Dose optimization in surgical prophylaxis: sub-inhibitory dosing of vancomycin increases rates of biofilm formation and the rates of surgical site infection.

Antibiotic stewardship is viewed as having great public health benefit with limited direct benefit to the patient at the time of administration. The objective of our study was to determine if inappropriate administration of antibiotics could create conditions that would increase the rates of surgical infection. We hypothesized that sub-MIC levels of vancomycin would increase Staphylococcus aureus growth, biofilm formation, and rates of infection. S. aureus MRSA and MSSA strains were used for all experiments. Bacteria were grown planktonically and monitored using spectrophotometry. Quantitative agar culture was used to measure planktonic and biofilm bacterial burden. A mouse abscess model was used to confirm phenotypes in vivo. In the planktonic growth assay, increases in bacterial burden at » MIC vancomycin were observed in USA300 JE2 by 72 h. Similar findings were observed with ½ MIC in Newman and SH1000. For biofilm formation, USA300 JE2 at » and ½ MIC vancomycin increased biofilm formation by approximately 1.3- and 2.3-fold respectively at 72 h as compared to untreated controls. Similar findings were observed with Newman and SH1000 with a 2.4-fold increase in biofilm formation at ½ MIC vancomycin. In a mouse abscess model, there was a 1.2-fold increase with sub-MIC vancomycin at 3 days post infection. Our study showed that Sub-optimal vancomycin dosing promoted S. aureus planktonic growth and biofilm formation, phenotypic measures of bacterial virulence. This phenotype induced by sub-MIC levels of vancomycin was also observed to increase rates of infection and pathogenesis in our mouse model. Risks of exposure to sub-MIC concentrations with vancomycin in surgical procedures are greater as there is decreased bioavailability in tissue in comparison to other antibiotics. This highlights the importance of proper antibiotic selection, stewardship, and dosing for both surgical prophylaxis and treatment of infection.

Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class.

The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We designed PLG0206, an engineered antimicrobial peptide, to address these limitations. PLG0206 has broad-spectrum activity against >1,200 multidrug-resistant (MDR) ESKAPEE clinical isolates, is rapidly bactericidal, and displays potent anti-biofilm activity against diverse MDR pathogens. PLG0206 displays activity in diverse animal infection models following both systemic (urinary tract infection) and local (prosthetic joint infection) administration. These findings support continuing clinical development of PLG0206 and validate use of rational design for peptide therapeutics to overcome limitations associated with difficult-to-drug pharmaceutical targets.

Preoperative ultrasound predicts the intraoperative diameter of the quadriceps tendon autograft more accurately than preoperative magnetic resonance imaging for anterior cruciate ligament reconstruction.

PURPOSE: Sizing of potential autografts is essential to match the native anterior cruciate ligament (ACL) dimensions when performing ACL reconstruction (ACLR). We aimed to investigate the accuracy and reliability of the thickness and cross-sectional area (CSA) assessments for the prediction of the intraoperative diameter of the QT autograft using preoperative ultrasound and MRI. METHODS: Thirty patients (mean age ± standard deviation, 19.9 ± 5.0 years), who underwent ACLR using QT autograft, were included. The maximum thickness of the QT was assessed at 15 and 30 mm proximal using ultrasound with a long axis image, and at 15 mm proximal to the superior pole of the patella using MRI with a sagittal image. The CSA was assessed at the central 10 mm of the medial-lateral QT width at 30 mm proximal using ultrasound with a short axis image, and at 15 mm proximal to the superior pole of the patella using MRI with an axial image. Intraoperatively, QT autograft was harvested with a 10 mm width and the diameter was measured using a graft sizing device. RESULTS: Intra- and inter-observer reliabilities of all measurements using ultrasound and MRI were good (Intra-class correlation coefficient, 0.720-0.941). Correlation coefficient with the intraoperative diameter of the QT autograft was higher in ultrasound (R = 0.738-0.791, P < 0.001) than MRI (R = 0.449-0.543, P = 0.002-0.013). CONCLUSIONS: Preoperative ultrasound predicted the intraoperative diameter of the QT autograft more accurately than MRI. Ultrasound may be used clinically to assure a sufficiently large QT autograft diameter to match the diameter of the patient's native ACL. LEVEL OF EVIDENCE: Level III.

