Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis

OBJECTIVE: The use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practiced despite lack of proven benefit. We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares. METHODS: Patients starting allopurinol for crystal-proven chronic gouty arthritis were randomized to receive colchicine 0.6 mg po bid or placebo in a randomized, prospective, double blind, placebo controlled trial. Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl. Treatment arms were analyzed regarding frequency of flares, likelihood of any flare or multiple flares, severity of flares on the visual analog scale (VAS), and length of flares in days. RESULTS: Forty-three subjects were studied. Subjects treated with colchicine experienced fewer total flares (0.52 vs 2.91, p = 0.008), fewer flares from 0 to 3 months (0.57 vs 1.91, p = 0.022), fewer flares 3-6 months (0 vs 1.05, p = 0.033), less severe flares as reported on VAS (3.64 vs 5.08, p = 0.018), and fewer recurrent gout flares (p = 0.001). Colchicine was well tolerated. CONCLUSION: Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares, and reduces the likelihood of recurrent flares. Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data.     

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout

OBJECTIVE: Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl). METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28. RESULTS: Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups. CONCLUSION: Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.     

Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase: A twenty‐eight–day,multicenter, phase II,randomized, double‐blind,placebo‐controlled,dose‐response clinical trial examining safety and efficacy in patients with gout

Objective

Gout affects ∼1–2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (≥8.0 mg/dl).

Methods

We conducted a phase II, randomized, double‐blind, placebo‐controlled trial in 153 patients (ages 23–80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28.

Results

Greater proportions of febuxostat‐treated patients than placebo‐treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40‐mg, 44% in the 80‐mg, and 59% in the 120‐mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40‐mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8–13%). Incidences of treatment‐related adverse events were similar in the febuxostat and placebo groups.

Conclusion

Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.

     

Temporal evolution of urate crystal deposition over articular cartilage after successful urate-lowering therapy in patients with gout: An ultrasonographic perspective

Objective: To detect evolution of ultrasonographic signs of deposition of monosodium urate crystals (MSUC) in gouty joints by serial ultrasonography after initiation of urate-lowering therapy (ULT).

Methods: Adult gout patients were examined by serial ultrasonography after initiation of ULT with target serum uric acid (SUA) Results: Thirty-eight male patients with gout with mean age of 50?±?11?years, median disease duration of 48 months and baseline mean SUA level of 8.8?±?1.5?mg/dL were recruited. Ultrasonographic evidence of MSUC deposition was detected in 89.74% of first metatarsophalangeal (MTP) joints and 27.63% of knee joints. Double contour sign (DCS), tophi, and hyperechoic spots (HES) were detected in 77.63%, 43.42%, and 19.74% of first MTPs, respectively. SUA level normalizes and plateaus after fourth month of follow-up. DCS thickness reduced significantly throughout the follow-up period. Overall, 86.25% DCS and 100% HES disappeared with median time of 6 months and 5.7 months, respectively. SUA normalization was the only significant predictor of DCS disappearance.

Conclusions: Serial ultrasonographic determination of DCS, tophi, or HES during hypouricemic therapy is a noninvasive, effective method to detect the lowering of burden of urate load in gouty joints.     

Effects of febuxostat on serum urate level in Japanese hyperuricemia patients

Abstract

Objective. We assessed the efficacy and adverse effects of febuxostat in male hyperuricemia patients. Subjects and methods. This was a 12-week, multicenter, open-label, uncontrolled study. The enrolled subjects were 89 hyperuricemic male patients (12 overexcretors, 56 normal excretors, and 21 underexcretors). The endpoint was percent change in serum urate level. Results. The concentration of urate in serum before and 12 weeks after beginning administration of febuxostat in the overexcretors was 9.34 ± 1.48 and 5.59 ± 1.17 mg/dl, respectively, while those were 8.59 ± 1.24 and 5.41 ± 1.35 mg/dl, respectively, in the normal excretors, and 8.29 ± 1.01and 5.11 ± 1.71 mg/dl, respectively, in the underexcretors. After 12 weeks, the rate of change in serum urate after beginning administration of febuxostat was ? 0.384 ± 0.186 in the overexcretors, ? 0.368 ± 0.128 in the normal excretors, and ? 0.365 ± 0.217 in the underexcretors, with no significant differences among them. A common adverse event related to febuxostat was gout flare. Conclusion. Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.     

