Cost-Effectiveness of Universal Asymptomatic Preoperative SARS-CoV-2 Polymerase Chain Reaction Screening: A Cost-Utility Analysis.

BACKGROUND: An early report has shown the clinical benefit of the asymptomatic preoperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening test, and some clinical guidelines recommended this test. However, the cost-effectiveness of asymptomatic screening was not evaluated. We aimed to investigate the cost-effectiveness of universal preoperative screening of asymptomatic patients for SARS-CoV-2 using polymerase chain reaction (PCR) testing. METHODS: We evaluated the cost-effectiveness of asymptomatic screening using a decision tree model from a payer perspective, assuming that the test-positive rate was 0.07% and the screening cost was 8500 Japanese yen (JPY) (approximately 7601 US dollars [USD]). The input parameter was derived from the available evidence reported in the literature. A willingness-to-pay threshold was set at 5 000 000 JPY/quality-adjusted life-year (QALY). RESULTS: The incremental cost of 1 death averted was 74 469 236 JPY (approximately 566 048 USD) and 291 123 368 JPY/QALY (approximately 2 212 856 USD/QALY), which was above the 5 000 000 JPY/QALY willingness-to-pay threshold. The incremental cost-effectiveness ratio fell below 5 000 000 JPY/QALY only when the test-positive rate exceeded 0.739%. However, when the probability of developing a postoperative pulmonary complication among SARS-CoV-2-positive patients was below 0.22, asymptomatic screening was never cost-effective, regardless of how high the test-positive rate became. CONCLUSIONS: Asymptomatic preoperative universal SARS-CoV-2 PCR screening is not cost-effective in the base case analysis. The cost-effectiveness mainly depends on the test-positive rate, the frequency of postoperative pulmonary complications, and the screening costs; however, no matter how high the test-positive rate, the cost-effectiveness is poor if the probability of developing postoperative pulmonary complications among patients positive for SARS-CoV-2 is sufficiently reduced.

Determinants of Gait Parameters in Patients With Severe Hip Osteoarthritis.

OBJECTIVE: To investigate the characteristics and symptoms of patients with hip osteoarthritis that are associated with spatiotemporal gait parameters, including their variability and asymmetry. DESIGN: A retrospective, cross-sectional study. SETTING: University hospital. PARTICIPANTS: The study analyzed the gait analysis data of 155 patients (N=155) with hip osteoarthritis who were admitted to a university hospital for total hip replacement and were able to walk on a treadmill without a handrail. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The dependent variables were gait parameters during treadmill walking. These included gait speed, stride length, cadence, coefficient of variation of stride length and stride time, swing time symmetry index, and step symmetry index. Single and multiple regression analyses were conducted using independent variables of the characteristics and symptoms of the patients, including age, sex, height, pain, leg-length discrepancy, and muscle strength of the affected and normal sides measured with a hand-held dynamometer (iliopsoas, gluteus medius, and quadriceps). RESULTS: In the analysis, gait speed and stride were the dependent variables, whereas age, height, and muscle strength on the affected side were the significant independent variables (P<.05). Additionally, pain demonstrated a marginal association with gait speed (P=.053). Only the leg-length discrepancy correlated with cadence. When the coefficient of variation of the stride length was the dependent variable, age and muscle strength on the affected side were significant. For the swing time symmetry index, only the muscle strength on the affected side was significant. Furthermore, the step symmetry index only correlated with leg-length discrepancy. The muscle strength on the affected side was the only significant independent variable for the coefficient of variation of the stride time. CONCLUSIONS: The results revealed that each of the frequent clinical symptoms of hip osteoarthritis, such as pain, muscle weakness, and leg-length discrepancy, can explain different aspects of gait performance.

Epidemiologic Survey of Myxofibrosarcoma Using Data from the Bone and Soft Tissue Tumor Registry in Japan.

