Strategy of carotid artery stenting as first-line treatment and carotid endarterectomy for carotid artery stenosis: A single-center experience.

Background: The main surgical options for stenosis of the carotid artery are carotid endarterectomy (CEA) and carotid artery stenting (CAS). The number of CAS procedures performed in Japan greatly exceeds that of CEA procedures. In this study, we used data from a single center to examine CAS and CEA for carotid artery stenosis. Methods: The subjects were patients with carotid artery stenosis who underwent CAS or CEA between January 2012 and May 2020. CAS was the first-choice treatment. CEA was used in cases with vulnerable plaques, a relatively low risk of general anesthesia, and no anatomical features disadvantageous for endarterectomy. Results: A total of 140 cases (102 CAS and 38 CEA) were examined. There were more elderly patients in the CAS group. The CEA group had a higher rate of vulnerable plaques and only one case with an unfavorable anatomy for CEA. Major adverse events (stroke) occurred in two CAS cases. In multivariate logistic analysis, postoperative ischemic lesions were independently associated with age (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.01-1.26, P = 0.026) and vulnerable plaque (OR = 5.54, 95% CI: 1.48-20.70, P = 0.011) in the CAS group, but not in the CEA group. Conclusion: The results reflect the treatment algorithm at our hospital, indicating that triage is accurate. Thus, it is beneficial to assign cases based primarily on plaque vulnerability and anatomical risk for CEA, and to not hesitate to perform CEA simply because of old age. CAS as first-line treatment and CEA are effective and safe, which reflect the treatment situation in Japan.

Klebsiella invasive liver abscess syndrome presenting with a central nervous system manifestation secondary to latent cholecystitis: a case report.

BACKGROUND: Brain abscess is a life-threatening event. Moreover, when Klebsiella pneumoniae is the cause, rapid diagnosis and appropriate treatment are required. Klebsiella invasive liver abscess syndrome, a bloodstream metastatic infection of potentially aggressive nature, has been recognized to cause infection in the central nervous system, and concern for Klebsiella liver abscess syndrome is increasing globally. CASE PRESENTATION: A 73-year-old Japanese woman was admitted to the institution complaining of aggravated dysarthria and weakness in the right upper extremities with onset 5 days earlier. Magnetic resonance imaging revealed a brain abscess in the left basal ganglia, and abdominal computed tomography revealed a liver abscess in liver segment 7. The patient's dysarthria symptoms became increasingly worse over the next few days, so surgical drainage via frontotemporal craniotomy was performed on admission day 3, and subsequent culture from the brain abscess showed growth of Klebsiella pneumoniae. On admission day 9, percutaneous transhepatic drainage of the liver segment 7 abscess was undertaken. The pus culture also showed growth of Klebsiella pneumoniae, thus associating the liver abscess with the brain abscess. Following long-term conservative treatment with antibiotics and abscess drainage, the liver abscess disappeared. However, the patient continuously presented with right upper quadrant pain, and abdominal computed tomography showed swelling of the gallbladder. Consequently, percutaneous transhepatic gallbladder drainage was initially administered, and the bile culture was also positive for Klebsiella pneumoniae. For radical treatment, a laparoscopic cholecystectomy was performed on admission day 99. The postoperative period was complicated by an intraabdominal abscess; however, conservative therapy was successful. She was subsequently discharged, and 12-month follow-up revealed no further sequelae. CONCLUSIONS: We describe a rare case of Klebsiella liver abscess syndrome, which first presented with a central nervous system manifestation. Our patient was successfully treated via an early surgical intervention and subsequent antibiotic therapy. Although surgical drainage remains the cornerstone treatment for brain abscess, when a brain abscess is found, and there is a high index of suspicion for the existence of a liver abscess, Klebsiella liver abscess syndrome should be considered as a possible diagnosis.

Radiological and clinical features of twig-like middle cerebral artery in comparison with moyamoya angiopathy: a multicenter retrospective study.

