Effect of anaesthesia on cemented hemiarthroplasty -A multicentre retrospective study (TRON study).

INTRODUCTION: This study aimed to investigate the survival rate, postoperative complications, and walking ability in cemented hemiarthroplasty (HA) for displaced femoral neck fractures according to the anaesthesia method. METHODS: We conducted a retrospective study of a multicentre group (the TRON group). Three hundred fifty-eight patients who underwent cemented HA between 2015 and 2019 were selected; 289 patients of ≥75 years of age with no missing data were included. Patient background factors were matched and patients were assigned to spinal anaesthesia (SA) and general anaesthesia (GA) groups. The primary outcome was death at any time during the follow-up period. Secondary outcomes included postoperative complications and walking ability assessed using the Parker mobility score (PMS). Overall survival was evaluated using the Kaplan-Meier method, and differences were compared using the log-rank test. The incidence of each complication and PMS were compared between the two groups using Fisher's exact test. RESULTS: Overall survival during follow-up was significantly higher in the SA group in comparison to the GA group (p = 0.037). In the SA and GA groups, the survival rate at 3 months postoperatively was 98.4% and 95.5%, respectively. The incidence of postoperative pneumonia was significantly higher in the GA (p = 0.012), and PMS at 3 months postoperatively was significantly higher in the SA group (p = 0.016). CONCLUSION: The survival rate of elderly patients who underwent cemented HA was better in the SA group. General anaesthesia in cemented HA may be associated with lower life expectancy, increased incidence of pneumonia, and decreased walking ability.

Comparison Between Cz-C3/C4 and C3-C4 Montages to Protect Against Peripheral Stimulation in Transcranial Facial Motor-Evoked Potential Monitoring.

INTRODUCTION: In facial motor-evoked potential monitoring, efforts to reduce peripheral stimulation are necessary because it can cause false-negatives. The effects of peripheral stimulation on Cz-C3/C4 and C3-C4 montages were compared. METHODS: Facial motor-evoked potentials were recorded from bilateral orbicularis oculi (Oculi) and oris (Oris) muscles. The double-train approach combining single-pulse and five-train pulse stimulation was used to determine the effect of peripheral stimulation. If the five-train pulse produced a significant waveform, it was defined as "total success." In total success cases, "true success" was defined as a case in which no waveform appeared after the single pulse at the threshold level of the five-train pulse. The total and true success rates and the threshold value of Oculi and Oris were compared between Cz-C3/C4 and C3-C4 montages. RESULTS: Thirty-six muscles each of Oculi and Oris of 18 patients were used for the analysis. True success was more likely to be obtained by the Cz-C3/C4 montage than the C3-C4 montage in Oculi (42% vs. 22%, p = 0.039). Both Oculi and Oris had higher thresholds to elicit facial motor-evoked potentials with the Cz-C3/C4 montage (Oculi: 101.7 vs. 71.4 mA, p = 0.038; Oris: 94.8 vs. 73.1 mA, p = 0.016). CONCLUSIONS: Cz-C3/4 montage is more effective at reducing peripheral stimulation compared with the C3-4 montage. This effect was primarily seen in the orbicularis oculi muscle. It should be noted that the Cz-C3/C4 montage has a higher threshold than the C3-C4 montage in facial muscles. In facial motor-evoked potential monitoring, the Cz-C3/C4 montage may be more suitable to eliminate peripheral stimulation.

The efficacy and safety of adaptive servo-ventilation therapy for heart failure with preserved ejection fraction.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy.

Number of concomitant drugs with thrombocytopenic adverse effects and the extent inflammatory response resolution are risk factors for thrombocytopenia in patients treated with linezolid for more than 14 days.

