Behçet's disease-induced massive small intestinal bleeding successfully treated with adalimumab.

We herein report a case of Behçet's disease in a 27-year-old female who suffered from generalized skin rashes for one week. After hospitalization, massive bloody stools accompanying hypovolemic shock occurred. Emergency abdominal computed tomography-angiography failed to detect the bleeding source. Esophagogastroduodenoscopy also demonstrated no definite bleeding points. Ileocolonoscopy showed multiple large and deep ulcers with some blood coating and mild oozing in the terminal ileum. We initially performed epinephrine injection and hemoclips for her intestinal bleeding. However, massive bloody stools still continued. Thus, we prescribed a loading dose of 160 mg adalimumab followed by weekly 80 mg adalimumab subcutaneous injections to the patient. Following this treatment, her gastrointestinal bleeding gradually subsided and completely stopped within a few days. After three-week therapy with adalimumab, capsule endoscopy showed several healing ulcers without bleeding in the distal to the terminal ileum. She continues to be treated with adalimumab, azathioprine, and mesalazine without recurrent bleeding.

The association between serum vitamin D level and risk and prognosis of melanoma: a systematic review and meta-analysis.

BACKGROUND: Vitamin D has antineoplastic effects, but the synthesis of vitamin D requires ultraviolet radiation, a known risk factor for melanoma. OBJECTIVE: To investigate the correlations between serum vitamin D levels and risk and prognosis of melanoma. METHODS: A systematic review and meta-analysis were conducted. Online databases were searched on 31 Oct 2018. RESULTS: Twenty-five studies with a total of 11166 patients with melanoma were included. There was no significant difference in serum vitamin D levels between patients with melanoma and controls [standardized mean difference (SMD), -0.185; 95% confidence interval (CI), -0.533 to 0.162]. However, the prevalence of vitamin D deficiency was significantly higher in patients with melanoma than that in controls (odds ratio, 2.115; 95% CI, 1.151-3.885). In terms of prognosis, serum vitamin D levels were significantly higher in melanoma patients with lower Breslow thickness (≦1 vs. >1 mm: SMD, 0.243; 95% CI, 0.160-0.327). Moreover, melanoma patients with lower vitamin D levels had a significantly higher mortality rate (hazard ratio, 1.558; 95% CI, 1.258-1.931). CONCLUSIONS: Vitamin D deficiency is associated with higher Breslow thickness and mortality in melanoma patients.

Safety in moderate-to-severe plaque psoriasis patients with latent tuberculosis treated with guselkumab and anti-tuberculosis treatments concomitantly: results from pooled phase 3 VOYAGE 1 & VOYAGE 2 trials.

BACKGROUND: Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new-onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)-23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics. OBJECTIVES: Safety in moderate-to-severe psoriasis patients with LTBI treated with guselkumab (IL-23 inhibitor) and LTBI treatment was evaluated. METHODS: In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo â†’ guselkumab crossover occurred at week 16 and adalimumab â†’ guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab-treated patients receiving and not receiving LTBI treatment. RESULTS: At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab-treated patients without LTBI (LTBI-) through week 100. Two cases of active TB occurred in LTBI- patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI- patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI- patients. CONCLUSIONS: No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long-term treatment with guselkumab was generally well-tolerated through up to 2 years in patients receiving LTBI medications.

Association of use of Chinese herbal medicines and the risk of fracture in patients with osteoporosis: a population-based cohort study.

