Understanding the long-term impact of incident osteoporotic fractures on healthcare utilization and costs in Korean postmenopausal women.

This study provides long-term evidence that healthcare resource utilization and costs of care in women who experienced incident osteoporotic fractures remained higher than those in women without fractures over a span of 5 years. These findings emphasize the importance of early diagnostics and treatment for osteoporosis. PURPOSE: To evaluate healthcare resource utilization (HCRU) and costs of care over 5 years after the incident osteoporotic fractures (OF) in postmenopausal women. METHODS: We used data from the National Health Insurance Service databases 2011-2018. Women aged ≥ 50 years with incident OF (OF group) were matched to women without OF (non-OF group). HCRU (inpatient, outpatient, and emergency room [ER] visits) and costs of care (inpatient, outpatient, and ER visits) during the 5-year follow-up period were derived after propensity score matching (PSM). Additionally, we identified women with subsequent fractures within the first 2 years after the incident OF. RESULTS: After PSM, 47,238 OF and 134,813 non-OF women were identified. HCRU rates and costs of care were highest in the first year after OF and decreased substantially, but remained higher in the OF group during the entire follow-up period. The increase in cumulative HCRU rates over 5 years was highest in inpatient admissions with ER visits (138% higher in OF vs non-OF). The cumulative total costs over 5 years were 73% higher in the OF group than in the non-OF group, which was mostly driven by inpatient costs. Trends were similar for women with subsequent fractures, but they generally showed higher HCRU and costs than those in the total OF group. CONCLUSION: OF imposes a substantial and sustained economic burden on women, resulting in an approximately twofold increase in the cumulative cost over 5 years compared to women without fracture, which highlights the need for early diagnostics and treatment of osteoporosis.

Estimating the economic burden of osteoporotic fractures in a multinational study: a real-world data perspective.

Fracture-related costs vary by country. A standardized methodology and presentations were proposed to fairly assess the economic burden of osteoporotic fracture. Results indicated substantial costs of osteoporotic fractures for pharmacy, hospitalization, emergency care, and outpatient visits in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. PURPOSE: The objective of this multinational, retrospective matched cohort study was to use a standardized methodology across different healthcare systems to estimate the burden of osteoporotic fracture (OF) in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. METHODS: Within each country, healthcare resource utilization and direct costs of care were compared between patients with newly identified OF and a propensity score-matched cohort without OF during follow-up periods of up to 5 years. RESULTS: Across all five countries, the OF cohort had significantly higher rates and length of inpatient admissions compared with the non-OF cohort. In each country, the adjusted total costs of care ratio between OF and non-OF cohorts were significant. The adjusted cost ratios for pharmacy, inpatient care, emergency care, and outpatient visits were similarly higher in the OF cohort across countries. CONCLUSION: The current study demonstrates the substantial economic burden of OF across different countries when compared with matched non-OF patients. The findings would assist stakeholders and policymakers in developing appropriate health policies.

To restrict or not to restrict? Practical considerations for optimizing dietary protein interactions on levodopa absorption in Parkinson's disease.

Administration of levodopa for Parkinson's disease (PD) has remained the most effective therapy for symptom management despite being in use for over 50 years. Advancing disease and age, changing tolerability and gastrointestinal (GI) dysfunction may result in change in dietary habits and body weight, as well as unpredictable motor fluctuations and dyskinesias. Dietary proteins which convert into amino acids after digestion are implicated as major factors that inhibit levodopa absorption. For people living with PD (PwP) who experience motor fluctuations, low protein diets (LPD) and protein redistribution diets (PRD) may be effective and are often recommended as a non-pharmacologic approach for improving levodopa bioavailability. However, there is a lack of consensus on a standard definition of these diets and appropriate treatment algorithms for usage. This may be due to the paucity of high-level evidence of LPD and PRD in PwP and whether all or specific subgroups of patients would benefit from these strategies. Managing diet and protein intake with proper education and monitoring may reduce complications associated with these diets such as dyskinesias and unintentional weight loss. Additionally, alterations to medications and GI function may alter levodopa pharmacokinetics. In this narrative review we focus on 1) mechanisms of dietary protein and levodopa absorption in the intestine and blood brain barrier, 2) dietetic approaches to manage protein and levodopa interactions and 3) practical issues for treating PwP as well as future directions to be considered.