Prolonged treatment with linezolid (LZD) is known to cause thrombocytopenia. However, some patients do not develop thrombocytopenia despite long-term administration of LZD. To determine the risk factors for LZD-associated thrombocytopenia in patients undergoing long-term LZD therapy, we conducted a retrospective cohort study among 212 patients receiving LZD treatment between December 2011 and June 2014 at a tertiary referral university hospital in Nagoya, Japan. Of the 217 patients who received LZD, 37 were treated with LZD for more than 14 days and were enrolled in the study. We compared data on demographic characteristics, underlying disease, microbiology, concomitant drugs, and laboratory tests between the thrombocytopenia group and the non-thrombocytopenia group. Thrombocytopenia was defined as having a platelet count < 100 × 103/µL or a ≥ 50% reduction in platelet count compared to baseline. Among the 37 patients who received LZD for more than 14 days, 17 (45.9%) developed thrombocytopenia. Multivariate logistic regression revealed that both the number of concomitant drugs with thrombocytopenic adverse effects (DTADE) (OR = 1.690; 95% CI = 1.037-2.754; P = 0.035) and a small decrease in the level of C-reactive protein (CRP) 14 days post-administration (OR = 0.965; 95% CI = 0.939-0.993; P = 0.013) were associated with thrombocytopenia during long-term LZD therapy. Therefore, the number of concomitant DTADE and a small decrease in CRP on the 14th day of treatment were key factors for the appearance of LZD-associated thrombocytopenia in patients with long-term LZD therapy. Our findings may be useful for preventing thrombocytopenia in patients treated with LZD for longer than 14 days.

[Successful treatment of pre-engraftment disseminated fusariosis with high-dose liposomal amphotericin B in a cord blood transplant recipient].

A 47-year-old man with acute myeloid leukemia and myelodysplastic-related changes relapsed after an allogenic bone marrow transplant and received a cord blood transplant as salvage therapy. The patient developed febrile neutropenia that was resistant to broad-spectrum antibiotics and multiple, painful, nodular skin lesions on his trunk and extremities before engraftment. A skin biopsy and blood culture found mold, and the subsequent microscopic examination, mass spectrometry, and DNA sequencing of the fungal colonies identified Fusarium solani. The patient's fever and skin lesions began to improve with the administration of liposomal amphotericin B at 5 mg/kg/day. Neutrophilic engraftment occurred on day 19. Stage 3 acute skin graft-versus-host disease was cured by the application of topical steroid. Unexpectedly, a change from liposomal amphotericin B to voriconazole on day 38 exacerbated the Fusarium infection. The Fusarium infection was finally cured by the administration of liposomal amphotericin B for a total of 19 weeks. Neutrophilic engraftment, an immediate definitive diagnosis, the sufficient and long-term administration of appropriate antifungal medication, and avoidance of the systemic administration of steroids might have contributed to the successful outcome of this patient.

Active surveillance in response to the identification of a single carbapenemase-producing Escherichia coli at a Japanese university hospital.

This report described the experience of active surveillance culture implemented in response to the identification of a single carbapenemase-producing Escherichia coli in a Japanese university hospital. It revealed a horizontal transmission event and an additional asymptomatic carrier of carbapenemase-producing Escherichia coli with unique drug susceptibility and resistance gene profiles. Early implementation of active surveillance culture as a part of multifaceted infection control measures appeared to be useful to control further transmission of carbapenemase-producing Escherichia coli even in the low endemic facility. Further investigations on the timing and usefulness of active surveillance culture in the control of carbapenemase-producing Enterobacteriaceae would be warranted.

Risk factors for and role of OprD protein in increasing minimal inhibitory concentrations of carbapenems in clinical isolates of Pseudomonas aeruginosa.