After utilizing a large population-based claims database and the application of propensity score match approach to reduce the confounding effects, we found that the use of Chinese herbal medicines (CHMs) was related to the lower risk of sequent osteoporotic fracture by 27% among the individuals with osteoporosis. The predominant effect was observed in those receiving CHMs for more than two years. INTRODUCTION: Osteoporosis (OS) is a highly disabling condition that can lead to fragility fracture, thus posing greater burdens of functional limitations for the affected individuals. It is unclear if the use of Chinese herbal medicines (CHMs) could reduce the risk of fracture due to OS. This study aimed to investigate the association of CHMs and the subsequent osteoporotic fracture risk among OS patients. METHODS: This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 250,699 newly diagnosed OS patients aged 20 years or older between 1998 and 2010. We recruited 103,325 CHM users following the onset of OS (CHM users) and randomly selected 103,325 subjects without CHM usage as controls (non-CHM users) by propensity score matching according to the demographic characteristics and comorbidities at enrollment. All enrollees were followed until the end of 2012 to record the incidence of osteoporotic fracture. We applied the Cox proportional hazard regression model to compute the hazard ratio (HR) of the risk of osteoporotic fracture. RESULTS: During the 15-year follow-up period, 7208 CHM users and 11,453 non-CHM users sustained osteoporotic fracture, with an incidence rate of 9.26 and 12.96, respectively, per 1000 person-years. We found that CHM users had a significantly reduced risk of osteoporotic fracture compared to non-CHM users (adjusted HR 0.73; 95% confidence interval [CI] = 0.70-0.75). Those treated with CHMs for longer than 730 days had a lower fracture risk by 54%. Some commonly used CHMs, such as Yan hu suo (Rhizoma Corydalis), Huang Qin (Scutellaria Baicale), Jie Geng (Platycodon grandifloras), Xiang Fu (Cyperus rotundus), Hai Piao Xiao (Cuttlebone Sepium), Jia-Wei-Xiao-Yao-San, Ge-Gen-Tang, Shao-Yao-Gan-Cao-Tang, and Du-Huo-Ji-Sheng-Tang, are related to the lower risk of fracture. CONCLUSIONS: The use of CHMs was associated with lower risk of osteoporotic fracture for OS patients, suggesting that it could be integrated into conventional therapy to prevent subsequent bone fracture.

Serum homocysteine, folate and vitamin B12 levels in patients with psoriasis: a systematic review and meta-analysis.

BACKGROUND: Patients with psoriasis are at increased risk for cardiovascular comorbidities. Previous studies examined the possible contribution of serum homocysteine, folate and vitamin B12 to cardiovascular risks in patients with psoriasis but had conflicting conclusions. OBJECTIVES: To perform a systematic review and meta-analysis of studies on serum homocysteine, folate and vitamin B12 levels in patients with psoriasis. METHODS: Online databases were searched on 15 February 2018 to include studies comparing serum homocysteine, folate and vitamin B12 levels between patients with psoriasis and controls. A random effects model was adopted to estimate odds ratios for dichotomous data and standardized mean differences (SMDs) for continuous data. RESULTS: A comprehensive literature search identified 24 studies eligible for inclusion. Compared with controls, patients with psoriasis had a significantly higher serum homocysteine level [SMD 0·41, 95% confidence interval (CI) 0·21-0·61; I2 = 76·7%, 18 studies], a higher prevalence of hyperhomocysteinaemia (odds ratio 3·48, 95% CI 2·08-5·83; I2 = 41·1%, seven studies) and a lower serum folate level (SMD -0·94, 95% CI -1·49 to -0·40; I2 = 95·6%, 14 studies). However, there was no difference in serum vitamin B12 levels between patients with psoriasis and the control group (SMD 0·004, 95% CI -0·49 to 0·50; I2 = 92%, 11 studies). Metaregression analysis revealed a significant inverse correlation between the SMD of homocysteine levels and folate levels. CONCLUSIONS: Patients with psoriasis might have higher serum homocysteine and lower folate levels than control patients without psoriasis. However, due to significant heterogeneity and other limitations, the associations require further examinations in more studies.

Association of use of rehabilitation services with development of osteoporosis among patients with rheumatoid arthritis: a nationwide population-based cohort study.

This is the first study that has found that rehabilitation services (RS) intervention, following the onset of rheumatoid arthritis (RA), may significantly reduce the risk of osteoporosis in RA patients. Those patients who received more than five sessions of RS had the greatest benefit for the prevention of osteoporosis. INTRODUCTION: People with rheumatoid arthritis have increased risk of developing osteoporosis (OP). It remains unclear whether use of rehabilitation services can reduce the risk of developing OP. We conducted a longitudinal cohort study to compare the effect of RS on the risk of OP in Taiwanese individuals with RA. METHODS: A national health insurance database was used to identify 2693 newly diagnosed RA patients, 20-70 years old, between 1998 and 2007. Among them, 808 received RS after the onset of RA (RS users) and 1885 patients did not receive RS (non-RS users). All enrollees were followed until the end of 2012 to record incident cases of OP. A Cox proportional hazards regression model was used to compute adjusted hazard ratios (aHRs) for the relationship of use of RS with OP. RESULTS: During the 15-year follow-up, 358 RS users and 1238 non-RS users developed OP, corresponding to incidence rates of 87.24 and 129.27 per 1000 person-years, respectively. Use of RS was significantly associated with a lower risk of OP (aHR 0.62; 95% confidence interval [CI] = 0.56-0.71). Those who received more than five sessions of RS had the greatest benefit (aHR 0.47; 95% CI = 0.38-0.56). CONCLUSIONS: The integration of RS into the clinical management of patients with RA may decrease their risk of developing OP.

