Histologically Proven Recurrent Synovitis after Nivolumab Treatment.

A 58-year-old woman with rheumatoid arthritis was diagnosed with methotrexate-associated Hodgkin lymphoma. After receiving several chemotherapy regimens, she started nivolumab treatment. Two weeks later, she was hospitalized with worsening finger, wrist, and elbow joint pain. A synovial biopsy of the wrist joint showed villous synovial proliferation and linear infiltration of CD68-/CD3-positive T cells (with more CD8 than CD4 T cells) but no CD20-positive B cells or CD138-positive macrophages. These findings corresponded to synovitis associated with immune-related adverse events, which are induced mainly by T cells and are different from typical rheumatoid arthritis (RA), in which B cells play a central role.

A Half-Century Dialysis Survivor: Clinical and Autopsy Findings.

A man in his 20s initiated intermittent peritoneal dialysis in the late 1960s. He subsequently transitioned to hemodialysis and survived for more than 50 years, spanning low-flux and high-flux hemodialysis eras. He underwent surgery for cervical and lumbar spinal canal stenosis after 30 and 35 years, respectively, and both surgeries revealed similar degrees of severe amyloid deposition. At autopsy, significant improvement was seen in lumbar amyloid deposition. During the previous 25 years, serum ß2 microglobulin levels had decreased from 40 mg/L and been maintained at 20 mg/L. This case indicates that advances in dialysis therapy aimed at lowering ß2 microglobulin concentrations have reduced highly deposited amyloid.

A Novel Grading System of Destructive Lumbar Spondyloarthropathy Based on Evaluation of the Facet Joints.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To develop and evaluate a new grading system for destructive lumbar spondyloarthropathy (DLSA) by assessing bony destruction of the facet joints; to evaluate interrater reliability; and to determine the association between anteroposterior (AP) dural sac diameter at the lumbar level and the new grading. SUMMARY OF BACKGROUND DATA: The characteristics of DLSA are unknown, hindering clinical care and research. Imaging to determine the cause of DLSA may positively contribute to patient outcome or well-being by providing prognostic information. PATIENTS AND METHODS: In the magnetic resonance images (MRIs), we measured an axial midline AP dural sac diameter and evaluated bone destruction caused by amyloidosis at the level of the center of each lumbar disk of the lumbar spine. Two orthopedic surgeons independently evaluated each case at two-month intervals and assigned the grade by rating bone destruction at each lumbar level. Weighted κ and intraclass correlation coefficients for interrater reliability were calculated. In addition, the correlation between the AP diameter of the spinal dural sac at the lumbar level and the new MRI-based DLSA grade was examined. RESULTS: The sample size of 82 patients was reached by examining records of 118 consecutive patients. The mean (SD) age of the included patients was 65 (7.2) years, and 36 (43.9%) were women. The grading of DLSA showed moderate to good interrater reliability at both assessments (κ, 0.59-0.78). Intraclass correlation coefficient showed substantial to excellent agreement (intraclass correlation coefficient, 0.63-0.86). The AP diameter of the spinal dural sac at the lumbar level showed a significant correlation with the new grading ( P <0.001). CONCLUSIONS: The new MRI-based grading system for DLSA has good interrater reliability, although the strength of agreement varies somewhat. The new grading system correlates with AP dural sac diameter. Thus, this classification focused on facet erosion, which leads to functional incompetence may be helpful in surgical decision-making.

Association Between Simultaneous Bilateral Total Hip Arthroplasty Without Any Anticoagulant or Antiplatelet Therapy and Deep Venous Thrombosis: A Cohort Study.