PURPOSE: This study examined the risk factors for, and molecular mechanisms underlying, the increase in carbapenem minimum inhibitory concentrations (MICs) in clinical isolates of Pseudomonas aeruginosa. METHODOLOGY: Consecutive clinical isolates of P. aeruginosa were collected. The MicroScan WalkAway system detected more than fourfold increases in the MICs of carbapenems in P. aeruginosa isolates serially recovered from some patients during their clinical course. The clinical risk factors associated with this increase were examined by multiple logistic regression analysis. Western blot analysis and nucleotide sequencing of the oprD gene of 19 clonally related and paired P. aeruginosa isolates from the same patients were undertaken to examine the mechanisms underlying the increase in MICs. RESULTS: The results showed that prior use of carbapenems (OR, 2.799; 95 % CI, 1.088-7.200; P=0.033) and the use of ventilators or tracheostomies (OR, 2.648; 95 % CI, 1.051-6.671; P=0.039) were risk factors for increased carbapenem MICs. Analysis of the underlying mechanisms revealed that loss of functional OprD protein due to mutation of the oprD gene tended to occur in P. aeruginosa isolates with imipenem MICs of more than 8 µg ml-1; a reduction in OprD expression was observed in P. aeruginosa isolates with imipenem MICs of 4 or 8 µg ml-1. This difference in the resistance mechanism was not correlated with the MICs of meropenem. CONCLUSION: This difference in the resistance mechanism of P. aeruginosa indicates a critical breakpoint at an imipenem MIC of 8 µg ml-1, in accordance with EUCAST criteria. Reducing carbapenem use will prevent P. aeruginosa clinical isolates from developing resistance to carbapenems.

Collaboration with an infection control team for patients with infection after spine surgery.

BACKGROUND: The risk of infection, including surgical site infection (SSI), after spine surgery has increased due to aging and more immunocompromised hosts. An infection control team (ICT) is responsible for management of health care-associated infections at our institution. METHODS: The study subjects were 40 patients (18 men and 22 women with an average age of 54 years) referred to the ICT after spine surgery since 2010. Pathogenic bacteria and treatment in these cases were reviewed. RESULTS: Collaboration with the ICT involved guidance on use of antibiotics for infection in 30 patients (16 SSI and 14 non-SSI) and a search for the infection focus for fever of unknown origin in 10 patients (7 patients were found to have urinary tract infections and 2 patients were found to have pneumonia). The detection rate of causative bacteria in ICT consultation was 88% (35 out of 40 patients). SSI patients with instrumentation involved had a significantly higher rate of methicillin-resistant Staphylococcus aureus infection compared with those without instrumentation (42% vs 13%; P < .05). DISCUSSION: All cases of SSI with instrumentation involved were cured by ICT support without removal of instrumentation. Early assistance from the ICT was important for prevention of worsening of methicillin-resistant S aureus infection. CONCLUSIONS: Collaboration with the ICT was helpful for detection of pathogenic bacteria and allowed appropriate use of antibiotics at an early stage.

Pneumococcal biliary tract infections - How rare are they?

Pneumococcal biliary tract infections (PBTIs) were reported as rare due to the bacterium's bile solubility. The purpose of this study was to determine the occurrence and clinical characteristics of PBTIs. A retrospective case series review was conducted from January 2006 to August 2014 at a tertiary referral university hospital in Japan. Patients with a blood or bile culture positive for Streptococcus pneumoniae diagnosed with definite cholangitis or cholecystitis according to Tokyo Guideline 2013 were enrolled in this study. Data on clinical information, treatments, and outcomes were collected. During 104 months, 48 cases of positive blood cultures and 13 cases of positive bile cultures were recorded, and after excluding 43 and 5 of these, respectively, a total of 10 patients were diagnosed with PBTI. Most patients (9/10) had biliary tract problems and biliary devices in place. PBTIs were not rare; conversely, they were a relatively common cause of pneumococcal bacteremia in this center treating a high volume of biliary tract illnesses.

The first point prevalence survey of health care-associated infection and antimicrobial use in a Japanese university hospital: A pilot study.

