Does the pregnancy-related adaptation of gait biomechanics after childbirth recover to its pre-pregnancy state?: A systematic review.

BACKGROUND: Although changes in the gait biomechanics during pregnancy are known to occur, it is unclear whether they return to their original state after childbirth. RESEARCH QUESTION: The objective of the current systematic review is to summarize existing literature reporting the biomechanical characteristics of gait in postpartum women and to identify knowledge gaps that calls for future investigations in this population. METHODS: Relevant articles were selected using MEDLINE (PubMed), Scopus (Elsevier), Embase (Elsevier), and Web of Science (Clarivate Analytics). Articles were included if they met the following criteria: They must (1) include postpartum women, (2) report measures related to three-dimensional (3D) kinematics and/or kinetics, (3) have been published after 1990, and (4) have been published in English. RESULTS AND SIGNIFICANCE: The current systematic review included a total of 14 articles, five of which compare the data from postpartum women with nulliparous women or pre-pregnancy data. We observed that gait biomechanics changes of postpartum women could persist for more than 5 years after the childbirth. This review provides novel viewpoints on the biomechanics of postpartum women's gait and recommendations for future studies to fully understand these changes and improve postpartum women's physical and mental wellbeing.

A macrocyclic kinase inhibitor overcomes triple resistant mutations in EGFR-positive lung cancer.

Brigatinib-based therapy was effective against osimertinib-resistant EGFR C797S mutants and is undergoing clinical studies. However, tumor relapse suggests additional resistance mutations might emerge. Here, we first demonstrated the binding mode of brigatinib to the EGFR-T790M/C797S mutant by crystal structure analysis and predicted brigatinib-resistant mutations through a cell-based assay including N-ethyl-N-nitrosourea (ENU) mutagenesis. We found that clinically reported L718 and G796 compound mutations appeared, consistent with their proximity to the binding site of brigatinib, and brigatinib-resistant quadruple mutants such as EGFR-activating mutation/T790M/C797S/L718M were resistant to all the clinically available EGFR-TKIs. BI-4020, a fourth-generation EGFR inhibitor with a macrocyclic structure, overcomes the quadruple and major EGFR-activating mutants but not the minor mutants, such as L747P or S768I. Molecular dynamics simulation revealed the binding mode and affinity between BI-4020 and EGFR mutants. This study identified potential therapeutic strategies using the new-generation macrocyclic EGFR inhibitor to overcome the emerging ultimate resistance mutants.

More than 20 years' follow-up of metatarsal neck shortening oblique osteotomy for rheumatoid forefoot deformity.

BACKGROUND: In recent years, advances in pharmacotherapy for rheumatoid arthritis (RA) have dramatically improved the control of disease activity. However, a significant number of patients still develop forefoot deformity. The purpose of this study was to investigate the results of more than 20 years' follow-up of metatarsal neck shortening oblique osteotomy (SOO) for forefoot deformity in patients with RA. METHODS: The metatarsal neck SOO was performed on 163 feet in 108 patients between January 1985 and December 1996 in the authors' hospital. For the patients, who met the survey criteria, an observational study was performed clinically and radiologically at the baseline and at more than 20 years after surgery. RESULTS: A retrospective cohort study was conducted on 36 feet in 22 patients, all of whom were female, and the mean age at surgery was 45.6 (35.0-63.0) years old. The follow-up period was 25.1 (21.0-31.0) years. The presence of painful callosities in the surgically treated feet without revised surgeries decreased from 32 feet (100%) to 4 feet (12.5%) at the last follow-up with mild pain that did not cause any footwear problems. Re-osteotomy at the metatarsal of the lessor toe was performed on four feet in two patients. Radiologically, among 128 toes without revised surgeries, 85% were able to have the joint space preserved, and 89% maintained a pain-free condition without any recurrence of deformity. The mean total Japanese Society for Surgery for the Foot (JSSF) RA foot and ankle score was 64.0/100, and the visual analogue scale (VAS) of overall satisfaction was 62 (0: dissatisfied, 100: highly satisfied). The overall satisfaction had a positive correlation with calcaneal pitch and negative correlation with joint space narrowing at the talocrural joint. CONCLUSIONS: Metatarsal neck SOO appeared to be effective for patients with RA. The deformity was corrected and retained for a long time.

