Parkinson's disease and skin cancer risk: a nationwide population-based cohort study in Korea.

BACKGROUND: Previous studies have reported that patients with Parkinson's disease (PD) have a significantly lower risk of cancer. Studies reporting prevalence of skin cancers in Parkinson's disease mostly involve Caucasians. OBJECTIVE: A nationwide population-based study was conducted to determine the risk of skin cancer in patients diagnosed with PD in Korea. METHODS: Data obtained from National Health Insurance Claims records were used to retrieve information about 70 780 patients with newly diagnosed PD between January 2010 and December 2015. The control group included 353 900 sex- and age-matched patients without PD. In this nationwide population-based cohort study, we investigated the association between PD and skin cancer. RESULTS: The overall hazard ratio (HR) of skin cancers in patients with PD was 1.169 (95% CI, 1.005-1.359) compared with non-PD group. Among patients with PD, males aged above 65 had a 2.8-fold increase in the risk for melanoma development than the non-PD group (HR, 2.825; 95% CI, 1.395-5.721). In addition, female PD patients aged above 65 years showed a 1.3-fold increase in non-melanoma skin cancer risk than the non-PD group (HR, 1.305; 95% 1.073-1.589). CONCLUSION: Compared with the general population, Korean patients diagnosed with PD had a greater risk of skin cancer. Especially, male patients aged 65 years and above, and diagnosed with PD had a significant risk of melanoma development compared with control.

Ascites associated with uterine leiomyoma in a 22-year-old woman with systemic lupus erythematosus.

Ascites in systemic lupus erythematosus (SLE) patients has a variety of etiologies, which usually require different treatment options. Our case was a 22-year-old patient with an unusual combination of ascites, uterine leiomyoma and SLE. The patient presented with painless ascites of an inflammatory nature. However, the ascites was not related to peritonitis and SLE disease activity. The ascites disappeared following laparotomy and tumor resection without additional medication. Gynecologic benign tumors including uterine leiomyoma can be the cause of ascites in SLE patients. Clinicians should be aware of that possibility in case painless ascites occurs in females with SLE.

Utility of QuantiFERON-TB assay for prediction of tuberculosis development in kidney transplant patients in an intermediate-tuberculosis-burden country: lack of evidence for enhanced prediction for short-term tuberculosis development.

INTRODUCTION: Although a latent tuberculosis (TB) infection is a risk factor for active TB, the diagnosis of latent TB infection is difficult in end-stage renal disease patients. PATIENTS AND METHODS: We retrospectively compared the results of the QuantiFERON-TB (QFT) test and the tuberculin skin test in patients on the waiting list for kidney transplantation (KT), and investigated whether the QFT test can predict TB development in KT recipients in an intermediate-TB-burden country. RESULTS: The incidence of post-KT TB was 283 cases/100,000 patient-years among 1274 KT recipients at the Seoul National University Hospital. The overall standardized incidence ratio of TB was 4.358 compared with the general population. A past history of TB infection, smoking history, myocardial infarction after KT, and pneumocystis infection were significant predictors of subsequent TB development (adjusted odds ratios were 3.618, 2.959, 9.993, and 5.708, respectively). Among the 129 recipients who had the QFT test, 42 patients (32.5%) had positive a QFT. At a median follow-up of 8.4 ± 6.8 months, 1 patient with positive QFT results developed TB after KT, and 1 of the 87 patients with negative QFT results developed TB after KT. In both of these 2 cases, active TB developed despite isoniazid prophylaxis. Among 272 patients on the waiting list for KT, the tuberculin skin test and QFT were positive in 22.8% and 35.3%, respectively. The degree of agreement between the 2 tests was poor (κ = 0.352). CONCLUSIONS: The QFT test did not predict subsequent short-term TB development. Furthermore, a long-term and larger-scale study is needed to confirm our results.

LIM kinase-2 induces programmed necrotic neuronal death via dysfunction of DRP1-mediated mitochondrial fission.

