Ampicillin/sulbactam versus cefazolin plus aminoglycosides for antimicrobial prophylaxis in management of Gustilo type IIIA open fractures: A retrospective cohort study.

BACKGROUND: The antibiotic regimens for prophylaxis in the management of open fractures remain controversial. Although the use of aminoglycosides is widely accepted for treatment of Gustilo type III open fractures, aminoglycosides are often avoided in patients with risk factors. This study aimed to compare efficacy and safety of two regimens, cephazolin plus aminoglycoside (amikacin or gentamicin) and ampicillin/sulbactam (ABPC/SBT), in patients with Gustilo type IIIA open fractures. METHODS: A total of 95 Gustilo type IIIA fractures in 90 patients were retrospectively reviewed in this study. The cohort was categorized into two groups that were treated in accordance with the institutional prescribed regimen in different periods: (1) cefazolin plus aminoglycoside (January 1, 2014-September 30, 2017) and (2) ABPC/SBT monotherapy (October 1, 2017-September 30, 2020). Cefazolin was used at 1-2 g every 8 h, aminoglycoside (amikacin or gentamicin) was used daily depending on body weight, and ABPC/SBT was used at 3 g every 8 h The antibiotic administration was continued within 3 days or until successful soft tissue coverage was achieved. The infection rate and the incidence of acute kidney injury (AKI) in both groups were assessed. RESULTS: ABPC/SBT was used in 34 patients (36 fractures), and 56 patients (59 fractures) received cefazolin plus aminoglycoside for antibiotic prophylaxis. Infection developed in 2 of 36 fractures in ABPC/SBT group and 4 of 59 fractures in the cefazolin plus aminoglycoside group (p > 0.99). The average serum creatinine levels on admission, baseline, and peak during the hospital stay were not significantly different between the two groups. One case of AKI was identified in each group, indicating that incidence rate of AKI was not significantly different between the two groups. CONCLUSION: We demonstrated the non-inferiority of ABPC/SBT therapy over cefazolin plus aminoglycoside regimen for type IIIA open fractures. The ABPC/SBT regimen may be an alternative option for managing Gustilo type IIIA open fractures. Further prospective studies with larger samples are needed to verify these results.

Does Abatacept Increase Postoperative Adverse Events in Rheumatoid Arthritis Compared with Conventional Synthetic Disease-modifying Drugs?

OBJECTIVE: To investigate whether abatacept (ABA) causes more adverse events (AE) than conventional synthetic disease-modifying antirheumatic drugs (csDMARD) after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: A retrospective multicenter nested case-control study was performed in 18 institutions. Patients receiving ABA (ABA group) were matched individually with patients receiving csDMARD and/or steroids (control group). Postoperative AE included surgical site infection, delayed wound healing, deep vein thrombosis or pulmonary embolism, flare, and death. The incidence rates of the AE in both groups were compared with the Mantel-Haenszel test. Risk factors for AE were analyzed by logistic regression model. RESULTS: A total of 3358 cases were collected. After inclusion and exclusion, 2651 patients were selected for matching, and 194 patients in 97 pairs were chosen for subsequent comparative analyses between the ABA and control groups. No between-group differences were detected in the incidence rates of each AE or in the incidence rates of total AE (control vs ABA: 15.5% vs 20.7% in total, 5.2% vs 3.1% in death). CONCLUSION: Compared with csDMARD and/or steroids without ABA, adding ABA to the treatment does not appear to increase the incidence rates of postoperative AE in patients with RA undergoing orthopedic surgery. Large cohort studies should be performed to add evidence for the perioperative safety profile of ABA.

Attenuated Legionella pneumophila Survives for a Long Period in an Environmental Water Site.

Legionella pneumophila is known as a human pathogen and is ubiquitous in natural and artificial aquatic environments. Many studies have revealed the virulence traits of L. pneumophila using clinical strains and a number of studies for characterizing environmental strains are also reported. However, the association between the virulence and survivability in the environment is unclear. In the present study, L. pneumophila was isolated from environmental water sites (Ashiyu foot spa, water fountain, and public bath), and the serogroups of isolated strains were determined by serological tests. Isolated strains were found to belong to serogroups SG1, SG2, SG3, SG4, SG5, SG8, SG9, and SG13. Untypeable strains were also obtained. Isolated strains were used for intracellular growth assay in a human monocytic cell line, THP-1. Among these strains, only an untypeable strain, named AY3, failed to replicate in THP-1. In addition, AY3 was maintained for a long period in an environmental water site, Ashiyu foot spa 2. Further, we compared the characteristics of several strains isolated from Ashiyu foot spa 2 and a clinical strain, Togus-1. AY3 failed to replicate in THP-1 cells but replicated in an amoeba model, Dictyostelium discoideum. Compared with Togus-1, the culturable cell number of environmental strains under stress conditions was higher. Moreover, biofilm formation was assessed, and AY3 showed the same degree of biofilm formation as Togus-1. Biofilm formation, replication in amoebae, and resistance against stress factors would explain the predominance of AY3 at one environmental site. Although the mechanism underlying the difference in the ability of AY3 to replicate in THP-1 cells or amoebae is still unclear, AY3 may abandon the ability to replicate in THP-1 cells to survive in one environment for a long period. Understanding the mechanisms of L. pneumophila in replication within different hosts should help in the control of Legionnaires' disease, but further study is necessary.

