downregulation of CCL5 and MIF in myeloma cells; and downregulation of C-C motif chemokine receptor 5, a receptor for CCL5, and induction of interferon regulatory factor 8, a critical transcription factor for monocytic differentiation, in PBMCs. In the present study of the molecular mechanisms underlying MDSC induction, we identified a novel effect of LEN and POM of inhibiting MDSC induction via overlapping regulatory effects in myeloma cells and normal PBMCs.

Sequential therapy of four cycles of bortezomib, melphalan, and prednisolone followed by continuous lenalidomide and dexamethasone for transplant-ineligible newly diagnosed multiple myeloma.

The combinations of melphalan, bortezomib, and prednisolone (VMP) and of lenalidomide and dexamethasone (Rd) are standard treatment strategies for transplant-ineligible newly diagnosed multiple myeloma (NDMM). To make the most of these two strategies, we investigated the efficacy and feasibility of first-line treatment with 4 cycles of VMP followed by continuous Rd therapy in a multi-institutional phase 2 study in Japanese patients with transplant-ineligible NDMM. Thirty-six patients of median age 74 years old with NDMM initially received 35-day cycles of VMP: oral melphalan (6 mg/m2) and prednisolone (60 mg/m2) on days 1 to 4 and bortezomib (1.3 mg/m2) on days 1, 8, 15, and 22. After 4 cycles of VMP, treatment was switched to 28-day cycles of Rd, which was continued until disease progression or emergence of an unacceptable adverse event (AE) in 33 patients, while one patient who achieved CR after VMP continued VMP at the physician's discretion. The overall response rates after VMP and after Rd were 66.7% and 86.1%, including CR rates of 5.6% and 36.1%, respectively. In a median follow-up period of 34.3 months, the progression-free survival and overall survival rates at 3 years were 43.2% and 81.3%, respectively. Grade 3-4 hematological AEs included neutropenia (39% with VMP and 24% with Rd) and thrombocytopenia (11% with VMP and 3% with Rd). There was no death due to an AE. In conclusion, sequential therapy with VMP followed by Rd is effective and mostly feasible for transplant-ineligible NDMM. The study is registered as UMIN000034815.

Horndeski theory and beyond: a review.

This article is intended to review the recent developments in the Horndeski theory and its generalization, which provide us with a systematic understanding of scalar-tensor theories of gravity as well as a powerful tool to explore astrophysics and cosmology beyond general relativity. This review covers the generalized Galileons, (the rediscovery of) the Horndeski theory, cosmological perturbations in the Horndeski theory, cosmology with a violation of the null energy condition, degenerate higher-order scalar-tensor theories and their status after GW170817, the Vainshtein screening mechanism in the Horndeski theory and beyond, and hairy black hole solutions.

Dual targeting of bromodomain-containing 4 by AZD5153 and BCL2 by AZD4320 against B-cell lymphomas concomitantly overexpressing c-MYC and BCL2.

Despite the recent therapeutic progress, the prognoses of diffuse large B-cell lymphomas (DLBCLs) that concomitantly overexpress c-MYC and BCL2, i.e., double hit lymphoma (DHL) and double expressing lymphoma (DEL), remain poor. This study examined triple targeting of c-MYC, BCL2 and the B-cell receptor (BCR) signaling pathway for DHL and DEL. We first used AZD5153, a novel bivalent inhibitor for bromodomain-containing 4 (BRD4), in DHL- and DEL-derived cell lines, because BRD4 regulates disease type-oriented key molecules for oncogenesis. AZD5153 was more effective than conventional monovalent BRD4 inhibitors, JQ1 and I-BET151, in inhibiting cell proliferation of a DHL-derived cell line and two DEL-derived cell lines, with at least 10-fold lower half growth inhibitory concentrations. AZD5153 caused G1/S cell cycle blockade, while the apoptosis-inducing effect was relatively modest. At the molecular level, AZD5153 was potent in downregulating various molecules for oncogenesis, such as c-MYC, AKT2 and MAP3K; those involved in the BCR signaling pathway, such as CD19, BLNK and CD79B; and those associated with B-cell development, such as IKZF1, IKZF3, PAX5, POU2AF1 and EBF1. In contrast, AZD5153 did not decrease anti-apoptotic BCL2 proteins, and did not activate pro-apoptotic BH3-only proteins, except BAD. To augment cell death induction, we added a novel BH3-mimicking BCL2 inhibitor AZD4320 to AZD5153, and found that these two agents had a mostly synergistic antitumor effect by increasing cells undergoing apoptosis in all three cell lines. These results provide a rationale for dual targeting of BRD4 and BCL2 using AZD5153 and AZD4320 as a therapeutic strategy against DHL and DEL.

The efficacy and safety of sitafloxacin and garenoxacin for the treatment of pneumonia in elderly patients: A randomized, multicenter, open-label trial.

