Roxadustat-Induced Central Hypothyroidism in Renal Anemia Patients: Insights From Antineutrophil Cytoplasmic Antibody-Related Vasculitis Cases.

The introduction of hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors in Japan in 2019 for treating renal anemia in hemodialysis patients has resulted in an adverse event: central hypothyroidism. Although this adverse event was not widely recognized by the public, it was first documented in Japan in 2021. Despite limited case reports on roxadustat, an oral HIF-PH inhibitor that induces central hypothyroidism, this condition typically improves rapidly upon discontinuation of the drug. In this report, we present rare cases of roxadustat-induced central hypothyroidism in two patients: a woman in her 80s and a man in his 60s, neither of whom had prior thyroid disease. Both patients developed central hypothyroidism shortly after starting roxadustat treatment for renal anemia associated with antineutrophil cytoplasmic antibody-related vasculitis. Notably, neither patient had pituitary tumors or other pituitary hormone disorders. Thyroid function improved with levothyroxine treatment, even when oral roxadustat was continued. Roxadustat may induce central hypothyroidism, highlighting the importance of regularly measuring and evaluating thyroid function when administering this drug to monitor possible changes in thyroid hormone levels.

Prevalence and risk factors of osteonecrosis of the femoral head in patients with ANCA-associated vasculitis: a multicentre cohort study.

OBJECTIVE: We aimed to determine the prevalence and risk factors for osteonecrosis of the femoral head (ONFH) in a multicentre cohort of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: One hundred and eighty-six AAV patients who underwent radiographs and MRI screening of bilateral hip joints at more than 6 months after initial remission induction therapy (RIT) were retrospectively assessed for the presence of ONFH. RESULTS: Among 186 AAV patients, 33 (18%) were diagnosed with ONFH. Among the patients with ONFH, 55% were asymptomatic and 64% had bilateral ONFH. Seventy-six per cent of ONFH joints were in precollapse stages (stage ≤2), whereas 24% of ONFH joints were in collapse stages (stage ≥3). Moreover, 56% of the precollapse stage joints were already at risk of future collapse (type ≥C-1). Even in asymptomatic ONFH patients, 39% of the precollapse stage joints were type ≥C-1. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH in AAV patients (OR 1.072, 95% CI 1.017 to 1.130, p=0.009). Rituximab use was a significant beneficial factor against ONFH (p=0.019), but the multivariate analysis rejected its significance (p=0.257). CONCLUSION: Eighteen per cent of AAV patients developed ONFH, and two-thirds of the ONFH joints were already in collapse stages or at risk of future collapse. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH. A rapid reduction of glucocorticoids in RIT and early detection of precollapse ONFH by MRI may decrease and intervene ONFH development in AAV patients.

Suppressor of cytokine signalling 3 (SOCS3) expressed in podocytes attenuates glomerulonephritis and suppresses autoantibody production in an imiquimod-induced lupus model.

OBJECTIVE: Recently, podocytes have been recognised not only as a physical barrier to prevent urinary protein loss but also as producers of proinflammatory cytokines. However, the roles of podocytes in the pathogenesis of lupus nephritis (LN) remain largely unknown. This study aims to determine the roles of suppressor of cytokine signalling (SOCS) family members expressed in glomeruli in the regulation of LN. METHODS: We investigated the expression of SOCS family members in glomeruli in murine lupus model induced by repeated epicutaneous administration of the TLR7/8 agonist imiquimod. We also investigated the roles of SOCS3 expressed in podocytes in the imiquimod-induced glomerulonephritis and systemic autoimmunity by using podocyte-specific SOCS3-deficient mice (podocin-Cre x SOCS3fl/fl mice (SOCS3-cKO mice)). Finally, we investigated the expression of proinflammatory cytokines and chemokines in SOCS3-deficient podocyte cell lines. RESULTS: qPCR analysis revealed that among SOCS family members, SOCS3 was preferentially induced in glomeruli on epicutaneous administration of imiquimod and that interleukin 6 (IL-6) induced SOCS3 expression in podocyte cell lines. SOCS3-cKO mice exhibited severe glomerulonephritis, high levels of serum creatinine and urine albumin and decreased survival rate compared with control SOCS3-WT mice. Levels of anti-double-strand DNA antibody, SOCS (GC) formation and the numbers of follicular helper T (Tfh) cells and GC B cells in the spleen were higher in SOCS3-cKO mice than those in SOCS3-WT mice. Serum IL-6 levels and expression of IL-6 mRNA in glomeruli were also elevated in SOCS3-cKO mice. IL-6-induced IL-6 expression was enhanced in SOCS3-deficient podocyte cell lines compared with that in SOCS3-sufficient podocyte cell lines. CONCLUSION: SOCS3 expressed in podocytes plays protective roles for the development of glomerulonephritis and inhibits autoantibody production in the imiquimod-induced lupus model presumably by suppressing IL-6 production of podocytes.

