Can Intra-articular Injection of Glucocorticoids Be an Alternative Intervention to Achieve Remission in Patients With Rheumatoid Arthritis Exhibiting Low Disease Activity? A Single-Center Longitudinal Study.

BACKGROUND/OBJECTIVE: This study aimed at investigating whether a single intra-articular (IA) injection of triamcinolone acetonide (TA) could facilitate to achieve clinical remission in patients with rheumatoid arthritis (RA) exhibiting low disease activity (LDA). METHODS: This longitudinal study included 22 patients with RA exhibiting LDA involving wrist arthritis at our institution between April 2016 and March 2019. A single IA injection of 20 mg TA was administered into the symptomatic wrist joint. Efficacy was assessed by the primary end point of proportion of patients reaching clinical remission. Secondary end points included Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index, adverse events, and ultrasonographic assessment of the injected wrist joints. RESULTS: Remission rates were 40% and 50% at weeks 4 and 12, respectively, and were maintained at approximately 50% until week 24. The secondary outcomes of CDAI, SDAI, and Health Assessment Questionnaire Disability Index were improved significantly at week 4, and the improvements in CDAI and SDAI continued up to week 24. Ultrasonography showed that synovial hypertrophy, power Doppler signals, and the combined score were significantly reduced at weeks 4, 12, and 24 compared with the baseline. No patient developed severe, irreversible adverse events. CONCLUSIONS: Approximately half of the patients with RA exhibiting LDA who received a single IA injection of TA into the wrist joints achieved clinical remission without serious adverse events in the midterm period, suggesting that IA injection of TA might be considered as an alternative intervention to achieve remission in patients with RA exhibiting LDA.

Dislocation is a Leading Cause of Decreased Survival Rate in Primary Total Hip Arthroplasty Performed by Low-Volume Surgeons: Long-Term Retrospective Cohort Study.

BACKGROUND: This study aimed to evaluate the complications and long-term survival of primary total hip arthroplasty (THA) performed by low-volume (LV) surgeons at a LV hospital. We also determined the relationship between complications and revisions. METHODS: This retrospective cohort study included 220 THAs in 194 patients treated at our institution between 1998 and 2008, who received a minimum of a 10-year follow-up. The median annual THA volume at this hospital was 23 procedures (range, 11-32), and the annual volume per surgeon ranged from 1 to 19. We investigated the 90-day mortality and rates of periprosthetic joint infections, dislocations, and periprosthetic fractures up to the last visit (median follow-up, 11.8 years). Kaplan-Meier survival was calculated with revision as the end point. RESULTS: Postoperative infections, dislocations, and fractures at any time during the follow-up period were reported for 1 hip (0.5%), 23 hips (9.8%), and 4 hips (1.8%), respectively. One death occurred within the first 90 days postoperatively. Fifteen hips required revision surgery, and the survival rate was 95.5% at 5 years and 94.1% at 10 years. Of 10 hips that required early revision surgery within 5 years after the index surgery, 9 were revisions to address recurrent dislocation. CONCLUSION: The risk of dislocation was high. A high number of patients who underwent THA by LV surgeons required early revision because of dislocation. To achieve optimal long-term survivorship, LV surgeons should consider measures to reduce the risk of dislocation.

A low-volume surgeon is an independent risk factor for leg length discrepancy after primary total hip arthroplasty: a case-control study.

PURPOSE: Leg length discrepancy (LLD) is one of the bothersome complications that reduce patient satisfaction after total hip arthroplasty (THA). This study aimed to investigate the independent risk factors of LLD after primary THA. METHODS: This is a case-control study of 163 THAs for 163 patients at our institution between April 2015 and March 2018. The relevant data about the general characteristics of the patients (age, sex, body mass index, and diagnosis), surgery (surgical approach, type of femoral stem fixation, and surgeon volume), and radiological findings (Dorr classification and pre-operative LLD) were reviewed to identify the risk factors of ≥ 5 mm post-operative LLD according to radiological measurement and to calculate odds ratios (OR) via logistic regression analysis. RESULTS: The median (interquartile) absolute value of post-operative LLD was 3.9 (2.3-7.4) mm, and 57 (35.0%) patients had LLD of ≥ 5 mm. After controlling for possible confounders, a low-volume surgeon was considered the only independent risk factor of post-operative LLD (adjusted OR: 8.26; 95% confidence interval: 3.48, 19.60; P < 0.001). Among the 103 patients performed by high-volume surgeons, 82 (79.6%) had LLD of < 5 mm, whereas among the 60 patients performed by low-volume surgeons, only 24 (40.0%) achieved LLD of < 5 mm (P < 0.001). CONCLUSION: A low-volume surgeon is associated with an increased risk of a post-operative LLD after primary THA, and the importance of measurements should be recognized to prevent post-operative LLD and achieve optimal outcomes. Moreover, surgeons must inform patients about the risk of developing LLD pre-operatively.

Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts.

Expression of CD56 has recently been introduced as one of the adverse prognostic factors in acute promyelocytic leukemia (APL). However, the clinical significance of CD56 antigen in APL has not been well elucidated. We assessed the clinical significance of CD56 antigen in 239 APL patients prospectively treated with all-trans retinoic acid and chemotherapy according to the Japan Adult Leukemia Study Group APL97 protocol. All patients were prospectively treated by the Japan Adult Leukemia Study Group APL97 protocol. The median follow-up period was 8.5 years. Positive CD56 expression was found in 23 APL patients (9.6%). Expression of CD56 was significantly associated with lower platelet count (P = 0.04), severe disseminated intravascular coagulation (P = 0.04), and coexpression of CD2 (P = 0.03), CD7 (P = 0.04), CD34 (P < 0.01) and/or human leukocyte antigen-DR (P < 0.01). Complete remission rate and overall survival were not different between the two groups. However, cumulative incidence of relapse and event-free survival (EFS) showed an inferior trend in CD56(+) APL (P = 0.08 and P = 0.08, respectively). Among patients with initial white blood cell counts of 3.0 × 10(9)/L or more, EFS and cumulative incidence of relapse in CD56(+) APL were significantly worse (30.8% vs 63.6%, P = 0.008, and 53.8% vs 28.9%, P = 0.03, respectively), and in multivariate analysis, CD56 expression was an unfavorable prognostic factor for EFS (P = 0.04). In conclusion, for APL with higher initial white blood cell counts, CD56 expression should be regarded as an unfavorable prognostic factor.

Long-term outcome and prognostic factors of elderly patients with acute promyelocytic leukemia.

Studies focused on elderly acute promyelocytic leukemia (APL) are relatively limited. To evaluate prognostic impact in elderly APL, we compared the long-term outcome of elderly APL patients (60-70 years) with younger patients (15-59 years) treated with all-trans retinoic acid combined with anthracycline and cytarabine in the Japan Adult Leukemia Study Group (JALSG) APL97 study. Of 283 evaluable patients, 46 (16.3%) were elderly who had more frequent lower platelet (P = 0.04), lower albumin (P = 0.006) and performance status 3 (P = 0.02), higher induction death rate due to differentiation syndrome (P = 0.03), and non-relapse mortality (NRM) during consolidation therapy (P = 0.001). Overall survival was significantly inferior in elderly patients (P = 0.005), but disease-free survival and cumulative incidence of relapse were not. Better therapeutic approaches should be considered to reduce NRM during induction and consolidation therapy in elderly APL. This study was registered at http://www.umin.ac.jp/ctrj/ under C000000206.

Incidence and predictors of fragility fracture in postmenopausal rheumatoid arthritis patients receiving oral bisphosphonates: a longitudinal observational study.