BACKGROUND: Myxofibrosarcoma is a common sarcoma among older patients, with locally infiltrative behavior and a predilection for local postoperative recurrence. Some studies have reported the factors affecting prognosis, although only a few have mentioned the previous staging classification systems. This study investigated the clinical overview and prognosis of myxofibrosarcoma to determine the optimal treatment. METHODS: This retrospective study analyzed the records of 349 patients with myxofibrosarcoma in the nationwide Bone and Soft Tissue Tumor Registry in Japan from 2006 to 2015. Clinical features, treatment options, and patient outcomes were investigated. RESULTS: Ultimately, 349 patients were identified. The overall survival rates were 93.1% at 2 years and 84.3% at 5 years. A multivariate analysis was performed using the Cox proportional hazards model. The study identified four significant prognostic factors for survival: tumor size, depth, compartment status, and location. The prognostic score was calculated by summing the scores of all the factors. The overall survival rate was 69.3% at 5 years for the patients with prognostic scores of 6 or higher. Conversely, the patients with prognostic scores of 2 or lower had a survival rate of 95.6% at 5 years. CONCLUSIONS: Among myxofibrosarcomas, those larger than 5 cm, deep-seated, invaded into the external compartment, or in axial body parts were associated with a significantly worse prognosis. Adjuvant radiotherapy and chemotherapy did not contribute significantly to a better prognosis. Previous staging classification systems are impractical for prognosis prediction. Therefore, new classifications are needed. Further research on new treatment methods for patients with a poor prognosis will be crucial in the future.

Changing trends in the risk factors for second primary malignancies after autologous stem cell transplantation for multiple myeloma before and after the introduction of proteasome inhibitors and immunomodulatory drugs.

The incidence of second primary malignancies (SPM) in long-term survivors of multiple myeloma (MM) is increasing because of increased life expectancy. We retrospectively analyzed the risk factors for SPM in patients with MM after autologous stem cell transplantation (ASCT) before and after the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs). In total, 2,340 patients newly diagnosed with MM who underwent ASCT between 1995 and 2016 were enrolled in this study. Forty-three patients developed SPM (29 solid, 12 hematological, and 2 unknown tumors), with cumulative incidence rates of 0.8% and 2.5% at 24 and 60 months, respectively. The cumulative incidence rates of hematological and solid SPM at 60 months were 0.8% and 1.8%, respectively. The overall survival (OS) rate at 60 months after ASCT was 62.9% and the OS rates after the diagnosis of SPM at 24 months were 72.2% for hematological SPM and 70.9% for solid SPM. Multivariate analysis revealed that the use of IMiDs (P=0.024) and radiation (P=0.002) were significant independent risk factors for SPM. The probabilities of developing SPM and death due to other causes (mainly MM) at 60 months were 2.5% and 36.5%, respectively, indicating that the risk of SPM was lower than that of death from MM. Furthermore, SPM between the pre-novel and novel agent eras (ASCT between 2007 and 2016) groups significantly increased (1.9% vs. 4.3% at 60 months; P=0.022). The early occurrence of SPM after ASCT should be monitored cautiously.

Anti-CD38 antibody isatuximab monotherapy for Japanese individuals with relapsed/refractory multiple myeloma: An update of the phase 1/2 ISLANDs study.