Lanreotide in the management of small bowel angioectasias: seven-year data from a tertiary centre

Background and aims: Haemorrhage from small bowel angioectasias (SBAs) can be debilitating to patients who are very often elderly and have multiple comorbidities. Our aim was to assess the use of lanreotide in addition to endotherapy in patients with SBAs.

Method: Patients with SBAs on capsule endoscopy (CE) who received lanreotide injections from January 2010 to till the present day at the Royal Hallamshire Hospital in Sheffield were included. Baseline demographics were recorded. Efficacy was evaluated in terms of improvement in mean haemoglobin, transfusion requirements and bleeding episodes.

Results: Twelve patients (67% males, mean age 74 SD?±?15.5 years) were included. All patients had multiple comorbidities. Lanreotide was given at a dosage of 60?mg (42%), 90?mg (33%) or 120?mg (25%). It was given at a four-week interval in 75% of patients and at a six-week interval in 17% of patients. One patient (8%) received a single dose. The mean duration of treatment was 19 months SD?±?14.5. Only 17% of patients had their lanreotide stopped due to cholelithiasis.

There was a significant improvement in mean haemoglobin: 86.8 versus 98.0 (131–166?g/L, p?=?.012). The mean number of bleeding episodes (4.18 versus 1.09, p?=?.010) and packed red cells (323 versus 152, p?=?.006) received improved. Patients required less DBEs?±?APCs after starting lanreotide (19 versus 11 p?=?.048).

Conclusion: Lanreotide is a useful adjuvant treatment to therapeutic enteroscopy in patients with refractory obscure gastrointestinal bleeding due to SBAs. It improves haemoglobin levels, reduces transfusion requirements, bleeding episodes and number of DBEs. Overall, it has a good safety profile.     

Children with untreated coeliac disease have sub-clinical cardiac dysfunction: a longitudinal observational analysis

Introduction: We assessed cardiac function (CF) in celiac disease (CD) patients and the effect of gluten-free diet (GFD) on CF.

Methods: Prospective evaluation of CF using conventional and tissue doppler echocardiography in 50 CD patients (age 4.2?±?1.1 years) at diagnosis and after a year of GFD (group 1), 100 CD children (group 2; 47 compliant and 53 non-compliant) in follow-up and 25 healthy controls.

Results: Untreated CD (n?=?50) children had larger left ventricle end diastolic dimension (35.33?±?0.87 vs. 32.90?±?0.91 mm; p?=?.04), reduced (<55%) left ventricular ejection fraction (20% vs. 0%; p?=?.01) and a higher (>0.6) myocardial performance index (MPI, 66% vs. 0%; p ≤ .01) as compared to controls. Re-evaluation after one year with good dietary compliance showed changes in isovolumic relaxation time (72.5?±?4.2 vs. 50.62?±?2.69; p?=?.0001) and deceleration time (121.05?±?10.1 vs. 99.87?±?8.5; p?=?.02), reflecting improved cardiac diastolic function. GFD compliant patients had lower MPI than non-compliant (0.60?±?.03 vs. 0.66?±?.08; p?=?.04), reflecting improvement in load-independent echocardiographic parameters.

Conclusions: Subclinical cardiac dysfunction is common in CD children at diagnosis. Improvement

in echocardiographic parameters occurs with GFD and non-compliant children continue to have

persistent cardiac dysfunction.     

Smoking is associated with severity of liver fibrosis but not with histological severity in nonalcoholic fatty liver disease. Results from a cross-sectional study

Objectives: To assess the influence of smoking on histological disease severity and fibrosis in real-world NAFLD patients.

Material and methods: Consecutive NAFLD patients were identified with liver biopsies performed between 2008 and 2015. Characteristics such as smoking status and total number of pack years were collected. Biopsies were revised and BRUNT fibrosis and NAFLD activity score (NAS) determined. Patients with a high NAS (≥5) were compared to patients with a low NAS (<5) and with advanced fibrosis (stage 3–4) to patients with no-early fibrosis (stage 0–2). Patients with a history of smoking (current or past smoker) were defined ever smokers.