Addition of a Vascular Bundle Accelerates Bone Union in Femoral Bone Defects.

BACKGROUND: The Masquelet method has become increasingly popular for the treatment of bone defects in recent years. In this method, an induced membrane (IM) with abundant blood circulation, stem cells, and osteogenesis-promoting factors is formed by implanting bone cement during the first surgery. This IM stimulates bone formation in the bone defect after implantation of the bone graft during the second surgery. However, the Masquelet method requires two surgeries and thus a longer treatment period. In the present study, we investigated whether bone defects could be reconstructed in a single surgery by introducing a vascular bundle into the bone defect as an alternative to the IM, in addition to bone grafting. METHODS: Thirty-six 12-week-old female Sprague-Dawley rats were used. After creating a 5-mm long bone defect in the femur, a mixture of autologous and artificial bone was grafted into the defect, and a saphenous arteriovenous vascular bundle was introduced. The animals were divided into three groups: the control group (bone defect only), the BG group (bone grafting only), and the BG + V group (bone grafting + vascular bundle introduction). After surgery, radiological and histological evaluations were performed to assess osteogenesis and angiogenesis in bone defects. RESULTS: In the BG + V group, significant bone formation was observed in the bone defect on radiological and histological evaluations, and the amount of bone formation was significantly higher than that in the other two groups. Furthermore, cortical bone continuity was observed in many specimens in the BG + V group. On histological evaluation, the number of blood vessels was also significantly higher in the BG + V group than in the other two groups. CONCLUSION: Our results suggest that the introduction of a vascular bundle in addition to bone grafting can promote bone formation in bone defects and allow for complete bone defect reconstruction in a single surgery.

Humoral immune response against BNT162b2 mRNA COVID-19 vaccine in patients with rheumatic disease undergoing immunosuppressive therapy: A Japanese monocentric study.

We investigated serum total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain after BNT162b2 mRNA vaccination against coronavirus disease 2019 (COVID-19) in Japanese patients taking various immunosuppressive medications for rheumatic disease. In 212 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers (controls), all of whom had received 2 doses of BNT162b2 vaccine, serum antibody titers of SARS-CoV-2 spike protein were analyzed at least 14 days after the second dose. Many of the patients were taking immunosuppressive agents to manage their rheumatic disease. The antibody titers against SARS-CoV-2 spike protein in these patients were significantly lower than those in controls. The analysis of therapeutic agents revealed that the antibody titers in patients treated with rituximab were much lower than those in controls. In patients treated with tacrolimus, baricitinib, azathioprine, mycophenolate mofetil, abatacept, tumor necrosis factor inhibitors, cyclosporine, interleukin-6 inhibitors, methotrexate, or glucocorticoids, antibody titers were moderately lower than those of controls. Interleukin-17 and interleukin-23 inhibitors did not impair the humoral response. In addition, the combination of methotrexate with various immunosuppressive agents reduced titers, although not significantly. In Japanese patients with rheumatic disease, many immunosuppressants impaired the immune response to the BNT162b2 vaccine. The degree of decline in antibody titers differed according to immunosuppressant. When used concomitantly with other immunosuppressants, methotrexate may impair the immune response to the BNT162b2 vaccine. However, immunomodulatory treatments such as interleukin-17 and -23 inhibitors may not attenuate this response in patients with rheumatic disease.

Factors influencing physical activity in postpartum women during the COVID-19 pandemic: a cross-sectional survey in Japan.