In situ cross-sectional area of the quadriceps tendon using preoperative magnetic resonance imaging significantly correlates with the intraoperative diameter of the quadriceps tendon autograft.

PURPOSE: Preoperative assessment to determine the sizes of potential autografts is necessary for individualized anterior cruciate ligament reconstruction (ACLR). However, no study has investigated the prediction of the intraoperative diameter of the quadriceps tendon (QT) autograft based upon preoperative imaging. This study investigated the correlation between the intraoperative diameter of a QT autograft and in situ thickness or cross-sectional area (CSA) measured using preoperative MRI. METHODS: Thirty-one knees of 31 patients (mean age 20.9 ± 5.0 years) who underwent individualized anatomic ACLR using all soft tissue QT autograft were included retrospectively. At 15 mm proximal to the superior pole of the patella, the maximum QT thickness was assessed in the sagittal plane and the CSA was assessed at the central 10 mm of the QT in the axial plane. The angle between the axial plane and a line perpendicular to the QT longitudinal axis was used to calculate an adjusted CSA using a cosine function. Intraoperatively, each QT autograft was harvested with 10 mm width and the diameter was measured using a graft sizing device. RESULTS: Intra- and inter-observer reliabilities of all measurements using preoperative MRI were excellent (intra-class correlation coefficient, 0.833-0.970). Significant correlations were observed between the thickness, CSA, or adjusted CSA, and the intraoperative diameter (R = 0.434, 0.607, and 0.540, respectively; P < 0.05). CONCLUSIONS: The CSA correlated most strongly with the QT autograft diameter. For individualized anatomic ACLR, measuring in situ CSA can be useful for preoperative planning of appropriate graft choices prior to surgery. LEVEL OF EVIDENCE: III.

Prospective study of early chronic pancreatitis diagnosed based on the Japanese diagnostic criteria.

BACKGROUND: Chronic pancreatitis (CP) is a fibro-inflammatory disease of the pancreas. Early diagnosis and intervention, before CP becomes established and irreversible, are essential to improve the long-term outcomes. The world's first diagnostic criteria for early CP were proposed in Japan in 2009, but their clinical utility remains elusive. This study aimed to clarify whether patients with early CP progress to definite CP. METHODS: This is a multicenter, prospective study. Patients diagnosed as having early CP according to the Japanese diagnostic criteria were prospectively followed for 2 years. Clinical profiles including symptoms, drinking and smoking status, laboratory data, imaging findings and treatments were analyzed. RESULTS: Among the 83 patients who completed the 2-year follow-up period, four (4.8%) patients progressed to definite CP. The diagnosis of 48 (57.8%) patients was unchanged, and that of 31 (37.3%) patients was downgraded. All the four progressive patients were male, alcohol-related, smokers (3 current and 1 ever), and continued drinking. Comparison of the clinical profiles between the progression group (n = 4) and non-progression group (n = 79) revealed that etiology (alcohol-related), smoking status and presence of acute pancreatitis episodes were associated with the progression to definite CP. CONCLUSIONS: The Japanese diagnostic criteria could identify some patients before the progression to definite CP, while the majority of the patients did not progress. TRIAL REGISTRATION NUMBER: UMIN000015992.

Efficacy of golimumab for preventing large joint destruction in patients with rheumatoid arthritis as determined by the ARASHI score.