Results: Fifty-six patients were included (mean age 49?±?14.3, 68.9% males and 39.3% history of smoking). Ever smokers had a higher fibrosis score than never smokers; two (IQR 0–3) versus one (IQR 1–1.5) (p?=?.040). Patients with advanced fibrosis smoked significantly more pack years than patients with no-early fibrosis; 10.6 (IQR 0–25.8) versus 0 (IQR 0–7) (p?=?.011). There is a weak to moderate correlation between fibrosis stage and number of pack years (Spearman’s Rho?=?0.341, p?=?.012). There was no difference in NAS between never and ever smokers; 2.8?±?1.5 versus 3.3?±?1.4 (p?=?.205). Patients with NAS <5 had a median number of pack years of 0 (IQR 0–9) versus a median of 10.3 pack years (IQR 0–24) in patients with NAS ≥5 (p?=?.127).

Conclusion: Smoking is associated with severity of NAFLD-related liver fibrosis but not with histological disease severity. This supports the recommendation to cease smoking for NAFLD patients.     

Effect of body weight on fixed dose of diclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis

Objective: The aim of this study was to assess the influence of patient body weight on the clinical effect of 100?mg diclofenac administered as a single dose for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP).

Materials and methods: All patients subjected to endoscopic retrograde cholangiopancreatography (ERCP) from 2009 to 2014 were evaluated for inclusion. In total, 772 patients were included of whom 378 (49%) received diclofenac prophylaxis.

Results: In the diclofenac prophylaxis group, body weight was higher in patients with PEP (mean?±?SD: 82?±?18?kg) than in patients without PEP (74?±?18?kg) (p?=?0.029). In patients not receiving prophylaxis, body weight was not associated with the occurrence of PEP (mean?±?SD: 77?±?18 vs 75?±?18?kg, respectively, p?=?0.450). In an adjusted analysis, higher patient body weight was inversely associated with the clinical effect of 100?mg diclofenac for the prophylaxis of PEP.

Conclusions: High patient body weight was associated with a reduced effect of 100?mg diclofenac for prophylaxis of PEP.     

Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28‐week,phase III,randomized, double‐blind,parallel‐group trial

Objective

To compare the urate‐lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.

Methods

Subjects (n = 1,072) with hyperuricemia (serum urate level ≥8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to ≤2.0 mg/dl) renal function were randomized to receive once‐daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.

Results

Significantly (P ≤ 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.

Conclusion

At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.     

A systematic review and meta-analysis on the safety and efficacy of febuxostat versus allopurinol in chronic gout

Objective

To evaluate the safety and efficacy of febuxostat compared to allopurinol for the treatment of chronic gout.

Methods

We did a systematic review and meta-analysis of randomized and non-randomized controlled trials that compared oral febuxostat to oral allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios (RR) were calculated with random effects and were reported with corresponding 95% confidence intervals (CI).

Results

From 1076 potentially relevant citations, 7 studies and 25 associated publications met inclusion criteria; 5 studies were ultimately included in the analysis. Febuxostat did not reduce the risk of gout flares compared with allopurinol (RR = 1.16, 95% CI = 1.03–1.30, I² = 44%). Overall, the risk of any adverse event was lower in febuxostat recipients compared to allopurinol (RR = 0.94, 95% CI = 0.90–0.99, I² = 13%). Patients receiving febuxostat were more likely to achieve a serum uric acid of <6 mg/dl than allopurinol recipients (RR = 1.56, 95% CI = 1.22–2.00, I² = 92%). Subgroup analysis did not indicate any significant difference between high- and low-dose febuxostat on the risk of gout flares.

Conclusion

Although febuxostat was associated with higher likelihood of achieving a target serum uric acid level of <6 mg/dl, there was significant heterogeneity in the pooled results. There was no evidence that febuxostat is superior to allopurinol for clinically relevant outcomes. Given its higher cost, febuxostat should not be routinely used for chronic gout.     

Diffusion-weighted magnetic resonance imaging of parotid glands before and after abatacept therapy in patients with Sjögren’s syndrome associated with rheumatoid arthritis: Utility to evaluate and predict response to treatment

Objective: To compare parotid diffusion-weighted images (DWIs) taken before and after abatacept therapy in patients with Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA) and to examine the utility in evaluation and prediction of response to therapy.

Methods: DWIs of the parotid glands taken at baseline and 52 weeks after initiation of abatacept were analyzed in nine SS patients with RA using relative standard deviation (RSD) of the entire glands and signal intensity ratio (SIR) within the residual parenchyma. The correlation between changes in RSD and SIR and changes in salivary secretion based on Saxon’s test was examined. Furthermore, baseline characteristics were compared in patients with increased and decreased salivary secretion after treatment. The predictive power of the parameter at baseline was examined using receiver operating characteristic (ROC) analysis.

