Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan.

Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long-term urate-lowering treatment. Urate-lowering drugs should be used during the inter-critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate-lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia.

Combination of photothermal and photodynamic inactivation of cancer cells through surface plasmon resonance of a gold nanoring.

We demonstrate effective inactivation of oral cancer cells SAS through a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) effects based on localized surface plasmon resonance (LSPR) around 1064 nm in wavelength of a Au nanoring (NRI) under femtosecond (fs) laser illumination. The PTT effect is caused by the LSPR-enhanced absorption of the Au NRI. The PDT effect is generated by linking the Au NRI with the photosensitizer of sulfonated aluminum phthalocyanines (AlPcS) for producing singlet oxygen through the LSPR-enhanced two-photon absorption (TPA) excitation of AlPcS. The laser threshold intensity for cancer cell inactivation with the applied Au NRI linked with AlPcS is significantly lower when compared to that with the Au NRI not linked with AlPcS. The comparison of inactivation threshold intensity between the cases of fs and continuous laser illuminations at the same wavelength and with the same average power confirms the crucial factor of TPA under fs laser illumination for producing the PDT effect.

Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.

OBJECTIVE: To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. DESIGN: National prospective cohort study. SETTING: 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. PARTICIPANTS: 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). CONCLUSIONS: Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Cancer cell uptake behavior of Au nanoring and its localized surface plasmon resonance induced cell inactivation.

Au nanorings (NRIs), which have the localized surface plasmon resonance (LSPR) wavelength around 1058 nm, either with or without linked antibodies, are applied to SAS oral cancer cells for cell inactivation through the LSPR-induced photothermal effect when they are illuminated by a laser of 1065 nm in wavelength. Different incubation times of cells with Au NRIs are considered for observing the variations of cell uptake efficiency of Au NRI and the threshold laser intensity for cell inactivation. In each case of incubation time, the cell sample is washed for evaluating the total Au NRI number per cell adsorbed and internalized by the cells based on inductively coupled plasma mass spectrometry measurement. Also, the Au NRIs remaining on cell membrane are etched with KI/I2 solution to evaluate the internalized Au NRI number per cell. The threshold laser intensities for cell inactivation before washout, after washout, and after KI/I2 etching are calibrated from the circular area sizes of inactivated cells around the illuminated laser spot center with various laser power levels. By using Au NRIs with antibodies, the internalized Au NRI number per cell increases monotonically with incubation time up to 24 h. However, the number of Au NRI remaining on cell membrane reaches a maximum at 12 h in incubation time. The cell uptake behavior of an Au NRI without antibodies is similar to that with antibodies except that the uptake NRI number is significantly smaller and the incubation time for the maximum NRI number remaining on cell membrane is delayed to 20 h. By comparing the threshold laser intensities before and after KI/I2 etching, it is found that the Au NRIs remaining on cell membrane cause more effective cancer cell inactivation, when compared with the internalized Au NRIs.

Juvenile gout in Taiwan associated with family history and overweight.

OBJECTIVE: To examine the clinical features of juvenile gout and its possible association with familial juvenile hyperuricemic nephropathy (FJHN). METHODS: A total of 543 cases of juvenile gout from the Ho-Ping Gout Database were enrolled, and 5269 gouty cases with onset age of 40 to 50 years were selected as a control group. Clinical and laboratory data were compared between the 2 groups. RESULTS: In patients with juvenile gout, body mass index, serum urate concentration, 24-hour urinary uric acid excretion, and creatinine clearance were significantly higher than those in the control group (p < 0.0001), while fractional excretion of uric acid was significantly lower. Only 15% of the juvenile gout cases fulfilled the features of FJHN. The percentage of familial aggregation in juvenile gout was about 1.9-fold higher than that in the control group (44.3% vs 23.8%; p < 0.0001). CONCLUSION: Juvenile gout in Taiwan is associated with overweight and hereditary background, while FJHN may not be primarily responsible.

Manifestations of metabolic syndrome associated with male gout in different age strata.

We examined the components of metabolic syndrome associated with gout in different age strata by a large-scale case-controlled study. Totally, 12,179 gouty subjects were divided into three groups according to their ages at first visit: young- (19-44 years), middle- (45-64 years), and old-aged (>or=65 years) groups. Their clinical and laboratory data, as well as the risk of gout by the metabolic syndrome, were analyzed in three age groups and compared with a control population. The numbers of the cases in the young-, middle-, and old-aged groups in the gout population were 4,698, 4,847, and 2,634, respectively. The serum urate level and the percentage of positive family history of gout were the highest in young-aged group and declined with increasing age. When compared with the data of the control population, the incidence of overweight (body mass index, >or=24.2 kg/m(2)) and hypertriglyceridemia (triglyceride, >or=2.26 mmol/l) were significantly higher in the gout population for all age groups. The incidence of type 2 diabetes was significantly higher in the gout as well for all age groups, and the odds ratio was highest in the young-aged group [odds ratio (95% confidence interval), 5.55 (3.05-10.09)]. In all, except for the old-aged groups, the incidence of hypercholesterolemia was significantly higher in the gout than in the control population, whereas the incidence of hypertension was significantly higher in the gout than in the control population only in the old-aged group. Various clinical and laboratory data were suggested to be the risks of gout in different degrees between age strata.

Severity of gouty arthritis is associated with Q-wave myocardial infarction: a large-scale, cross-sectional study.

To examine whether serum urate level and other aspects of gouty arthritis are independently associated with Q-wave myocardial infarction (QWMI) in gouty population, we performed a cross-sectional study. A total of 22,572 gouty cases were enrolled. QWMI was defined as a positive finding by resting electrocardiographic criteria excluding the conditions producing pseudoinfarction. The variables of gout were tested univariately and multivariately, controlling for the covariates by logistic regression analysis. The above analysis was then repeated in subgroups of young-aged (<50 years), old-aged (> or = 50 years), male, and female patients. Increased serum urate level was significantly associated with QWMI in all subjects and male subgroup [odds ratio (OR), 1.120; 95% confidence interval (CI), 1.020-1.229; OR, 1.106; 95% CI, 1.001-1.223, respectively, for each mg/dl increment]. After controlling for serum urate level and the covariates, increased affected joint count was also independently associated with QWMI finding in all subjects, male and old-aged subgroups (OR, 1.098; 95% CI, 1.014-1.189; OR, 1.094; 95% CI, 1.005-1.192; OR, 1.095; 95% CI, 1.001-1.199, respectively). Tophi formation was independently associated with QWMI in young-aged subgroup (OR, 2.494; 95% CI, 1.159-5.366). None of the variables of gout including hyperuricemia was significantly associated with QWMI in female subgroup after controlling for covariates. This study first demonstrates that gout is associated with QWMI by both the severity of gouty arthritis and serum urate level, while the association of urate to QWMI could be different between age strata and genders.