Experience of musculoskeletal ultrasound scanning improves physicians' physical examination skills in assessment of synovitis.

OBJECTIVE: Musculoskeletal ultrasound (US) is more sensitive than physical examination in detecting synovitis and helps physicians to understand its pathophysiology. In this study, we aimed to determine if the experience in musculoskeletal US scanning is independently associated with improved physical examination skills to detect synovitis. METHOD: Seventy patients with rheumatoid arthritis and twenty-three physicians were enrolled. Patients were first assessed by multiple physicians with a range of clinical/sonographic experience for the swelling of the wrist, metacarpophalangeal and proximal interphalangeal (PIP) joints and next underwent US assessment performed by another physician experienced in musculoskeletal US. We then calculated the positive/negative predictive values (PPV/NPV) of joint swelling to identify US-detected synovial hypertrophy. Finally, the factors independently associated with the accuracy of clinical assessment were identified by using multivariate analyses. RESULTS: One thousand five hundred forty joints were assessed 6116 times in total for swelling. Overall, PPV and NPV of joint swelling were 51.7% and 88.3%, respectively. Multivariate analyses identified wrist joint, tenderness, male and greater patients' age as the factors significantly associated with higher PPV. In addition, there was a trend that longer experience in rheumatology clinical practice was associated with higher PPV (p = 0.058). On the other hand, longer experience in musculoskeletal US, PIP joint and positive rheumatoid factor were identified as the significant factors for higher NPV, while wrist joint, tenderness, presence of osteophyte and obesity as those for lower NPV. CONCLUSION: Our data suggest that the experience in musculoskeletal US improves physical examination skills particularly to avoid overestimation.Key Points• Physicians with longer US experience are less likely to overestimate synovitis by physical examination.• Musculoskeletal US is a useful tool for rheumatologists to improve their physical examination skill.• Presence of osteophytes, joint tenderness and obesity influence the accuracy of physical examination of joints.

Comparative Study for Alignment of Extramedullary Guides versus Portable, Accelerometer-Based Navigation in Total Knee Arthroplasty.

The use of portable, accelerometer-based navigation (PN) devices for positioning of the components of total knee arthroplasty (TKA) is emerging as an alternative to standard extramedullary (EM) systems, which was needed to the image intensifier. The aim of our study was to compare the accuracy of component positioning in TKA using an EM and PN systems. Data from 100 consecutive primary TKAs, performed by multiple surgeons in 87 patients between October 2010 and June 2015, were analyzed. Coronal and sagittal plane alignments of the TKA components, relative to the mechanical axis of the limb, were evaluated by radiography. The mean postoperative coronal alignment angle of the femoral (α) and tibial (ß) components was comparable between the groups (α: PN, 89.9 ± 2.2 degrees; EM, 89.9 ± 1.6 degrees and ß: PN, 90.1 ± 1.4 degrees; EM, 89.6 ± 1.3 degrees). Groups were also comparable with regard to mean postoperative sagittal alignment angle of the femoral and tibial components (γ: PN, 2.3 ± 3.3 degrees; EM, 1.8 ± 1.7 degrees and σ: PN, 89.7 ± 2.5 degrees; EM, 90.1 ± 1.3 degrees). The incidence rate of a component malalignment > 3 degrees in the coronal and sagittal planes of the mechanical axis of the knee was comparable between the groups. In conclusion, the coronal and sagittal alignments for the femoral components was less accurate compared with tibial component alignment, especially in the PN group, and the sagittal alignment of the femoral component was less accurate than coronal alignment for both groups. Both the PN and EM systems provide satisfactory coronal and sagittal component alignments in TKA. Further technical improvement of the PN system could further improve its application for accurate component implantation in TKAs.