BACKGROUND: The association of simultaneous bilateral total hip arthroplasty (THA) with postoperative deep venous thrombosis (DVT) remains controversial. The aim of the study is to determine whether simultaneous bilateral THA without chemoprophylaxis has a higher risk than unilateral THA without chemoprophylaxis. METHODS: This is a population-based retrospective cohort study of all adults who underwent primary THA without any anticoagulant or antiplatelet therapy between July 2012 and March 2021 at the Department of Orthopedic Surgery, Toranomon Hospital, Tokyo, Japan. The association of simultaneous bilateral THA with postoperative DVT was examined by unadjusted analysis and overlap propensity score weighting. The primary outcome was the incidence of DVT (confirmed by ultrasonography of the lower limb veins) within 7 days postoperatively. RESULTS: Of the 557 consecutive patients who underwent primary THA in the study period, 458 met the inclusion criteria. The mean (standard deviation) age of these patients was 67 (11.7) years, and 364 (79.5%) were women; 75 (16.4%) of the 458 patients underwent simultaneous bilateral THA, and 383 (83.6%), unilateral THA. A total of 64 patients (14.0%) developed a postoperative venous thromboembolism, all of which were a distal DVT. The overlap weighting analysis found no significant difference in the incidence of postoperative DVT complications among patients who underwent simultaneous bilateral THA and those who underwent unilateral THA (31.1 [13.6%] vs 22.9 [10.0%], respectively; risk ratio, 1.36; 95% confidence interval, 0.67 to 2.77; P = .40). CONCLUSIONS: Our findings indicate that the occurrence of DVT within 7 days after surgery is not significantly different between patients undergoing simultaneous bilateral THA or unilateral THA without any anticoagulant or antiplatelet therapy. LEVEL OF EVIDENCE: Level II-III.

Effect of loaded exercise for renal osteodystrophy.

We performed bone histomorphometric analysis of biopsy specimens from two patients with hyper- and hypoparathyroidism and a history of long-term hemodialysis (HD) because of diabetes. Case 1, a 53-year-old man with hyperparathyroidism, had been on HD for 22 years, and Case 2, a 54-year-old woman with hypoparathyroidism, for 20 years. Intact parathyroid hormone levels were 1070 and 3 pg/mL, respectively. Case 1 had mixed renal osteodystrophy (fibrous tissue volume to total volume [Fb.V/TV], 5.21%; osteoid volume to bone volume [OV/BV], 19.8%), and Case 2 had adynamic renal osteodystrophy (Fb.V/TV, 0%; OV/BV, 0.54%). Case 1 showed cortical bone thinning (cortical width, 0.2 mm) and porosis (cortical porosity, 14.1%), but case 2 did not (cortical width, 0.84 mm; cortical porosity, 11.6%). Trabecular connectivity of cancellous bone was preserved in both patients, with a bone volume to total volume of 18.2% in case 1 and 35.1% in case 2. Both patients had been doing daily strength training and treadmill walking (2-3 h/day) for over 10 years. Although case I showed cortical thinning and porosis, we suggest that long-term loaded exercise therapy may help to preserve cancellous trabecular bone in both hyperparathyroidism and hypoparathyroidism.

Dialysis-related carpal tunnel syndrome in the past 40 years.

PURPOSE AND METHOD: Patients on hemodialysis develop carpal tunnel syndrome (CTS) due to an accumulation of dialysis-related ß2 microglobulin (ß2m) amyloid (DRA). In Japan, dialysis technology has progressed remarkably in the past 40 years and has increased the time until patients require surgery for CTS. However, unclear is whether the time from the start of hemodialysis to the first surgery for CTS is associated with ß2m clearance by the different hemodialysis techniques. Therefore, we retrospectively evaluated ß2m clearance, serum ß2m levels, and the change in the length of this period in patients across 4 periods according to the year that first surgery for CTS was performed: period 1, 1982-1989; period 2, 1990-1999; period 3, 2000-2009; and period 4, 2010-2019. RESULT: A total of 222 patients who met the selection criteria were included. Mean ß2m clearance was -1.8 ± 16.7% in period 1, and improved to 65.4 ± 8.6% in period 3. Accordingly, the serum ß2m value after hemodialysis decreased significantly. The time from the start of hemodialysis to the first surgery for CTS was 12.4 ± 2.9 years in period 1 but increased to 21.8 ± 6.3 years in period 3. In multivariable linear regression analysis, the significant factors contributing to ß2m clearance were periods 2, 3, and 4. In particular, the relation between removal of ß2m and the extension of the dialysis vintage in period 1 and 2 was remarkable compared with periods 3 and 4. CONCLUSION: Our findings indicate that improvement of ß2m clearance via advances in dialysis technology might result in a significant extension in the time between starting HD and the first surgery for CTS.