BACKGROUND: Point prevalence surveys (PPSs) in Japanese hospitals have not yet been reported. The purpose of this pilot PPS study was to evaluate the epidemiology of health care-associated infections (HAIs) and antimicrobial use in a Japanese tertiary university hospital. METHODS: A 1-day, cross-sectional PPS was performed at a Japanese university hospital. Data on demographics, active HAIs, and antimicrobial use of all inpatients were collected using a data collection form. RESULTS: Of 841 patients, 85 (10.1%) had 90 active HAIs, and 308 patients (36.6%) were administered 494 antimicrobials. Among the 90 HAIs and 58 pathogens, the most frequent infection and isolated pathogen were pneumonia (20.0%) and Enterobacteriaceae (27.6%), respectively. Of the 118 antimicrobials used for treatment of HAIs, carbapenems were the most frequently administered category of antimicrobials (22.9%). In regard to antimicrobials for surgical prophylaxis, 37 of 119 (31.1%) were administered to patients on postoperative day 3 or later, and 48 of 119 (40.3%) were administered orally. CONCLUSIONS: The incidence of HAIs is higher than in other developed countries. The social and medical situation in Japan may affect patient demographics, active HAIs, and antimicrobial use. Multicenter PPSs are necessary to uncover the real epidemiology of HAIs and antimicrobial use in Japan.

Massive mediastinal cryptococcosis in a young immunocompetent patient.

Pulmonary cryptococcosis with lymph node involvement is relatively rare in immunocompetent patients. We report a case of pulmonary cryptococcosis with massive mediastinal lymphadenopathy in an immunocompetent young patient. In this report, a 17-year-old boy presented with high-grade fever and persistent cough. Chest X-ray and computed tomography showed massive mediastinal lymphadenopathy. Endobronchial ultrasound-guided transbronchial needle aspiration revealed histological evidence of cryptococcal lymphadenitis. He was treated with liposomal amphotericin B plus flucytosine followed by fluconazole and recovered.

Concomitant methotrexate and tacrolimus augment the clinical response to abatacept in patients with rheumatoid arthritis with a prior history of biological DMARD use.

This observational retrospective study examined whether abatacept efficacy could be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients with rheumatoid arthritis (RA) who experienced failure with prior biological disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic efficacy is difficult to achieve. All patients with a prior biological DMARD history who were treated with abatacept for 52 weeks and registered in a Japanese multicentre registry were included. Clinical efficacy and safety of abatacept according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5 vs. -5.4 %, p = 0.035) and 24 (-25.0 vs. -11.0 %, p = 0.036). ABT-MTX and ABT-TAC groups had a significantly higher proportion of patients who achieved low disease activity (LDA) within 52 weeks compared with the respective baselines, while no significant change was observed in the ABT-mono group. A higher proportion of patients in the ABT-TAC group achieved EULAR moderate response compared with the ABT-mono group at week 52 (66.7 vs. 35.0 %, p = 0.025). Multivariate logistic regression analysis revealed that concomitant TAC use was independently associated with the achievement of LDA and EULAR response at 52 weeks, while concomitant MTX use was not. Concomitant TAC use may offer a suitable option for RA patients treated with abatacept after prior biological DMARD failure, likely because both abatacept and TAC affect T cell activation.

Importance of methotrexate therapy concomitant with tocilizumab treatment in achieving better clinical outcomes for rheumatoid arthritis patients with high disease activity: an observational cohort study.

OBJECTIVE: The purpose of this study was to identify the effects of concomitant use of MTX and baseline characteristics for remission in the treatment of RA with tocilizumab (TCZ) in daily clinical practice. METHODS: A total of 240 RA patients who received TCZ were selected from the multicentre Tsurumai Biologics Communication Registry. Predictive baseline factors for remission [28-item DAS (DAS28) < 2.6] at 52 weeks were determined by logistic regression analysis. To confirm whether the associations varied by the level of baseline disease activity, we also assessed the model including the interaction term (each baseline variable × DAS28). RESULTS: In total, 49.3% of the study participants used MTX with TCZ. Even after controlling for the baseline DAS28, shorter disease duration (≤3 year) [odds ratio (OR) 3.58 (95% CI 1.81, 7.07)], less structural damage [Steinbroker stage ≤II, OR 2.33 (95% CI 1.32, 4.12)] and concomitant prednisolone use [OR 0.38 (95% CI 0.21, 0.68)] showed significant predictive values for remission. Concomitant MTX use failed to show a significant association with remission, whereas a significant interaction was observed among concomitant MTX use × DAS28 (P = 0.006). In patients with high baseline disease activity (DAS28 > 5.1), concomitant MTX use was associated with increased odds for remission [adjusted OR for all baseline variables 2.54 (95% CI 1.11, 5.83)], while no association was indicated between them in patients with low to moderate baseline disease activity (DAS28 ≤ 5.1). CONCLUSION: Concomitant MTX use is an important component of TCZ treatment for RA patients with high disease activity.