Comparison of functional recovery in the very early period after surgery between plate and nail fixation for correction of stable femoral intertrochanteric fractures: a controlled clinical trial of 18 patients.

PURPOSE: This study aimed to compare the differences in functional recovery between patients undergoing plate and nail fixation in the very early period after surgery. METHOD: This study was designed as a controlled clinical trial that included 18 patients who were surgically treated with either dynamic hip screw as plate fixation or proximal femoral nail as nail fixation for stable intertrochanteric fractures. In particular, all patients selected for the study reported walking completely independently without the use of walking aids prior to sustaining their initial fracture. In all, 8 patients (mean age, 73.8 years; range, 65-89 years) were treated with plate fixation (group plate) and 10 patients (mean age, 79.7 years; range, 70-90 years) were treated with nail fixation (group nail). Functional evaluations were assessed every week after surgery using the Japanese Orthopaedic Association (JOA) hip functional scores and active range of motion (ROM) of the hip joint. RESULTS: The recovery of activities of daily living (ADLs) according to JOA hip functional scores at week 4 after surgery was significantly better in group nail than in group plate (P = .03), whereas active ROM of hip flexion improved significantly in group plate than in group nail at weeks 3 and 4 after surgery (P = .04 and P = .02, respectively). CONCLUSIONS: The results suggested that nail fixation may provide a more rapid recovery of ADLs than that of plate fixation in the very early period after surgery. However, plate fixation may provide better ROM of hip flexion than that of nail fixation.

Increased blood flow in the anterior humeral circumflex artery correlates with night pain in patients with rotator cuff tear.

BACKGROUND: Night pain is a particularly vexing symptom in patients with rotator cuff tear. It disturbs sleep and decreases quality of life, and there is no consensus regarding its etiology. Based on arthroscopic surgical observations of synovitis around the rotator interval or capsule surface in rotator cuff tear, we hypothesized that blood flow from the artery feeding the capsule increases blood supply to the synovium. This study aimed to investigate the relationship between blood flow and night pain using pulse Doppler ultrasonography. METHODS: A series of 47 consecutive patients with rotator cuff tear was evaluated. The peak systolic velocity and resistance index of blood flow in the ascending branch of the anterior humeral circumflex artery were evaluated using pulse Doppler ultrasonography. We also investigated 20 normal shoulders in healthy volunteers. The peak systolic velocity and resistance index were compared between affected and unaffected sides in patients and between dominant and nondominant sides in controls. RESULTS: Anterior humeral circumflex artery peak systolic velocity and resistance index did not differ between sides in control subjects or in patients with rotator cuff tear without night pain. However, anterior humeral circumflex artery peak systolic velocity and resistance index did differ significantly between sides in patients with rotator cuff tear with night pain. CONCLUSIONS: This study revealed anterior humeral circumflex artery hemodynamics in patients with rotator cuff tear and normal subjects using Doppler ultrasonography. Night pain, particularly involving aching, appears to be related to the hemodynamics. These findings suggest that investigating the hemodynamics of patients with rotator cuff tear with night pain may lead to greater understanding of the etiology of this symptom.

Fatal fat embolism syndrome in a case of isolated L1 vertebral fracture-dislocation.

Although fat embolism syndrome is a well-known complication of fractures of the long bones or pelvis, fat embolism syndrome occurring subsequent to fracture of the lumbar spine is rare. We report a fatal case of fat embolism syndrome characterized by fat and bone marrow embolism that occurred 36 h after an isolated fracture-dislocation of the L1 vertebra. A postmortem examination was performed and pathological finding demonstrated fat and bone marrow tissue which were disseminated in the bilateral pulmonary arteries. We need to be aware of the possibility of fat embolism syndrome as a complication of spinal fractures, including isolated vertebral body fractures.

Characteristics of upper extremity injuries sustained by falling during snowboarding: a study of 1918 cases.