The primary analysis of the phase 1/2 ISLANDs study in Japanese individuals with relapsed/refractory multiple myeloma (RRMM) showed that isatuximab monotherapy was well tolerated and effective, even in participants with high-risk cytogenetic abnormalities. Here, we report a prespecified second analysis conducted 20 months after the first dosing of the last participant (ClinicalTrials.gov identifier: NCT02812706). The primary objectives were to evaluate the safety and tolerability of isatuximab in phase 1 and to evaluate the efficacy of isatuximab, including assessment of overall response rate (ORR) at the recommended dose (RD), in phase 2. In phase 1, three participants received isatuximab 10 mg/kg every week (QW) for 4 weeks/cycle followed by every 2 weeks (Q2W) and five participants received 20 mg/kg QW/Q2W. Since no dose-limiting toxicities occurred in phase 1, 20 mg/kg QW/Q2W was identified as the RD for the phase 2 study (n = 28). At the time of data cut-off, three participants (one in phase 1 and two in phase 2) continued to receive isatuximab; disease progression and treatment-related adverse events were the most common reasons for treatment discontinuation. The overall safety profile was consistent with the primary analysis. One death, not related to isatuximab treatment, was reported since the first analysis. The ORR and clinical benefit rate remained unchanged from the primary analysis at 36.4% (95% confidence interval [CI]: 20.4%-54.9%) and 54.5% (95% CI: 36.4%-71.9%), respectively. The median progression-free survival (PFS) was 5.6 months, longer than the median PFS reported in the primary analysis (4.7 months), whereas median overall survival was not reached. Overall, isatuximab 20 mg/kg QW/Q2W had an acceptable safety and tolerability profile and showed promising antitumor activity in Japanese individuals with RRMM.

TNFα-dependent mTOR activity is required for tenotomy-induced ectopic ossification in mice.

INTRODUCTION: Ectopic ossifications often occur in skeletal muscles or tendons following local trauma or internal hemorrhage, and occasionally cause severe pain that limits activities of daily living. However, mechanisms underlying their development remain unknown. MATERIALS AND METHODS: The right Achilles tendon in 8-week-old female or male mice was dissected. Some mice were injected intraperitoneally either with phosphate-buffered saline, dimethyl sulfoxide, cimetidine, rapamycin, celecoxib or loxoprofen for 10 weeks. One week after surgery, immunohistochemical analysis was performed for mTOR, TNFα or F4/80. Ten weeks after surgery, ectopic ossification at the tenotomy site was detected by 3D micro-CT. RESULTS: Ectopic ossification was seen at dissection sites in all wild-type mice by dissection of the Achilles tendon. mTOR activation was detected at dissection sites, and development of ectopic ossification was significantly inhibited by administration of rapamycin, an mTOR inhibitor, to wild-type mice. Moreover, administration of the histamine 2 blocker cimetidine, which reportedly inhibits ectopic ossification in tendons, was not effective in inhibiting ectopic ossification in our models. TNFα-expressing F4/80-positive macrophages accumulate at dissection sites and that ectopic ossification of the Achilles tendon dissection was significantly inhibited in TNFα-deficient mice in vivo. Ectopic ossification is significantly inhibited by administration of either celecoxib or loxoprofen, both anti-inflammatory agents, in wild-type mice. mTOR activation by Achilles tendon tenotomy is inhibited in TNFα-deficient mice. CONCLUSION: The TNFα-mTOR axis could be targeted therapeutically to prevent trauma-induced ectopic ossification in tendons.

Low energy availability reduces bone mass and gonadal function in male mice.

INTRODUCTION: In women, the female athlete triad, marked by low energy availability, functional hypothalamic amenorrhea and osteoporosis, is a recognized risk for stress fractures. Stress injuries also occur in men, but by contrast risks and mechanisms underlying them are less characterized. MATERIALS AND METHODS: 5 week-old wild-type male mice were fed ad libitum (ad) or subjected to 60% food restriction (FR) for five weeks. In both groups, some mice were allowed access to an exercise wheel in cages to allow voluntary wheel running (ex) and/or treated with active vitamin D analogues. Mice were sacrificed and analyzed at 10 weeks of age. RESULT: Male FR mice exhibited significantly reduced testicle weight, serum testosterone levels and bone mass. Such bone losses in FR male mice were enhanced by exercise. Histological analysis revealed that both bone-resorbing and -forming activities were significantly reduced in FR or FR plus exercise (FR + ex) mice, mimicking a state of low bone turnover. Significantly reduced bone mass in FR or FR + ex male mice was significantly rescued by treatment with active vitamin D analogues, with significant restoration of osteoblastic activities. Serum levels of insulin-like growth factor I (IGF-I), which is critical for bone remodeling, were significantly lower in FR versus control male mice. CONCLUSIONS: Low energy availability puts men at risk for stress injuries as well, and low energy availability is upstream of gonadal dysfunction and osteoporosis in males. Active vitamin D analogues could serve as therapeutic or preventive options for stress injuries in men.