Long-term use of glucocorticoid exacerbates bone lesions in postmenopausal women with rheumatoid arthritis.

Glucocorticoid-induced osteoporosis is osteoporosis arising due to long-term use of glucocorticoids. Despite decades of intense research, the effects of long-term use of glucocorticoids in humans on bone cells and bone structural changes remain unclear. We performed post-mortem histomorphometric analysis of bone from two female patients with rheumatoid arthritis aged 64 and 85 years. Our two patients had been treated with glucocorticoids for 19 and 14 years, respectively. In Case 1, all markers of cancellous bone volume were markedly decreased compared with the age-matched reference range. Connectivity of cancellous bone trabecula was absent. Only a few island bones were noted. There was prominent thinning of the cortical bone and extension of the bone marrow cavity into the cortical bone with prominent cortical porosis. Cortical nodes between the endocortical surface and the trabecula disappeared due to endocortical resorption. Stoppage of lamellar structure was observed because the bone resorption by osteoclasts surpassed bone formation by osteoblasts. Empty lacunae characterised by disappearance of osteocytes were visible. In Case 2, all volume markers of cancellous bone were decreased to the same extent as Case 1. However, cortical porosis was more prominent than Case 1. These two cases suggest that use of glucocorticoid therapy >10 years can induce severe osteoporosis in elderly rheumatoid arthritis women with higher disease activity and that the disappearance of cancellous bone is the common characteristic. The 85-year-old woman was characterised by cortical porosis.

Case report: Osteomalacia due to bisphosphonate treatment in a patient on hemodialysis.

BACKGROUND: No publications have reported on osteomalacia in patients receiving intermittent cyclical therapy with etidronate (a bisphosphonate) and undergoing long-term hemodialysis (HD). CASE PRESENTATION: We report on a 46-year-old Japanese man admitted to our hospital for further examination of left forearm pain. Maintenance HD was started at age 24 years, and the man had been on HD since then. At age 38 years, surgical parathyroidectomy was performed for secondary hyperparathyroidism; iliac crest bone biopsy performed at the same time showed osteitis fibrosa. The active vitamin D3 preparation calcitriol was started, and intermittent cyclical etidronate therapy was introduced 2 years later for osteoporosis. At age 45 years, the patient stopped taking calcitriol because of hypercalcemia but continued with etidronate. At age 46 years, a pseudofracture with a Looser zone occurred in the left ulna, and left femur bone biopsy revealed osteomalacia. Etidronate was discontinued, and calcitriol was restarted; open reduction and internal fixation with an angular stability plate were performed. Union of the bone was achieved 10 months after the operation. At age 49 years, a lumber bone biopsy confirmed improved bone morphometry. CONCLUSIONS: We believe that intermittent cyclical etidronate therapy without administration of active vitamin D3 during long-term HD might have induced osteomalacia, resulting in the ulna insufficiency fracture. Therefore, we propose that administration of active vitamin D3 is essential to prevent osteomalacia in patients on long-term HD who are receiving bisphosphonates and have potential vitamin D3 deficiency.

New bone-like tissue formation in calcific tendinopathy: A case report.

Currently, the pathogenesis of nontraumatic heterotopic ossification (HO), e.g., bone-like tissue in calcific tendinopathy remains unclear. Here, we report a 75-year-old, right-handed Japanese woman who had been on hemodialysis for 3 years and was admitted to our hospital to evaluate pain and swelling of the right forearm. She worked as a cook, and her main job over the 3 most recent years had been the frequent and continuous shredding of cabbage. A radiograph showed the highly radiopaque material on the dorsal aspect of the right wrist and in the right shoulder. The biopsy of this radiopaque material revealed HO with marrow, as well as calcified material. Histomorphometric analysis of the HO identified a severe type of osteitis fibrosa with a fibrous tissue volume to total volume of 19.8% (>0.5% required for diagnosis) and an osteoid volume to bone volume of 20.0% (>15% required for diagnosis). We found more woven bone-like tissue than lamellar bone-like tissue. However, the intact parathyroid hormone level was 3-times the normal upper limit with 203 pg/mL, but histomorphometric analysis of the right iliac crest revealed normal bone structure. These findings indicate that the frequent and continuous shredding action with the right hand contributed to the nontraumatic HO localized on the dorsal aspect of the right wrist.