OBJECTIVES: The objective of this study is to investigate the inhibitory effect of golimumab on large joint destruction in patients with rheumatoid arthritis. METHODS: We recruited 45 patients with rheumatoid arthritis and evaluated the radiographic severity of large joint destruction using the assessment of rheumatoid arthritis by scoring of large joint destruction and healing in radiographic imaging (ARASHI) score. We evaluated 450 large joints including the elbow, shoulder, hip, knee, and ankle at baseline and 52 weeks after treatment with golimumab. Rapid radiographic progression (RRP) and rapid radiographic improvement (RRI) were calculated and the correlation between large joint destruction and clinical factors was analyzed. RESULTS: The mean age of the study population was 61.29 ± 14.71 years old, and most patients (91.1%) were female. The mean disease duration was 12.6 ± 12.48 years. The cohort included patients in all clinical stages of disease as defined by the Steinbroker criteria (I:7, II:10, III:9, IV:19) as well as clinical classes 2 (n = 18), 3 (n = 26), and 4 (n = 1) and the mean disease activity score-CRP (DAS28-CRP) was 4.431 ± 1.044. Patients were treated with methotrexate (mean dose 6.44 ± 1.78 mg/week), prednisolone (PSL) (mean dose 1.078 ± 1.871 mg/d), and golimumab (44.4% of 100 mg). RRP was evident in 20% of the large joints treated with golimumab, and, therefore, golimumab was effective at inhibiting large joint destruction in 80% of joints. RRI was evident in 33.3% of large joints following golimumab treatment. We also observed that EULAR response criteria significantly correlated with the ARASHI change score at 52 weeks after treatment. The total ARASHI status score significantly correlated with the Sharp-van der Heijde score, but not with the delta total sharp score. Multiple regression analyses revealed that the total ARASHI change score was only correlated with EULAR response criteria significantly. CONCLUSIONS: Golimumab therapy was effective at inhibiting large joint destruction of RA patients who have good clinical response, including higher improvement of the shoulder and ankle joints than other large joints.

Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis.

OBJECTIVE: Corticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP. DESIGN: We conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5-7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis. RESULTS: Between April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed. CONCLUSIONS: Maintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks. TRIAL REGISTRATION NUMBER: UMIN000001818; Results.

Analysis of Mitogen-Activated Protein Kinases in Bone and Cartilage of Patients with Rheumatoid Arthritis Treated with Abatacept.

The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (ß-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase. The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control. These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

Simultaneous Treatment with Subcutaneous Injection of Golimumab and Intra-articular Injection of Triamcinolone Acetonide (K-Method) in Patients with Rheumatoid Arthritis Undergoing Switching of Biologics: Retrospective Case-Control Study.

BACKGROUND: Tight control of severe rheumatoid arthritis (RA) in patients with high disease activity, even when using biologics, is sometimes difficult using a treat-to-target strategy. Switching from one biologic to another is associated with lower efficacy than that in treatment-naive cases. We developed the K-method that involves simultaneous treatment with golimumab and intra-articular joint injection of triamcinolone acetonide (TA) in patients undergoing switching of biologics. We performed this retrospective case-control study to investigate the efficacy of achieving an immediate treatment response using the K-method. METHODS: This study involved 20 patients with RA (control group, 10 patients; K-method group, 10 patients). Patients in the control group were switched to golimumab from other biologics without intra-articular injection of TA. The K-method involved injection of 1 mL of TA (40 mg/mL) and 2 mL of 1% lidocaine hydrochloride into swollen or painful joints on the same day as golimumab treatment. A quick response one day after treatment was compared between the two groups according to the disease activity score 28 based on C-reactive protein (DAS28 CRP), clinical disease activity index (CDAI), simplified disease activity index (SDAI), European League Against Rheumatism (EULAR) response, and remission rate. These parameters were investigated for 24 weeks. RESULTS: The K-method group showed significant improvements in DAS28 CRP, CDAI, and SDAI at one day, 12 weeks, and 24 weeks compared with the control group. The number of swollen and tender joints and the patient and doctor global visual analog scale scores were also significantly different between the two groups. The remission rates based on DAS28 CRP were 30% at one day, 50% at 12 weeks, and 60% at 24 weeks in the K-method group. The EULAR good/moderate response rates were 80% at one day, 90% at 12 weeks, and 90% at 24 weeks in the K-method group; however, these rates were only 10%, 40%, and 40%, respectively, in the control group. No adverse events occurred in either group. CONCLUSION: Simultaneous treatment with biologics and intra-articular injection of TA is useful for cases involving switching of biologics for RA. This strategy is safe and practical for RA treatment.

SDF-1 and CXCR4 in synovium are associated with disease activity and bone and joint destruction in patients with rheumatoid arthritis treated with golimumab.

