Ileocolonoscopic findings in patients with ankylosing spondylitis: a single center retrospective study.

BACKGROUND/AIMS: In some Western countries, up to 50% of patients with ankylosing spondylitis (AS) have subclinical gut inflammation. This study was conducted to evaluate the prevalence and severity of gut inflammation and to determine clinical factors associated with colonic inflammation in Korean AS patients who performed ileocolonoscopy without evidence of established inf lammatory bowel diseases before. METHODS: One hundred and eight AS patients who underwent ileocolonoscopy were included in this study. Patients were divided into two groups based on gross ileocolonoscopic findings; patients with inflammatory lesions, and patients without inflammatory lesions. RESULTS: Inf lammatory lesions in ileocolonoscopic findings were found in 40 patients. The Ankylosing Spondylitis Disease Activity Score C-reactive protein was higher in the group with inflammatory lesions and gut lesions were found often in the terminal ileum. The risk of inflammatory lesions was higher for AS patients whose symptoms required ileocolonoscopy than for AS patients who underwent routine ileocolonoscopy screening (odds ratio, 3.96). However, abnormal lesions were detected also in 17.6% of the patients who underwent ileocolonoscopy for routine screening and most of them were erosion and ulcer. Among patients with inflammatory lesions (n = 40), 23 showed subclinical gut inflammation associated with AS and 17 were diagnosed finally as Crohn's disease (n = 12), intestinal tuberculosis (n = 4), and ulcerative colitis (n = 1). CONCLUSIONS: Our findings suggest that ileocolonoscopy might be recommended regularly in AS patients even without gastrointestinal symptoms, especially in the patients with high AS activity.

Safety of tumor necrosis factor inhibitor therapy in patients with a prior malignancy.

AIM: There is insufficient evidence to determine whether tumor necrosis factor inhibitor (TNFi) therapy is safe in patients with a recent history of cancer. The purpose of our study was to explore the influence of TNFi therapy on cancer-related outcomes in patients who had undergone curative cancer treatment. METHODS: The medical records of 814 patients who received TNFi therapy at a single rheumatology clinic, between June 2005 and May 2014 were retrospectively reviewed. Among them, the data from patients having received anticancer treatment before starting TNFi therapy were collected and cancer-related outcomes were evaluated. RESULTS: Twenty patients of 814 had a history of malignancy before initiating TNFi therapy. Over the duration of TNFi exposure (median, 54.0 months; interquartile range [IQR], 23.25-72.0 months), there was no recurrence of the previous cancer. In eight patients with early-stage cancer, TNFi therapy was initiated < 5 years after conclusion of previous anticancer treatments. Notably, over the duration of the ongoing treatment follow-up period (median, 33.5 months; IQR, 13.0-75.75 months), cancer recurrence was also not identified. CONCLUSION: TNFi therapy in patients with a history of an early-stage localized cancer may not be contraindicated, even if TNFi is initiated < 5 years from completion of curative cancer treatment.

Clinical outcomes of hydronephrosis in patients with systemic lupus erythematosus.

AIM: Hydronephrosis is a rare complication of systemic lupus erythematosus (SLE). Bladder and/or gastrointestinal involvement in SLE are associated with development of hydronephrosis, but the management and treatment outcomes of hydronephrosis are largely unknown. Therefore, we investigated the clinical manifestations and factors associated with the treatment response in patients with SLE complicated by hydronephrosis. METHOD: A retrospective analysis was performed of all 634 SLE patients who underwent computed tomography and/or ultrasonography between January 1998 and December 2013. We reviewed the clinical characteristics and treatment outcomes of patients with SLE-associated hydronephrosis. RESULTS: Hydronephrosis was identified in 15 patients with SLE complicated by cystitis and/or enteritis. All patients were treated initially with moderate to high doses of corticosteroids. A follow-up imaging study showed that 11 (73.3%) of 15 patients experienced improvements in hydronephrosis, and urinary obstruction was resolved without urological intervention in the majority of these patients (8/11, 72.7%). The four patients who experienced no improvement in hydronephrosis were older than those who responded to treatment (median age [interquartile range]; 43.0 [37.5-53.0] years vs. 28.0 [21.0-38.5] years; P = 0.026). In addition, delayed treatment (≥ 1 month after onset of symptoms) with corticosteroids was more frequently observed in the non-responding patients than in the responding patients (P = 0.011). CONCLUSION: Our findings suggest that treatment with corticosteroids alone leads to favorable outcomes in patients with SLE-associated hydronephrosis, except when treatment is delayed, particularly in elderly patients.