BACKGROUND: The aim of this study was to investigate factors influencing postpartum physical activity (PA), taking into consideration psychosocial perceptions during the coronavirus disease 2019 (COVID-19) pandemic by comparing health-related quality of life (HRQoL) scores. METHODS: A web-based cross-sectional survey of 787 postpartum women was conducted between March and October 2021. After applying the exclusion criteria, 590 women were analyzed. The International Physical Activity Questionnaire Short Form, was used to assess the level and amount of PA. The Short Form-12 Health Survey version 2 (SF-12v2) was used to measure HRQoL. Logistic regression analyses were used to determine whether sociodemographic factors and psychosocial perceptions during the COVID-19 pandemic were associated with the level of PA. Based on the current national guidelines for exercise in Japan, respondents were classified by weekly PA level as an Inactive group and an Active group to assess the influence of PA on HRQoL. RESULTS: Mean total PA was 19.3 total metabolic equivalents hour/week, and the prevalence of an inactive lifestyle was 45.9% among respondents. Each year of age was associated with an odds ratio (OR) of 0.92 (95% CI 0.87-0.97) for becoming physical inactivity during postpartum. Factors positively associated with more active levels were greater number of days for delivery (OR = 1.00; 95% CI 1.00-1.01), multiparity (OR = 1.50; 95% CI 1.00-2.23), having someone to talk about childcare and the individual's partner (OR = 2.04; 95% CI 0.96-4.36) and not having anxiety symptoms (OR = 0.58; 95% CI 0.35-0.97). The Active group had significantly higher HRQoL scores than the Inactive group in the following scales: physical component summary (p < 0.001), mental component summary (p = 0.041). CONCLUSIONS: The influential factors for postpartum PA level were younger age, longer duration after childbirth, multiparity and not having anxiety symptoms, which correlated positively with PA. The presence of someone with whom can talk to about childcare and partner issues was associated with the maintenance of higher PA among postpartum women, suggesting that factor as a positive influence on PA under unsettled conditions.

Skin extension with a digito-lateral flap and early active finger extension training for Dupuytren contracture: A retrospective study.

In the surgical management of Dupuytren contracture (DC), Y-V plasty (YV) and Z-plasty (ZP) are techniques often used for skin extension. However, achieving sufficient skin extension with these procedures alone is often difficult. Therefore, we addressed this issue with an adjunctive digito-lateral flap (DLF) and report the clinical results of the surgery using a DLF in addition to YV and ZP. Fifteen patients with DC (15 affected fingers) underwent partial fasciectomy using a DLF in addition to YV or ZP, and early active finger extension training was performed immediately after the operation. The flap survival rate, preoperative and postoperative extension angle, Tonkin contracture improvement (TCI) rate, and Tubiana staging grades were evaluated. The contracture sites were at 4 proximal interphalangeal (PIP) and 3 metacarpophalangeal (MP) joints of the little finger and 4 PIP and MP joints each of the ring and little fingers. All the flaps survived, and the extension angle improved at the final observation from a preoperative mean of -45° to -3° and -55° to 5° for the PIP and MP joints, respectively. One patient with PIP joint contracture treated in the early stage of the study experienced a persistent 5° limitation of extension, even though the TCI rate was satisfactory (91.9%) and the outcome was "good." Full extension of the joints was achieved in 15 patients, in whom the TCI rate was 100% and the outcome was "very good." This technique was able to solve 3 important steps to achieve full extension: intraoperatively, wound closure, and rehabilitation. We attained and maintained long-term full extension intraoperatively and immediately after surgery and obtained very good treatment results, as shown in this study. In conclusion, highly favorable clinical outcomes were achieved through the combination of a DLF with YV and ZP. Skin extension with a DLF is a useful surgical technique for DC.

Postoperative early and proactive grip strength training program for distal radius fractures promotes earlier recovery of grip strength: A retrospective study.

ABSTRACT: The use of volar locking plates (VLPs) for distal radius fractures has remarkably improved clinical outcomes; however, there are some reports of delayed recovery of grip strength. Since January 2019, we have been conducting an early and proactive grip strength training program (EGTP). In this program, 20 minutes of grip strength training-using a gripper with a load of 0.7 kg-was initiated from 2 weeks after surgery; the load was then gradually increased. From 6 weeks postsurgery, daily home grip strength training was performed using a gripper with a load of 5 kg, provided to the patient.We investigated whether the introduction of the EGTP could lead to earlier recovery of grip strength. We also examined whether the EGTP caused postoperative correction loss at the fractured site, or contributed to the early improvement of wrist function.Thirty-nine patients who underwent surgery using VLPs for distal radius fractures were included in this study; 20 followed the EGTP (EGTP group) and 19 patients did not (NGTP group). For these patients, grip strength and range of motion of the wrist joint were evaluated both 3 and 6 months postoperatively. The Quick Disabilities of the Arm, Shoulder, and Hand (qDASH) scores were also evaluated 6 months postoperatively. Additionally, corrective losses of radial inclination (RI), palmar tilt (PT), and ulnar variance (UV)-occurring from immediately postsurgery to 6 months after surgery-were evaluated.At both 3 and 6 months postoperatively, the grip strength of the EGTP group was significantly higher than that of the NGTP group. Regarding range of motion, only palmar flexion was significantly improved in the EGTP group at 3 months postoperatively. Conversely, no differences in corrective losses of RI, PT, and UV, or in qDASH scores, were observed between the two groups.The results of this study suggest that the EGTP can provide early recovery of grip strength and palmar flexion of the wrist without causing corrective loss at the fracture site.

