Long-Term Outcome of Neonatal Seizure with PACS2 Mutation: Case Series and Literature Review.

Phosphofurin Acidic Cluster Sorting Protein 2 (PACS2)-related early infantile developmental and epileptic encephalopathy (EIDEE) is a rare neurodevelopmental disorder. EIDEE is characterized by seizures that begin during the first three months of life and are accompanied by developmental impairment over time. In this article, we present three patients with EIDEE who experienced neonatal-onset seizures that developed into intractable seizures during infancy. Whole exome sequencing revealed a de novo heterozygous missense variant in all three patients in the p.Glu209Lys variant of the PACS2 gene. We conducted a literature review and found 29 cases to characterize the seizure patterns, neuroimaging features, the usage of anticonvulsants, and the clinical neurodevelopmental outcomes of PACS2-related EIDEE. The seizures were characterized by brief, recurring tonic seizures in the upper limbs, sometimes accompanied by autonomic features. Neuroimaging abnormalities were observed in the posterior fossa region, including mega cisterna magna, cerebellar dysplasia, and vermian hypoplasia. The long-term prognosis ranges from low-average intelligence to severe developmental retardation, emphasizing the importance of early recognition and accurate diagnosis by pediatric neurologists to provide personalized patient management.

Prevalence and risk of thyroid diseases in myasthenia gravis.

OBJECTIVES: To estimate the prevalence of thyroid diseases and the cumulative risk of thyroid diseases during a follow-up period after myasthenia gravis (MG) diagnosis compared with non-MG controls. MATERIALS AND METHODS: We used the Taiwan National Health Insurance Database linked to Registry of Catastrophic Illness database to identify patients with MG. The controls were composed of those who did not have MG and were matched with the MG patients by sex, age, and the index date. We recorded thyroid disease histories before and after the index date. RESULTS: Our study included 5813 MG patients and 29 065 controls. The prevalence of thyroid diseases in the MG patients at diagnosis was 18.4%, which was nearly 3.9-fold greater than that in the control group. (Odds ratio [OR] 3.895, 95% Confidence interval [CI] 3.574-4.246) After excluding pre-existing thyroid diseases, the incidence of comorbid thyroid diseases was 8.7% in the MG patients and 4% in the control group. The MG patients had a 2.36-fold increased risk of developing thyroid diseases compared to the control group. (crude hazard ratio [HR] 2.360, 95% CI 2.095-2.659) The cumulative probabilities of developing thyroid diseases at 1, 5, and 10 years after the index date were 21.6%, 24.9%, and 28.7%, respectively, in the MG patients, while the cumulative probabilities were 6.5%, 8.8%, and 11.8%, respectively, in control group (log-rank test <0.0001). CONCLUSIONS: The current population-based study showed a higher prevalence of pre-existing thyroid diseases and a higher cumulative probability of thyroid diseases during follow-up after MG diagnosis than in the general population.

Correlation of anti-acetylcholine receptor antibody levels and long-term outcomes of juvenile myasthenia gravis in Taiwan: a case control study.

BACKGROUND: Myasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis. METHODS: Patients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic. RESULTS: A total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161). CONCLUSIONS: Juvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.

Temporal relationships between systemic lupus erythematosus and comorbidities.