Sphingolipid identification and skin barrier recovery capacity of a milk sphingolipid-enriched fraction (MSEF) from buttermilk powder.

OBJECTIVE: In this study, we isolated the milk sphingolipid-enriched fraction (MSEF) of sweet buttermilk powder and conducted a clinical trial for evaluating its efficacy in skin barrier recovery. METHODS: Milk sphingolipid-enriched fraction was isolated via solvent extraction of buttermilk powder, and further concentrated by removing the phospholipids and neutral lipids. A cream containing 1% MSEF was used during clinical trials to assess for water holding and skin barrier recovery capacities. RESULTS: The main components of the MSEF were sphingomyelin, glucosylceramide and lactosylceramide, confirmed by TLC, HPLC, MS and NMR. The MSEF cream-treated group had a significantly higher (P < 0.05) water holding capacity, compared with the base cream (vehicle) group. Compared with that in the base cream group, transepidermal water loss (TEWL) recovery increased in the presence of the sphingolipid-containing MSEF cream (MSEF group), with a significant difference (P < 0.05) recorded on day 14. CONCLUSION: The MSEF cream contributed to improving the water holding capacity and skin barrier recovery of damaged skin. Therefore, sphingolipid-containing MSEF can be useful for strengthening or repairing skin barrier function.

OBJECTIF: Dans la présente étude, nous avons isolé la fraction enrichie en sphingolipides du lait (milk sphingolipid-enriched fraction, MSEF) du lait de baratte doux en poudre et mené un essai clinique pour évaluer l'efficacité de la récupération de la barrière cutanée. MÉTHODES: La fraction enrichie en sphingolipides du lait est isolée par l'extraction de solvant du lait de baratte en poudre, et ensuite concentrée en enlevant les phospholipides et les lipides neutres. Une crème contenant un pourcent (1%) de la fraction enrichie en sphingolipides du lait (MSEF) est utilisée pendant des essais cliniques visant à évaluer les capacités de la rétention d'eau et de la récupération de la barrière cutanée. RÉSULTATS: Les principales composantes de la fraction enrichie en sphingolipides du lait (MSEF) étaient la sphingomyéline, la glucosylcéramide, et le lactosylcéramide, confirmées par la chromatographie sur couche mince (TLC), la chromatographie liquide à haute performance (CLHP), la spectrométrie de masse (MS) et la RMN(NMR). La groupe traitée par la crème enrichie en sphingolipides du lait (MSEF) avait une capacité de la rétention d'eau beaucoup plus élevée (P < 0.05), par rapport au groupe utilisant la crème de base (véhicule). Comparé au groupe utilisant la crème de base, la récupération de la perte d'eau transépidermique (TEWL) a augmenté en présence de la fraction enrichie en sphingolipides du lait (MSEF), avec une différence significative (P < 0.05) enregistrée au 14ème jour. CONCLUSION: La crème enrichie en sphingolipides du lait (MSEF) a contribué à améliorer les capacités de la rétention d'eau et de la récupération de la barrière cutanée de la peau endommagée. Par conséquent, la fraction enrichie en sphingolipides du lait (MSEF) peut être utile pour renforcer ou réparer la fonction de barrière cutanée.

Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain.

OBJECTIVE: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). DESIGN: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. RESULTS: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500-3,000 mm Hg), strong upregulation of NGF (200-250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 µM) or systemic (3 mg kg-1) morphine administration. CONCLUSIONS: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.

Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento / The First Year of the AEVD Primary Cutaneous Lymphoma Registry