OBJECTIVE: Twig-like middle cerebral artery (T-MCA) is a rare congenital anomaly that is difficult to distinguish from moyamoya angiopathy (MMA), given the similarity of the angioarchitectures. The aim of this study was to gain insights into the radiological and clinical features of T-MCA and to distinguish this condition from MMA. METHODS: A multicenter retrospective study was conducted in 29 patients with T-MCA and 57 patients with MMA. Demographic, radiological, and clinical data were compared between the patients with T-MCA and those with MMA. RESULTS: The T-MCA group tended to be older than the MMA group (mean age 47 ± 18 vs 39 ± 22 years). Twenty patients with T-MCA (69%) were initially diagnosed with MMA. All T-MCA cases had twig-like networks and steno-occlusive changes involving the MCA. The T-MCA group had a higher incidence of intracranial aneurysms (35% vs 11%) and coexisting arterial anomalies (48% vs 12%). T-MCA and MMA cases had significant differences in involvement of the internal carotid artery terminus (0% vs 100%) and posterior cerebral artery (0% vs 23%), and in transdural anastomosis (0% vs 51%). T-MCA cases were less likely to present with stroke (59% vs 86%) and more likely to be asymptomatic (28% vs 12%). Of the patients with stroke, those with T-MCA had more hemorrhagic strokes (41% vs 29%) and fewer ischemic strokes (59% vs 71%) compared to those with MMA. CONCLUSIONS: This study suggests that T-MCA is a different disease entity from MMA based on significant differences in the radiological and clinical features. Neurosurgeons should recognize this anomaly and understand the key features that differentiate T-MCA from MMA.

A Case of Aneurysmal Subarachnoid Hemorrhage with Middle Cerebral Artery Aplasia at 30 Weeks of Pregnancy.

Objective: We report a case of subarachnoid hemorrhage (SAH) that occurred at 30 weeks of pregnancy and was treated by coil embolization in a woman with middle cerebral artery (MCA) aplasia. Case Presentation: A 40-year-old woman who was 30 weeks pregnant presented to the emergency department with a half-day history of headache and nausea. She had sudden onset headache and her symptom did not improve. There was no neurological deficit. Head CT at the referring hospital revealed SAH. The fetal state was stable. There was no sign of threatened premature delivery. Head MRA revealed aplasia of the left MCA and aneurysm with a daughter sac at the A1 segment of the anterior cerebral artery (ACA). Head DSA revealed that the A1 aneurysm with a daughter sac arose from the anomalous collateral artery leading to a plexiform network. The diagnosis was SAH due to rupture of an A1 aneurysm. Performance of less invasive coil embolization seemed to be possible and was carried out under general anesthesia. The operation was completed after placing one coil and confirming that most of the aneurysmal dome was embolized, including the daughter sac. There was no cerebral vasospasm and no obvious neurological deficit. Antiplatelet drugs were only required for 10 days after the operation. Pregnancy was stable and the patient delivered a baby by cesarean section at 38 weeks of pregnancy. Conclusion: A rare case of aneurysmal SAH in a pregnant woman with MCA aplasia was successfully treated by endovascular surgery.

Acute Tetraparesis with Respiratory Failure after Steroid Administration in a Patient with a Dural Arteriovenous Fistula at the Craniocervical Junction.

A 63-year-old man developed vomiting, paraparesis, dysuria, bulbar palsy, and orthostatic hypotension over a period of 5 months. Neuroradiological examinations showed a swollen lower brainstem with a dural arteriovenous fistula at the craniocervical junction (DAVF-CCJ). A steroid was administered intravenously in the hospital to relieve brainstem edema. A few hours later, however, the patient developed acute tetraparesis with respiratory failure. Recently, there have been several reports describing the acute worsening of paraparesis in patients with a spinal dural arteriovenous fistula after steroid treatment. In addition to these reports, the present case suggests the risk of administering steroids to patients with DAVF-CCJ, especially those with brainstem dysfunction.

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.

Ternary inclusion complex formation and stabilization of limaprost, a prostaglandin E1 derivative, in the presence of α- and ß-cyclodextrins in the solid state.