OBJECTIVES: The aim of this study was to determine whether the levels of stromal cell-derived factor (SDF)-1 and its receptor C-X-C chemokine receptor 4 (CXCR4) in synovium were correlated with clinical outcome and bone and joint destruction in rheumatoid arthritis (RA) patients being treated with golimumab. METHODS: Synovial tissues were obtained from 15 golimumab-treated patients and were assessed for SDF-1 and CXCR4 using a new immunohistological scoring system (IH score). The IH score was used to assess correlations between synovial SDF-1 or CXCR4 and the disease activity score (DAS28 CRP), Rooney score, tumor necrosis factor alpha, interleukin-6 (IL-6), CD4, CD20, CD68 and the Assessment of RA by Scoring of Large-Joint Destruction and Healing in Radiographic Imaging (ARASHI) score. Receiver-operating characteristic (ROC) curves were used to predict ARASHI scores from the CXCR4 IH scores. RESULTS: SDF-1 strongly correlated with the DAS28 CRP and serum IL-6. CXCR4 correlated with synovial CD4 and the ARASHI score. ROC analysis of CXCR4 and ARASHI scores >10 indicated a cutoff of 12 points on the IH score for predicting joint destruction during treatment. CONCLUSIONS: Synovial SDF-1 correlated with disease activity, and its receptor CXCR4 was related to joint destruction in RA patients treated with golimumab.

Biologic-free remission by orthopaedic surgery in non-responder to infliximab for rheumatoid arthritis.

The aim of this study was to investigate remission and biologic-free remission after orthopaedic surgery and related clinical factors in non-responder to infliximab for rheumatoid arthritis (RA). We analyzed 74 patients who were treated with 3 mg/kg infliximab and methotrexate and underwent orthopaedic surgery after non-responder to infliximab with disease activity score (DAS) 28 (CRP) of ≥3.2. The rates of remission and biologic-free remission at 52 weeks after orthopaedic surgery were investigated and the clinical factors related to remission and biologic-free remission were analyzed by logistic regression and receiver-operating characteristic analyses. The rates of total remission and biologic-free remission were 37/74 (50 %) and 9/74 (12.2 %), respectively. Regarding orthopaedic surgery, the rates of remission and biologic-free remission were 25/38 (65.8 %) and 7/38 (18.4 %) for synovectomy, 7/20 (35 %) and 0/20 (0 %) for arthroplasty, and 5/16 (31.3 %) and 2/16 12.5) for others including spine surgery and foot surgery. DAS28(CRP) at baseline was significantly related to both remission and biologic-free remission. Prednisolone was negatively associated with remission, and DAS28(CRP) was related to biologic-free remission by logistic regression analyses. DAS28(CRP) below 3.7 was cutoff point for acquiring biologic-free remission of non-responder to infliximab after orthopaedic surgery. Therefore orthopaedic surgery may be effective to obtain remission or biologic-free remission in RA patients treated with biologics.

Incidence and outcome of lung involvement in IgG4-related autoimmune pancreatitis.

We evaluated the incidence and outcome of lung involvement in 35 patients with autoimmune pancreatitis (AIP). Our results indicate that lung involvement is commonly observed in AIP (40%). In addition, corticosteroid treatment improved the lung lesions and appeared to reduce the probability of relapse compared with pancreatic lesions (0% vs 36%). This is the first report to assess the long-term outcome of lung involvement in AIP (52 ± 33 months).

Predictive factors related to the efficacy of golimumab in patients with rheumatoid arthritis.

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metallo-proteinase (MMP)-3, TNF-α, and IL-6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.

Analysis of clinical factors related to the efficacy of shoulder arthroscopic synovectomy plus capsular release in patients with rheumatoid arthritis.