Diaphyseal femoral fracture due to severe vitamin D3 deficiency and low parathyroid hormone levels on long-term hemodialysis: a case report.

INTRODUCTION: Currently, there are no reports of diaphyseal femoral fracture equivalent to atypical femoral fractures (AFFs) in patients receiving long-term hemodialysis (HD). CASE REPORT: A 56-year-old Japanese man receiving long-term HD for 34 years was admitted to our hospital due to a delay in postoperative healing. The patient began maintenance hemodialysis at 22 years of age. The patient then underwent surgical parathyroidectomy (PTX) for secondary hyperparathyroidism at 43 years of age, which resulted in decreased levels of parathyroid hormone (PTH). Thereafter, this patient's serum 1,25(OH)2 D3 level was very low because active vitamin D3 derivative was not administered. At 54 years of age, a transverse fracture of the femoral shaft equivalent to AFF occurred. Surgery with open reduction and internal fixation using intramedullary nailing was performed; however, the delay of postoperative healing continued for 16 months. A left iliac crest bone biopsy was performed and showed osteoid-like lesion and an increase of woven bone. The patient received active vitamin D3 derivative and recombinant human PTH (1-34) derivative. Twenty-nine months after the first surgery, a reoperation was performed. Simultaneously, a right iliac crest bone biopsy was performed. Bone morphometrical improvement was confirmed. Six months after resurgery, the bone union was achieved. Severe vitamin D3 deficiency and decreased levels of PTH may induce a higher osteoid state and an increase of woven bone, which may then attribute to the development of diaphyseal femoral fracture and impairment of postoperative bone healing. It is hypothesized that treatment with active vitamin D3 and teriparatide acetate may be a therapeutic option via the accelerated formation of lamellar bone for refractory diaphyseal femoral fracture of long-term dialysis.

Destructive Spondyloarthropathy in Patients on Long-Term Peritoneal Dialysis or Hemodialysis.

Destructive spondyloarthropathy (DSA) is the most serious spinal complication of dialysis-related amyloidosis in patients on long-term hemodialysis (HD), but we could not find any information about DSA in patients on peritoneal dialysis (PD) for over 10 years. We retrospectively evaluated factors contributing to DSA in HD and PD patients. Sixty-seven patients on dialysis for 10 to 19 years were compared between a PD group (n = 23) or a HD group (n = 44). In the PD group, nine patients (39%) developed DSA. The mean age of DSA patients was significantly higher than that of non-DSA patients (66.2 ± 10.0 vs. 51.0 ± 12.8 years, P = 0.03). The frequency of cervical spine DSA did not show any difference between the PD and HD groups, but the frequency of lumbar spine DSA showed a significant difference (22% vs. 5%, P = 0.04). The serum beta-2 microglobulin (B2MG) level was significantly higher in PD patients than in HD patients (38.4 mg/L vs. 27.4 mg/L, P = 0.0025). Mechanical stress such as elevation of the intra-abdominal pressure due to infusion of PD fluid (1500 mL to 2000 mL) for over 10 years might contribute to lumbar DSA in patients on long-term PD.

What can we learn from a patient on dialysis for 42 years?

We performed autopsy on a 60-year-old Japanese man who had received dialysis for 42 years. He started on intermittent peritoneal dialysis in 1968, which was combined with hemodialysis in 1969. His serum calcium-phosphate balance and his blood pressure had been controlled well. Carpal tunnel syndrome occurred in 1984. Then lumbar spinal canal stenosis (SCS) occurred in 1997, followed by cervical SCS in 2000, destructive lumbar spondyloarthropathy (DSA) in 2002, and pathological fracture of the right femoral neck due to an enlarging bone cyst in 2006. All of his surgical specimens showed dialysis-related deposition of beta2MG amyloid (dialysis-related amyloidosis: DRA). Thereafter, lumbar and cervical spinal palsy progressed. In 2009, he developed severe paralytic ileus with dilatation of the sigmoid colon, and subsequently died of peritonitis due to necrotizing cholecystitis. Autopsy showed massive DRA deposits in his intestinal blood vessels and thickened spinal dura, resulting in the above-mentioned intestinal and spinal complications. However, his arterial tree, including the aorta and coronary arteries, showed very little atheroma. Strict control of the Ca-P balance and blood pressure may have prevented cardiovascular disease, while progress in dialysis technology delayed fatal complications of DRA and allowed this patient to survive on dialysis for 42 years.