Immunogenicity against the BNT162b2 mRNA COVID-19 Vaccine in Rheumatic Disease Patients Receiving Immunosuppressive Therapy.

Objective To investigate the serum total antibody (immunoglobulin M and immunoglobulin G) titre against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain following BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination in Japanese rheumatic disease patients undergoing immunosuppressive therapy. Methods The serum antibody titre against SARS-CoV-2 spike protein was analysed in 123 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers who had received 2 doses of the BNT162b2 mRNA vaccine with at least 14 days elapsing since the second dose. Results The antibody titre in rheumatic disease patients was significantly lower than that in healthy subjects (p<0.0001). The antibody titres of the 41 patients who received biologics or Janus kinase inhibitors and the 47 patients who received conventional immunosuppressive agents were significantly lower than those of the 35 patients who did not receive immunosuppressive agents (p<0.0001 and p<0.0001, respectively). In addition, the mean antibody titre of the 43 patients on methotrexate was significantly lower than that of the 80 patients not on methotrexate (p=0.0017). Conclusion Immunogenicity to the BNT162b2 mRNA COVID-19 vaccine in rheumatic disease patients was found to be reduced under immunosuppressive treatment. In particular, methotrexate seems to be associated with a decreased antibody response.

Lasso loop technique using bioabsorbable thread to treat intra-articular distal radius fracture.

ABSTRACT: This article introduces our lasso loop technique (LLT) using a bioabsorbable thread for the treatment of intra-articular distal radius fractures with displaced dorsal bone fragment containing articular surface (DBF). We also examined whether the articular gap is sufficiently reduced and maintained by the LLT, along with the results of other radiological and clinical evaluations. We retrospectively reviewed 19 patients who underwent LLT for intra-articular distal radius fracture with a displaced DBF. Patient radiographic images and medical records were used to investigate radiological characteristics, symptoms, physical findings, and the Quick Disabilities of the Arm, Shoulder, and Hand scores. Sagittal-view computed tomography showed that the mean preoperative articular gap was 2.6 mm, but the gap was reduced by LLT, and the gap immediately postoperatively was <1.0 mm in all patients. No re-displacement of the DBF was evident from immediately postoperatively to 6 months postoperatively. Postoperatively, no losses of correction in palmar tilt, radial inclination, or ulnar variance were seen in the evaluation of plain radiographs, and satisfactory joint range of motion, grip strength, and the Quick Disabilities of the Arm, Shoulder, and Hand score were obtained. No significant complications due to LLT were observed. LLT appears to offer a simple and effective procedure to reduce displaced DBF with little risk of complications. LLT may become a useful option in the treatment of intra-articular distal radius fractures with displaced DBF.

Rapalink-1 and Hydroxychloroquine Exhibit an Additive Effect in Undifferentiated Pleomorphic Sarcoma by Inducing Apoptosis.

BACKGROUND/AIM: Advanced undifferentiated pleomorphic sarcoma (UPS) has a poor prognosis and there are few treatments that can improve overall survival. Recently, Rapalink-1, a third-generation mammalian target of rapamycin (mTOR) kinase inhibitor, has been developed and shown to be effective against other tumours. However, mTOR inhibitors have been shown to induce autophagy and resistance to anti-cancer drugs. This study aimed to investigate the antitumor effects of Rapalink-1 with an autophagy inhibitor. MATERIALS AND METHODS: The antitumor effect of Rapalink-1 and/or hydroxychloroquine in three UPS cell lines was examined via cell viability analysis, western blotting, flow cytometry and immunofluorescence. RESULTS: Rapalink-1 decreased cell proliferation and inhibited the PI3K/mTOR pathway. Combined treatment with Rapalink-1 and hydroxychloroquine enhanced the antitumor effect compared to treatment with Rapalink-1 alone by blocking the autophagy-inducing effect of mTOR inhibitors. CONCLUSION: Combined treatment with Rapalink-1 and hydroxychloroquine may be used as a potential therapeutic agent against UPS.