OBJECTIVE: To examine the burden of comorbidities prior to and after the diagnosis of SLE and its impact on mortality. METHODS: We identified 1605 incident cases of SLE and 6284 matched controls from the UK primary care. The risks of comorbidities before (prevalence; odds ratios) and after SLE diagnosis (incidence; hazard ratios) and the impact of comorbidities at diagnosis on all-cause mortality were estimated. RESULTS: At diagnosis, SLE was associated with adjusted odds ratios (95% CI) of 2.25 (1.97-2.56), 3.37 (2.49-4.57) and 3.54 (1.89-6.63) for a Charlson comorbidity index of 1-2, 3-4 and ≥5, respectively. Following diagnosis, SLE also associated with increased risk of developing any comorbidity with an adjusted hazard ratio (95% CI) of 1.30 (95% CI, 1.13-1.49). At diagnosis, SLE was associated with a greater risk of cancer, cardiovascular, renal, liver, rheumatological and neurological diseases as well as depression, anaemia and psoriasis. Risks of developing incident comorbidity in the categories of neoplasm, cardiovascular, genitourinary, metabolic/endocrine, gastrointestinal and hepatic diseases, chronic pulmonary diseases, musculoskeletal/connective tissue and neurological diseases were higher in SLE patients. People with SLE had higher mortality risk compared with controls, with adjusted hazard ratio of 1.91 (95% CI, 1.62-2.26); after further adjusting for comorbidities this reduced to 1.64 (1.37-1.97). Comorbidities at SLE diagnosis accounted for 27.6% of the apparent difference in mortality between SLE patients and matched controls. CONCLUSION: People with SLE have increased risks of multiple comorbidities both prior to and after diagnosis and this contributes significantly to all-cause mortality.

Immunotherapy for anti-NMDA receptor encephalitis: Experience from a single center in Taiwan.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an anti-neuronal antibody-mediated inflammatory brain disease that causes severe psychiatric and neurological deficits in previously healthy patients. The aims of this study were to demonstrate the clinical characteristics of patients diagnosed with anti-NMDA receptor encephalitis and to compare the different treatment strategies among these patients. METHODS: Patients presenting with newly acquired psychiatric and/or neurological deficits were studied retrospectively from 2009 to 2017. Patients with evidence of anti-NMDA receptor antibodies in serum and/or cerebrospinal fluid were enrolled. The modified Rankin scale was used to assess the initial status and outcomes of the enrolled patients. Details of the clinical presentations and results of investigations were analyzed. RESULTS: All (n = 24) of the patients received first-line immunotherapy (steroids, and/or intravenous immunoglobulin, and/or plasma exchange), and 14 patients received second-line immunotherapy (rituximab and/or cyclophosphamide). The mean time between the first- and second-line treatment was 13 days. During the first 6 months, 20 patients (20/24, 83%) achieved a good outcome (modified Rankin Scale score ≤2) and 15 patients (15/24, 62.5%) completely recovered. Four patients (17.7%) relapsed, and three patients (12.5%) had associated tumors. CONCLUSION: Immunotherapy is an effective treatment for anti-NMDA receptor encephalitis. Rituximab and/or cyclophosphamide are treatment options for those who cannot tolerate or do not respond to first-line immunotherapy. Prospective studies are necessary to investigate the role of rituximab and cyclophosphamide in anti-NMDA receptor encephalitis.

Urate-lowering treatment and risk of total joint replacement in patients with gout.

Objectives: To examine whether gout is an independent risk factor for total joint replacement (TJR) and whether urate-lowering treatment (ULT) reduces this risk. Methods: Using the Taiwan National Health Insurance database and the UK Clinical Practice Research Datalink, 74 560 Taiwan patients and 34 505 UK patients with incident gout were identified and age and sex matched to people without gout. Cox proportional hazards models and condition logistic regression were used to examine the risk of TJR in gout patients and the association between cumulative defined daily dose (cDDD) of ULT and TJR. Results: The prevalence rates of TJR in the patients at the time of diagnosis of gout and in people without gout were 1.16% vs 0.82% in Taiwan and 2.61% vs 1.76% in the UK. After a gout diagnosis, the incidence of TJR was higher in the patients with gout compared with those without (3.23 vs 1.91 cases/1000 person-years in Taiwan and 6.87 vs 4.61 cases/1000 person-years in the UK), with adjusted HRs of 1.56 (95% CI 1.45, 1.68) in Taiwan and 1.14 (1.05, 1.22) in the UK. Compared with patients with gout with <28 cDDD ULT, the adjusted ORs for TJR were 0.89 (95% CI 0.77, 1.03) for 28-90 cDDD, 1.03 (0.85, 1.24) for 90-180 cDDD and 1.12 (0.94, 1.34) for >180 cDDD ULT in Taiwan. In the UK, the respective ORs were 1.09 (0.83, 1.42), 0.93 (0.68, 1.27) and 1.08 (0.94, 1.24). Conclusion: This population-based study provides evidence from two nation populations that gout confers significant TJR risk, which was not reduced by current ULT.