ANTECEDENTES Y OBJETIVO: Los linfomas primarios cutáneos son enfermedades poco frecuentes. Este artículo describe el Registro de linfomas cutáneos primarios de la AEDV y sus primeros resultados. PACIENTES Y MÉTODOS: Registro de enfermedad de pacientes con linfomas cutáneos primarios. Los centros participantes recogieron datos prospectivamente de todos los pacientes, incluyendo datos del diagnóstico, de los tratamientos, de las pruebas realizadas y del estado actual del paciente. Se realizó un análisis descriptivo. RESULTADOS: En diciembre del 2017 el registro tenía datos de 639 pacientes pertenecientes a 16 hospitales universitarios. Un 60% eran hombres y los diagnósticos, por orden de frecuencia, fueron: micosis fungoide/síndrome de Sézary (MF/SS) (348 casos; 55%), linfoma cutáneo primario de células B (LCCB) (184; 29%), trastorno linfoproliferativo de células T CD30+ (LTCD30+) (70; 11%) y otro tipo de linfoma T (OLT) (37; 5%). El número de casos incidentes recogidos durante el primer año fue de 105 (16,5%). En los pacientes con MF/SS, el diagnóstico más frecuente fue MF clásica (77,3%). La mitad de estos casos se diagnosticaron en estadio IA. La mayoría de los pacientes estaban en remisión parcial (32,5%) o enfermedad estable (33,1%). Los tratamientos más usados fueron los corticoides tópicos (90,8%) seguidos de fototerapia. En los pacientes con LCCB el diagnóstico más frecuente fue el linfoma de la zona marginal (50%). Casi todos los pacientes tuvieron afectación exclusivamente cutánea y casi la mitad fue T1a. La mayoría (76,1%) estaba en remisión completa. Los tratamientos más utilizados fueron la cirugía (55,4%) y la radioterapia (41,9%). En los pacientes con LTCD30+, el diagnóstico más frecuente fue la papulosis linfomatoide (68,6%). La mayoría fueron clasificados T3b (31,4%). La mitad de los casos estaban en remisión completa. Los tratamientos más frecuentes fueron los esteroides tópicos (68,6%), seguidos de la quimioterapia sistémica (32,9%). CONCLUSIÓN: Las características del paciente con linfoma cutáneo primario en España no difieren de otras series descritas en la literatura. El registro facilitará al grupo de linfomas de la AEDV realizar investigación clínica

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical coricosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

Antihistamine use and the risk of injurious falls or fracture in elderly patients: a systematic review and meta-analysis.

Despite their anticholinergic side effects, first-generation antihistamines are widely prescribed to elderly patients. A systematic review was conducted to synthesize real-world evidence. First-generation antihistamine use is considerably associated with an increased risk of injurious falls or fracture among the elderly. INTRODUCTION: First-generation antihistamines are considered potentially inappropriate for elderly patients owing to anticholinergic side effects. We aimed to determine whether elderly patients taking antihistamines are at increased risk of injurious falls or fracture. METHODS: We identified studies in MEDLINE, EMBASE, and several local databases through November 2016. Observational studies on the association between antihistamine use and the risk of injurious falls or fracture were selected. Quality of the studies and the level of evidence were assessed. The random-effects model was employed for meta-analysis, and heterogeneity was examined based on I-square and Cochrane's Q test. Subgroup analyses were performed when the heterogeneity among studies could not be explained. RESULTS: From 473 identified studies, five (three case-control studies, one cohort study, and one case-crossover study) were included in our analysis based on eligibility criteria. First-generation antihistamine use showed significantly increased risk of injurious falls or fracture (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.49-2.76, heterogeneity: p = 0.41, I2 = 0%). Studies including antihistamines of all generations or containing no generation information were dealing with falls during hospitalization. Among these studies, the association was statistically significant without heterogeneity (OR 2.89, 95% CI 1.71-4.89, heterogeneity: p = 0.42, I2 = 0%). Due to the small number of studies included and unadjusted results, meaningful interpretation based on subgroup analysis was limited. CONCLUSIONS: First-generation antihistamine use is considerably associated with increased risk of injurious falls or fracture among the elderly. Clinicians need to exercise caution when prescribing first-generation antihistamines to elderly patients.

The First Year of the AEVD Primary Cutaneous Lymphoma Registry. / Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Analysis of the number of enlarged pores according to site, age, and sex.

BACKGROUND: Increasing the number of enlarged pores causes cosmetic problems. The difference in the number of enlarged pores according to facial site, age, and sex is unclear. OBJECTIVE: To analyze the distribution of the number of enlarged pores according to facial site, age, and sex. METHODS AND MATERIALS: We analyzed the number of the enlarged pores and the percentage of wrinkles in the nose, forehead, and cheek from 434 polarized images. The measurement results were analyzed according to site, age, and sex. Relationship between enlarged pore counts and wrinkle severity was also analyzed. The study was conducted by using DermaVision,™ which can take cross-polarization, parallel polarization, and ultraviolet light images. RESULTS: The enlarged pores of the nose and forehead were more prominent than in the cheeks. Pore counts were increased with age, and the increment was significant between the 30's and 40's. There was no significant difference by gender. Enlarged pore counts were related to wrinkle severity. CONCLUSIONS: The number of enlarged pores differs depending on body site and increased with age. The enlarged pore counts correlate with wrinkle severity and the correlation varies depending on the body site.

