Correlation between synovitis detected on enhanced-magnetic resonance imaging and a histological analysis with a patient-oriented outcome measure for Japanese patients with end-stage knee osteoarthritis receiving joint replacement surgery

Osteoarthritis (OA) is a disease that primarily results in the degeneration and destruction of the articular cartilage. However, synovitis that occurs secondarily by this primary phenomenon is crucial for both the structural and symptomatic progression of the disease. The Japanese Knee Osteoarthritis Measure (JKOM) was created as an outcome measure for Japanese patients with knee OA. This study was conducted to determine whether synovitis in knee OA correlates with the current disability of patients with knee OA who required total knee arthroplasty (TKA). Thirty-four Japanese patients with end-stage knee OA who required TKA were included in this study. The visual analog scale (VAS, 0–100) for pain and the JKOM score, as well as the Western Ontario and McMaster Universities Arthritis Index (WOMAC), were examined before the operation. Synovial samples were taken at the time of the operation. A histological analysis and gadolinium-enhanced magnetic resonance imaging (Gd-MRI) were conducted to evaluate synovitis. Correlations between the synovitis score evaluated by histological analysis and Gd-MRI with either the pain VAS score or the JKOM score were examined using Spearman’s rank correlation coefficient. Neither the synovitis scores evaluated by the histological analysis nor those by a Gd-MRI correlated with the pain VAS score (n?=?34, r?=?0.25, p?=?0.18 and r?=?0.08, p?=?0.75, respectively) and WOMAC (n?=?14, r?=?0.35, p?=?0.22 and r?=?0.45, p?=?0.16, respectively) of the patients. However, they significantly correlated with the JKOM score of the patients (n?=?34, r?=?0.55, p?=?0.001 and r?=?0.71, p?=?0.001, respectively). The severity of synovitis in OA was closely correlated with the current functional impairment and disability of the patients receiving TKA with end-stage knee OA.     

Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.     

Neural cell adhesion molecule is a cardioprotective factor up-regulated by metabolic stress

Screening for cell surface proteins up-regulated under stress conditions may lead to the identification of new therapeutic targets. To search for genes whose expression was enhanced by treatment with oligomycin, a mitochondrial-F₀F₁ ATP synthase inhibitor, signal sequence trapping was performed in H9C2 rat cardiac myoblasts. One of the genes identified was that for neural cell adhesion molecule (NCAM, CD56), a major regulator of development, cell survival, migration, and neurite outgrowth in the nervous system. Immunohistochemical analyses in a mouse myocardial infarction model revealed that NCAM was strongly expressed in residual cardiac myocytes in the infarcted region. Increased expression of NCAM was also found during the remodeling period in a rat model of hypertension-induced heart failure. Lentivirus-mediated knockdown of NCAM decreased the cell growth and survival following oligomycin treatment in H9C2 cells. In primary rat neonatal cardiac myocytes, NCAM was also found to be up-regulated and played a protective role following oligomycin treatment. Analyses of downstream signaling revealed that knockdown of NCAM significantly decreased the basal AKT phosphorylation level. In contrast, NCAM mimetic peptide P2d activated AKT and significantly reduced oligomycin-induced cardiomyocyte death, which was abolished by treatment with the PI3K inhibitor LY-294002 as well as overexpression of the dominant-negative AKT mutant. These findings demonstrate that NCAM is a cardioprotective factor up-regulated under metabolic stress in cardiomyocytes and augmentation of this signal improved survival.     

Analysis of HLA‐DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA‐DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC

Aims: Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA‐DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1–452‐month observation period. Results: Anti‐gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20–850.1) and anti‐centromere antibodies (OR, 2.36, 95% CI, 1.28–4.35) were significant risk factors for jaundice‐ and nonjaundice‐type progression, respectively. HLA‐DRB1*0405 and *0803 predisposed patients to anti‐gp210 (OR, 1.61, 95% CI, 1.08–2.39) and anti‐centromere (OR, 2.30, 95% CI, 1.41–3.73) antibody production, respectively. HLA‐DRB1*1502 and *0901 patients were predisposed to nonjaundice‐type progression (OR, 1.98, 95% CI, 1.13–3.40 and OR, 1.78, 95% CI, 1.02–3.03), while HLA‐DRB1*0803 and *0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48–3.41 and OR, 1.53, 95% CI, 1.11–2.11, respectively). Stratifying patients by HLA‐DRB1 alleles revealed that anti‐gp210 antibodies was a strong risk factor, regardless of the HLA‐DRB1 alleles for jaundice‐type progression, while anti‐centromere antibodies was a significant risk factor for nonjaundice‐type progression in patients with HLA‐DRB1*0405 (OR, 6.89, 95% CI, 2.18–26.56) and ‐DRB1*0803 (OR, 5.42, 95% CI, 1.47–24.62) but not other HLA‐DRB1 alleles. Conclusions: HLA‐DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.     