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.

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.

Deep learning-based prediction model for postoperative complications of cervical posterior longitudinal ligament ossification.

PURPOSE: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM. RESULTS: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%). CONCLUSION: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods.

Natural history and surgical outcomes of idiopathic spinal cord herniation.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: Although surgery is frequently selected for the treatment of idiopathic spinal cord herniation (ISCH), its impact on functional outcomes has yet to be fully understood given the limited number of patients in previous studies. This study aims to evaluate the symptomatic history and surgical outcomes of ISCH. SETTING: Three institutions in Japan. METHODS: A total of 34 subjects with ISCH were retrospectively enrolled and followed up for at least 2 years. Demographic information, imaging findings, and clinical outcomes were collected. Functional status was assessed using the JOA score. RESULTS: The types of neurologic deficit were monoparesis, Brown-Sequard, and paraparesis in 5, 17, and 12 cases, with their mean disease duration being 1.2, 4.2, and 5.8 years, respectively. Significant differences in disease duration were observed between the monoparesis and Brown-Sequard groups (p < 0.01) and between the monoparesis and paraparesis groups (p = 0.04). Surgery promoted significantly better recovery rates from baseline. Correlations were observed between age at surgery and recovery rate (p < 0.01) and between disease duration and recovery rate (p = 0.04). The mean recovery rates were 82.6%, 51.6%, and 29.1% in the monoparesis, Brown-Sequard, and paraparesis groups, respectively. The monoparesis group had a significantly higher recovery rate than did the Brown-Sequard (p = 0.045) and paraparesis groups (p < 0.01). CONCLUSIONS: Longer disease duration was correlated with the progression of neurologic deficit. Older age, and worse preoperative neurologic status hindered postoperative functional recovery. These results highlight the need to consider surgical timing before neurologic symptoms deteriorate.

In Vivo Metacarpophalangeal Joint Kinematics After Silicone Implant Arthroplasty in Patients With Rheumatoid Arthritis.

PURPOSE: The aim of this study was to determine the potential mechanism of implant fracture using 3-dimensional motion analysis of patients with rheumatoid arthritis. METHODS: Active flexion motion in 9 hands (34 fingers) of 6 female patients with rheumatoid arthritis who previously underwent hinged silicone metacarpophalangeal joint arthroplasty was examined using 4-dimensional computed tomography. Positions of the proximal phalanges relative to the metacarpals were quantified using a surface registration method. The deformation of the silicone implant was classified in the sagittal plane in the maximum flexion frame. The longitudinal bone axis of the proximal phalanx and the helical axis of the proximal phalanx were evaluated in 3-dimensional coordinates based on the hinge of the silicone implant. RESULTS: Nineteen fingers were classified into group 1, in which the silicone implant moved volarly during flexion without buckling of the distal stem. Twelve fingers were classified into group 2, in which the distal stem of the silicone implant buckled. Three fingers were classified into group 3, in which the base of the distal stem had already fractured. Quantitatively, the longitudinal bone axes of the proximal phalanges were displaced from dorsal to volar in the middle stage of flexion and migrated in the proximal direction in the late phase of flexion. The helical axes of the proximal phalanges were located on the dorsal and proximal sides of the hinge, and these tended to move in the volar and proximal directions as the metacarpophalangeal joint flexed. CONCLUSIONS: Volar and proximal translation of the proximal phalange was observed on 4-dimensional computed tomography. CLINICAL RELEVANCE: Proximal displacement of the bone axis late in flexion appears to be a contributing factor inducing implant fractures, because the pistoning motion does not allow the implant to move in the proximal direction.