The Combination of Modified Mitchell's Osteotomy and Shortening Oblique Osteotomy for Patients with Rheumatoid Arthritis: An Analysis of Changes in Plantar Pressure Distribution.

The present study aims to evaluate changes in plantar pressure distribution after joint-preserving surgery for rheumatoid forefoot deformity. A retrospective study was performed on 26 feet of 23 patients with rheumatoid arthritis (RA) who underwent the following surgical combination: modified Mitchell's osteotomy (mMO) of the first metatarsal and shortening oblique osteotomy of the lateral four metatarsals. Plantar pressure distribution and clinical background parameters were evaluated preoperatively and one year postoperatively. A comparison of preoperative and postoperative values indicated a significant improvement in the visual analog scale, Japanese Society for Surgery of the Foot scale, and radiographic parameters, such as the hallux valgus angle. A significant increase in peak pressure was observed at the first metatarsophalangeal joint (MTPJ) (0.045 vs. 0.082 kg/cm2; p < 0.05) and a significant decrease at the second and third MTPJs (0.081 vs. 0.048 kg/cm2; p < 0.05, 0.097 vs. 0.054 kg/cm2; p < 0.05). While overloading at the lateral metatarsal heads following mMO has been reported in previous studies, no increase in peak pressure at the lateral MTPJs was observed in our study. The results of our study show that this surgical combination can be an effective and beneficial surgical combination for RA patients with mild to moderate joint deformity.

Combined administration of rifampicin, ethambutol, and clarithromycin for the treatment of tenosynovitis of the hand caused by Mycobacterium avium complex: Case series and literature review.

ABSTRACT: We report the clinical results and problems of combined administration of rifampicin, ethambutol, and clarithromycin (REC) for the treatment of Mycobacterium avium complex (MAC) infection of the hand (hand MAC).Participants included 7 patients with hand MAC. After resection of the infected lesion, REC was prescribed for 12 months. For these patients, the site of infection, clinical course after initiation of REC, adverse drug effects (ADEs), and incidence of recurrence were evaluated.Sites of infection were the flexor tenosynovium in 5 patients, extensor tenosynovium in 1 patient, and both flexor and extensor tenosynovium in 1 patient. ADEs of REC occurred in 5 patients, and included visual disturbance caused by ethambutol in 2 patients, liver function abnormality caused by rifampicin in 2 patients, and fever with diarrhea caused by rifampicin in 1 patient. For 2 of these 5 patients, desensitization therapy was applied and REC was able to be reinstated. In the remaining 3 patients, the causative drugs were discontinued and levofloxacin, a new quinolone, was administered. Complete healing was achieved in 5 patients, and recurrence was observed in 2 patients. These 2 patients with recurrence included 1 patient in whom REC was completed and 1 patient in whom REC therapy was modified due to ADE.REC provided relatively good clinical results as a treatment for hand MAC. However, recurrences were observed even after the completion of REC and the use of an alternative drug. Optimal duration of REC and appropriate alternative drugs need to be identified in the future.

Arthrodesis of the digital joint using intraosseous wiring in patients with rheumatoid arthritis.

OBJECTIVE: Digital joints affected by rheumatoid arthritis often have severe deformity and/or dislocation, and arthrodesis in a functional position is required. METHODS: Arthrodesis was performed using intraosseous wiring (modified Lister's method) from January 2011 to December 2015, and we investigated the union rate, postoperative complications, and patient satisfaction with the operation at the final follow-up. The DASH score, grip power, and pinch power were also investigated before the operation and at the final follow-up. RESULTS: Arthrodesis was performed for 90 digital joints in 56 patients. Bone union was obtained in 85 of 89 joints (96%). Wire removal was needed due to subcutaneous protrusion in 20 joints and superficial infection in five joints. The mean preoperative DASH score of 50.5 improved to 45.2 at the final follow-up. The pulp pinch power of the index fingers through the little fingers changed significantly. In the questionnaire regarding the operated digit using a visual analogue scale (VAS, 0 [worst] to 100 [best]), the overall satisfaction was 70. CONCLUSION: With this approach, we achieved painless stability as well as deformity correction. A restored prehensile pattern and improvement in the activities of daily life can thus be expected after surgery.