Usefulness of arterial blood gas analysis and D-dimer measurement in the assessment of pulmonary embolism after orthopedic surgery.

BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) after spinal or lower extremity surgery are well recognized as common complications. Since 1995 we have investigated the incidence of PE after orthopedic surgery using ventilation-perfusion (V/Q) lung scans, and the prevalence of PE was about 10%. With a view to detecting early-stage PE by simple examinations, we evaluated the use of both the blood gas analysis and the D-dimer measurement after spinal or lower extremity surgery. METHODS: Altogether, 85 patients who underwent spinal or lower extremity surgery were eligible for the study. Pneumatic sequential leg compression devices (PSLCDs) were utilized continuously both intra- and postoperatively. Arterial blood gas analysis and D-dimer measurement were performed pre- and postoperatively on days 3 and 7. We set lung scan criteria as follows: postoperative decrease in Pa(O2) (deltaPa(O2) by > or = 10 torr (group G), postoperative D-dimer of > or = 1 microg/ml (group D), or both. Patients with the criteria went on to undergo lung scans, and PE was diagnosed by the existence of any mismatch between ventilation-perfusion (V/Q) lung scans. RESULTS: A total of 44 (51.8%) patients met the lung scan criteria and underwent perfusion lung scans, 10 (11.7%) of whom were diagnosed as PE. In groups G and D, about 30% showed PE. Moreover, six (85.7%) of the seven patients with both criteria showed a significant increase (83.7%) in the prevalence of PE. CONCLUSIONS: Patients with the above criteria showed a high prevalence of PE. Moreover, 10 (11.7%) of the 85 patients were diagnosed as having PE, which corresponded to the prevalence in our former studies where lung scans were performed in all patients. The blood gas analysis and the D-dimer measurement may be utilized as the first screening examinations.

Evaluation of quality of life in brachial plexus injury patients after reconstructive surgery.

To evaluate the subjective satisfaction of brachial plexus injury (BPI) patients after surgery based on the medical outcomes study 36-item short form health survey (SF-36) and to correlate their SF-36 scores with upper extremity functions. Four items were assessed statistically for 30 patients: SF-36 scores after BPI surgery were compared with Japanese standard scores; the correlation between SF-36 scores and objective joint functions; difference in SF-36 scores between each type of BPI; and influence of each joint function on the SF-36 scores. The SF-36 subscale: PF--physical functioning, RP--role-physical, BP--bodily pain, and the summary score PCS--physical component summary, were significantly inferior to the Japanese standard scores. SF-36 is more sensitive to shoulder joint function than to elbow and finger joint functions. Little correlation was found between SF-36 scores and objective evaluations of joint functions. Greater effort is needed to improve the quality of life (QOL) of BPI patients. This study showed that SF-36 is not sensitive enough to evaluate regional conditions. A region- or site-specific questionnaire is required to evaluate upper extremity surgery.

Pelvic insufficiency fracture related to autosomal dominant polycystic kidney disease.

We report the case of a patient with autosomal dominant polycystic kidney disease (ADPKD) and an insufficiency-type fracture of the pelvis. A 60-year-old Japanese woman was admitted because of pain in the right ischium and pubis that began suddenly with no precipitating cause. Computed tomography showed the bony pelvis to be compressed by enlarged dependent kidneys and an enlarged liver. We relieved compression on the pelvic bones by means of transarterial embolization (TAE) to the kidneys and liver after initiation of hemodialysis therapy. The fracture healed gradually after TAE, and the patient could walk 4 months later. In an iliac bone specimen obtained before TAE, cancellous bone was intact, but periosteal and endosteal surfaces of cortical bone showed marked resorption and were irregular. Normally, many ligaments are connected tightly to the periosteal surface, supporting the cortical bone. However, because of extensive surface resorption associated with pressure from enlarged kidneys, connections between ligaments and the periosteal surface presumably became fragile, promoting an insufficiency fracture from unapparent external forces. Thus, ADPKD is a potential cause of insufficiency fracture owing to abnormalities of cortical bone.