BACKGROUND: Although many studies have reported the predictors of fractures in patients with rheumatoid arthritis (RA) who are not receiving anti-osteoporotic treatments or who are receiving unspecified treatments, studies focusing on the predictors of fracture in patients with RA who are currently being treated with oral bisphosphonates (BP) are quite scarce. This study aims to investigate the incidence and predictors of fragility fracture in postmenopausal patients with RA receiving oral BP. METHODS: This retrospective longitudinal observational study comprised 98 postmenopausal RA patients receiving oral BP for a minimum of 6 months between April 2015 and December 2020. The cumulative incidence of fragility fractures including vertebral and nonvertebral fractures was investigated using the Kaplan-Meier method. Cox proportional hazards analysis was used to analyze baseline predictors of future fragility fractures. To determine a cutoff value of continuous predictors, the receiver-operating characteristic curve was applied. RESULTS: Twenty patients developed fractures during the study period, with a cumulative incidence of 6.1% at 12 months, 10.5% at a median follow-up of 28 months, and 14.4% at 36 months. Multivariable Cox hazards analysis showed a history of prior vertebral fracture (hazard ratio [HR] 6.26, 95% confidence interval [CI] 1.99‒19.68, P = 0.001) and dose of methotrexate (HR 0.87, 95% CI 0.76‒0.99, P = 0.041) to be independent predictors. The cutoff value for methotrexate dose was 4 mg/week. CONCLUSIONS: We found a cumulative incidence of any fractures of 10.5% at 28 months in patients with RA currently being treated with oral BP. A history of prior vertebral fractures and methotrexate dose were positive and negative predictors for fractures, respectively. Practitioners should consider selecting another anti-osteoporotic drug in patients with RA who remain at risk despite receiving oral BP.

The first case of feline Prototheca wickerhamii infection in Japan.

A 3-year-old castrated male domestic short-haired cat was presented with nodules on the left nasal wing and the left earflap. Prototheca cells were found after excision biopsy of one of the nodules located on the left earflap. The patient cat was generally in good condition without skin problems. Prototheca wickerhamii was isolated from all 6 masses after they were surgically nucleated. The cat was recovered two months after intervention with no recurrence of skin nodules. This report deals with the first case of feline protothecosis in Japan.

26S rDNA-based phylogenetic investigation of Japanese cattle-associated Prototheca zopfii isolates.

The study has been conducted to assess the applicability of partial 26S ribosomal DNA sequence for the phylogenic analysis of P.zopfii and to arrive relationships between specific genotype of P.zopfii and clinical mastitis. The phylogenetic analysis indicated that all genotype 2 isolates were grouped into the cluster of type strain of P.zopfii. Thus, all mastitis isolates in Japan were identified as P.zopfii genotype 2 and were independent of the cluster of the genotype 1 isolates. In one clinical case, a fecal isolate could not be identified by the 18S rDNA-based genotype specific PCR-assay and appeared to belong to a same cluster with the type strain of P. blaschkeae by 26S rDNA analysis. The isolate was the first isolation in Japan.

Insufficiency fracture at the distal diaphysis of the radius after synovectomy combined with the Sauvé-Kapandji procedure in a patient with rheumatoid arthritis.

We report here a rare case of insufficiency fracture at the distal diaphysis of the radius in a patient with rheumatoid arthritis (RA) after synovectomy combined with the Sauvé-Kapandji procedure. A 71-year-old woman who had been diagnosed with RA had been consecutively treated with several disease-modifying antirheumatic drugs. She had undergone synovectomy of the right wrist combined with the Sauvé-Kapandji procedure, due to a tendon rupture, 2 years before the current presentation (first visit). Although she had not experienced any recent trauma, the wrist pain had increased after she had lifted up the bedding at the funeral of her friend about 1 month prior to her first visit. Radiographs of her right wrist taken at the second visit showed a fracture at the distal diaphysis of the radius at the level of the excision osteotomy of the distal ulna; however, no displacement of the distal fragment was observed. We immobilized her forearm in a long-arm cast. However, after 3 weeks of cast immobilization, a displacement of the distal fragment was observed. A manual reduction of the displacement was performed and the arm was again immobilized in a long-arm cast. However, 1 week later, a displaced distal fragment was again observed. Subsequently, she received an open reduction and internal fixation using a volar locking plate and screws with an autologous iliac crest bone graft. Bone union was completed by 8 months following the operation.

Prototheca zopfii genotypes isolated from cow barns and bovine mastitis in Japan.

