Prevalence and clinical outcomes of vitamin D deficiency among Japanese multiple myeloma patients: a single-center observational study.

PURPOSE: Vitamin D plays a crucial role in skeletal metabolism and holds significant importance in the pathophysiology of multiple myeloma (MM). This study aimed to determine the prevalence of vitamin D deficiency among Japanese MM patients and its correlation with clinical outcomes. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed in 68 MM patients at a single institution in Japan, analyzing their association with clinical status, laboratory parameters including procollagen type 1 N-propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), health-related quality of life (HR-QOL) scores, and overall survival. Additionally, patients with suboptimal 25(OH)D levels received cholecalciferol supplementation (1000 IU/day), and changes in laboratory parameters were monitored. RESULTS: The median 25(OH)D level was 22 ng/ml, with 32% and 51% of patients exhibiting vitamin D deficiency (< 20 ng/ml) and insufficiency (20-29 ng/ml), respectively. The 25(OH)D levels were unrelated to sex, age, MM stage, or bone lesions, but the vitamin D-deficient group showed a tendency towards lower HR-QOL scores. Among patients achieving complete remission, vitamin D supplementation increased P1NP, while TRACP-5b remained unchanged. Overall survivals from vitamin D measurement and from MM diagnosis were significantly worse in the vitamin D-deficient group compared to the vitamin D-insufficient/-sufficient group. CONCLUSION: The study identified a considerable number of Japanese MM patients with insufficient serum vitamin D levels, with one-third being deficient. Additionally, vitamin D deficiency predicted poor overall survival in Japanese MM patients. Further investigation is required to determine whether vitamin D supplementation can improve the frailty and survival of vitamin D-deficient MM patients.

Once Monthly Elotuzumab and Lenalidomide Plus Dexamethasone for Multiple Myeloma: A Multicenter Observation Study.

INTRODUCTION: Elotuzumab and lenalidomide plus dexamethasone (ERd) is a standard salvage chemotherapy for multiple myeloma, and elotuzumab is commonly administered every 2 weeks after cycle 3 (conventional ERd). Alternatively, elotuzumab may often be used every 4 weeks (monthly ERd) in real-world practice. The purpose of this multicenter observational study was to investigate the efficacy and tolerability of monthly ERd. METHODS: We investigated the efficacy and tolerability between conventional and monthly ERd regimens for the myeloma patients in six institutes retrospectively. RESULTS: Seventy-five patients were included in this study. The median patient age was 68 years. The median number of prior chemotherapies was two (1-5). The number of patients with prior lenalidomide exposure was 57 (76.0%). The numbers of progressive disease (PD) and non-PD before ERd were 23 (30.7%) and 52 (69.3%), respectively. The frequency of PD before ERd was significantly lower in the monthly ERd group than in the conventional ERd group. In 26.9 months of median follow-up period, the 2-year progression-free survival (PFS) rate in the monthly ERd group was significantly longer than that in the conventional ERd group (95.0% and 62.0%, hazard ratio 0.082, p = 0.002). However, no significant difference in PFS between these two ERd groups was found using multivariate analysis. The complete response rates were similar between the monthly and conventional ERd groups (55.0% and 32.7%, p = 0.109). There was no significant difference in the incidence of adverse events between the monthly and conventional ERd groups (35.0% and 54.5%, p = 0.192). There was no significant difference in the kinetics of the mean absolute lymphocyte count, CD4, CD8, CD16, CD56, and CD57 positive lymphocyte counts, and CD4 to CD8 ratio between the monthly and conventional ERd groups. DISCUSSION: The efficacy and tolerability of monthly ERd were similar to those of conventional ERd. Thus, monthly ERd might be a reasonable option, considering the quality of life of patients and convenience.

Internet survey on factors associated with care-seeking behaviours of people with chronic musculoskeletal pain in Japan.

Purpose: Many people with chronic musculoskeletal pain (CMP) seek healthcare from conventional and complementary and alternative medicine. However, treatment/therapy is not always adequate, patients often change healthcare providers, and some patients are left untreated. This study clarified care-seeking behaviours and explored factors behind the behaviours in people with CMP. Methods: Using a Japanese cross-sectional online survey, participants aged ≥ 20 years with non-cancer/fracture CMP lasting for ≥ 6 months and presenting ≤1 month, interfering with daily living activities and/or work were enrolled. We summarized and analysed the characteristics and factors associated with choice of healthcare providers; information on socio-demographics, including employment; ability to use healthcare, including income; and need for healthcare, including pain intensity, using a logistic regression model. Results: Among the 9105 respondents, 24.5% consulted physicians, 18.3% complementary and alternative medicine practitioners, and 57.2% were untreated. More respondents who had moderate-severe pain visited physician, more regularly employed and with high income visited complementary and alternative medicine, and less respondents who had moderate-severe pain were untreated. These were found to be associated with the respective healthcare use versus untreated. Conclusions: People with severe conditions, higher income and regular employment, and less severe conditions have visited physicians, complementary and alternative medicine practitioners and none, respectively. By applying this result at each type of healthcare provider, it may be possible to treat patients more appropriately.

