Clinical Characteristics and Disease Burden of Patients with Moderate-to-Severe Generalized Pustular Psoriasis Flares in Taiwan.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. METHODS: This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008-December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. RESULTS: Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients' mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87-61.78), 14.08 (95% CI 3.04-65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08-0.54) and 0.07 (95% CI 0.006-0.78), respectively. CONCLUSIONS: Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals' care and outcomes.

Risk of breast cancer among patients with psoriasis: a systematic review and meta-analysis.

Relevant evidence regarding the risk of incident breast cancer in patients with psoriasis is lacking. Hence, this systematic review and meta-analysis aimed to assess the risk of breast cancer in patients with psoriasis. We searched the PubMed, Cochrane Library, and Embase databases from inception to December 31, 2021, for relevant cohort studies without language limitations. The Newcastle-Ottawa Scale was used to determine the quality of the selected papers. A random-effects model meta-analysis was performed to obtain the pooled hazard ratio (HR) with a 95% confidence interval (CI) for breast cancer in relation to psoriasis. We also performed a subgroup analysis of patients with mild-to-moderate-to-severe psoriasis. We included seven cohort studies, all of which were considered high quality, and three of them provided data for meta-analysis. The risk for breast cancer did not increase among patients with psoriasis (pooled HR: 1.11, 95% CI 0.97-1.27; I2 = 67%). In the subgroup analysis, the risk for breast cancer did not significantly increase among patients with mild psoriasis (pooled HR: 1.04, 95% CI 0.97-1.12; I2 = 6%), and the risk for breast cancer did not significantly increase among those with moderate-to-severe psoriasis (pooled HR: 0.96, 95% CI 0.72-1.28; I2 = 0%). Patients with mild or moderate-to-severe psoriasis are not at an elevated risk of breast cancer.

Effects of Preoperative Chronic Steroid Use on Postoperative Outcomes in Orthopedic Surgery: A Systematic Review and Meta-Analysis.

Higher rates of postoperative complications have been found in preoperative chronic steroid users. However, the effects of preoperative chronic steroid use on outcomes in orthopedic surgery were unclear. We performed a systematic review of cohort studies examining the effects of chronic steroid use on postoperative outcomes following orthopedic surgery and searched PubMed, Embase, and CENTRAL through 29 April 2023. We included 17 studies with 1,546,562 patients. No increase in 30-day mortality (adjusted odds ratio (aOR) 1.40, 95% confidence interval (CI) 0.64-3.09) and composite thromboembolic events (aOR 1.61, 95% CI 0.99-2.63) but increases in 30-day overall complications (aOR 1.42, 95% CI 1.16-1.75), wound dehiscence (aOR 2.91, 95% CI 1.49-5.66), infectious complications (any infection (aOR 1.61, 95% CI 1.44-1.80), sepsis (aOR 2.07, 95% CI 1.34-3.21), superficial surgical site infection (SSI) (aOR 1.73, 95% CI 1.03-2.89) and deep SSI (aOR 1.96, 95% CI 1.26-3.05)), re-admission (aOR 1.62, 95% CI 1.48-1.77), both 30-day (aOR 1.28, 95% CI 1.03-1.59) and 1-year re-operation (aOR 1.78, 95% CI 1.09-2.92), pulmonary embolism (aOR 5.94, 95% CI 1.52-23.29), and deep vein thrombosis (aOR 2.07, 95% CI 1.24-3.46) were detected in preoperative steroid users. An increased risk of adverse outcomes following orthopedic surgery in chronic steroid users was found.

Association of Psoriasis With Hearing Loss: A Systematic Review and Meta-Analysis.