Factors related to outcomes in lupus-related protein-losing enteropathy.

BACKGROUND/AIMS: Protein-losing enteropathy (PLE), characterized by severe hypoalbuminemia and peripheral edema, is a rare manifestation of systemic lupus erythematosus. This present study aimed to identify the distinctive features of lupus-related PLE and evaluate the factors related to the treatment response. METHODS: From March 1998 to March 2014, the clinical data of 14 patients with lupus PLE and seven patients with idiopathic PLE from a tertiary center were reviewed. PLE was defined as a demonstration of protein leakage from the gastrointestinal tract by either technetium 99m-labelled human albumin scanning or fecal α1-antitrypsin clearance. A positive steroid response was defined as a return of serum albumin to ≥ 3.0 g/dL within 4 weeks after initial steroid monotherapy, and remission as maintenance of serum albumin ≥ 3.0 g/dL for at least 3 months. A high serum total cholesterol level was defined as a level of ≥ 240 mg/dL. RESULTS: The mean age of the lupus-related PLE patients was 37.0 years, and the mean follow-up duration was 55.8 months. Significantly higher erythrocyte sedimentation rate and serum total cholesterol levels were found for lupus PLE than for idiopathic PLE. Among the 14 patients with lupus PLE, eight experienced a positive steroid response, and the serum total cholesterol level was significantly higher in the positive steroid response group. A positive steroid response was associated with an initial high serum total cholesterol level and achievement of remission within 6 months. CONCLUSIONS: In lupus-related PLE, a high serum total cholesterol level could be a predictive factor for the initial steroid response, indicating a good response to steroid therapy alone.

Outcome of takayasu arteritis with inactive disease at diagnosis: the extent of vascular involvement as a predictor of activation.

OBJECTIVE: Some patients with Takayasu arteritis (TA) have inactive disease at the time of diagnosis. The objective of our study was to investigate the clinical outcomes and factors that predict disease activation in patients with clinically inactive TA. METHODS: The medical records of patients diagnosed with TA between 1990 and 2012 were reviewed. At the time of diagnosis, patients were identified as having inactive disease according to the National Institutes of Health definition. Patients who went on to develop active disease during followup were classified as the "activation group". The pattern of vascular involvement was classified according to the International Conference on TA, 1994. RESULTS: A total of 59 patients with TA were classified as having inactive disease at the time of diagnosis. During the followup, 13 (22.0%) of these experienced TA activation (median followup, 37.0 mos; activation group). The remaining 46 (78.0%) did not experience disease activation (stable group). Renovascular hypertension was more common in the activation group than in the stable group (5/13, 38.5% vs 4/46, 8.7%, p = 0.019). Further, type V, which is the most extensive, was more common in the activation group (12/13, 92.3%) than in the stable group (18/46, 39.1%, p = 0.008). Multivariate analysis identified type V disease (OR 10.969, 95% CI 1.144-105.182, p = 0.038) as being significantly associated with an increased risk of disease activation. CONCLUSION: Substantial portions of patients with clinically inactive TA at the time of diagnosis experienced disease activation during followup. Type V disease may be an important predictive factor for disease activation in patients with clinically inactive TA.

TNF-α confers resistance to Fas-mediated apoptosis in rheumatoid arthritis through the induction of soluble Fas.

AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis that is characterized by hyperplastic synovial tissue containing activated synovial fibroblasts. Contradictory findings in the apoptosis of fibroblast-like synoviocytes (FLS) have been described elsewhere, showing that RA FLS have an enhanced susceptibility to Fas (also known as CD95)-mediated apoptosis in vitro in contrast to the observed lack of apoptosis in the RA synovium in vivo. However, the potential mechanisms responsible for this discrepancy remain under investigation. The soluble form of Fas (sFas) was found to inhibit Fas-induced apoptosis by binding to Fas ligand (FasL), thereby preventing the interaction between FasL and membrane-bound Fas. MAIN METHODS: We determined the levels of soluble FasL (sFasL) and sFas in patients with RA and the effects of proinflammatory mediators, including TNF-α, on the induction of apoptotic mediators in RA FLS. KEY FINDINGS: The levels of sFasL and sFas were significantly elevated in the synovial fluids of RA patients compared with control subjects. In addition, we found that the sFas is substantially induced in RA FLS by TNF-α, which were abundantly present in the synovial fluid of RA. SIGNIFICANCE: These findings suggest that TNF-α confers resistance to Fas-mediated apoptosis through sFas induction, which could explain the apparent resistance of RA synovial cells to apoptosis in vivo.