This study is the first investigation on Japanese isolates of Prototheca zopfii from bovine mastitis and the cow-barn surroundings by molecular characterization to clarify routes of infection for bovine protothecal mastitis. We performed isolation of Prototheca from cow-barn surroundings (drinking water, sewage and feces) and milk samples from cases of bovine mastitis. Genotypes of the 32 isolates of P. zopfii from cow-barn surroundings and 67 isolates from mastitis were analyzed by genotype-specific PCR assays and restriction fragment length polymorphism (RFLP) assays. All mastitis isolates were identified as P. zopfii genotype 2. Conversely, 29 isolates from cow-barn surroundings were identified as P. zopfii genotypes 1 and 3 isolates as genotype 2, respectively. Given these results, both genotypes of P. zopfii could exist in cow-barn surroundings, but no sites were identified as frequent sources of P. zopfii genotype 2. P. zopfii isolates should thus be further explored with regard to genotype to clarify the reservoir of etiological agents in bovine Prototheca mastitis.

[Elevation of Epstein-Barr virus (EBV)-DNA in the peripheral blood of a patient with age-related EBV-associated B-cell lymphoproliferative disorder].

A 69-year-old man was admitted to our hospital with fever and right neck lymphadenopathy. A neck lymph node biopsy was performed. In the specimens, immunoblasts were present with an admixture of small T lymphocytes and macrophagocytes. Immunohistochemcal staining of immunoblasts was positive for CD20, CD30 and EBER. Epstein-Barr virus (EBV) serology showed elevated IgG antibody to VCA, and EBV DNA was detected in the peripheral blood. Since he showed latency II without immunodeficiency disease, we diagnosed age-related EBV-associated B-cell lymphoproliferative disorder (EBV-LPD) as a result of aging and EBV infection. He was treated with 6 courses of the CHOP regimen plus rituximab, and achieved complete remission. EBV-DNA became undetectable at remission. In age-related EBV-LPD, there is some possibility that EBV-DNA in the peripheral blood is valuable as a tumor biomarker.

Living donor liver transplantation in a recipient with anti-Fy(a) and Jk(a) antibodies.

We report a case of a living donor liver transplantation using right lobe graft to a recipient having anti-Fy(a) and Jk(a) antibodies. The red blood cell (RBC) antigens of the donor were Fy (a+) and Jk (a-). We attempted to eliminate donor RBCs remaining in the graft by perfusing histidine-tryptophan-ketoglutarate. Further, Fy (a-)/Jk (a-) RBC concentrates were transfused during the operation. However, the anti-Fy(a) titer increased approximately 8-fold on the seventh postoperative day. On the same day, serum levels of transaminase and total bilirubin increased presumably due to acute cellular rejection. Steroid administration immediately reduced levels of transaminase, total bilirubin and anti-Fy(a) titer. The increase of anti-Fy(a) titer may be due to a secondary immune response to the donor's Fy(a) antigen on RBCs remaining in the graft.

Membranous nephropathy associated with donor lymphocyte infusion following allogeneic bone marrow transplantation.

Nephrotic syndrome after hematopoietic stem cell transplantation (HSCT) followed by donor lymphocyte infusion (DLI) has never been described. We report the case of a myelodysplastic syndrome (MDS) patient who developed nephrotic syndrome with membranous nephropathy 18 months after allogeneic HSCT and 4 months after DLI. A 50-year-old woman with MDS underwent allogeneic bone marrow transplantation from her HLA-matched brother. MDS relapsed 55 days after transplantation, donor lymphocytes were infused as adoptive immunotherapy, and complete remission was achieved. Four months after the third DLI, the patient developed nephrotic syndrome with proteinuria up to 9 g/day. Renal biopsy revealed granular deposits of immunoglobulin G along the glomerular basement membrane, and subepithelial electron-dense deposits. A diagnosis of membranous nephropathy was made. For maintenance of the immunotherapeutic effect of DLI, minimum doses of immunosuppressive therapy for decreasing proteinuria were administered, and improvement of nephrotic syndrome and persistent complete remission of MDS were achieved.

Multicenter prospective study of interferon alpha versus allogeneic stem cell transplantation for patients with new diagnoses of chronic myelogenous leukemia.