Bone Union Enhancement by bFGF-Containing HAp/Col in Prefabricated Vascularized Allo-Bone Grafts.

BACKGROUND: We have developed a prefabricated vascularized allo-bone graft (PVAG) by implanting the saphenous vascular bundles of recipient rats into transplanted donor bones in a flow-through manner. We previously demonstrated that the angiogenetic and bone formative abilities of the PVAG are stimulated by the addition of a basic fibroblast growth factor (bFGF)-containing hydroxyapatite/collagen (HAp/Col). This study aimed to demonstrate that the bone union ability of the PVAG is similarly stimulated by the bFGF-containing HAp/Col composite. METHODS: Sprague-Dawley donor rats (n = 32) and Wistar recipient rats (n = 32) were used in this study. The PVAG was fixed to the femur of the recipient rat using K-wire (dimeter: 0.7 mm) pinning, followed by suturing with a 4-0 nylon suture. Recipients were divided into four groups: with or without vascular bundles, and with or without bFGF-containing HAp/Col. Rats were sacrificed 6 weeks after transplantation, and bone union, bone resorption, and angiogenesis were radiologically and histologically evaluated. RESULTS: Radiological analysis revealed a significant increase in callus formation and union rate, while histological analysis showed a significant increase in bone formation and angiogenesis in the group treated with both vascular bundles and bFGF. Bone resorption did not significantly increase in any of the evaluated groups. CONCLUSION: Osteogenic cells, osteoconductive scaffolds, growth factors, and mechanical environment are known to be important factors in the process of fracture healing. The PVAG developed herein contains osteogenic cells, osteoconductive scaffolds, and growth factors. In addition, the PVAG is rigidly fixed to the fracture site, providing a stable mechanical environment. Together, these four factors contributed to a good bone union. Furthermore, this method did not promote bone resorption. Thus, the addition of a vascular bundle and bFGF-containing HAp/Col makes it possible to create an ideal vascularized allo-bone graft for the reconstruction of massive bone defects.

Changes in radiographic findings and plantar pressure distribution following forefoot reconstructive surgery for patients with rheumatoid arthritis.

Objectives: To evaluate changes in radiographic findings and plantar pressure distribution after rheumatoid forefoot surgery.Methods: This study was performed on patients with rheumatoid arthritis (RA) who underwent Swanson implant arthroplasty for the 1st metatarsophalangeal (MTP) joint combined with shortening oblique osteotomy at the 2nd through 5th metatarsal necks (group Sw, 55 feet). The following two groups were used as controls: group NS, consisting of 75 feet in RA patients without scheduled forefoot surgery, and group HC, consisting of 24 feet in healthy female subjects. Plantar pressure distribution, and radiographic findings of hallux valgus angle, the angle between the metatarsal bones, talocalcaneal angle, calcaneal pitch angle and calcaneo-first metatarsal angle (CFMA) were measured pre- and one year postoperatively. Peak pressure was measured in nine sections.Results: Calcaneal pitch angle decreased and CFMA increased in group Sw. Peak pressure at the 1st interphalangeal joint (IP) and the 2nd and 3rd MTPs in group Sw decreased, while that at midfoot increased.Conclusion: While the clinical outcome in group Sw was favorable, postoperative longitudinal arch decreased. Postoperative peak pressure at the 2nd through 5th MTPs was comparable with that in group NS; however, it was significantly lower than that in group HC.

Overall benefits provided by orthopedic surgical intervention in patients with rheumatoid arthritis.