BACKGROUND: Little epidemiological research on characteristics of upper extremity injuries resulting from snowboarding has been conducted, particularly in relation to snowboarding stance, falling direction, and the side of the body where the injury occurs. HYPOTHESIS: Snowboarding stance and the direction of the fall may influence the frequency of the side or the location of the upper extremity injury. STUDY DESIGN: Descriptive epidemiology study. METHODS: This study analyzed the information obtained from 1918 patients with fractures or dislocations of the upper extremity (excluding the fingers and scapula) sustained during snowboarding/sliding between 2000 and 2008. Diagnosis, injured part and side, stance (regular or goofy), and falling directions were prospectively analyzed. Associations among these parameters were also analyzed. RESULTS: As characterized by skill level, patients were beginners (57.9%), intermediates (38.0%), and experts (4.0%). Eighty-eight percent had not received instruction from licensed instructors. Diagnoses included wrist fractures (53.7%), upper arm fractures (16.8%), shoulder dislocations (11.5%), and elbow dislocations (9.8%). In sum, 1742 (90.8%) patients were in regular stance when they fell, whereas 176 (9.2%) were in goofy stance. There was a significant difference in the prevalence of the injured side between the 2 stances. When the injured sides were classified according to the sliding direction, wrist fractures (61.7%) occurred on the side opposite the sliding direction, whereas shoulder dislocations (65.6%), upper arm fractures (82.9%), and elbow dislocations (79.8%) occurred on the same side as the sliding direction. When the injured sides were classified according to the falling direction, wrist fractures (68.1%) and elbow dislocations (63.5%) occurred because of backward falls, and shoulder dislocations (68.9%) and upper arm fractures (60.7%) occurred because of forward falls. CONCLUSION: Two snowboarding stances as well as 2 falling directions had a significant influence on the frequency of the injured side in the upper extremity.

Functional bracing for delayed union of a femur fracture associated with Paget's disease of the bone in an Asian patient: a case report.

Paget's disease of the bone is a common metabolic bone disease in most European countries, Australia, New Zealand, and North America. Conversely, this disease is rare in Scandinavia, Asia, and Africa. In Japan, it is extremely rare, with a prevalence of 0.15/100000. Paget's disease is a localized disorder of bone remodeling. Excessive bone resorption and abnormal bone formation result in biomechanically weakened bone and predispose patients to fracture. Delayed union and non-union of fractures have been reported in patients with Paget's disease. Therefore, open reduction and internal fixation of fractures has been recommended to prevent such complications. Here we report an unusual case of a 63-year-old Asian woman with delayed union of a femur fracture secondary to Paget's disease, which was treated successfully by functional bracing.

The therapeutic outcome of minimally invasive synovectomy assisted with arthroscopy in the rheumatoid knee.

The purpose of the present study was to retrospectively evaluate the therapeutic outcome of minimally invasive synovectomy assisted with arthroscopy (MISAA). From 1995 to 2003, MISAA was performed on 30 knees of 18 rheumatoid arthritis patients. The mean follow-up period was 74.4 months. Radiographic assessment according to Larsen's radiological classification, the conversion ratio to total knee arthroplasty (TKA), and postoperative change of the range of flexion were evaluated retrospectively. There were 10 knees in grade I, 14 knees in grade II, and 6 knees in grade III, preoperatively. All the knees in grade I and 8 of 14 knees in grade II maintained the same grade until the latest follow-up. The other 6 knees in grade II and all the knees in grade III deteriorated to grade IV and were converted to TKA after MISAA. The mean range of flexion significantly increased postoperatively except the knees that were converted to TKA. MISAA is effective for rheumatoid knees in grade I or II, and improves range of flexion.

An unusual meniscal ganglion cyst that triggered recurrent hemarthrosis of the knee.

A 58-year-old woman suffered spontaneous recurrent hemarthrosis of the knee. In the clinical course, pigmented villonodular synovitis was mostly suspected, but in arthroscopic surgery the lateral meniscus appeared to be upturned and stuck into the lateral pouch with the meniscal ganglion cyst. It was suggested that meniscal tear with meniscal ganglion cyst was related with recurrent hemarthrosis. Generally, both the meniscal ganglion cysts and spontaneous recurrent hemarthrosis are highly rare conditions. In this case, we speculated that a negligible power could induce the meniscal tear with recurrent hemarthrosis in the particular situation in which the meniscal ganglion cyst existed. In other words, the meniscal ganglion cyst might basically and physically relate with hemorrhagic condition. Arthroscopically, the meniscal ganglion cyst was removed together with the anterior segment of the lateral meniscus. Recurrent hemarthrosis was treated successfully by resection of the meniscus.