We compared interferon alpha (IFN-alpha) therapy with stem cell transplantation (SCT) for patients with chronic-phase chronic myelogenous leukemia in a multicenter prospective study to investigate the optimal indication and timing of SCT, especially from HLA-matched unrelated donors. Of 257 eligible patients, 145 patients who were younger than 50 years were assigned to the IFN-alpha cohort (n = 87) or the SCT cohort (n = 58), according to family donor availability. In the IFN-alpha cohort, 52 patients received IFN-alpha and chemotherapy (the IFN1 group), and 35 patients received an SCT from an unrelated donor (the U-SCT group). In the SCT cohort, 47 patients received an SCT from a related donor (the R-SCT group). In the IFN1 group, 88% of the patients achieved a complete hematologic response, and 33% achieved a complete cytogenetic response. At a median follow-up period of 53 months, the predicted 6-year survival rate was 72% in the IFN1 group, 81% in the R-SCT group, and 81% in the U-SCT group. When overall survival was evaluated for the IFN-alpha and R-SCT cohorts by intention to treat according to family donor availability, the 6-year survival rates were 76% and 84%, respectively. When the outcomes of the U-SCT and IFN1 groups were compared, the survival rate of U-SCT group patients was significantly better than for IFN1 group patients without a major cytogenetic response and seemed better for IFN1 group patients younger than 35 years. Therefore, U-SCT may be recommendable to patients who fail to achieve a major cytogenetic response in IFN-alpha therapy and to younger patients.

[Necessity of a 24-hour system of blood transfusion testing].

The preventive effects of a 24-hour system of blood transfusion testing on mistyping of transfused blood was examined. Blood transfusion tests have been performed by blood transfusion technologists during working hours and by physicians at other times. In March 2000, we introduced a system in which technologists perform blood transfusion tests after working hours. Technologists of the Blood Transfusion Unit and Central Clinical Laboratory perform the test jointly, and column agglutination technology was introduced as the test method. A computer system setup exclusively for the testing was also introduced to perform computer cross-matching. Since transfusion error is likely to occur during emergency blood transfusion, a manual was established to prioritize safety. After introduction of the system, mistyping that may have been caused by inaccurate blood test results markedly decreased, confirming the usefulness of this system for prevention of mistyping. In addition, transfusion errors also decreased in wards and the improved system increased the safety of the entire medical care system. The frequency of mistyping was about 1% when physicians performed blood typing, showing the importance of clinical technologists for blood transfusion tests.

[Unrelated HLA-mismatched cord blood transplantation using nonmyeloablative conditioning in an adult patient with very severe aplastic anemia].

An adult patient suffering from G-CSF-resistant very severe aplastic anemia received a cord blood transplantation from a three-loci HLA-mismatched unrelated donor after nonmyeloablative conditioning. Cord blood was infused after conditioning with fludarabine (180 mg/m2) and cyclophosphamide (100 mg/kg). Cyclosporin A and short-term methotrexate were used for prophylaxis against acute GVHD. Engraftment was achieved on day 23, and there was no serious GVHD. A full-donor type T-cell chimerism was obtained by day 30. Normal hematopoiesis and complete chimerism have been maintained 14 months after transplantation.

[Splenic marginal zone lymphoma associated with antiphospholipid antibodies].

A 61-year-old woman experienced a high fever with anemia and APTT prolongation after suffering a herpes zoster virus infection. Physical examination revealed a large splenomegaly without lymphadenopathy. Laboratory evaluations were positive for lupus anticoagulant (LA) and monoclonal IgM-kappa protein. LA was associated with the presence of anti-beta2GPI antibody, anti-cardiolipin antibody, and anti-prothrombin antibody. Moreover, the results of factors IX, XI, and XII assays and CRP and FDP-E were disturbed. A splenectomy was performed, and a splenic marginal zone lymphoma (SMZL) was diagnosed. All hematological findings rapidly recovered after the splenectomy. No thrombotic events occurred after the splenectomy even though thrombosis prophylaxis was not performed. The clinical course suggested that the SMZL-producing antibody induced immunological abnormalities in the labolatory tests. Since the patient suffered disease progression soon after the splenectomy, an autologous peripheral stem cell transplantation with rituximab administration was performed.

Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with Collagen-Induced Arthritis.