BACKGROUND: The relation between psoriasis and hearing loss has been unclear. OBJECTIVE: To investigate the association of psoriasis with hearing loss. METHODS: We searched MEDLINE and Embase on 12th November 2022 for studies on the association between psoriasis and hearing loss. We conducted a random-effects model meta-analysis to calculate pooled mean difference (MD) in the pure tone thresholds, pooled odds ratio for sensorineural hearing loss, and pooled hazard ratio for sudden sensorineural hearing loss related to psoriasis. RESULTS: We included 12 case-control/cross-sectional and 3 cohort studies with 202,683 subjects. Psoriasis was associated with hearing loss at 500 Hz (pooled MD 2.21, 95% CI (CI) 0.13 to 4.29), 1000 Hz (pooled MD 2.97, 95% CI 1.01 to 4.93), 2000 Hz (pooled MD 5.13, 95% CI 2.45 to 7.82), 4000 Hz (pooled MD 9.3, 95% CI 5.1 to 13.51), and 6000 Hz (pooled MD 11.04, 95% CI 5.05 to 17.03). Patients with psoriasis had increased odds for sensorineural hearing loss (pooled odds ratio 3.85, 95% CI 1.07-13.9) and risk for sudden sensorineural hearing loss (pooled hazard ratio 1.45; 95% CI 1.22-1.71). CONCLUSION: Psoriasis is associated with hearing loss, especially at high frequencies.

Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: Cases of inflammatory bowel disease (IBD) following isotretinoin use have been reported previously, but whether isotretinoin exposure is associated with IBD has been unclear. OBJECTIVE: The aim was to evaluate whether isotretinoin use is associated with IBD. METHODS: We performed a systematic review and searched MEDLINE, Embase, and CENTRAL databases from inception to January 27, 2023 for relevant case-control and cohort studies. Our outcome was the pooled odds ratio (OR) for IBD and its two subtypes (Crohn disease and ulcerative colitis) in relation to isotretinoin exposure. We conducted a random-effects model meta-analysis and a sensitivity analysis by excluding low-quality studies. A subgroup analysis was undertaken by including studies considering antibiotic use. A trial sequential analysis (TSA) was performed to test the robustness of the conclusiveness of our results. RESULTS: We included eight studies (four case-control and four cohort studies) with a total of 2,522,422 participants. The meta-analysis found no increased odds for IBD among patients receiving isotretinoin (OR 1.01; 95% confidence interval [CI] 0.80-1.27). Nor did the meta-analysis find increased odds for either Crohn disease (OR 0.87; 95% CI 0.65-1.15) or ulcerative colitis (OR 1.27; 95% CI 0.94-1.73) associated with isotretinoin exposure. The sensitivity and subgroup analyses produced similar results. In TSA, the Z-curve reached the futility boundaries when using relative risk reduction thresholds ranging from 5% to 15%. CONCLUSION: This meta-analysis with TSA found no evidence of an association of isotretinoin use with IBD. Isotretinoin should not be withheld because of unnecessary concerns for the development of IBD. PROSPERO REGISTRATION NO: CRD42022298886.

Biologic Disease-Modifying Antirheumatic Drugs for Preventing Radiographic Progression in Psoriatic Arthritis: A Systematic Review and Network Meta-Analysis.

The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66-8.29), etanercept (OR 4.19, 95% CI 1.65-10.61), certolizumab pegol (OR 2.83, 95% CI 1.55-5.2), secukinumab 300 mg (OR 2.63, CI 1.62-4.27), infliximab (OR 2.54, CI 1.13-5.69), ixekizumab (OR 2.22, 95% CI 1.06-4.65), golimumab (OR 2.21, 95% CI 1.24-3.93), and abatacept (OR 1.54, 95% CI 1.03-2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) -0.59, 95% CI -0.87, -0.3), etanercept (SMD -0.51, 95% CI -0.78, -0.23), adalimumab (SMD -0.45, 95% CI -0.64, -0.26), ixekizumab (SMD -0.37, 95% CI -0.62, -0.12), secukinumab 300 mg (SMD -0.33, 95% CI -0.50, -0.15), golimumab (SMD -0.33, 95% CI -0.58, -0.09), secukinumab 150 mg (SMD -0.25, 95% CI -0.43, -0.07), certolizumab pegol (SMD -0.23, 95% CI -0.44, -0.03), and ustekinumab (SMD -0.19, 95% CI -0.35, -0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression.

Real-World Effects of Biologics on Renal Function in Psoriatic Patients: A Retrospective Study.