Reactivation of Tert in the medial prefrontal cortex and hippocampus rescues aggression and depression of Tert(-/-) mice.

The role of telomerase reverse transcriptase (TERT) has been extensively investigated in the contexts of aging and cancer. Interestingly, Tert(-/-) mice exhibit additional but unexpected aggressive and depressive behaviors, implying the potential involvement of TERT function in mood control. Our conditional rescue experiments revealed that the depressive and aggressive behaviors of Tert(-/-) mice originate from Tert deficiency in two distinct brain structures. Reactivation of Tert in the hippocampus was sufficient to normalize the depressive but not the aggressive behaviors of Tert(-/-) mice. Conversely, re-expression of Tert in the medial prefrontal cortex (mPFC) reversed the aggressive but not the depressive behavior of Tert(-/-) mice. Mechanistically, decreased serotonergic signaling and increased nitric oxide (NO) transmission in the hippocampus transduced Tert deficiency into depression as evidenced by our observation that the infusion of a pharmacological agonist for serotonin receptor 1a (5-HTR1A) and a selective antagonist for neuronal NO synthase into the hippocampus successfully normalized the depressive behavior of Tert(-/-) mice. In addition, increased serotonergic transmission by the 5-HTR1A agonist in the mPFC was sufficient to rescue the aggressive behavior of Tert(-/-) mice. Thus, our studies revealed a novel function of TERT in the pathology of depression and aggression in a brain structure-specific manner, providing direct evidence for the contribution of TERT to emotional control.

Forma familiar de cutis verticis gyrata primario esencial / A Familial Form of Primary Essential Cutis Verticis Gyrata

No disponible

Antimelanogenic effects of luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino.

BACKGROUND: Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research. OBJECTIVES: To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects. METHODS: The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM). RESULTS: Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7-sulfate and luteolin 7-sulfate. Luteolin 7-sulfate inhibited human TYR more strongly than hispidulin 7-sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7-sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7-sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α-melanocyte-stimulating hormone and l-tyrosine than arbutin. CONCLUSIONS: This study demonstrates that luteolin 7-sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation.

A Large National Cohort Study of the Association between Bisphosphonates and Osteonecrosis of the Jaw in Patients with Osteoporosis: A Nested Case-control Study.

The purpose of this study was to examine the association between bisphosphonate exposure and osteonecrosis of the jaw (ONJ) in Korean patients with osteoporosis. A nested case-control study was performed using the claims database during 2002 to 2010 provided by the National Health Insurance Service. We identified a cohort of individuals with diagnosis of osteoporosis during 2002 to 2010. Cases and controls were identified during 2004 to 2010, and the date of potential cases of ONJ was defined as the index date. Bisphosphonate exposure was evaluated during 2 y prior to the index date. The association between bisphosphonate exposure and ONJ was tested by performing a conditional logistic regression analysis for matched data, and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Subjects were classified as nonuser, recent user, past user, or continuous user, depending on the prescription of bisphosphonates in 2 periods (1 to 2 y and 0 to 1 y prior to the index date). Continuous users were defined as patients who were exposed to bisphosphonate in both periods. We also examined the impact of bisphosphonate medication compliance by measuring the cumulative duration of exposure (CDE) on the risk of ONJ. A total of 212 cases with ONJ and 2,120 controls matched by sex, age, income level, and insurance type were identified among 109,787 patients with osteoporosis out of 1,025,340 enrollees in the sample cohort. The odds of having ONJ after adjusting for patient comorbidities significantly increased in continuous users of bisphosphonates (OR, 3.9; 95% CI, 2.4 to 6.2) compared to nonusers. Increased odds of ONJ were observed as CDE increased. The adjusted OR in patients with 1.5 y < CDE ≤ 2 y prior to the index date was 7.8 (95% CI, 4.0 to 15.5) versus nonusers. Our study results support significantly increased occurrences of potential ONJ in patients with osteoporosis who were exposed to bisphosphonates compared to those without exposure.