Shoulder synovectomy is a well-known surgical treatment for rheumatoid arthritis. However, synovectomy alone is insufficient for improving range of motion clinically. We investigated the clinical factors related to the efficacy of shoulder synovectomy performed with capsular release in patients with rheumatoid arthritis. Fifty-four shoulders of 54 patients (12 males, 42 females; mean age 53.3 years) with rheumatoid arthritis were treated by synovectomy plus capsular release. The patients had a mean disease duration of 8.33 years, a mean follow-up period of 5.02 years, and 66.7% received biological treatment. The disease activity score 28 using C-reactive protein, range of motion of the shoulder, and Japanese Orthopaedic Association (JOA) score assessment were used to investigate clinical factors, analyzed by multiple regression analysis, associated with improved outcome. The average disease activity score 28 using C-reactive protein and JOA score improved significantly from 4.29 and 36.7 to 3.11 and 84.6, respectively, with the restoration of range of motion. Multiple regression analysis showed that disease duration and prednisolone were significantly associated with flexion degree and JOA score. Larsen grade and JOA score were not correlated significantly. There was no significant difference in the JOA score between the groups with or without biological medicinal treatment. Shoulder arthroscopic synovectomy performed with capsular release with or without biological treatment effectively improved function. Short disease duration and low prednisolone dose in rheumatoid arthritis were important for prediction of efficacy.

DWI findings of autoimmune pancreatitis: comparison between symptomatic and asymptomatic patients.

PURPOSE: To compare the MR findings including diffusion-weighted imaging (DWI) between symptomatic and asymptomatic patients with autoimmune pancreatitis (AIP) and to determine whether DWI can be used as an objective biomarker for symptomatic AIP, which is considered an indication for steroid therapy. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board. MRI scans from 37 patients with AIP (symptomatic, n = 19; asymptomatic, n = 18) were retrospectively evaluated. The imaging studies were performed on a 1.5 Tesla scanner and assessed for parenchymal enlargement, narrowing of the main pancreatic duct, hypointensity on fat-suppressed T1-weighted images (FS-T1WI), a capsule-like rim, extrapancreatic lesions, and hyperintensity on DWI. The findings were compared by univariate and multivariate logistic regression analysis. Apparent diffusion coefficient (ADC) values were also calculated. RESULTS: Multivariate analysis showed that hyperintensity on DWI were most significantly associated with the symptoms of AIP (odds ratio = 28.2; P = 0.003). Interobserver agreement for DWI was also high. The ADC values were significantly lower in symptomatic than in asymptomatic patients (0.94 ± 0.17 versus 1.16 ± 0.16 × 10(-3) mm(2)/s, P < 0.001). Receiver operating characteristic curve analysis of the ADC values to differentiate between symptomatic and asymptomatic patients showed that sensitivity was 68.4%, specificity 83.3%, and AUC 0.74. CONCLUSION: Signal intensity on DWI and ADC value were well correlated with the active symptoms of AIP patients. DWI may be useful as an objective biomarker for determining the indication for steroid therapy.

Rare combination of familial adenomatous polyposis and gallbladder polyps.

Familial adenomatous polyposis is associated with a high incidence of malignancies in the upper gastrointestinal tract (particularly ampullary adenocarcinomas). However, few reports have described a correlation between familial adenomatous polyposis and gallbladder neoplasms. We present a case of a 60-year-old woman with familial adenomatous polyposis who presented with an elevated mass in the neck of the gallbladder (measuring 16 mm × 8 mm in diameter) and multiple small cholecystic polyps. She had undergone a total colectomy for ascending colon cancer associated with familial adenomatous polyposis 22 years previously. The patient underwent laparoscopic cholecystectomy under a preoperative diagnosis of multifocal gallbladder polyps. Pathologic examination of the resected gallbladder revealed more than 70 adenomatous lesions, a feature consistent with adenoma of the gallbladder. This case suggests a requirement for long-term surveillance of the biliary system in addition to the gastrointestinal tract in patients with familial adenomatous polyposis.

Body mass index influences the outcome of acute pancreatitis: an analysis based on the Japanese administrative database.