BACKGROUND: Patients with severe psoriasis are prone to deterioration of renal function. Whether biologics with potent anti-inflammatory action can prevent deterioration of renal function in psoriatic patients was unclear. OBJECTIVE: To investigate the effects of different biologics on renal function in patients with severe psoriasis. METHODS: By using the Chang Gung Research Database in Taiwan during 2006-2018, we analyzed the changes in renal function of psoriatic patients from 2 years before biologic treatments to baseline (start of biologic treatment) to after 2 years' treatment with different classes of biologics (anti-TNF, anti-IL-12/23, and anti-IL-17 agents). The renal function was evaluated by estimated glomerular filtration rate (eGFR) and the staging of chronic kidney disease (CKD). We further analyzed the risk factors of progression on the staging of CKD during biologics treatment. RESULTS: We included 601 patients with severe psoriasis receiving continuous use of biologics for ≥ 2 years. We detected no significant differences between pre-biologic treatment with conventional systemic treatment and post-biologic treatment in the levels of eGFR and progression of CKD staging among psoriatic patients receiving different classes of biologics. Most patients (97.8%) remained at stable CKD stage, while progression of CKD stage over time occurred in 13 patients (2.2%), with seven treated with anti-TNF biologics and six treated with anti-IL-12/23 biologics. Of note, all 52 patients receiving anti-IL-17 biologics had stable CKD. Progression of CKD during biologics use was associated with lower baseline levels of eGFR, higher baseline CKD stage, older age, diabetes, and dyslipidemia. Further multiple logistic regression analysis showed diabetes as an independent factor for the deterioration of renal function during biologic treatment. CONCLUSIONS: Biologic treatments failed to improve but did not worsen renal function of psoriatic patients during a 2-year follow-up period. Diabetes is an important risk factor for the deterioration of renal function.

Associations of thiazide use with skin cancers: a systematic review and meta-analysis.

BACKGROUND: Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides. METHODS: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analysed separately. A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use. RESULTS: We included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.16, 95% CI 1.08-1.24; HR 1.26, 95% CI 1.04-1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06-1.65; HR 1.61, 95% CI 0.97-2.67), and melanoma (OR 1.11, 95% CI 1.02-1.20; HR 1.03, 95% CI 0.93-1.14). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43-4.57; HR 1.20, 95% CI 1.00-1.45). Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05-1.33), nodular (OR 1.23, 95% CI 1.08-1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08-1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. However, the associations of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide. CONCLUSIONS: Hydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions. TRIAL REGISTRATION: PROSPERO CRD42021234317 .

Efficacy and Safety of Topical Mechanistic Target of Rapamycin Inhibitors for Facial Angiofibromas in Patients with Tuberous Sclerosis Complex: A Systematic Review and Network Meta-Analysis.

Previous studies have suggested that the topical mechanistic target of rapamycin (mTOR) inhibitors may be effective in treating facial angiofibromas in patients with tuberous sclerosis complex (TSC). Various concentrations of topical sirolimus for TSC have been tested, but their comparative efficacy and safety remained unclear. To assess the effects of topical mTOR inhibitors in treating facial angiofibromas, we conducted a systematic review and network meta-analysis (NMA) and searched MEDLINE, Embase, and Cochrane Library for relevant randomized controlled trials on 14 February 2022. The Cochrane Collaboration tool was used to assess the risk of bias of included trials. Our outcomes were clinical improvement and severe adverse events leading to withdrawal. We included three trials on 261 TSC patients with facial angiofibromas. The NMA found when compared with placebo, facial angiofibromas significantly improved following the application of various concentrations of topical sirolimus (risk ratio being 3.87, 2.70, 4.43, and 3.34 for 0.05%, 0.1%, 0.2%, and 1%, respectively). When compared with placebo, all concentrations of topical sirolimus did not differ in severe adverse events leading to withdrawal. The ranking analysis suggested topical sirolimus 0.2% as the most effective drug. In conclusion, topical sirolimus 0.05-1% are effective and safe in treating facial angiofibromas in patients with TSC, with topical sirolimus 0.2% being the most effective.

Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease: A Systematic Review and Meta-analysis.

IMPORTANCE: Psoriasis, venous thromboembolism (VTE), and peripheral vascular disease (PVD) share similar mechanisms involving chronic inflammation. However, the associations between psoriasis and VTE or PVD are unclear. OBJECTIVE: To determine the association of psoriasis with incident VTE and PVD. DATA SOURCES: MEDLINE, Embase, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for relevant publications from their respective inception through May 21, 2021. No restrictions on language or geographic locations were imposed. STUDY SELECTION: Two authors independently selected cohort studies that investigated the risk for incident VTE or PVD in patients with psoriasis. Any discrepancy was resolved through discussion with 2 senior authors until reaching consensus. Only 13 initially identified studies met the selection criteria for qualitative review, and only 9 of these for quantitative analysis. DATA EXTRACTION AND SYNTHESIS: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Two authors independently extracted data and assessed the risk of bias of included studies by using the Newcastle-Ottawa Scale. Disagreements were resolved by discussion with 2 other authors. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratios (HRs) with the corresponding confidence intervals for incident VTE and PVD. Subgroup analyses based on arthritis status, psoriasis severity, sex, and geographic location were also performed. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident VTE and PVD associated with psoriasis. RESULTS: A total of 13 cohort studies with 12 435 982 participants were included. The meta-analysis demonstrated a significantly increased risk for incident VTE (pooled HR, 1.26; 95% CI, 1.08-1.48) and PVD (pooled HR, 1.27; 95% CI, 1.16-1.40) among patients with psoriasis. Subgroup analyses illustrated increased risk for incident VTE among participants with psoriatic arthritis (pooled HR, 1.24; 95% CI, 1.01-1.53), women (pooled HR, 1.89; 95% CI, 1.36-2.61), and those in Asia (pooled HR, 2.02; 95% CI, 1.42-2.88) and Europe (pooled HR, 1.28; 95% CI, 1.06-1.53). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found an increased risk for incident VTE and PVD among patients with psoriatic disease. Typical presentations of VTE or PVD should not be overlooked in patients with psoriasis. Risk factors, such as obesity, physical inactivity, smoking, and varicose veins, should be identified and treated in patients with psoriasis, and medications like hormone-related therapies should be prescribed with caution.

Rosacea, Germs, and Bowels: A Review on Gastrointestinal Comorbidities and Gut-Skin Axis of Rosacea.

Rosacea is a chronic inflammatory disease with complicated pathophysiology that involves genetic and environmental elements and dysregulation of innate and adaptive immunity, neurovascular responses, microbiome colonization or infection, resulting in recurrent inflammation. Rosacea has been reported associated with various gastrointestinal diseases including inflammatory bowel disease, celiac disease, irritable bowel syndrome, gastroesophageal reflux disease, Helicobacter pylori (HP) infection, and small intestine bacterial overgrowth (SIBO). The link may involve common predisposing genetic, microbiota, and immunological factors, comprising the theory of the gut-skin axis. Although the evidence is still controversial, interestingly, medications for eradicating SIBO and HP provided an effective and prolonged therapeutic response in rosacea, and conventional therapy for which is usually disappointing because of frequent relapses. In this article, we review the current evidence and discuss probable mechanisms of the association between rosacea and gastrointestinal comorbidities.

Bladder volume reproducibility after water consumption in patients with prostate cancer undergoing radiotherapy: A systematic review and meta-analysis.