Longterm retention rate and risk factor for discontinuation due to insufficient efficacy and adverse events in Japanese patients with rheumatoid arthritis receiving etanercept therapy.

OBJECTIVE: Assessing retention rate and risk factor for drug discontinuation is important for drug evaluation. We examined a 3-year retention rate and the risk factor for discontinuation due to insufficient efficacy (IE) and adverse events (AE) in Japanese patients with rheumatoid arthritis (RA) who are receiving etanercept (ETN). METHODS: Data were collected from 588 patients treated with ETN as a first biologic from the Tsurumai Biologics Communication Registry. Baseline characteristics for the incidence of both IE and AE were analyzed using the Cox proportional-hazards regression model. Patients were divided into groups based on age and concomitant methotrexate (MTX). Drug retention rates were calculated using the Kaplan-Meier method and compared among groups using the log-rank test. RESULTS: ETN monotherapy without concomitant MTX [MTX(-)] was significantly related to a higher incidence of discontinuation due to IE [hazard ratio (HR) = 2.226, 95% CI 1.363-3.634]. Older age and MTX(-) were significantly related to a higher incidence of discontinuation due to AE [HR = 1.040, 1.746, 95% CI 1.020-1.060, 1.103-2.763, respectively]. The MTX(-)/≥ 65 years group had the lowest retention rate (p < 0.001). The discontinuation rate due to IE was lower in the MTX(+)/< 65 years group compared to < 65 years/MTX(-), ≥ 65 years/MTX(-) group (p = 0.006, p < 0.001, respectively). The discontinuation rate due to AE was highest in the MTX(-)/≥ 65 years group (p < 0.001). CONCLUSION: Our findings suggest that the risk of discontinuation due to IE was high in the patients who did not use concomitant MTX and that the risk of discontinuation due to AE was high in elderly patients who did not use concomitant MTX.

Alexithymia, depression, inflammation, and pain in patients with rheumatoid arthritis.

OBJECTIVE: We previously reported that depression and inflammation have independent effects on pain severity in patients with rheumatoid arthritis (RA). Alexithymia is a personality trait characterized by deficits in cognitive processing and regulation of emotions. A broad association between alexithymia and various health problems has been suggested, including depression, inflammation, and pain. The objective of this study was to examine the independent influence of alexithymia on pain perception and its relationship to depression and inflammation. METHODS: We evaluated 213 RA outpatients who completed self-administered questionnaires, including the Beck Depression Inventory-II (BDI-II) to measure depression severity, the 20-item Toronto Alexithymia Scale (TAS-20) to measure degree of alexithymia, and a visual analog scale to quantify perceived pain. Serum C-reactive protein (CRP) levels were measured to quantify inflammation severity. RESULTS: An initial significant positive association between the TAS-20 score and pain severity (P = 0.01) lost significance after controlling for BDI-II score and CRP level using regression analysis. An interaction was observed among alexithymia, depression, and inflammation with regard to perceived pain. Among those without alexithymia, pain severity increased linearly with the CRP tertile levels regardless of the presence of depression (P < 0.001 for trend). No linear association between pain severity and CRP level was observed among those with alexithymia. Moreover, depressed patients with alexithymia (BDI-II score ≥14 and TAS-20 score ≥61) reported severe pain even at low CRP levels. CONCLUSION: Alexithymia might have a substantial role in pain perception as well as depression in patients with RA. A biopsychosocial approach is essential to achieve better pain control.