Prostate-selective α antagonists increase fracture risk in prostate cancer patients with and without a history of androgen deprivation therapy: a nationwide population-based study.

INTRODUCTIONS: Prostate-selective α antagonists are recommended for relief of lower urinary tract symptoms in prostate cancer patients despite uncertainty of fracture risk as an addition to androgen deprivation therapy (ADT). The purpose of this study is to estimate fracture risk associated with these medications in prostate cancer patients who did and did not receive ADT. METHODS: The Taiwan National Health Insurance database was used to identify prostate cancer patients. We identified all 90-day person-quarters exposed to and not exposed to prostate-selective α antagonists. A generalized estimating equation model was used to estimated adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for fracture associated with prostate-selective α antagonists with consideration for confounding by indication bias using propensity score. RESULTS: During 1997-2008, 16,601 persons received a diagnosis of prostate cancer, among whom 13,694 received ADT. Among prostate cancer patients receiving ADT, fracture was significantly more common in person-quarters with prostate-selective α antagonist use than in quarters without such treatment (OR, 1.08; 95% CI, 1.00-1.18). Prostate-selective α antagonist use was most strongly associated with femur fracture (OR, 1.22; 95% CI, 1.09-1.38), followed by skull fracture (OR, 1.29; 95% CIs: 0.93-1.80). Among patients who did not receive ADT, fracture was more common in person-quarters with prostate-selective α antagonist use than in those without medication use (OR, 1.19; 95% CI, 0.91-1.55). CONCLUSIONS: Prostate-selective α antagonist is associated with an increased fracture risk, particular for fractures in skull and femur. Patients should be well-informed on this potential risk before taking prostate-selective α antagonists.

Schizencephaly in children: A single medical center retrospective study.

BACKGROUND: The aim of this study was to evaluate the clinical, and neuroimaging features, outcomes, and other associated systemic disorders in children with schizencephaly at a single medical center in Taiwan. METHODS: We retrospectively reviewed the medical records and magnetic resonance images (MRI) of children with schizencephaly between January 2000 and December 2014. The MRI findings of schizencephaly were recorded along with the presence of associated cerebral disorders. Clinical, electroencephalographic and additional systemic disorders were also recorded. RESULTS: A total of 21 patients (13 males and 8 females) were included in the study. According to the location of schizencephaly, the patients were classified into two groups: unilateral (n = 16) and bilateral (n = 5). The majority of the patients with neurological deficits were detected before 1 year of age, especially in bilateral clefts. The most common initial presentation was hemiparesis in unilateral schizencephaly, and seizures in bilateral schizencephalies. Ventriculomegaly was the most common associated cerebral disorder, and the most common additional systemic disorders included congenital heart disease, hydronephrosis, and strabismus. Seventeen patients suffered from epileptic seizures with generalized tonic-clonic seizures being the most common. Eight patients developed refractory epilepsy. The majority of the patients had motor deficits, intellectual disabilities, and language deficits, especially in bilateral clefts. CONCLUSIONS: This study demonstrates that the clinical features of schizencephaly vary widely, with their severity closely related to the cleft. Determining the type, size, and extent of schizencephaly is useful to plan management and predict the prognosis.

Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan.