Results: Abatacept improved salivary secretion from 2076?±?1535 at baseline to 2857?±?1431?mg/2?min at 52 weeks (n?=?9, p?=?.05). Increase of salivary secretion was significantly higher in patients with decreased RSD (n?=?6) than increased RSD (n?=?3) (1241?±?713, –137?±?142?mg/2?min, p?=?.02). The increase and decrease in RSD completely accorded with those of salivary secretion. Furthermore, SIR was the only parameter that was significantly different between patients with posttreatment increase and decrease in salivary secretion (p?=?.04). ROC analysis showed the sensitivity and specificity of SIR at baseline of ≥13.0?×?10^?2 for the prediction of the response to abatacept were 75.0% and 83.3%, respectively.

Conclusions: Parotid DWI seems to be useful for evaluating and predicting the response in salivary secretion to abatacept in SS patients with RA.     

Synovial inflammation analyzed by 3-T magnetic resonance imaging in etanercept-treated patients with rheumatoid arthritis indicates persistent disease activity despite of clinical remission: A pilot study

Abstract

Objectives: To evaluate joint inflammation using 3-T MRI in rheumatoid arthritis (RA) patients treated with conventional disease modifying anti-rheumatic drugs (cDMARDs) as compared to inhibitors for tumor necrosis factor α (TNFi) over 12 months.

Methods: Prospective epidemiologic clinical pilot study using the RA MRI system (RAMRIS), the visual analog scale (VAS, 0–100) and the Disease Activity Score 28-joint count (DAS28) at baseline, 4, and 12 months after initiation of etanercept (ETA). Ten patients with inadequate response to two cDMARDs were treated with ETA and compared to 10 patients responding to cDMARDs.

Results: In cDMARD patients, parameters at baseline and 12 months did not change: VAS: 21.0?±?11.3 and 20.2?±?24.6; DAS28: 2.1?±?0.6 and 2.9?±?1.0; and RAMRIS: 11.0?±?2.3 and 11.8?±?2.8, respectively. In contrast, in the ETA-patients the same parameters were as follows at baseline, 4, and 12 months: VAS: 46.3?±?7.9, 23.9?±?7.1, and 24.0?±?6.3 (each p?=?.04); DAS28: 3.8?±?0.4, 2.8?±?0.3 (ns), and 2.5?±?0.3 (p?=?.01); and RAMRIS: 28.9?±?5.0, 25.8?±?4.7 (ns), and 24.6?±?4.5 (ns). Comparing ETA and cDMARD patients, RAMRIS was significantly different.

Conclusion: The data suggest that synovial inflammation and DAS28 remission are separate entities in RA. MRI scoring before starting a treatment may therefore indicate the requirement for TNFi.     

Novel fork-tip needles versus standard needles for EUS-guided tissue acquisition from solid masses of the upper GI tract: a matched cohort study

Background: There are very few available data on the novel SharkCore? needles for EUS-FNB.

Aim: Comparison of the performance of the SharkCore? needles with the standard EUS-FNA needles for the diagnosis of solid upper GI masses.

Patients and methods: Single-center, retrospective cohort study in an academic tertiary referral hospital. Patients were matched 1:1 for the site of the lesion and the presence or absence of rapid on-site evaluation (ROSE).

Results: A total of 102 patients were included. There was no statistically significant difference in the mean number of passes (3.3?±?1.3 versus 3.4?±?1.5; p?=?.89). Similar results were observed at the subgroup with ROSE (4.3?±?1.3 versus 3.7?±?1.5; p?=?.26). More histological specimens were obtained with the SharkCore? needles compared to standard needles (59 versus 5%; p?<?.001). Diagnostic test characteristics were not significantly different (sensitivity: 91.5 versus 85.7; specificity: 100 versus 100%; accuracy: 92.2 versus 85.4% for SharkCore? versus standard needles, p?>?.05 in all cases). At multivariable analysis, there was no statistically significant difference in the mean number of passes in all patients (p?=?.23) and in the ROSE subgroup (p?=?.66). However, the SharkCore? needle obtained significantly more histological material than the standard needle (odds ratio 66; 95% confidence interval: 11.8, 375.8, p?<?.001). There was no significant difference in complication rates (p?=?.5).

Limitations: Retrospective study, single-center.

Conclusion: The SharkCore needles were similar to standard FNA needles in terms of the number of passes to reach diagnosis, but obtained significantly more histological specimen.     