HLA-Cw6 and psoriasis.

Psoriasis is a multifactorial disease with a strong genetic background. HLA-Cw6 is one of the most strongly associated psoriasis susceptibility alleles. It is repeatedly observed to affect disease course, phenotypic features, severity, comorbidities and treatment outcomes. To the best of our knowledge, the roles of HLA-Cw6 in psoriasis have not yet been thoroughly reviewed. The worldwide frequency of the HLA-Cw6 allele varies greatly, with it being generally higher in white people than in Asians. The allele is associated with type I early-onset psoriasis. Stress, obesity and streptococcal pharyngitis are commonly observed in HLA-Cw6-positive patients. Phenotypically, HLA-Cw6 has been found to be associated with guttate psoriasis. In addition, patients carrying the allele are more likely to have arm, leg and trunk involvement, and the Koebner phenomenon. Patients with psoriatic arthritis with HLA-Cw6 more often have early onset and tend to show cutaneous symptoms before musculoskeletal symptoms. HLA-Cw6-positive patients have been shown in several studies to be more responsive to methotrexate and ustekinumab. However, this difference in ustekinumab efficacy was only moderate in a post-hoc analysis of a pivotal phase III study. HLA-Cw6 positivity also tends to be less frequent in high-need patients who fail conventional therapy. Small studies have also investigated the role of HLA-Cw6 in remission of psoriasis during pregnancy, and with the comorbidities of photosensitivity and atherosclerosis. Given the diverse nature of psoriasis pathogenesis, as well as the difference of HLA-Cw6 positivity in different ethnic groups, more studies are needed to confirm the role of HLA-Cw6 in psoriasis.

Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial.

BACKGROUND: Guselkumab, an anti-interleukin-23 monoclonal antibody, has demonstrated significant efficacy in phase III psoriasis trials. OBJECTIVES: To evaluate the efficacy and safety of guselkumab in patients with moderate-to-severe plaque psoriasis who had an inadequate response to ustekinumab. METHODS: In this phase III, randomized, double-blind study, 871 patients received open-label ustekinumab (45 mg or 90 mg) at weeks 0 and 4. At week 16, 268 patients with an inadequate response to ustekinumab [Investigator's Global Assessment (IGA) ≥ 2] were randomized (double-blind) to guselkumab 100 mg or to continue ustekinumab; 585 of 871 patients (67%) with IGA 0/1 at week 16 continued open-label ustekinumab. The primary end point was the number of visits at which randomized patients achieved IGA 0/1 and at least a two-grade improvement (from week 16) from week 28 to week 40. Improvement ≥ 90% or 100% in Psoriasis Area and Severity Index (PASI 90/100) and Dermatology Life Quality Index (DLQI) of 0/1 were also assessed. RESULTS: The mean number of visits at which patients achieved IGA 0/1 and at least a two-grade improvemen (week 28-40) was significantly greater in the guselkumab group vs. the randomized ustekinumab group (1·5 vs. 0·7; P < 0·001); greater proportions of patients in the guselkumab group achieved IGA 0/1 and at least a two-grade improvement at week 28 (31·1% vs. 14·3%; P = 0·001) and week 52 (36·3% vs. 17·3%; P < 0·001). Greater proportions of patients treated with guselkumab achieved PASI 90, PASI 100 and DLQI 0/1 at week 52. After week 16, 64·4% of patients in the guselkumab group and 55·6% in the ustekinumab group had at least one adverse event (AE); infections were the most frequent AE type. Overall, 6·7% (n = 9) of patients in the guselkumab group had at least one serious AE compared with 4·5% (n = 6) for the ustekinumab group. CONCLUSIONS: Patients treated with ustekinumab who did not achieve an IGA of 0/1 by week 16 derived significant benefit from switching to guselkumab.

Tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: long-term safety and efficacy in an open-label extension study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported. OBJECTIVES: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis. METHODS: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75). RESULTS: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52-62% of patients and PASI 75 by 56-74% of patients at each study visit through month 54. CONCLUSIONS: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253).

The role of ß-blockers in dermatological treatment: a review.

Many systemic medications have been used off-label in cutaneous diseases. Use of ß-adrenergic-blocking agents has risen in popularity among dermatologists since the discovery of their efficacy in treating infantile haemangioma. There has also been an increase in the interest of the applications of ß-blockers in other skin disorders. Overall, ß-blockers are effective in treating diseases of vascular origin and promote wound healing. They are relatively safe and inexpensive medications that could be included in the armamentarium against skin diseases.

Secular trends in incidence and recurrence rates of hip fracture: a nationwide population-based study.

We assessed the incidence of hip fracture and second hip fractures in Taiwan from 2001 to 2012. Age-standardized incidence rates decreased after 2005. However, mortality rate after first hip fracture was substantial compared to second hip fracture rate in a competing risk model. INTRODUCTION: The aim of the study is to assess the incidence rates (IRs) of hip fractures, including changes in trends and medical costs, and second hip fractures in the Taiwanese population. METHODS: The number of hip fractures and the associated medical costs were obtained from the annual report of the Ministry of Health and Welfare, Taiwan, for individuals ≥50 years of age. The data of population at risk were retrieved from annual population reports from the Ministry of the Interior, Taiwan. The incidence of second hip fractures was evaluated from the National Health Insurance Research Database of Taiwan for insured individuals aged ≥50 years from 2001 to 2011 with follow-up until 2013 using a competing risk model. RESULTS: The IR for the entire population increased from 332.7 to 336.5 per 100,000 person-years during 2001-2005 and decreased thereafter. This secular change was driven by a decrease in hip fractures for both men and women. The 10-year cumulative incidence rate of second hip fracture was 11.2% (95% CI 11.0-11.5%) in women and 7.9% (95% CI 7.6-8.1%) in men. Adjusted by consumer price index (CPI), the costs of hospitalization due to hip fracture increased from NTD 1.17 billion in 2001 to NTD 1.43 billion in 2012. However, the CPI-adjusted costs of each admission decreased from NTD 74944 in 2001 to NTD 65791 in 2012. CONCLUSIONS: Since 2006, the IR of hip fractures has been declining in Taiwan. The 10-year cumulative IR of mortality is substantial for individuals who with first hip fracture.

Degenerative effects of cobalt-chloride treatment on neurons and microglia in a porcine retina organ culture model.

In order to understand the pathological processes of retinal diseases, experimental models are necessary. Cobalt, as part of the vitamin B12 complex, is important for neuronal integrity. However, it is known that high quantities of cobalt induce cytotoxic mechanisms via hypoxia mimicry. Therefore, we tested the degenerative effect of cobalt chloride (CoCl2) on neurons and microglia in a porcine retina organ culture model. Organotypic cultures of porcine retinas were cultured and treated with different concentrations of CoCl2 (0, 100, 300 and 500 µM) for 48 h. After four and eight days, CoCl2 induced a strong degeneration of the porcine retina, starting at 300 µM. A loss of retinal ganglion cells (RGCs, Brn-3a), amacrine cells (calretinin) and bipolar cells (PKCα) was observed. Additionally, a high expression of hypoxia induced factor-1a (HIF-1a) and heat shock protein 70 (HSP70) was noted at both points in time. Also, the Caspase 3 protein was activated and P21 expression was induced. However, only at day four, the Bax/Bcl-2 ratio was increased. The effect of CoCl2 was not restricted to neurons. CoCl2 concentrations reduced the microglia amount (Iba1) and activity (Iba1 + Fcγ-Receptor) at both points in time. These damaging effects on microglia were surprising, since CoCl2 causes hypoxia and a pro-inflammatory environment. However, high concentrations of CoCl2 also seem to be toxic to these cells. Similar degenerative mechanisms as in comparison to retinal ischemia animal models were observed. In summary, an effective and reproducible hypoxia-mimicking organotypic model for retinal degeneration was established, which is easy to handle and ready for drug studies.

Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis.

SUMMARY: Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel. INTRODUCTION: Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities. METHODS: The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line. RESULTS: A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels. CONCLUSION: The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.