Methotrexate upregulates circadian transcriptional factors PAR bZIP to induce apoptosis on rheumatoid arthritis synovial fibroblasts.

BACKGROUND: Effects of methotrexate (MTX) on the proliferation of rheumatoid arthritis (RA) synovial fibroblasts are incompletely understood. We explored actions of MTX in view of circadian transcriptions of synovial fibroblasts. METHODS: Under treatment with MTX, expression of core circadian clock genes, circadian transcriptional factor proline and acidic amino acid-rich basic leucine zipper (PAR bZIP), and proapoptotic molecule Bcl-2 interacting killer (Bik) was examined by real-time polymerase chain reaction. Protein expression of circadian clock gene PERIOD2 (PER2) and CYTOCHROME C was also examined by western blotting and ELISA. Promoter activities of Per2 and Bik were measured by Luciferase assay. Expression of PER2, BIK, and CYTOCHROME C and morphological changes of the nucleus were observed by fluorescent immunostaining. Synovial fibroblasts were transfected with Per2/Bik small interfering RNA, and successively treated with MTX to determine cell viabilities. Finally, synovial fibroblasts were treated with MTX according to the oscillation of Per2/Bik expression. RESULTS: MTX (10 nM) significantly decreased cell viabilities, but increased messenger RNA expression of Per2, Bik, and PAR ZIP including D site of the albumin promoter binding protein (Dbp), hepatic leukemia factor (Hlf), and thyrotroph embryonic factor (Tef). MTX also increased protein expression of PER2 and CYTOCHROME C, and promoter activities of Per2 and Bik via D-box. Under fluorescent observations, expression of PER2, BIK, and CYTOCHROME C was increased in apoptotic cells. Cytotoxicity of MTX was attenuated by silencing of Per2 and/or Bik, and revealed that MTX was significantly effective in situations where Per2/Bik expression was high. CONCLUSIONS: We present here novel unique action of MTX on synovial fibroblasts that upregulates PAR bZIP to transcribe Per2 and Bik, resulting in apoptosis induction. MTX is important in modulating circadian environments to understand a new aspect of pathogenesis of RA.

TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells.

Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca2+ chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α. Oscillation phase and amplitude of Bmal1, transcriptional activator Rorα, transcriptional repressor Rev-erbα, and histone acetyltransferases (p300 and Cbp) were evaluated by quantitative real-time PCR. As results, TNF-α did not influence the oscillation phase of Rev-erbα, while enhanced those of Rorα, resulting in over-expression of Bmal1. When Ca2+ influx was inhibited by BAPTA-AM, TNF-α-mediated up-regulation of Rorα was cancelled, however, that of Bmal1 was still apparent. When we further explored another pathway between TNF-α and Bmal1, TNF-α suppressed the expression of Rev-erbα in the absence of Ca2+ influx, as well as those of p300 and Cbp genes. Finally, actions of TNF-α, in increasing Bmal1/Rorα and decreasing Rev-erbα, were cancelled by C646 treatment or silencing of both p300 and Cbp. In conclusion, we determined a novel role of TNF-α in inducing Bmal1 via dual calcium dependent pathways; Rorα was up-regulated in the presence of Ca2+ influx and Rev-erbα was down-regulated in the absence of that. Results proposed that inhibition of p300/CBP could be new therapeutic targets for RA.

Development and validation of a new radiographic scoring system to evaluate bone and cartilage destruction and healing of large joints with rheumatoid arthritis: ARASHI (Assessment of rheumatoid arthritis by scoring of large joint destruction and healing in radiographic imaging) study.