PURPOSE: We aimed to evaluate the validity of cancer diagnosis in the National Health Insurance (NHI) database, which has routinely collected the health information of almost the entire Taiwanese population since 1995, compared with the Taiwan National Cancer Registry (NCR). METHODS: There were 26,542,445 active participants registered in the NHI database between 2001 and 2012. National Cancer Registry and NHI database records were compared for cancer diagnosis; date of cancer diagnosis; and 1, 2, and 5 year survival. In addition, the 10 leading causes of cancer deaths in Taiwan were analyzed. RESULTS: There were 908,986 cancer diagnoses in NCR and NHI database and 782,775 (86.1%) in both, with 53,192 (5.9%) in the NHI database only and 73,019 (8.0%) in the NCR only. The positive predictive value of the NHI database cancer diagnoses was 94% for all cancers; the positive predictive value of the 10 specific cancers ranged from 95% (lung cancer) to 82% (cervical cancer). The date of diagnosis in the NHI database was generally delayed by a median of 15 days (interquartile range 8-18) compared with the NCR. The 1, 2, and 5 year survival rates were 71.21%, 60.85%, and 47.44% using the NHI database and were 71.18%, 60.17%, and 46.09% using NCR data. CONCLUSIONS: Recording of cancer diagnoses and survival estimates based on these diagnosis codes in the NHI database are generally consistent with the NCR. Studies using NHI database data must pay careful attention to eligibility and record linkage; use of both sources is recommended.

Association Between Use of Non-Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation.

Importance: Non-vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective: To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants: Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016. Exposures: NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin. Main Outcomes and Measures: Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. Results: Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P < .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone. Conclusions and Relevance: Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs.

Clinical features and outcomes of invasive pneumococcal disease in a pediatric intensive care unit.

BACKGROUND: Invasive pneumococcal disease (IPD) results in high morbidity and mortality globally each year, although it is a vaccine-preventable disease. This study aimed to characterize the clinical features of IPD in a pediatric intensive care unit (PICU) in Taiwan. The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the private sector in October 2005. The estimated coverage rate of PCV7 vaccination in 2010 was 45.5% among children <5 years of age. METHODS: We conducted a retrospective study at a single center in northern Taiwan for invasive pneumococcal disease in a PICU from 2009 to 2013. Demographic characteristics, clinical courses, serotype, antibiotic susceptibility, and outcomes were analyzed. RESULTS: Over the 5-year study period, 2167 patients were admitted to the PICU; 48 (2.2%) had IPD. There were 29 female and 19 male patients. Their mean age was 3.7 years (range 0.7-12.5 years, with the peak age at 2-5 years; n = 30, 63%). Pneumonia was the most frequent type (n = 38, 79%), followed by meningitis (n = 10, 21%). In total, three patients died, all within 72 h after admission; the final diagnoses were all meningitis. Thirty-four children with pneumonia received chest tube insertion for pleural effusion drainage. Of them, 22 (65%) finally still underwent video-assisted thoracoscopic surgery. Eight (17%) children had hemolytic uremic syndrome, and seven of them underwent hemodialysis. In total, 37 serotypes were detected; 95% were covered by PCV13. Serotype 19A was most common (54%) overall; however, in those with meningitis, serotype 19 F was most common. CONCLUSIONS: Meningitis is the most severe type of invasive pneumococcal disease in our pediatric intensive care unit. It may progress rapidly even when subjects are given antibiotics promptly. The most common serotype in meningitis is 19 F, which is vaccine preventable. Thus, universal mass pneumococcal vaccination is still needed.

Anti-N-methyl-D-aspartate receptor encephalitis in Taiwan--a comparison between children and adults.