Comparable satisfaction and clinical outcomes after surgery for adolescent idiopathic scoliosis in the adult (AISA) between the US and Japan.

BACKGROUND: The impact of ethnicity on the surgery outcomes of adolescent idiopathic scoliosis in the adult (AISA) is poorly understood. This study aimed to compare the surgery outcomes for AISA between the United States (US) and Japan (JP). METHODS: 171 surgically treated AISA (20-40y) were consecutively collected from 2 separate multicenter databases. Patients were propensity-score matched for age, gender, curve type, levels fused, and 2y postop spinal alignment. Demographic and radiographic parameters were compared between the US and JP at baseline and 2y post-op. RESULTS: A total of 108 patients were matched by propensity score (age; US vs. JP: 29 ± 6 vs. 29 ± 7y, females: 76 vs. 76%, curve type [Schwab-SRS TypeT; TypeD; TypeL; TypeN]: 35; 35; 30; 0 vs. 37; 33; 30; 0%)] levels fused: 10 ± 4 vs. 10 ± 4, 2y thoracic curve:17 ± 13 vs. 17 ± 12°, 2y CSVL: 10 ± 8 vs. 11 ± 9 mm). Similar clinical improvement was achieved between US and JP (function; 4.2 ± 0.9 vs 4.3 ± 0.6, p = 0.60, pain; 3.8 ± 0.9 vs 4.1 ± 0.8, p = 0.13, satisfaction; 4.3 ± 0.9 vs 4.2 ± 0.7, p = 0.61, total; 4.0 ± 0.8 vs 4.1 ± 0.5, p = 0.60). The correlation analyzes indicated that postoperative SRS-22 subdomains correlated differently with satisfaction (all subdomains moderately correlated with satisfaction in the US while only pain and mental health correlated moderately with satisfaction in JP ([function: r = 0.61 vs 0.29, pain: r = . 72 vs 0.54, self-image: r = 0.72 vs 0.37, mental health: r = 0.64 vs 0.55]). CONCLUSIONS: Surgery for AISA was similarly effective in the US and JP. Satisfaction for spinal surgery among patients in different countries may not be different unless the procedure limits an individual's unique lifestyle that the patient expected to resume.

Persistent low bone mineral density in adolescent idiopathic scoliosis: A longitudinal study.

BACKGROUND: Since osteopenia has been reported to potentially associated with the progression of scoliosis, bone mineral density (BMD) might have some influences on adolescent idiopathic scoliosis (AIS). However, little is known about longitudinal BMD changes in AIS patients. This study aimed to investigate whether osteopenia in preoperative AIS patients persist at bone maturity, and to evaluate the association between BMD and AIS severity. METHODS: We reviewed 61 AIS patients who underwent surgery when they were Risser grade 4 or below and less than 20 years old (16.6 ± 1.9 years), were followed until they were at least 18 years old and had a Risser grade of 5, and followed at least 2 years after the surgery (mean follow-up 4.9 ± 1.7 years). We evaluated radiographical parameters and proximal femur BMD before surgery and at the final follow-up. A BMD of less than the mean minus 1SD was considered as low BMD. Based on preoperative BMD, 37 patients were assigned to normal BMD (N) group (1.02 ± 0.08 g/cm2) and 24 patients to low BMD (L) group (0.82 ± 0.06 g/cm2). RESULTS: All patients in the N-group had normal BMD at the final follow-up. In the L group, 15 patients (62.5%) had low BMD at the final follow-up (L-L group; preoperative 0.79 ± 0.05 g/cm2 and final follow-up 0.78 ± 0.05 g/cm2). The mean preoperative Cobb angle was significantly larger in the L-L group (67.8 ± 11.2°) than in those with normal BMD at the final follow-up (L-N group, 55.6 ± 11.8°) or the N-N group (50.8 ± 7.6°). Preoperative BMD was significantly negative correlated with the preoperative Cobb angle. The age at surgery and mean preoperative BMI were similar in the L-N and L-L groups. CONCLUSIONS: Of AIS patients with low preoperative BMD, 62.5% still had low BMD after reaching bone maturity, and low BMD was associated with the severity of scoliosis.