OBJECTIVE: This study aimed to investigate the relationship between body mass index (BMI) and risk of death in patients with acute pancreatitis (AP) using a Japanese national administrative database. METHODS: We analyzed a total of 6002 patients with AP. We collected patient information, including sex, age, BMI, severity of AP based on the Japan Pancreas Society scoring system, and prognosis. We classified BMI into 5 categories (underweight [BMI, <18.5], normal range [18.5-24.9], preobese [25-29.9], obese class I [30-34.9], and obese class II/III [>35]) and investigated the relationship between each category and risk of death in AP. RESULTS: There was a good correlation between the Japanese AP severity score and in-hospital mortality. Overall mortality of severe pancreatitis was 7.0% (n = 2245). Mortality in each BMI category was as follows: underweight, 6.4%; normal range, 3.6%; preobese, 2.4%; obese class I, 3.2%; and obese class II/III, 5.7%. Underweight and obese class II/III patients had significantly higher relative risk (RR) of death in AP compared with preobese patients after adjusting for sex, age, and severity of AP (RR, 2.7; 95% confidence interval, 1.6-4.5; and RR, 6.4; 95% confidence interval, 1.9-20.9, respectively). CONCLUSIONS: Underweight or overweight was the independent risk factor for mortality in AP.

Application of a new immunohistology scoring system (IH score): analysis of TNF-α in synovium related to disease activity score in infliximab-treated patients with rheumatoid arthritis.

OBJECTIVES: This study aimed to analyze the relationship between the expression of tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) in synovium and the disease activity score (DAS) 28 (C-reactive protein, CRP) in treatment of infliximab for rheumatoid arthritis (RA). METHODS: Synovial tissues were obtained from 16 infliximab-treated patients and assessed for TNF-α and IL-6 with a new immunohistology (IH) scoring system. The validation of IH score was performed and applied for the analysis of correlation between synovial TNF-α or IL-6 and DAS28 (CRP) in addition to Rooney score. RESULTS: The IH score had high internal validity; the IH score of TNF-α strongly correlated with serum CRP and matrix metalloprotease-3 (MMP-3), as well as DAS28 (CRP) and the Rooney score. IL-6 did not correlate with DAS28 (CRP). CONCLUSIONS: This study indicates that the IH score is useful as a new procedure to assess the cytokine expression easily and TNF-α in synovium correlates with disease activity in patients with RA treated with infliximab.

Pancreatic somatostatinoma diagnosed preoperatively: report of a case.

CONTEXT: Somatostatinoma is a rare neoplasm of the pancreas. Preoperative diagnosis is often difficult. CASE REPORT: We report a 72-year-old woman with a pancreatic head tumor measuring 37 mm in diameter, and enlargement of the lymph nodes on the anterior surface of the pancreatic head and the posterior surface of the horizontal part of the duodenum. Laboratory data showed an elevated plasma somatostatin concentration. Examination of a biopsy specimen of the pancreatic head mass obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed histopathological features of a neuroendocrine tumor. Immunohistochemical staining showed that the tumor cells were positive for somatostatin, leading to a preoperative diagnosis of pancreatic somatostatinoma. The patient underwent pylorus-preserving pancreaticoduodenectomy. The plasma somatostatin concentration decreased progressively after surgery. CONCLUSIONS: A rare case of pancreatic somatostatinoma with lymph node metastases was presented. Immunohistochemical analysis of a biopsy specimen obtained by EUS-FNA was useful for preoperative diagnosis.

Churg-Strauss syndrome manifesting as cholestasis and diagnosed by liver biopsy.

A 56-year-old woman was referred to our hospital due to fever and cholestatic liver dysfunction. Her eosinophil count was normal and she had no abdominal pain or neurological manifestations. We performed a liver biopsy and found fibrinoid necrosis of the hepatic artery with granulomatous reaction and eosinophilic infiltration in the portal area in the liver. Later, sensory abnormalities of the arms and legs appeared and the eosinophil count increased. Serum immunoglobulin E and immunoglobulin G4 were elevated and rheumatoid factor was strongly positive. Endoscopic retrograde cholangiopancreatography revealed no abnormality of the bile duct and pancreatic duct. We made a diagnosis of Churg-Strauss syndrome and began corticosteroid treatment. Fever and liver function immediately improved. In the present patient, Churg-Strauss syndrome manifested first in the liver, before hypereosinophilia and neural manifestations. We believe that Churg-Strauss syndrome is an autoimmune liver disease, and it is important to recognize that the liver may be involved in Churg-Strauss syndrome.