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3-10 days. The primary efficacy endpoint was the clinical cure rate at 5-10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6-95.6) and 88.9% (95% confidence interval: 77.4-95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients.

Efficacy and safety of cefditoren pivoxil for exacerbations of chronic obstructive pulmonary disease: A prospective multicenter interventional study.

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5-10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations.

Serum Soluble Interleukin-2 Receptor Is a Biomarker for Pneumocystis jirovecii Pneumonia among Patients with Rheumatoid Arthritis under Methotrexate Therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.

Intraoperative neuromonitoring during reverse shoulder arthroplasty.

BACKGROUND: The aim of this study was to evaluate the risk of nerve injury with neuromonitoring during reverse total shoulder arthroplasty. MATERIALS: This study included 15 shoulders of 15 patients (11 females and 4 males) who underwent reverse total shoulder arthroplasty. The mean age was 74.8 ± 4.4 years. Nine shoulders had cuff tear arthropathy, 4 had massive rotator cuff tears, 2 had osteoarthritis, and 1 had rheumatoid arthritis. The somatosensory evoked potentials of the median nerve, transcranial motor evoked potentials, and free-electromyograms from 6 upper-extremity muscles were measured intraoperatively. We defined a nerve alert as 50% amplitude attenuation or 10% latency prolongation of the somatosensory evoked potentials and transcranial motor evoked potentials and sustained neurotonic discharge on free-electromyogram. RESULTS: Thirty-one alerts were recorded in 11 patients. The axillary nerve was associated with 17 alerts. Eleven alerts occurred during the glenoid procedure and 5 alerts occurred during the humeral procedure. One patient who did not recover from the alert of the axillary nerve had clinically incomplete paralysis of the deltoid muscle. CONCLUSION: The present findings suggest that the axillary nerve was the nerve most frequently exposed to the risk of injury, especially during glenoid and humeral implantation.

Representative survey of frozen shoulder questionnaire responses from the Japan Shoulder Society: What are the appropriate diagnostic terms for primary idiopathic frozen shoulder, stiff shoulder or frozen shoulder?

BACKGROUND: Primary frozen shoulder has unknown etiology and significant restriction of active and passive motion. The distinction between frozen shoulder and stiff shoulder has been unclear. Therefore, the purposes of this study were to perform a survey regarding definition and classification of frozen shoulder proposed by the American Academy of Orthopedic Surgeons (AAOS) among the members of the Japan Shoulder Society (JSS) and to compare the results with those obtained among the members of the American Shoulder and Elbow Surgeons (ASES). METHODS: The Scientific Research Project Committee of the JSS prepared the questionnaire for frozen shoulder and stiff shoulder. Surveys were sent by e-mail on Jan 14, 2016 to JSS registered members and the response dead-line was set on March 13, 2016. RESULTS: The number of respondents was 230, including all directors, councilors, and senior doctors. Agreement with the definition of primary frozen shoulder was 67%, the classification of primary or secondary frozen shoulder was 53%, and the 3 divisions of secondary frozen shoulder was 53%. Diagnostic terms for the cases of shoulder stiffness with unknown etiology were as follows: frozen shoulder (31%), stiff shoulder (22%), periarthritis scapulohumeralis (16%), so called "Gojukata" in Japan, which means shoulder problems in their fifties (16%), idiopathic frozen shoulder (6%), primary frozen shoulder (4%), adhesive capsulitis (3%), others (2%). CONCLUSION: The survey shows lower rates of agreement among the JSS members than the ASES members for the definition of primary frozen shoulder, the classification of primary and secondary frozen shoulder, and the divisions of secondary frozen shoulder. To avoid confusion between stiff shoulder and frozen shoulder, the committee agrees to the ISAKOS recommendation that the term "frozen shoulder" should be used exclusively for primary idiopathic stiff shoulder.

Randomized, Double-Blind, Crossover Clinical Trial of the Effect of Calcium Alginate in Noodles on Postprandial Blood Glucose Level.

We conducted a prospective, randomized, double-blind, 3-group, 3-phase crossover study to evaluate the effect of calcium alginate (Ca-Alg) on the postprandial increase of blood glucose in 15 healthy adult subjects who were given udon noodles containing or not containing Ca-Alg (5 or 8%). The value of ΔCmax (difference between the maximum (Cmax) and pre-feeding (C0) blood glucose levels) was significantly reduced in both Ca-Alg groups, and the area under the blood glucose level-time curve over 120 min (ΔAUC, with C0 as the baseline) was also significantly reduced. Thus, supplementation of noodles with Ca-Alg significantly suppressed both the peak postprandial blood glucose level and the total amount of glucose absorption. Blood calcium (Ca) concentration was significantly increased at 120 min after ingestion, but there was no marked change of other parameter values. A questionnaire indicated that addition of Ca-Alg did not affect the acceptability of the noodles. These results indicate that Ca-Alg might a useful food additive for helping to prevent lifestyle-related diseases without adversely affecting individual eating habits.