Hidden blood loss in extreme lateral interbody fusion for adult spinal deformity.

BACKGROUND: Extreme lateral interbody fusion (XLIF) is often used with posterior spinal fixation (PSF) to treat adult spinal deformity (ASD). However, the amount of intraoperative blood loss (IBL) reported for XLIF may underestimate the total blood loss (TBL). The objective of this study was to determine the total perioperative blood loss in XLIF for ASD. METHODS: We assessed 30 consecutive ASD patients with Schwab-SRS type L (mean age: 68.7 ± 8.2 years; mean follow-up 2.0 ± 1.3 years) who were treated by multilevel XLIF (mean, 2.5 ± 0.6 levels) followed by PSF after 3-5 days. We calculated the TBL after XLIF by the Gross equation, by hemoglobin (Hb) balance, and by the Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) formula. We defined hidden blood loss (HBL) as the difference between the TBL and IBL. Pearson correlation, Spearman correlation, and multiple logistic regression analysis were performed to investigate the risk factors related to HBL. RESULTS: Post-XLIF blood tests showed a significant decrease in the Hb (from 11.8 ± 1.1 mg/dl to 10.6 ± 1.1 mg/dl) and hematocrit (from 36.0 ± 3.2% to 32.5 ± 3.2%). Although the mean IBL was relatively small (33 ± 52 mL), we calculated the TBL as 291 ± 171 mL (Gross equation) and the HBL as 258 ± 168 mL by Gross equation, which was 8 times greater than the IBL on average. There was no difference in the results obtained using the three methods. Multiple logistic regression analysis indicated preoperative lumber lordosis was the risk factor of high HBL (Odds ratio = 1.085, 95%CI: 1.006-1.170, p = 0.035). CONCLUSIONS: The HBL in XLIF was 8 times greater than the IBL. During the perioperative course of correction and fusion surgery for ASD with XLIF, surgeons need to pay attention not to underestimate the TBL.

Risk factors of AIS C incomplete cervical spinal cord injury for poor prognosis-The significance of anorectal evaluation.

BACKGROUND: Although the prognosis of incomplete cervical spinal cord injury (SCI) diagnosed as American Spinal Injury Association Impairment Scale grade C (AIS C) is generally favorable, some patients remain non-ambulatory. The present study explored the clinical factors associated with the non-ambulatory state of AIS C patients. METHODS: This study was a single-center retrospective observational study. Seventy-three participants with AIS C on admission were enrolled and divided into two groups according to ambulatory ability after one year. Prognostic factors of SCI were compared in ambulatory (A-group) and non-ambulatory participants (NA-group). Univariable and multivariable logistic regression analyses were performed on demographic information, medical history, mechanism of injury, presence of fracture, ASIA motor scores (MS) of the extremities, neurological findings, including an anorectal examination on admission, and imaging findings. RESULTS: Forty-one patients were included in the A-group and 32 in the NA-group. Univariable analysis revealed that the following factors were related to poor outcomes (p < 0.05): older age, history of cerebrovascular disorder, impairment/absence of S4-5 sensory score, deep anal pressure (DAP) (-), voluntary anal contraction (VAC) (-), anorectal tone (-), anal wink reflex (-), and low MS of the upper and lower extremities. In the multivariable analysis using age, presence or absence of sacral abnormality, and history of cerebrovascular disorders (adjusted for these three factors), older age and presence of sacral abnormality on admission were independent risk factors for a non-ambulatory state at the 1-year follow-up. CONCLUSIONS: Incomplete AIS C SCI individuals with older age and/or impairment of anorectal examination could remain non-ambulatory at 1-year follow-up.