Clinical efficacy of abatacept compared to adalimumab and tocilizumab in rheumatoid arthritis patients with high disease activity.

Favourable clinical results in rheumatoid arthritis (RA) patients with high disease activity (HDA) are difficult to achieve. This study evaluated the clinical efficacy of abatacept according to baseline disease activity compared to adalimumab and tocilizumab. This study included all patients registered in a Japanese multicenter registry treated with abatacept (n = 214), adalimumab (n = 175), or tocilizumab (n = 143) for 24 weeks. Clinical efficacy of abatacept in patients with HDA (DAS28-CRP > 4.1) and low and moderate disease activity was compared. Clinical efficacy of abatacept, adalimumab, and tocilizumab was compared in patients with HDA at baseline. In patients treated with abatacept, multivariate logistic regression identified HDA at baseline as an independent predictor for achieving low disease activity (LDA; DAS28-CRP < 2.7) [OR 0.26, 95 % CI 0.14-0.50] or remission (DAS28-CRP < 2.3) [OR 0.26, 95 % CI 0.12-0.56] at 24 weeks. In patients with HDA at baseline, logistic regression did not identify treatment with adalimumab or tocilizumab as independent predictors of LDA or remission compared to abatacept. Retention rates based on insufficient efficacy were significantly higher in patients treated with abatacept compared to adalimumab and lower than tocilizumab. Retention rates based on adverse events in patients treated with abatacept were significantly lower compared to tocilizumab. Clinical efficacy of abatacept was affected by baseline disease activity. There were no significant differences between the three different classes of biologics regarding clinical efficacy for treating RA patients with HDA, although definitive conclusions regarding long-term efficacy will require further research.

Clinical efficacy of abatacept in Japanese rheumatoid arthritis patients.

OBJECTIVES: The purpose of this study was to examine the treatment retention and efficacy of abatacept, the first member of a new class of biologic agents, in Japanese rheumatoid arthritis (RA) patients during clinical practice. METHODS: A retrospective multicenter study was conducted with patients who underwent abatacept therapy for 24 weeks (n = 143). RESULTS: Patients at baseline had a mean age of 63.5 years, a mean disease duration of 11.3 years, and a mean disease activity score in 28 joints (DAS28) of 4.5. Overall retention of abatacept treatment was 83.2 % at 24 weeks, when 46.2 % of patients achieved DAS28-defined low disease activity (LDA; DAS28 <3.2) and 26.6 % achieved DAS28-defined remission (DAS28 <2.6). LDA was achieved in a significantly higher proportion of patients without prior biologics therapy compared to those with prior biologics (60.9 vs. 34.2 %, p = 0.001). There was no significant difference between patients with or without concomitant methotrexate (MTX) therapy (45.2 vs. 47.5 %). CONCLUSIONS: Abatacept therapy appears to be highly effective and well tolerated during clinical treatment of RA. Abatacept was particularly effective in patients with no history of biologics use, and did not appear to be dependent on concomitant MTX therapy.

Monitoring C-reactive protein levels to predict favourable clinical outcomes from tocilizumab treatment in patients with rheumatoid arthritis.

OBJECTIVES: The inflammatory cytokine interleukin-6 (IL-6) directly stimulates C-reactive protein (CRP) expression. The present study aimed to examine how clinical treatment outcomes of rheumatoid arthritis (RA) with tocilizumab (TCZ), a humanised monoclonal anti-IL-6 receptor antibody, are related to CRP levels monitored for 52 weeks. METHODS: One hundred and twenty-two RA patients who underwent TCZ treatment between May 2008 and September 2009 were registered in the Tsurumai Biologics Communication Registry. Data were collected at initiation of treatment (baseline) and over 52 weeks for Disease Activity Score 28-ESR (DAS28-ESR), Boolean core measurements, serum CRP levels and matrix metalloproteinase-3 levels. To compare clinical results, patients were divided into three groups based on treatment time required to achieve normal CRP levels. RESULTS: Multivariate analysis using the Cox proportional-hazards regression model found that higher CRP levels at baseline was a significant and independent factor in predicting normal CRP levels over 52 weeks (hazard ratio 0.86 per 1 mg/dL). In contrast, disease duration, concomitant methotrexate use and previous tumour necrosis factor inhibitor failure were not significant factors. Patients with normal CRP levels at 12 weeks of TCZ treatment achieved better clinical outcomes, including remission based on DAS28-ESR criteria, compared to patients with elevated CRP levels at 12 weeks. CONCLUSIONS: Adequate suppression of pathological IL-6 signalling during TCZ treatment improves clinical outcomes and can be monitored with serum CRP levels, a readily available biomarker in clinical practice.