OBJECTIVE: To assess the reliability and sensitivity of a novel scoring method to evaluate the radiographic appearance of and longitudinal changes including joint remodeling in large joints with early and established rheumatoid arthritis (RA). METHODS: The ARASHI study group devised new radiographic scoring systems (Status score; range 0-16 points, and Change score; range -11 to 12 points) for evaluation of large joints with RA. Radiographs showing anterior/posterior views of large joints (shoulder, elbow, hip, knee, and ankle joints) taken at two time points (mean interval 2.3 years) were collected from 25 patients with established RA (5 patients for each of the 5 joints, 50 films in total), and an additional 5 films of each joint with severe joint destruction were collected from 5 different sets of RA patients. After consensus on the definition of each component and reader training, images were evaluated using the Larsen's grading system and the ARASHI Status and Change score by 9 independent senior orthopedic surgeons. The reliability was estimated by intra-class correlation coefficients (ICCs) and measurement error by 95% confidence intervals of minimum detectable change (MDC95). RESULTS: ARASHI Status score and Change score significantly correlated with Larsen's grade (r = 0.89, P < 0.0001) and follow-up-baseline differences in Larsen's grade (r = 0.83, P < 0.0001), respectively. Inter-reader ICCs were very high for both Status score (0.88, 95% confidence interval [CI], 0.83-0.92, P < 0.001) and Change score (0.92, 95% CI, 0.87-0.96, P < 0.001). Intra-reader ICCs were also very high for both Status score (0.92, 95% CI, 0.71-0.98, P < 0.001) and Change score (0.97, 95% CI, 0.91-0.99, P < 0.001). The MDC95 for inter-reader agreement were 4.18 (25% of maximum obtainable score, MOS) and 4.99 (21% of MOS) for Status score and Change score, respectively. The MDC95 for intra-reader agreement was acceptable with 2.82 (17% of MOS) and 3.02 (13% of MOS) for Status score and Change score, respectively. CONCLUSION: The ARASHI scoring method showed good inter-/intra-reader reliability with high ICCs and acceptable MDC95 with respect to each large joint and the components of both Status and Change scores. The results suggest that the ARASHI scoring method might be useful for the assessment of status, as well as longitudinal monitoring of destruction and remodeling of large joints with RA.

Analysis of perioperative clinical features and complications after orthopaedic surgery in rheumatoid arthritis patients treated with tocilizumab in a real-world setting: results from the multicentre TOcilizumab in Perioperative Period (TOPP) study.

OBJECTIVE: To evaluate perioperative changes in rheumatoid arthritis (RA) patients treated with tocilizumab. METHODS: We collected RA cases with tocilizumab and orthopaedic surgery from 1999 to 2010. Incidences of postoperative infections, delayed wound healing, and RA symptom flare-ups were extracted from the data for comparison with patients without these postoperative events. We also evaluated the changes in C-reactive protein (CRP) and body temperature in patients without postoperative complications with normal CRP before surgery, i.e., patients without postoperative events in whom the tocilizumab level was maintained, for each duration to discontinuation before surgery. RESULTS: A total of 161 cases (n = 122) were collected. The patients had mean age of 56.9 years, and mean disease duration of 12.8 years at operation. Joint replacement surgery was performed in 89 cases. Three patients had postoperative infections (two superficial and one organ/space surgical-site infection), 20 had delayed wound healing, and 36 had RA symptom flare-ups. Delayed wound healing occurred most commonly in patients who underwent spinal surgery (P = 0.0061, versus patients without delayed wound healing). CRP levels were high when tocilizumab was restarted in patients with RA symptom flare-ups (P = 0.0010, versus patients without RA symptom flare-ups). Increased postoperative CRP was observed in patients without postoperative events when the duration from final tocilizumab infusion to surgery was long. The changes in body temperature showed a similar trend to CRP. CONCLUSIONS: Although it has been demonstrated that infection rates in patients treated with tocilizumab are by no means high, incidence of delayed wound healing was significantly higher in cases with surgical interventions such as foot and spinal surgeries. Many patients treated with tocilizumab remained in a normal range of CRP even during the perioperative period. For prevention of perioperative complications, observation of postoperative conditions and surgical wounds, and subjective symptoms of patients are considered important.

Short-term outcome of finger joint synovectomy in rheumatoid arthritis.

Rheumatoid arthritis (RA) frequently affects finger joints, and persistent synovitis is believed to cause not only bone destruction but also various deformities of the fingers in the long run. Synovectomy of the finger joints is carried out when chronic swelling of the synovium does not respond to any conservative treatment with medication and rehabilitation. In the present study the short-term results of finger joint synovectomy in RA were reviewed in 49 finger joints. The subjects were evaluated at two time points, with average follow-up periods of 14 and 62 months, and the results were compared between the two follow-up time points. In regard to results, pain relief, swelling abatement, and only a little loss of motion were observed in most fingers. Moreover, only a few patients demonstrated progression of bone destruction, suggesting that synovectomy has a retarding effect and tends to be effective especially in the early stages of the disease. In conclusion, we recommend synovectomy for finger joints in RA patients before bone changes occur, and when chronic synovitis of the finger joints does not respond to any other conservative treatment.

Prospective study of methotrexate treatment for rheumatoid arthritis treated legitimately according to the government recommended 8 mg/week dose.