BACKGROUND: Since the discovery of antibodies against the N-methyl-D-aspartate receptor in 2007, anti-N-methyl-D-aspartate receptor encephalitis is increasingly recognized worldwide. We compare the clinical features of adults and children with this disorder in Taiwan. METHODS: Patients admitted to Chang Gung Memorial Hospital and Chang Gung Children's Hospital and those who were referred from other institutions because of unknown encephalitis from 2009 to 2013 were enrolled, and their clinical features were analyzed. Data on cases from a review of the literature were also included in the analysis. RESULTS: Twelve patients (10 females) aged between 7 years and 28 years with anti-N-methyl-D-aspartate receptor encephalitis were identified. Six patients (50%) were <18 years old, one of whom was male and three of whom had an underlying tumor. Overall, 91.6% of the patients presented with mood, behavioral, or personality changes; 91.6% developed seizures; 100% had stereotyped movements; 83.3% had autonomic instability; and 66.7% had hypoventilation. Responses to immunotherapy were slow and variable. Overall, 63.6% of the patients had a substantial recovery after immunotherapy or removal of the tumor, and one patient experienced neurological relapses. There were no significant differences in clinical manifestations between children and adults. CONCLUSIONS: Anti-N-methyl-D-aspartate receptor encephalitis is increasingly recognized in Taiwan. It is characterized by its clinical features, predominantly affects females with and/or without an ovarian tumor, and it is a potentially treatable disorder. It is important for neurologists to be familiar with the clinical presentations of the disease in children and young adults.

Limbic encephalitis in Taiwanese children and adolescence: a single center study.

BACKGROUND: Non-viral limbic encephalitis, which may be paraneoplastic or idiopathic, is increasingly recognized in adults and children. Early identification of potential patients, who have neuronal autoantibodies to intracellular or neuronal surface antigens in order to give appropriate immunotherapy, is key to improving the prognosis. This cross-sectional study describes the clinical manifestation and the serological evidence of the presence of neuronal antibodies in Taiwanese children with limbic encephalitis. METHOD: We enrolled children and adolescents who had been hospitalized due to nonviral limbic encephalitis. Serum samples from these patients were collected to screen antibodies against intracellular antigens [amphiphysin, Ma2, Ri, Yo, Hu and antiglutamic acid decarboxylase (GAD)] and neuronal surface antigens [N-methyl-d-aspartate (NMDA) receptor, γ-amino butyric acid (GABAB) receptor and voltage-gated potassium channel complexes (VGKCs)]. RESULTS: All of the 10 enrolled patients had acute onset of fever and rapid clinical deterioration. They had persistent neuropsychiatric symptoms and 90% developed refractory epilepsy, despite six patients having been treated with methylprednisolone pulse therapy or intravenous immunoglobulin (IVIG) at the acute stage. In the laboratory findings, half of the cases were positive for antibodies with regards to intracellular antigens (amphiphysin or GAD). The general outcomes, assessed by Glasgow Outcome Scale, were similar between patients with and those without the antibodies (Mann-Whitney U test, p = 0.43). One patient, who was positive for antibodies to amphiphysin 10 years after disease onset, still had a significant response to oral prednisolone therapy. At the end of the follow-up period, no cancer or insulin-dependent diabetes mellitus was detected in any of the patients. CONCLUSION: This study provides evidence for a potential association between antibodies and limbic encephalitis. The presence of antibodies, especially antibodies to GAD, may serve as an indicator for immunotherapy.

Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality.