Potential Application of Protamine for Antimicrobial Biomaterials in Bone Tissue Engineering.

Bacterial infection of biomaterials is a serious problem in the field of medical devices. It is urgently necessary to develop new biomaterials with bactericidal activity. Antimicrobial peptides and proteins (AMPs), alternative antibacterial agents, are expected to overcome the bacterial resistance. The aim of this study was to develop a new intelligent material in bone tissue engineering based on protamine-loaded hydroxyapatite (protamine/HAp) that uses AMPs rather than antibiotics. It was found that the adsorption of protamine to HAp followed the Langmuir adsorption model and was due to electrostatic and/or hydrophobic interactions. In vitro bacterial adhesion and growth on protamine/HAp was inhibited in a protamine dose-dependent manner. Adherent bacteria exhibited an aberrant morphology for high dosages of protamine/HAp, resulting in the formation of large aggregates and disintegration of the membrane. The released protamine from protamine/HAp also prevented the growth of planktonic bacteria in vitro. However, a high dosage of protamine from powders at loading concentrations over 1000 µg·mL-1 induced a cytotoxic effect in vitro, although those exhibited no apparent cytotoxicity in vivo. These data revealed that protamine/HAp (less than 1000 µg·mL-1) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.

Percutaneous Tendon Needling without Ultrasonography for Lateral Epicondylitis.

Percutaneous ultrasonic tendon needling has been used to treat persistent lateral epicondylitis, and its efficacy has been demonstrated. However, whether ultrasonography is necessary remains unclear. The purpose of this retrospective study was to evaluate the efficacy of percutaneous tendon needling without ultrasonography for lateral epicondylitis. A total of 36 patients who underwent tendon needling without ultrasonography for lateral epicondylitis were retrospectively included in the study. The tendinotic lesion was needled by fenestration approximately 20-30 times without sonographic assistance. The Visual Analogue Scale (VAS) pain score, the grip strength, and success rates were assessed at baseline and at 1, 3, 6, and 12 months after treatment. The Nirschl tennis elbow score was evaluated at baseline and at 6 and 12 months after the needling procedure. The mean VAS pain score and grip strength at 3, 6, and 12 months significantly improved compared to the baseline values. At 6 and 12 months, the success rates had significantly increased compared to the rates at 1 month. The mean Nirschl scores at 6 and 12 months were significantly better than the baseline value. No severe complications were observed during the study period. Percutaneous tendon needling without ultrasonography is a simple and safe technique. The procedure is effective for lateral epicondylitis that is unresponsive to conventional conservative treatments.

Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model.

The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.

Predictive model for major complications 2 years after corrective spine surgery for adult spinal deformity.

PURPOSE: ASD surgery improves a patient's health-related quality of life, but it has a high complication rate. The aim of this study was to create a predictive model for complications after surgical treatment for adult spinal deformity (ASD), using spinal alignment, demographic data, and surgical invasiveness. METHODS: This study included 195 surgically treated ASD patients who were > 50 years old and had 2-year follow-up from multicenter database. Variables which included age, gender, BMI, BMD, frailty, fusion level, UIV and LIV, primary or revision surgery, pedicle subtraction osteotomy, spinal alignment, Schwab-SRS type, surgical time, and blood loss were recorded and analyzed at least 2 years after surgery. Decision-making trees for 2-year postoperative complications were constructed and validated by a 7:3 data split for training and testing. External validation was performed for 25 ASD patients who had surgery at a different hospital. RESULTS: Complications developed in 48% of the training samples. Almost half of the complications developed in late post-op period, and implant-related complications were the most common complication at 2 years after surgery. Univariate analyses showed that BMD, frailty, PSO, LIV, PI-LL, and EBL were risk factors for complications. Multivariate analysis showed that low BMD, PI-LL > 30°, and frailty were independent risk factors for complications. In the testing samples, our predictive model was 92% accurate with an area under the receiver operating characteristic curve of 0.963 and 84% accurate in the external validation. CONCLUSION: A successful model was developed for predicting surgical complications. Our model could inform physicians about the risk of complications in ASD patients in the 2-year postoperative period. These slides can be retrieved under Electronic Supplementary Material.

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.