Limaprost/α-cyclodextrin (CD)/ß-CD ternary inclusion complex was prepared by freeze-drying a solution containing all three components. Under humid conditions, limaprost was more stable in the ternary α-/ß-CD inclusion complex than in the binary α- or ß-CD complex. Specifically, during storage at 30°C/75% relative humidity (R.H.) for 4 weeks, about 19% of limaprost degraded into 17S,20-dimethyl-trans-Δ(2)-prostaglandin A1 (referred as 11-deoxy-Δ(10)) in the ß-CD complex, 8.1% degraded in the α-CD complex, and only 2.2% degraded in the α-/ß-CD complex. The mechanism of limaprost stabilization in the presence of both CDs was investigated by Raman and solid-state NMR spectroscopy and powder X-ray diffractometry. The fast degradation of limaprost to 11-deoxy-Δ(10) in the ß-CD complex was due to the rapid crystallization of ß-CD from the complex, liberating the free amorphous drug, which is susceptible to degradation. The dissociation and crystallization of ß-CD from the inclusion complex were suppressed by freeze-drying limaprost in the presence of both α- and ß-CDs. In addition, the interaction between limaprost and the two CDs was reinforced by inclusion of different moieties of limaprost: α-CD predominantly included the alkyl ω-chain, whereas ß-CD included the five-membered ring. Thus, a stable ternary inclusion complex was formed that included limaprost, maintaining the amorphous state of the complex and dramatically stabilizing the drug under humid conditions.

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.

Ruptured Pseudoaneurysm after Gamma Knife Surgery for Vestibular Schwannoma.

Ruptured aneurysms of anterior inferior cerebellar artery (AICA) after radiotherapy for vestibular schwannoma (VS) are rare, and no definite treatment has been established for distal AICA pseudoaneurysms. We describe a 61-year-old man who underwent Gamma Knife surgery (GKS) for left VS. Follow-up magnetic resonance imaging (MRI) revealed partial regression of the tumor. Twelve years after GKS, he suffered from subarachnoid hemorrhage. Initial angiogram showed no vascular lesions; second left vertebral angiogram, 10 days after admission, demonstrated a pseudoaneurysm in the lateral pontine segment of the left AICA. The proximal portion of the AICA was occluded by a coil. Postoperative MRI revealed an infarction on the left side of the pons and brachium pontis. Although the patient suffered from mild postoperative cerebellar ataxia and facial and abducens nerve palsy, he was discharged 1 month postoperatively requiring no assistance with activities of daily living. Twelve months later, he recovered satisfactorily with a modified Rankin Scale grade of 1, and no recanalization of the aneurysm was found on MR angiography. Endovascular parent artery occlusion for ruptured aneurysms at distal AICA carries the risk of brain stem infarction, but should be considered when no other option is available such as after radiotherapy for VS.

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.

Formation of the ternary inclusion complex of limaprost with α- and ß-cyclodextrins in aqueous solution.

The inclusion mode of Limaprost in the presence of α- and ß-cyclodextrins (CDs) was investigated to gain insight into the stabilization mechanism of Limaprost-alfadex upon the addition of ß-CD in the solid state. The inclusion sites of α- and ß-CDs were studied by NMR spectroscopic and kinetic methods. With the addition of α- and ß-CDs, displacements in (13)C chemical shifts of prostaglandin F2α (PGF2α) were observed in the ω-chain and the five-membered ring, respectively, of the drug. Similar shift changes were observed with the addition of both α- and ß-CDs. In two-dimensional (2D) (1)H-NMR spectra, intermolecular correlation peaks were observed between protons of PGF2α and protons of both α- and ß-CDs, suggesting that PGF2α interacts with α- and ß-CDs to form a ternary complex by including the ω-chain with the former CD and the five-membered ring with the latter. In kinetic studies in aqueous solution, Limaprost was degraded to 17S,20-dimethyl-trans-Δ(2)-PGA1 (11-deoxy-Δ(10)) and 17S,20-dimethyl-trans-Δ(2)-8-iso-PGE1 (8-iso). The addition of α-CD promoted the dehydration to 11-deoxy-Δ(10), while ß-CD promoted the isomerization to 8-iso, under these conditions. In the presence of both α- and ß-CDs, dehydration and isomerization were also accelerated, supporting the formation of the ternary Limaprost/α-CD/ß-CD complex.