A needle penetrating the stomach cavity after acupuncture.

Although acupuncture is known as a safe procedure that is widely used in many countries, complications including infection, hemorrhage, hematoma, pneumothorax, nerve damage, and cardiac tamponade have been reported. A needle penetrating the stomach after acupuncture, however, is very rare. Here, we report the case of 47-year-old woman who experienced abdominal pain 2 days after receiving acupuncture. Upper gastrointestinal endoscopy identified an approximately 2.5-cm long needle in the posterior wall of the antrum. The needle was removed endoscopically using rat tooth forceps with no complications.

[Clinical usefulness of bile cytology obtained from biliary drainage tube for diagnosing cholangiocarcinoma].

BACKGROUND/AIMS: Biliary drainage is performed in many patients with cholangiocarcinoma (CCA) to relieve obstructive jaundice. For those who have undergone biliary drainage, bile cytology can be easily performed since the access is already achieved. This study aims to determine the clinical usefulness of bile cytology for the diagnosis of CCA and to evaluate factors affecting its diagnostic yield. METHODS: A total of 766 consecutive patients with CCA underwent bile cytology via endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage from January 2000 to June 2012. Data were collected by retrospectively reviewing the medical records. We evaluated the diagnostic yield of bile cytology with/without other sampling methods including brush cytology and endobiliary forcep biopsy, and the optimal number of repeated bile sampling. Several factors affecting diagnostic yield were then analyzed. RESULTS: The sensitivity of bile cytology, endobiliary forceps biopsy, and a combination of both sampling methods were 24.7% (189/766), 74.4% (259/348), and 77.9% (271/348), respectively. The cumulative positive rate of bile sampling increased from 40.7% (77/189) at first sampling to 93.1% (176/189) at third sampling. On multivariate analysis, factors associated with positive bile cytology were perihilar tumor location, intraductal growing tumor type, tumor extent ≥ 20 mm, poorly differentiated grade tumor, and three or more samplings. CONCLUSIONS: Although bile cytology itself has a low sensitivity in diagnosing CCA, it has an additive role when combined with endobiliary forceps biopsy. Due to the relative ease and low cost, bile cytology can be considered a reasonable complementary diagnostic tool for diagnosing CCA.

The Interleukin-1α Precursor is Biologically Active and is Likely a Key Alarmin in the IL-1 Family of Cytokines.

Among the 11 members of the IL-1 family cytokines, the precursors of IL-1α, IL-1ß, and IL-33 have relatively long N-terminal pro-sequences of approximately 100 amino acid residues prior to the N-terminus of the mature forms. Compared to the mature forms secreted from the cell, 80-90% of the primary translation product is in the intracellular compartment in the precursor form. However, the precursors are readily released from cells during infections but also with non-infectious conditions such a hypoxia and trauma. In this setting, the precursors act rapidly as "alarmins" in the absence of a processing mechanism to remove the pro-sequence and generate a mature form. In the case of IL-1α, the release of the precursor activates adjacent cells via receptor-mediated signaling. However, there are no data comparing the specific activity of the IL-1α precursor to the mature form. In the present study, we compared the precursor and mature forms of recombinant human IL-1α, IL-1ß, and IL-33 proteins on the induction of cytokines from A549 cells as well as from human peripheral blood mononuclear cells (PBMC). Similar to the mature form, the IL-1α precursor was active in inducing IL-6 and TNFα, whereas the precursor forms of IL-1ß and IL-33 were not active. On PBMC, precursor and mature IL-1α at 0.04 and 0.2 nM were equally active in inducing IL-6. Given the fact that during necrotic cell death, the IL-1α precursor is released intact and triggers IL-1 receptors on tissue macrophages, these data identify the precursor form of IL-1α as a key player in sterile inflammation.