BACKGROUND: To minimize toxicity due to radiotherapy in patients with prostate cancer, high bladder volume reproducibility is essential. Water consumption is often used to increase bladder volume reproducibility, but the optimal amount of water required to be consumed remains unclear. We aimed to analyzed the relationship between water consumption and bladder volume reproducibility in patients undergoing radiotherapy for prostate cancer. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials and cohort studies that assessed bladder volume change after water consumption in patients with prostate cancer undergoing radiotherapy. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant studies published from database inception up until July 4, 2020. The Newcastle-Ottawa Scale was used to evaluate the risk of bias in the included studies. The outcome was the mean difference (MD) of bladder volume after water consumption, evaluated through meta-analysis using a random-effects model. RESULTS: Ten cohort studies and one randomized controlled trial with a total of 417 patients were included. For 300-400 ml water consumption, the bladder volume MD between during treatment and at computer tomography-simulation (95% confidence interval [CI]) was -11.97 (-51.68 to 27.74), was -45.99 (-82.85 to -9.13) for 500-540 ml water consumption and -45.92 (-78.86 to -12.98) for water consumption until full-bladder sensation was reached. CONCLUSION: Consuming 300-400 ml of water potentially leads to the best bladder volume reproducibility; moreover, the higher the water consumption volume, the lower the bladder volume reproducibility.

Concomitant psoriasis and hidradenitis suppurativa responsive to adalimumab therapy: A case series.

Psoriasis and hidradenitis suppurativa are inflammatory dermatoses that have been associated with arthritis, metabolic syndrome, obesity, and smoking. They share common pathogenic mechanisms such as elevated levels of several proinflammatory cytokines including tumor necrosis factor (TNF), interleukin-17A, and impaired Notch pathway. Thus, treatments for both diseases are sometimes overlapping. Biological therapy such as adalimumab is effective for patients with hidradenitis suppurativa and psoriasis. Adalimumab is a monoclonal antibody that binds to TNF and inhibits the cytokine interaction with the TNF receptors, thus inhibiting the inflammatory cascade. Currently, data are lacking on the treatment for co-occurrence of psoriasis and hidradenitis suppurativa. This case series describes three patients with a diagnosis of concomitant psoriasis and hidradenitis suppurativa. In these cases, after 12 weeks of treatment with adalimumab 40 mg every other week, the average Psoriasis Area Severity Index score reduced from 21.4 to 2.9 for psoriasis, Hidradenitis Suppurativa-Physician's Global Assessment from 3.3 to 0.7, and pain Visual Analog Scale for hidradenitis suppurativa from 4.6 to 2. The results suggest that adalimumab is a treatment of choice for patients with concomitant hidradenitis suppurativa and psoriasis.

Predictors of hepatitis B and C virus reactivation in patients with psoriasis treated with biologic agents: a 9-year multicenter cohort study.

BACKGROUND: The increasing use of biologics is accompanied by a risk of hepatitis B (HBV) and C virus (HCV) reactivation. OBJECTIVE: To determine the predictors of HBV and HCV reactivation in patients with psoriasis receiving biologics. METHODS: This study screened 2060 patients with psoriasis (3562 treatment episodes) who were taking biologics from 2009 to 2018. There were 359 patients with psoriasis with HBV (561 treatment episodes) and 61 with HCV infection (112 treatment episodes). RESULTS: During 8809 and 1522 person-months of follow-up, 88 treatment episodes for HBV involved HBV reactivation, and 14 episodes of HCV involved reactivation. The reactivation rate was significantly higher in treatment episodes of chronic HBV infection than in that of occult HBV (34.3% vs 3.2%, P = .001) and resolved HBV (34.3% vs 5.0%, P < .001). The multivariate analysis revealed that being hepatitis B surface antigen seropositive, being hepatitis B e-antigen seropositive, and tumor necrosis factor-α-inhibitor therapy were risk factors for HBV reactivation, whereas antiviral prophylaxis was effective in reducing the risk of HBV reactivation. No predictors were significantly associated with HCV reactivation. LIMITATIONS: Observational design and a lack of a comparison group. CONCLUSION: Patients with psoriasis on biologics have a risk of HBV and HCV reactivations, particularly those who are seropositive for hepatitis B surface antigen and hepatitis B e-antigen and undergoing tumor necrosis factor-α-inhibitor therapy.

Association of psoriasis with colorectal cancer.