Arthroscopically assisted reduction and immobilization of intraarticular fracture of the distal end of the radius: several options of reduction and immobilization.

On the basis of preoperative computerized tomography scanning and newly developed 3-dimensional reconstruction technique, Doi classified intraarticular distal radial fracture to 2-, 3-, and 4-part type, according to the number of main fracture fragments in distal radial aspect. This classification system simply, as well as perspicuously, describes the status of joint surface, thereby providing an intuitionist and practical guideline for arthroscopy procedure. Between 1992 and 2003, 91 patients ranged from 21 to 79 years of age with intraarticular distal radius fracture were treated with an arthroscopically assisted operation at our department. Among these patients, 42, 34, and 15 cases were 2-, 3-, and 4-part type, accounting for 46%, 37%, and 17% respectively. Wrist arthroscopy was applied individually according to the different type, with the purpose of achieving <1mm reduction. Role of arthroscopy was postreduction examination for 14 cases, as K-wire guider in 13 cases, assisting reduction, and immobilization in 61 cases. Four of the 61 cases changed to ORIF. Immobilization methods include external fixator combined with K-wire or plate combined with pullout wire or screw. K-wire without other implant was applied to 6 cases. In 1 case, a screw was the only implant.

Selection of grip function in double free gracilis transfer procedures after complete paralysis of the brachial plexus.

Double free gracilis transfer (DFGT) procedures introduced by Doi et al have resulted in significant improvement in maintaining functional prehensile hand after total brachial plexus injury (TBPI). However, not all patients with satisfactory recovery of finger motion could improve their prehensile function. The use of reconstructed hand in daily activities was examined retrospectively to plan individual grip function, depending on the patient's own demand. Thirty patients who had had reconstruction with DFGT procedures were evaluated retrospectively according to total active motion (TAM), power grip, hook grip, and pinch function. Power grip was evaluated by holding a bottle and hook grip by lifting a weight. Only 11 patients (36%) had very light pulp-to-pulp pinch, 11 (36%) had power grip, and 25 (83%) had hook grip. The mean weight that could be carried by hook grip was 1.3 kg. The mean TAM was 43 degrees. Pain sensation was the only encouraging sensation recovery, radiating to the chest. Fine movements of the hand like pinching require well-developed exquisite control of movements. TBPI patients have the contralateral normal limb, which they always prefer, only using their reconstructed hand when the activity requires both hands, such as when holding a bottle to open its cap or lifting bags when the contralateral normal hand is already engaged. For performance of these actions, hook grip and power grip are the useful prehensile hand functions that can be obtained after DFGT. Selection of grip functions should be done according to patient needs, and the late-stage reconstructive hand operations should be decided according to preferred grip function.

Proposal of new category for congenital unilateral upper limb muscular hypertrophy.

According to congenital anomalies of the hand and forearm classifications, the common characteristic of overgrowth problems is the skeletal overgrowth of part or all of the hand. Congenital unilateral muscular hypertrophy of the upper extremity has been classified under the overgrowth (gigantism) problems as whole-limb hemihypertrophy. The common characteristic of overgrowth problems is the skeletal overgrowth of part or all of the hand, which is not prominent in these patients. Only 15 cases with this anomaly have been reported since 1962. These patients have abnormal muscles with hypertrophic appearance and changed tendon to muscle length ratio. This type of muscular hypertrophy shows an increase in the number of fibers in transverse section, as also seen in multiply innervated muscles like the sartorius and gracilis in humans. Although this phenomenon has a mosaic type distribution, there is no progression of the muscular hypertrophy during growth period. Hand deformities are not due to a part of progression of the disease but result of imbalance of the extrinsic and intrinsic muscles. The evolutionary changes of skeletal muscles should be investigated to explain this congenital phenomenon and might be classified in a different entity from the present categories.