Investigation of Werner protein as an early DNA damage response in actinic keratosis, Bowen disease and squamous cell carcinoma.

BACKGROUND: Werner protein (WRN) has DNA helicase activity and participates in recombination, replication and repair of DNA. Loss-of-function mutations in WRN gives rise to genetic instability and diseases such as premature ageing and cancer. Upregulation of WRN promotes proliferation and survival of cancer cells. AIM: To evaluate the expression pattern of WRN in closely related skin cancers and their correlation with age, sex and UV exposure. METHODS: Immunohistochemistry was used to investigate expression of WRN in formalin-fixed, paraffin wax-embedded tissue specimens of 9 squamous cell carcinoma (SCC), 15 actinic keratosis (AK), 11 Bowen disease (BD) and 11 normal-appearing peripheral tissue samples, obtained from patients during surgical resections. RESULTS: WRN expression was significantly increased in BD, AK and SCC compared with normal controls, with the mean WRN staining score being highest in BD, followed by AK and SCC. However, age, sex and sun exposure were not associated with WRN expression. CONCLUSIONS: To our knowledge, this is the first report to date investigating the expression of WRN in skin cancers. The overtly high expression of WRN in premalignant lesions and in in situ cancer, with relatively low WRN expression in SCC, may indicate that WRN contributes as a checkpoint for early DNA damage response in skin tumorigenesis.

Associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors in Korean obese women.

PURPOSE: It is important to identify a 'metabolically unhealthy obese' subset with higher cardiovascular risk among obese individuals. We investigated the associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors among Korean obese women. METHODS: This study was a sub-investigation of a double-blind randomized controlled trial that examined the additive effect of or list at on weight loss with sibutramine. A sample of 111 obese women were divided into T-carriers (CT/TT) or a homozygous CC group, according to the presence of the 825T allele at GNB3. These groups were compared to determine their associations with obesity-related metabolic risk factors, i.e., fasting plasma glucose, serum lipids, serum insulin/insulin resistance, and abdominal fat amounts. RESULTS: The allele frequencies of the GNB3 polymorphism were C allele = 59.5% and T allele = 40.5%. The T allele was found to be significantly associated with greater visceral fat and higher serum lipids, and these significances remained robust after adjusting for potential covariates. CONCLUSIONS: The GNB3 825T polymorphism is significantly associated with greater visceral fat and higher serum lipids in Korean obese women and it suggests that the GNB3 C825T is a determinant of obesity-related metabolic traits in this population.

Improving acne keloidalis nuchae with targeted ultraviolet B treatment: a prospective, randomized, split-scalp comparison study.

BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with fibrotic papules on the occipital scalp. Its treatment is limited and unsatisfactory. OBJECTIVES: To determine whether targeted ultraviolet B (tUVB) phototherapy will (i) improve the clinical appearance of AKN and (ii) induce extracellular matrix remodelling in affected lesions. METHODS: Eleven patients with AKN were enrolled in a prospective, randomized, split-scalp comparison study. One randomly selected side of the scalp was treated with tUVB up to three times weekly for 8 weeks. After week 8, both sides were treated for eight additional weeks. Assessment included lesion counts in two 3 × 3-cm regions of interest (ROIs), one on each side of the scalp (ROI-1: tUVB weeks 0-16, ROI-2: tUVB weeks 9-16), patient self-assessment and analysis of MMP1, MMP9, TGFB1 and COL1A1 mRNA expression by quantitative reverse-transcription polymerase chain reaction. RESULTS: Before treatment, the mean lesion count was similar between tUVB-treated and untreated sides (14·8 vs. 15·0). After 8 weeks of tUVB, the mean lesion count decreased significantly to 9·4 ± 1·2 (P =  0·03), with no change on the untreated side. With continued treatment, the mean lesion count in ROI-1 decreased further to 7 ± 1·5 (P = 0·04) after 16 weeks of tUVB. CONCLUSIONS: tUVB significantly improved the clinical appearance of AKN, led to patient satisfaction and was well tolerated.