A selective estrogen receptor modulator inhibits tumor necrosis factor-α-induced apoptosis through the ERK1/2 signaling pathway in human chondrocytes.

Tumor necrosis factor α (TNF-α) is a pleiotropic cytokine mediating inflammatory as well as cell death activities, and is thought to induce chondrocytic chondrolysis in inflammatory and degenerative joint diseases. Selective estrogen receptor modulators (SERMs), such as raloxifene, which are commonly used in clinical settings act as estrogen agonists or antagonists. It is assumed that estrogens have a potential role in cartilage protection; however, the precise molecular mechanism for the protective effects of estrogens is unclear. This study was designed to examine whether raloxifene inhibits TNF-α-induced apoptosis in human chondrocytes and to clarify the mechanisms involved. We also investigated the signaling pathways responsible for the anti-apoptotic effect of raloxifene. Apoptosis in chondrocytes was determined by DNA fragmentation assay and caspase-3 activation. Raloxifene significantly inhibited TNF-α-induced caspase-3 activation and cell DNA fragmentation levels in chondrocytes. The inhibitory effect of raloxifene was abolished by the estrogen receptor antagonist ICI 182,780. Extracellular signal-regulated kinase 1/2 (ERK1/2) regulates apoptosis, acting as an apoptotic or anti-apoptotic signal. TNF-α-induced apoptosis was significantly enhanced by the ERK1/2 pathway inhibitor PD98059. Raloxifene stimulated a further increase in ERK1/2 phosphorylation in TNF-α-treated chondrocytes. Furthermore, the anti-apoptotic effects of raloxifene were inhibited by PD98059. In addition, the anti-apoptotic effects of raloxifene were completely abolished in ERK1/2 siRNA-treated chondrocytes. These results suggest that raloxifene prevents caspase-3-dependent apoptosis induced by TNF-α in human chondrocytes by activating estrogen receptors and the ERK1/2 signaling pathway.

Pneumococcal polyarticular septic arthritis after a single infusion of infliximab in a rheumatoid arthritis patient: a case report.

INTRODUCTION: We present a case of Streptococcus pneumoniae polyarticular septic arthritis in a patient with rheumatoid arthritis receiving a single infusion of infliximab. CASE PRESENTATION: A 38-year-old Japanese man with a 5-year history of seronegative rheumatoid arthritis had previously received sulphasalazine and methotrexate therapies and was on regular low-dose prednisolone therapy. Despite these treatments, his disease activity remained high and infliximab was introduced in addition to methotrexate, prednisolone, and folic acid. However, he was admitted to hospital with a fever of 40.6°C, chills, and polyarthralgia eight days after the first infusion of infliximab. His joints were swollen, painful, and warm. Laboratory data showed marked acute inflammation. He was diagnosed with bacterial septic polyarthritis, and emergency surgical joint lavage and drainage was performed at the knees along with needle aspiration and lavage of the ankles and right wrist. He was then given intravenous antibiotic therapy for 31 days. He made a good recovery and was discharged on day 37. CONCLUSIONS: We believe this is the first reported case of severe pneumococcal septic arthritis requiring hospitalization in a patient treated with infliximab. S. pneumonia is now a well-recognized but uncommon cause of polyarticular septic arthritis that can lead to cessation of therapy, as in our patient's case.