Outcome of Direct Oral Anticoagulant Treatment for Acute Lower Limb Deep Venous Thrombosis After Total Knee Arthroplasty Or Total Hip Arthroplasty

Abstract

Objective: The aim of this study was to examine the treatment outcomes of edoxaban and apixaban on deep venous thrombosis (DVT) in Japanese patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Methods: We examined 100 patients receiving edoxaban or apixaban to treat lower limb DVT. The primary efficacy outcome was defined as the disappearance of DVT at three months post-treatment. The primary safety outcome was the change in hemoglobin (Hb) value after two and seven days of treatment compared with baseline, which was the start of treatment with edoxaban or apixaban.

Results: The primary efficacy outcome occurred in 61 of the 70 patients (87.1%) in the edoxaban group and in 28 of the 30 patients (93.3%) in the apixaban group. There was no significant difference between the edoxaban and apixaban groups in the disappearance of DVT at three months (p?=?.497). The change in Hb value from baseline to two days post-treatment was ?0.53?±?0.98 in the edoxaban group and ?0.06?±?0.75 in the apixaban group (p?=?.010). At seven days post-treatment, the changes in Hb were ?0.03?±?1.60 and 0.30?±?0.68 (p?=?.007) in the edoxaban and apixaban groups, respectively.

Conclusion: Edoxaban and apixaban were equivalent in efficacy. However, apixaban was superior to edoxaban in terms of the change in Hb value. In cases of major bleeding, both edoxaban and apixaban need to be used carefully when treating DVT.     

痛风合并慢性肾脏疾病的药物治疗

慢性肾脏疾病(CKD)正困扰越来越多的痛风患者,是痛风最常见的合并症.然而,目前痛风和CKD的随机对照试验比较有限,并且指南并没有明确的痛风合并CKD患者的用药指导.痛风的治疗主要是控制痛风发作以及降尿酸治疗.非甾体类抗炎药物和秋水仙碱是急性痛风发作的一线治疗药物.然而,对于CKD患者,非甾体类抗炎药物因肾损伤并不被推荐.同样,秋水仙碱的毒性在CKD患者中是加剧的,其剂量应根据肾功能情况酌减.类固醇激素的使用也需要权衡利弊,因此免疫治疗可能成为未来治疗手段的重要方面.别嘌呤醇、非布司他、促尿酸排泄药物及聚乙二醇重组尿酸酶用于控制急性发作后的高尿酸血症.然而,因CKD患者需要限制别嘌呤醇剂量,从而影响了其疗效.聚乙二醇重组尿酸酶有待进一步研究,非布司他未曾在肌酐清除率＜ 30 ml/min的患者中研究.     

Long-term outcomes of the randomized controlled trial comparing 5-aminolaevulinic acid and Photofrin photodynamic therapy for Barrett’s oesophagus related neoplasia

Objective: Photodynamic therapy (PDT) was used as therapy for early neoplasia associated with Barrett’s oesophagus (BE). This is 5-year follow-up of patients enrolled into randomised controlled trial of 5-aminolaevulinic acid (ALA) vs. Photofrin PDT.

Methods: Biopsies were taken from original Barrett’s segment during endoscopic follow up using Seattle protocol. Endoscopic mucosal resection (EMR)?±?radiofrequency ablation (RFA) was preferred therapy in patients who failed PDT and/or had recurrent neoplasia.

Results: Fifty eight of 64 patients enrolled in the original trial were followed up including 31 patients treated with ALA PDT (17 patients with ≤6?cm, 14 patients with >6?cm segment of BE) and 27 treated with Photofrin PDT (14 patients with ≤6?cm, 13 patients with >6?cm BE). Initial success was achieved in 65% (20/31) ALA and 48% (13/27) Photofrin patients (p?=?.289). Thirty five percent patients (7/20) relapsed in ALA group and 54% (7/13) relapsed in Photofrin group (p?=?.472). At a median follow-up of 67 months, no significant difference was found in long-term complete reversal of intestinal metaplasia (CR-IM) and complete reversal of dysplasia (CR-D) between ALA and Photofrin groups (78% vs. 63%; p?=?.18; 90% vs. 76%; p?=?.26). Original length of BE did not alter long-term outcome. Four patients from each group progressed to invasive oesophageal adenocarcinoma. Initial success of ALA PDT was associated with significantly better likelihood of long-term remission (p?=?.03).