Although the aberrant activation of cell cycle proteins has a critical role in neuronal death, effectors or mediators of cyclin D1/cyclin-dependent kinase 4 (CDK4)-mediated death signal are still unknown. Here, we describe a previously unsuspected role of LIM kinase 2 (LIMK2) in programmed necrotic neuronal death. Downregulation of p27(Kip1) expression by Rho kinase (ROCK) activation induced cyclin D1/CDK4 expression levels in neurons vulnerable to status epilepticus (SE). Cyclin D1/CDK4 complex subsequently increased LIMK2 expression independent of caspase-3 and receptor interacting protein kinase 1 activity. In turn, upregulated LIMK2 impaired dynamic-related protein-1 (DRP1)-mediated mitochondrial fission without alterations in cofilin phosphorylation/expression and finally resulted in necrotic neuronal death. Inhibition of LIMK2 expression and rescue of DRP1 function attenuated this programmed necrotic neuronal death induced by SE. Therefore, we suggest that the ROCK-p27(Kip1)-cyclin D1/CDK4-LIMK2-DRP1-mediated programmed necrosis may be new therapeutic targets for neuronal death.

Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma.

BACKGROUND: It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC). AIM: To reveal the clinical relevance of compact lipiodolisation after TACE. METHODS: We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not. RESULTS: Of the 490 patients, 409 (83.5%) were in Child-Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5-10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1-, 3- and 5-year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child-Pugh class, alpha-fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival. CONCLUSIONS: Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.

F-actin depolymerization accelerates clasmatodendrosis via activation of lysosome-derived autophagic astroglial death.

Clasmatodendrosis is an irreversible astroglial degenerative change, which includes extensive swelling and vacuolization of cell bodies and disintegrated and beaded processes. Since alteration in F-actin level influences on the formation of vacuoles/vesicles during exocytosis/endocytosis in astrocytes, we investigated whether F-actin polymerization involves clasmatodendrosis in the rat hippocampus following status epilepticus (SE). In the present study, vacuoles in clasmatodendrotic astrocytes showed LAMP-1 and LC3-II (a marker for autophagy) immunoreactivity. These findings reveal that clasmatodendrosis may be lysosome-derived autophagic astroglial death. Jasplakinolide (an F-actin stabilizer) infusion significantly decreased the size and the number of medium/large-sized vacuoles in each clasmatodendritic astrocyte accompanied by enhancement of phalloidin signals, as compared to vehicle-infusion. In contrast, latrunculin A (an F-actin-depolymerizing agent) infusion increased the size and the number of medium/large-sized vacuoles, which were dissociated adjacent to cell membrane. Therefore, our findings suggest that F-actin stabilization may inhibit lysosome-derived autophagic astroglial death during clasmatodendrosis.

ReLA/P65-serine 536 nuclear factor-kappa B phosphorylation is related to vulnerability to status epilepticus in the rat hippocampus.

Although nuclear factor-kappa B (NF-κB) is essential for neuron survival and its activation may protect neuron against oxidative-stresses or ischemia-induced neurodegeneration, NF-κB activation can contribute to inflammatory reaction and apoptotic cell death after brain injury and stroke. However, there are little data concerning the specific pattern of NF-κB phosphorylations in neuronal damage/survival induced by status epilepticus (SE). In the present study, NF-κB phosphorylation showed the cellular specific pattern in responses to SE. p52-S865, p52-Ser869, p65-Ser276, p65-Ser311, p65-Ser468, and p65-Ser529 NF-κB phosphorylation was significantly decreased in the CA1 and CA3 pyramidal cells vulnerable to SE, although neuronal specific nuclear antigen immunoreactivity was strongly detected. In contrast, p65-Ser536 NF-κB phosphorylation was enhanced in these neurons accompanied by TUNEL- and Fluoro-Jade B 244signals. These findings serve as the first comprehensive description of the cellular specific distribution of NF-κB phosphorylation in response to pilocarpine-induced SE in the rat hippocampus, and suggest that enhancement in p65-Ser536 NF-κB phosphorylation may be closely relevant to neuronal vulnerability to SE, while others may be involved in neuronal survival.