Complete resection after imatinib treatment of a gastrointestinal stromal tumor of the ileum with peritoneal metastases: Report of a case

A 70-year-old woman with a pelvic tumor had undergone exploratory laparoscopy at another institution, which revealed many peritoneal nodules. Immunohistochemical staining of a biopsy specimen of the peritoneal nodules was positive for KIT. Thus, a gastrointestinal stromal tumor (GIST) was diagnosed and imatinib treatment was begun. After 16 months of this treatment, the tumor size had decreased from 51 × 55 mm to 22 × 17 mm, and surgery was performed. Laparotomy revealed complete regression of the peritoneal lesions. The primary tumor was seen to arise from the small intestine and to loosely adhere to the rectum. We performed partial resection of the small intestine. Imatinib therapy was restarted 1 month postoperatively, and the patient is doing well after 12 months of follow-up. We report this case to show that there is the possibility of curative salvage surgery after long-term imatinib treatment in some patients with peritoneal metastases of a GIST.     

Effects of Electrode Implantation Angle on Thalamic Stimulation for Treatment of Tremor

Introduction. Chronic thalamic stimulation has been confirmed as an effective treatment for tremor. The optimal target has been commonly accepted to be situated within the ventral thalamus, but a standard trajectory of the deep brain stimulation (DBS) electrode has not yet been established. Materials and Methods. A 53‐year‐old man with an 11‐year history of essential tremor was treated by DBS of the thalamus. In this patient, we had a chance to compare the effects of different trajectory angles of the DBS electrode on tremor. Results. Intraoperative stimulation with the DBS electrode temporarily inserted at a high angle to the horizontal plane of the anterior commissure–posterior commissure (AC–PC) line to cover only the nucleus ventralis intermedius (Vim) was not effective. In contrast, stimulation with the DBS electrode permanently implanted at a low angle, covering a wide area extending from the nucleus ventralis oralis (Vo) to the Vim, reduced the tremor. Conclusion. We report on the case of a patient who showed different effects on tremor depending on the trajectory angle of the DBS electrode to the AC–PC line. The insertion trajectory of the DBS electrode may be an important factor for the treatment of tremor.     

Treatment of colorectal carcinoids: A new paradigm

It is often difficult to evaluate the grade of malignancy and choose an appropriate treatment for colorectal carcinoids in clinical settings. Although tumor size and depth of invasion are evidently not enough to stratify the risk of this rare tumor, the present guidelines or staging systems do not mention other clinicopathological variables. Recent studies, however, have shed light on the impact of lymphovascular invasion on the outcome of colorectal carcinoids. It has been revealed that the presence of lymphovascular invasion was among the strongest risk factors for metastasis along with tumor size and depth of invasion. Furthermore, tumors smaller than 1 cm, within submucosal invasion and without lymphovascular invasion, carry minimal risk for metastasis with 100% 5-year survival in the studies from Japan as well as from the USA. This would suggest that these tumors could be curatively treated by endoscopic resection or transanal local excision. On the other hand, colorectal carcinoids with either lymphovascular invasion or tumor size larger than 1 cm carry the risk for metastasis equivalent to adenocarcinomas. Therefore, it should be emphasized that histological examination of lymphovascular invasion is mandatory in the specimens obtained by endoscopic resection or transanal local excision, as this would provide useful information for determining the need for additional radical surgery with regional lymph node dissection. Although the present guidelines or TNM staging system do not mention the impact of lymphovascular invasion, this would be among the next promising targets in order to establish better guidelines and staging systems, particularly in early-stage colorectal carcinoids.