Conclusions: Initial response to PDT plays key role in long term outcome. RFA?±?EMR have, however, become preferred minimally invasive ablative therapy for BE-related neoplasia due to poor efficacy of PDT.     

Does the low FODMAP diet improve symptoms of radiation-induced enteropathy? A pilot study

Rationale: Patients with radiation-induced enteropathy (RE) after cancer treatment show similar symptoms as patients with irritable bowel syndrome (IBS). The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (LFD) is a widespread management strategy for IBS. We aimed to investigate if there may be a positive effect of LFD on symptoms and health-related quality of life (HRQOL) in patients with RE.

Methods: In an open non-controlled pilot study, 11 patients (all female) with RE-related IBS symptoms were recruited largely based on own initiative. All followed LFD for four weeks. IBS Severity Scoring System (IBS-SSS) and IBS Symptom Questionnaire (IBS-SQ) were used to assess symptoms. Short Form Nepean Dyspepsia Index (SF-NDI) and 12-item Short Form Health Survey (SF-12) evaluated HRQOL. A three day food record was used to estimate baseline intake of FODMAPs and to reveal dietary changes.

Results: FODMAP intake was successfully reduced, although LFD was found a burdensome intervention. IBS symptoms improved significantly based on mean total score of IBS-SSS and IBS-SQ, which changed from 310.2?±?60.7 to 171.4?±?107.2 (p?=?.001) and 27.4?±?4.1 to 15.7?±?10.1 (p?=?.002). HRQOL improved based on SF-NDI total score (30.5?±?9.4 to 18.3?±?8.2, p?=?.001) and based on mental (p?=?.047) and physical (p?=?.134) score of SF-12. Main additional dietary changes were reduced intake of energy, carbohydrates, and fiber.

Conclusion: Our findings from this small-scaled pilot study indicate that the LFD may alleviate symptoms and improve HRQOL in patients with RE. Further controlled studies with larger sample size should be conducted to verify our results and hopefully enable implementation of LFD as a future part of the management strategy for RE.     

Teprenone for the prevention of low-dose aspirin-induced gastric mucosal injury in Helicobacter pylori-negative patients

Abstract

Objectives: Low-dose aspirin is the standard treatment for the prevention of cardiovascular events in at-risk patients. We performed a randomized, placebo-controlled study to determine the efficacy of teprenone for primary prevention of gastrointestinal injury in patients taking LDA for vascular protection.

Methods: Patients were eligible for enrollment if they required aspirin 100?mg/day. Aspirin- naïve patients without gastroduodenal ulcer and Helicobacter pylori infection were randomized to receive teprenone 150?mg/day or placebo for 12?weeks. Primary outcome was assessed by the incidence rate of gastroduodenal ulcer. Secondary outcomes were assessed by the incidence rate of gastric mucosal injury, the improvement in modified Lanza score (MLS), gastrointestinal symptom rating scale (GSRS) and the change of gastric immunohistochemical expression for COX-1.

Results: Total of 130 patients were randomized, 64 in teprenone group and 66 in placebo group. There was no incidence of ulcer after 12?weeks in both groups. Incidence of gastric mucosal injury was higher in placebo group than in teprenone group (40.0 vs. 13.38%, p?=?.039). Mean change of MLS was higher in placebo group than in teprenone group (0.767?±?0.467 vs. 0.271?±?0.158, p?=?.003). Scores of mucosal edema, hyperemia and hemorrhage and the change of GSRS were not different between the two groups. Change of COX-1 immunoreactive score was higher in placebo group than in teprenone group (2.433?±?1.476 vs. 1.233?±?0.955, p?=?.001). There were no treatment-related adverse events.

Conclusions: Teprenone is effective in preventing gastric mucosal injury in patients taking LDA. Preventive effects of teprenone on LDA-related gastroduodenal ulcers require further investigation.     

Colchicine-responsive protracted gouty arthritis with systemic inflammatory reactions

Abstract

Acute gouty arthritis is a severe but self-limiting arthritis caused by inflammatory responses to urate crystals. Oral colchicines are effective for initial stages or prophylaxis, but generally, colchicines are ineffective for established gouty arthritis. We describe an unusual case of gouty arthritis with systemic inflammatory reactions, including high fever and polymyalgia. Refractory polyarthritis and high fever were eradicated by colchicine treatment. Genetic analysis revealed a heterozygous mutation in exon 2 of the MEFV gene (E148Q). This case underscores the possibility that MEFV gene mutations may modify the phenotype of gouty arthritis.