OBJECTIVE: To assess the associations between serum uric acid (SUA) level and mortality. METHODS: The study included 354 110 subjects without a history of gout and whose SUA levels were tested at Chang Gung Memorial Hospital in Taiwan. Cox regression models were used to estimate hazard ratios and 95% CIs for mortality in six predefined SUA strata (≤0.17, 0.18-0.29, 0.30-0.41, 0.42-0.53, 0.54-0.65 and ≥0.66 mmol/l), after adjusting for age, sex, SUA stratum, estimated glomerular filtration rate, fasting glucose, total cholesterol and history of hypertension, diabetes mellitus, coronary heart disease, stroke, heart failure or chronic kidney disease. RESULTS: There were 33 562 all-cause deaths during the study period. Crude all-cause mortality rates across the SUA strata were 52.5, 19.7, 17.4, 20.0, 28.0 and 41.1 deaths per 1000 person-years. Using the stratum 3 of SUA as a reference, the age- and sex-adjusted hazard ratios (95% CIs) across SUA strata were 2.79 (2.62, 2.96), 1.32 (1.28, 1.36), 1.00, 1.10 (1.07, 1.14), 1.42 (1.37, 1.48) and 2.12 (2.01, 2.23) for all-cause mortality; 2.24 (1.93, 2.59), 1.18 (1.10, 1.27), 1.00, 1.21 (1.14, 1.29), 1.74 (1.60, 1.88) and 2.53 (2.28, 2.81) for cardiovascular mortality and 3.41 (3.11, 3.73), 1.48 (1.42, 1.55), 1.00, 0.88 (0.84, 0.92), 0.91 (0.85, 0.98) and 1.23 (1.11, 1.36) for cancer-related mortality. CONCLUSION: Individuals with SUA levels at either extremes are at higher risk for all-cause and cardiovascular mortality. SUA levels of 0.30-0.41 mmol/l were associated with the lowest mortality rate and should be regarded as optimal.

Increased risk of cancer among gout patients: a nationwide population study.

OBJECTIVE: Few studies have investigated the association between gout and cancer. The present study examined the relative risk of cancer in a nationwide cohort. METHODS: The primary data source was the National Health Insurance database of Taiwan. Data recorded between 2000 and 2008 for subjects ≥20 years and with no history of malignancy were included for the analysis. A gout case definition was defined by records of gout diagnosis and anti-gout treatment (urate-lowering drugs, including allopurinol, benzbromazone, probenacid and sulfinpyrazone, and colchicine). Cox proportional hazards models were used to examine the association between gout and cancer. RESULTS: A total of 694,361 patients (355,278 men, 339,083 women) were included; among them, 25,943 had a history of gout. Mean age (±standard deviation) was 42.3±16.3 years. During 5,471,272 patient-years of follow-up, cancer was detected in 24,088 patients (1745 with gout and 22,343 controls). The most cancers were liver, lung, and colonic cancers. The overall incidence of cancer was significantly higher among gout patients than controls (8.7 vs. 4.2 cases per 1000 patient-years, P<0.001). After adjustment for age and sex, gout was found to be associated with a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.10-1.21; P<0.001) for cancer. Gout was most closely associated with prostate cancer, with an age- and sex-adjusted HR of 1.71 (1.45-2.02). On the other hand, gout tended to have an inverse, albeit insignificant, association with breast cancer (adjusted HR, 0.81; 95% CI, 0.63-1.04). CONCLUSION: Gout was associated with increased risk of cancer, particularly that of prostate cancer in males.

Neuroimaging correlation with neurological severity in tuberous sclerosis complex.

OBJECTIVE: To delineate the relationship between neurological severity and neuroimage of lesion load including specific topography of supratentorial cortical tubers and white matter lesions in tuberous sclerosis complex (TSC). METHODS: Twenty-five TSC patients more than 2 years of age who underwent conventional and fluid-attenuated inversion recovery sequence (FLAIR) magnetic resonance imaging (MRI) were retrospectively studied. Neurological severity score was designated for three items: seizure, developmental delay and/or mental retardation, and autism. A neuroimaging scoring system was designed to evaluate the load of the cerebrum lesions with respect to location and size of cortical tubers and white matter lesions based on FLAIR MRI. RESULTS: A linear trend was observed between MRI lesion score and neurological severity score (r=0.511; p=0.009). The lesion score in the left temporal lobe has positive correlation to neurological severity score (r=0.609; p=0.001). CONCLUSIONS: The brain lesion load was positively correlated with neurological prognosis in TSC patients. Patients with larger lesion load in the left temporal lobe may be correlated with increased neurological severity in right-handed patients with TSC.