Clinical squeal of the treatment of rheumatoid arthritis patients with methotrexate (MTX) according to the Japanese government recommended dose of 8 mg/week was evaluated prospectively. A total of 176 patients with active RA attending Konan Kakogawa Hospital and Kobe University Hospital were enrolled. Patients' profile at the start of study was Class 2.0 +/- 1.1 and X-ray stage 2.6 +/- 1.0. The effects of MTX treatment were evaluated by the American College of Rheumatology (ACR) core set, disease activity score of 28 joints (DAS28), and European League Against Rheumatism (EULAR) response criteria. A modified Sharp method was used to evaluate the radiographs. The improvement in the clinical signs and symptoms of the ACR core set was maintained for a 24-month period (p < 0.05). The ACR20/50/70 and DAS28 were also improved at the 12- and 24-month assessments. However, 82 of 130 patients (63.5%) were found to be nonresponders at 24 months of MTX therapy, as evaluated by EULAR response criteria. The X-ray study showed that joint destruction progressed despite the treatment. Thus, long-term MTX treatment performed in accordance with the Japanese 8 mg/week regimen appears to be favorable in terms of the signs and symptoms of RA; however, it is clearly insufficient for and cannot halt the progression of rheumatic joint destruction.

Total knee arthroplasty for rheumatoid knee with bilateral, severe flexion contracture: report of three cases.

The treatment of patients with severe flexion contracture of the rheumatoid knee, deprived of ambulation for long periods of time, is challenging. Based on three cases, we indicate the potential risks of posterior dislocation of the knee after total knee arthroplasty. In this pathological condition, surgeons must carefully select the type of implant in order to avoid this serious complication. We also emphasize the importance of working on disuse muscle atrophy of trunk (back, abdominal) and lower limbs, both of which play an integral role in ambulation. The personality of each rheumatoid patient should be carefully considered when considering surgical and rehabilitation options.

Long-term results of open elbow synovectomy for rheumatoid arthritis.

Long-term results of open synovectomy of the elbow with rheumatoid arthritis (RA) were reviewed in 15 elbows. The subjects were evaluated at two time points with average follow-up periods of 4 and 8.7 years, and the results were compared between the two follow-ups. The Mayo Clinic performance score showed significant improvement in pain, motion, and daily function from the intermediate to the long-term follow-up. Overall results were satisfactory with little time-dependent deterioration in radiological grading, confirming the long-term effectiveness of this procedure.

The effectiveness of RA wrist fusion using Beta-TCP without autogenous iliac bone grafting: a report of four cases.

Wrist arthrodesis is indicated for the rheumatoid hand especially in cases with severe destruction of the carpal bones. In the arthrodesis procedure for the rheumatoid wrist, autogenous iliac bone grafting is required in most cases. However, autogenous iliac bone graft necessitates the additional surgical intervention, and can be associated with the problem of inadequate bony quality or quantity. It is thought that use of the artificial bone substitute in the procedure can lessen the surgical morbidity while supplying the consistent material without shortage of graft quantity. We have performed arthrodesis of the rheumatoid wrist using beta-TCP for four patients. Clinical results of these patients were satisfactory both in pain relief and functional improvement with complete bony healing. Therefore, this procedure seems to be an effective option for the rheumatoid wrist with severe destructive changes.

Giant geode at the olecranon in the rheumatoid elbow--two case reports.

A single giant geode at the olecranon in a patient with rheumatoid arthritis (RA) is relatively rare, and may cause diagnostic difficulties or cause a spontaneous pathological fracture owing to weakness of the cortical bone associated with osteoporosis. We report two cases of patients presenting with single giant geodes at the olecranon. In one case we performed an open reduction and internal fixation with bone grafting for a pathological fracture due to the geode. In the other case we performed curettage of the geode with bone grafting to prevent a pathological fracture, and a synovectomy of the elbow. We suggest that the presence of a giant geode at the olecranon may necessitate surgical intervention to prevent the occurrence of a spontaneous pathological fracture.

Comparison of the Sauvé-Kapandji procedure and the Darrach procedure for the treatment of rheumatoid wrists.

Abstract In surgical treatment of the rheumatoid wrist, the Darrach procedure combined with synovectomy has been the treatment of choice in the past. However, owing to the significant ulnar carpal shift observed after the Darrach procedure, the Sauvé-Kapandji (S-K) procedure has become increasingly popular. The purpose of this study was to compare the clinical results of the S-K and Darrach procedures. Thirty-two wrists in the S-K-procedure group and 31 wrists in Darrach-procedure group were examined. Before and after surgery, clinical evaluations of pain, swelling, range of motion, grip strength, and radiological findings were performed and the results were compared. Both procedures resulted in decreased pain and swelling, as well as improved rotatory motion of the forearm. The S-K procedure was shown to be superior to the Darrach procedure in reducing ulnar carpal migration and improving grip strength. On the other hand, the prevention of carpal bone destruction could not be completely achieved in either procedure.