BACKGROUND: Various clinical reports suggest etanercept (ETN) has some efficacy in bone formation in rheumatoid arthritis (RA). To examine this effect, we investigated the gene expression of cytokines relevant to osteoblast/osteoclast differentiation, and evaluated histomorphometric findings in mature rats with collagen-induced arthritis (CIA). METHODS: Total RNA was extracted from knee joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the infiltrating pannus volume and pannus surface, and the following items in contact with pannus surface were measured: osteoclast number, osteoid surface, osteoid volume and labeling surface. These were evaluated in the distal femur with CIA with or without ETN administration. RESULTS: TNF-alpha, RANKL and OPG mRNA expressions, linked to osteoclastogenesis, were not significantly different with or without ETN administration. ETN administration significantly increased Wnt-1 mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression, the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus surface and osteoclast number, parameters of bone destruction, were not significantly different among groups. Osteoid volume, osteoid surface and labeling surface, parameters of bone formation, increased significantly with ETN administration. CONCLUSION: Our results suggest that ETN suppresses DDK-1 expression, and, as a result, Wnt expression is promoted and osteoblastogenesis becomes more active, independent of the regulation of osteoclast activity. Marked bone formation is attributed to the fact that ETN directly promotes osteoblastogenesis, not as a result of suppressing osteoclastogenesis.

Morphological and volumetric analysis of the development of atlantoaxial vertical subluxation in rheumatoid arthritis.

BACKGROUND: Cervical disorders in rheumatoid arthritis (RA) patients have been an important problem for a long time. Although the recent progression of the treatment strategies for RA might change the progression of atlantoaxial vertical subluxation (VS) in RA patients, to reveal the risk factors for VS progression should be important at present. Osteoporosis (OP) and RA share the same risk factors. The purposes of this study were to identify the progression of VS in RA, and to evaluate the relationship between the VS development and OP. METHODS: Eighty female patients with RA and 18 female patients with OP were retrospectively analyzed. The RA patients were divided into VS (10 patients) and non-VS groups (70 patients). Morphological parameters on coronal reconstructed computed tomography images were evaluated. Three-dimensional analysis was used to measure volumes and volumetric bone mineral densities (vBMDs) at the upper cervical spine (UCS). RESULTS: The VS group had higher age, longer RA symptom duration, and lower BMD at the lumbar spine compared to the non-VS group. Volumes and vBMDs at the UCS in RA group were greater than those in the OP group. In accordance with VS development, the lateral masses at the UCS became shorter, the C1 facet angle became sharper, and the volumes at the UCS decreased. However, there was no statistically significant relationship between vBMDs at the UCS and the VS development. CONCLUSION: The C1 facet angle became sharper with VS progression. Although 3-dimensional analysis revealed that decreases in the volumes at the UCS were associated with VS development, no significant relationship between OP and the VS development was observed.

Dic (17;20) (p11;q11) preceded MLL gene amplification in a patient with de novo mixed-lineage leukemia.

We report a case of acute mixed-lineage leukemia, as seen in a 65 year-old female with MLL gene amplification and biallelic loss of wild type p53 gene. The diagnosis was based on the findings that her bone marrow (BM) blasts expressed cytoplasmic CD3 (cyCD3), B-lineage antigens and myeloid antigens accompanied by clonal rearrangements of IgH gene. The BM blasts consisted of small-sized peroxidase-negative blasts (97%) and large-sized peroxidase-positive blasts (3%). The BM blasts showed a complex "karyotype," including dic(17;20) (p11;q11), -5 and add (11q23). Add (11q23) abnormality was found in sideline karyotypes as well as the stemline abnormality of dic(17;20) (p11;q11). For the p53 gene, which is located at 17p13, fluorescence in situ hybridization analysis showed the loss of one of two p53 alleles. Furthermore, polymerase chain reaction-single-strand conformation polymorphism and following nucleotide sequencing showed that the p53 gene was mutated at codon 215, leading to an amino acid substitution from Ser to Arg. For the MLL gene, southern blot analysis showed that the MLL gene locus was amplified but not rearranged at its breakpoint cluster region, which is usually rearranged in balanced translocations with many partner genes. These findings suggest that MLL gene amplification may in this case be based on the genetic instability caused by the preceding biallelic loss of the wild type p53 gene.