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.

Stabilizing effect of ß-cyclodextrin on Limaprost, a PGE1 derivative, in Limaprost alfadex tablets (Opalmon) in highly humid conditions.

Stabilization against humidity of Limaprost (a prostaglandin E1 derivative), which is currently marketed as Opalmon, was undertaken using ß-cyclodextrin (ß-CD). Aqueous solutions of Limaprost alfadex/dextran 40 were lyophilized with and without ß-CD. Limaprost alfadex lyophilized with ß-CD was more chemically stable in humid conditions than that without ß-CD. Moreover, the addition of ß-CD as an excipient to tablets of these lyophilized composites remarkably improved the stability of Limaprost, and Limaprost in this moisture-resistant formulation was chemically stable for 19 weeks at 30°C, 75% relative humidity (R.H.). Chemical analysis of Limaprost and its degradation products indicated that degradation proceeded in the inclusion form (i.e., within the CD cavity). Solid (2)H-NMR spectroscopic studies showed that ß-CD constrained the molecular mobility of water in the solid state. These results suggested that the stabilization of Limaprost by ß-CD was at least partly due to the restricted molecular mobility of water, which acted as a catalytic species for the degradation, and also to the protection of the five-membered ring of Limaprost from water catalytic dehydration through inclusion complex formation with ß-CD.

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.

Osteoprotegerin expression in bone marrow by treatment with tocilizumab in rheumatoid arthritis.

The aim of this study was to investigate histological changes of bone marrow in response to tocilizumab for rheumatoid arthritis (RA). After tocilizumab therapy, bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty (TKA). Control samples were obtained from ten RA patients who underwent MTX mono-therapy. Histological examination of structural differences between the tocilizumab and control groups in bone marrow was performed using hematoxylin and eosin (H&E) to evaluate differences. In immunohistochemical examination, the expression of seven molecules including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), CD68, osteoprotegerin (OPG), receptor activator of nuclear kappa B ligand (RANKL), CD4 and osteopontin (OPN) were compared between two groups. NTx was significantly low at 44.5 ± 2 nM BCE/mM Cr compared with control at 73.2 ± 8 nM BCE/mM Cr. Immunohistochemical examination revealed that the bone marrow tissues of the RA patients who underwent tocilizumab therapy demonstrated significant positive OPG as compared with the control. However, immunohistochemical examinations after tocilizumab revealed that TNF-α, IL-6, CD68, CD4, OPN and RANKL were not significantly different with control of MTX in bone marrow. Therefore, treatment with tocilizumab increased the expression of OPG as the histological changes with respect to inhibit RANKL-related bone resorption of bone marrow in RA.

[Munchausen syndrome, a factitious injury, presenting brain abscess and intraventricular hemorrhage: a case report].

Munchausen syndrome is a factitious disorder. Patients sometimes inflict injury on themselves in order to assume a sick role. The authors report a patient with Munchausen syndrome suffered from brain abscess, reopened wound and intraventricular hemorrhage. A 64-year-old male was admitted to our hospital after head injury. CT and MR imaging revealed a mass with surrounding edema in the right frontal lobe. The mass was surgically removed, and diagnosed as brain abscess. During the surgery, the authors noticed a small bone defect in the frontal bone above the brain abscess; therefore, we considered that head injury just concerned this lesion. There were no particular clues leading to other possible pathologies. After the first surgery, the patient presented atypical seizures several times. Once we discharged him from our hospital, we hospitalized him again because the wound had reopened. A subsequent operation was needed, and we removed the bone flap which we considered the origin of the infection. After the second surgery, he stabbed a nail into his head where the bone had been removed due to the previous surgery, and presented intraventricular hemorrhage. The hemorrhage decreased in size through non-surgical treatment and he was referred to the psychiatry department under a diagnosis of Munchausen syndrome. Diagnosis of this entity is difficult and often made at the later stage of hospitalization, because patients present a variety of complaints and clinical symptoms, which are hardly proved factitious. Early consideration of this syndrome will offer an early and accurate diagnosis, and is mandatory for a good prognosis.