OBJECTIVES: To clarify systemic effects of orthopedic surgical intervention in patients with rheumatoid arthritis (RA). METHODS: A prospective observational cohort study was performed in RA patients who were scheduled to have primary elective orthopedic surgeries. Assessments were performed at baseline, 6 and 12 months after surgery using J-HAQ, General Health, EQ-5D, BDI-II, DAS28-CRP(4) and CRP for all registered patients, DASH and grip power for patients with upper-extremity surgeries, TUG for patients with lower-extremity surgeries, and JSSF for patients with ankle and forefoot surgeries. RESULTS: There were 294 sites in 276 patients whose average age was 64 (19-89) years and average disease duration was 16 (1-60) years. Surgical site was shoulder in six patients, elbow in 26, wrist in 74, hand in 63, hip in 13, knee in 50, ankle in 12, and forefoot in 50. In total, physical function (J-HAQ, grip power, DASH, TUG, JSSF), quality of life (J-HAQ, General Health, EQ-5D) and depression (BDI-II) improved and disease activity (CRP, DAS28-CRP(4)) decreased significantly 6 and 12 months after surgery (p<.01), despite some differences in their outcomes by the preoperative disease activity and the surgical site. CONCLUSION: Overall benefits were provided by orthopedic surgical intervention generally in patients with RA.

Total Synthesis of Spiromamakone A and Structure Revision of Spiropreussione A.

Spiromamakone A is a racemic natural product having a naphthyl acetal group on a spiro[4,4]nonadiene skeleton. Its total synthesis was achieved by double oxa-Michael addition of 1,8-dihydroxynaphthalene to 2-(1-bromoalkylidene)-4-isopropoxy-4-cyclopentene-1,3-dione, which was prepared by palladium(II)-catalyzed ring expansion of 4-(1-alkynyl)-4-hydroxy-3-isopropoxy-2-cyclobuten-1-one, and a subsequent intramolecular aldol reaction. The synthesis using optically active intermediates enabled identification of the racemization step of spiromamakone A and revealed that spiromamakone A and spiropreussione A are identical; the latter had been reported as a constitutional isomer of the other.

Conjugate Addition to Acylketene Acetals Derived from 1,8-Dihydroxynaphthalene and Its Application To Synthesize the Proposed Structure of Spiropreussione A.

A conjugate addition of diverse nucleophiles to acylketene acetals derived from 1,8-dihydroxynaphthalene (DHN) is developed for the formation of its 3-oxoalkan-1-one acetals. The initial acylketene acetals are prepared via double oxa-Michael addition of DHN to 1-bromo-1-propyn-3-ones. Carbonucleophiles, including organocopper reagents and active methylene compounds, and heteroatom nucleophiles were introduced under basic conditions. This method is applied for synthesizing spiropreussione A; the proposed structure does not correspond to that of the authentic natural product.

The Efficacy of Minodronate in the Treatment of Glucocorticoid-induced Osteoporosis.

Objective To investigate the efficacy of minodronate in the treatment of glucocorticoid-induced osteoporosis (GIO). Methods The study population included patients in whom the administration of minodronate (50 mg, once every 4 weeks) had been newly started for the treatment of GIO in Niigata Rheumatic Center from 2012 to 2015. Patients who were bisphosphonate-naïve and those who switched from other bisphosphonates were classified into the naïve and switch groups, respectively. The changes in the bone mineral density (BMD) and bone metabolic markers after one year of minodronate treatment were retrospectively evaluated. We also compared the BMD and bone turnover marker changes of minodronate-naïve patients with those in whom alendronate or risedronate had been prescribed as a first bisphosphonate (control group). Results Minodronate was prescribed to 142 patients, and data were successfully obtained from 120 patients. New vertebral fractures were observed in 5 of the 142 patients; 1 fracture occurred during the cessation of minodronate for dental treatment, and 3 patients already had multiple vertebral fractures before the initiation of minodronate. The patients' tartrate-resistant acid phosphatase 5b (TRACP-5b) (-27.0%, p<0.001) and bone alkaline phosphatase (BAP) (-15.7%, p<0.01) levels were decreased, but no patients showed a decrease to below the normal range. One year of treatment with minodronate significantly increased the lumbar BMD in the naïve (+3.9%, p<0.001) and switch (+2.3%, p<0.001) groups. Although the femoral BMD did not change to a significant extent overall, the patients with a low young adult mean (YAM) (<80%) at baseline showed a significant increase in their femoral BMD (+2.1%, p=0.034) values. Compared with the control group, the minodronate-naïve group showed a significant decrease in the TRACP-5b levels and a significant increase in the lumbar BMD. Conclusion The administration of minodronate appears to be an effective treatment for GIO.