The Stat3 inhibitor F0648-0027 is a potential therapeutic against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a disease characterized by chronic joint inflammation, pain and joint destruction, leading to alteration in activities of daily living, yet pathological mechanisms underlying the condition are not fully clarified. To date, various therapeutic agents have been developed as RA therapy including DMARDs and/or biological agents that target inflammatory cytokines or inhibit JAK. Here we asked whether inhibiting signal transducer and activator of transcription 3 (Stat3) activity would antagonize RA. Stat3 forms dimers when activated and undergoes nuclear translocalization; thus we screened approximately 4.9 million small compounds as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening. We identified 15 as strong candidates as potential blockers of protein-protein interactions required for Stat3 dimerization using in silico screening from those compounds. Four of the 15 significantly inhibited expression of IL-6 and RANKL, both of which are direct targets of Stat3, induced by IL-6. Among four, one compound, F0648-0027, significantly inhibited arthritis development without apparent adverse effects in vivo in collagen-induced arthritis model mice. F0648-0027 also significantly blocked Stat3 phosphorylation and nuclear localization following IL-6 stimulation of fibroblasts. These data suggest that Stat3 is a target for collagen-induced arthritis in mice, and that F0648-0027 could serve as a therapeutic reagent against comparable conditions in humans.

Transverse Anderson localization of mid-infrared light in a chalcogenide transversely disordered optical fiber.

We successfully fabricate a transversely disordered optical fiber made of AsSe2 and As2S5 glasses for high-resolution mid-infrared image transport. By using the fabricated fiber, we experimentally observe transverse Anderson localization of mid-infrared light at the wavelength of 3 µm. Moreover, we numerically evaluate the localization in the fiber by using a cross-sectional image of the fiber.

Chalcogenide all-solid hybrid microstructured optical fiber with polarization maintaining properties and its mid-infrared supercontinuum generation.

In this paper, we report a successful fabrication of a highly nonlinear chalcogenide all-solid hybrid microstructured optical fiber with polarization maintaining properties and a mid-infrared SC generation. Up to 4.5 × 10-4 at 10 µm of the fiber birefringence can be realized by employing a single As2Se3 core and two As2S5 rods horizontally aligned in the AsSe2 cladding. The fiber possesses a near-zero and flattened all-normal chromatic dispersion profile over the wavelength range from 5 to 10 µm. The polarization maintaining properties of the fiber is experimentally confirmed and a broadband supercontinuum spectrum from 2 to 10 µm in the mid-infrared window was experimentally demonstrated.

Maximum number of bone cross-linked vertebrae: an index for BMD in diffuse idiopathic skeletal hyperostosis.

INTRODUCTION: The maximum number of vertebral bodies with bony bridges between adjacent vertebrae (max VB) helps assess the risk of fracture in diffuse idiopathic skeletal hyperostosis (DISH). In addition to max VB, the maximum thickness of bone cross-bridges (max TB) may be an index of bone mineral density (BMD). Therefore, this study investigated the relationship among max VB, max TB, and BMD. MATERIALS AND METHODS: The participants in this cross-sectional study were male patients (n = 123) with various max VB from the thoracic vertebrae to the sacrum without sacroiliac ankylosis. The participants were grouped by max VB. For example, a group with max VB from 4 to 8 would be listed as max VB (4-8). The relation between femur proximal BMD and mean max TB and max VB was assessed. Femur proximal BMD was then compared after adjusting for confounding factors. RESULTS: The results indicated that max VB was correlated with femur proximal BMD in max VB (0-8) and max VB (9-18) groups. The mean max TB was correlated only with femur proximal BMD in max VB (0-8). After adjusting, max VB (4-8) showed a significantly higher femur proximal BMD than max VB (0-3) and max VB (9-18). CONCLUSION: Femur proximal BMD and mean max TB showed different trends after max VB = 9, which suggests that max VB is an index of BMD, and that DISH has at least two possible populations in terms of BMD and bone cross-link thickness.