BACKGROUND: The relation between psoriasis and colorectal cancer (CRC) was largely unclear. OBJECTIVE: To investigate the association of psoriasis with CRC. METHODS: A systematic review and meta-analysis of observational studies that examined the association of psoriasis with CRC was performed. We searched MEDLINE and Embase on March 24, 2020, for relevant studies. The Newcastle-Ottawa scale was used to evaluate the risk of bias of included studies. We conducted a random-effects model meta-analysis and subgroup analysis according to sex. RESULTS: We included 9 cohort studies with 10,544,609 individuals. We found a significantly increased risk for CRC in patients with psoriasis (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.08-1.24). Subgroups analysis according to sex found significantly increased risk for CRC in female patients with psoriasis (HR, 1.41; 95% CI, 1.16-1.72) but not in male patients (HR, 1.18; 95% CI, 0.92-1.50). LIMITATIONS: No data on psoriatic arthritis. CONCLUSIONS: Patients with psoriasis have an increased risk for CRC. Gastroenterology consultation and colonoscopic examination are indicated for patients with psoriasis presenting with bowel symptoms.

Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Drug Survival of Biologics in Treating Ankylosing Spondylitis: A Systematic Review and Meta-analysis of Real-World Evidence.

BACKGROUND: The last decade has witnessed the increasing use of biologics for the treatment of ankylosing spondylitis (AS). Drug survival is an outcome incorporating real-world effectiveness and safety. However, the drug survival of biologics in treating AS is unclear. OBJECTIVE: The aim was to assess the drug survival of biologics (tumor necrosis factor inhibitors and anti-interleukin-17 monoclonal antibodies) in treating AS. METHODS: We conducted a systematic review and meta-analysis and searched the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases up to 13th May 2020. Studies that analyzed the drug survival of biologics for AS and reported the respective annual data for each biologic for at least 1 year were included. Two authors independently screened and selected studies and assessed their risk of bias. A third author was available for arbitrating discrepancies. The Newcastle-Ottawa Scale was employed to evaluate the risk of bias of included studies. We conducted a random-effects model meta-analysis to obtain pooled drug survival from year 1 to 5. We performed subgroup analyses for biologic-naïve patients, first-line versus second- and third-line biologics, discontinuation due to loss of effectiveness and adverse effects, and high-quality studies. RESULTS: We included 39 studies with 32,493 patients. The drug survival decreased from 76% at year 1 to 51% at year 5 for etanercept, from 75 to 51% for adalimumab, from 76 to 53% for infliximab, from 72 to 49% for golimumab, and from 63 to 57% for certolizumab pegol. The drug survival rate for secukinumab was 0.77 (95% confidence interval 0.64‒0.90) at year 1. Subgroup analyses on biologic-naïve patients and discontinuation due to adverse effects found no differences in the drug survival of various biologics except for a lower drug survival of infliximab in biologic-naïve patients. The drug survival for first-line biologics was higher than for second- and third-line biologics. CONCLUSION: To the best of our knowledge, this study is the first systematic review and meta-analysis on the drug survival of biological therapies for AS patients. The drug survival of all biologics in treating AS appeared comparable, but is higher in first-line biologics than second- and third-line biologics. To date there are scarce data on the drug survival of newly available biologics, for example, anti-interleukin-17 biologics. PROSPERO REGISTRATION NO: CRD42018114204.

Low molecular weight heparin for prevention of microvascular occlusion in digital replantation.

BACKGROUND: The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear. This is an update of the review first published in 2013. OBJECTIVES: To assess if treatment with subcutaneous LMWH improves the salvage rate of the digits in patients with digital replantation after traumatic amputation. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 17 March 2020. The authors searched PubMed, China National Knowledge Infrastructure (CNKI) and Chinese Electronic Periodical Services (CEPS) on 17 March 2020 and sought additional trials from reference lists of relevant publications. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials comparing treatment with LMWH versus any other treatment in participants who received digital replantation following traumatic digital amputation. DATA COLLECTION AND ANALYSIS: Two review authors (PL, CC) independently extracted data and assessed the risk of bias of the included trials using Cochrane's 'Risk of bias' tool. Disagreements were resolved by discussion. We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included two new randomised trials in this update, bringing the total number of included trials to four. They included a total of 258 participants, with at least 273 digits, from hospitals in China. Three studies compared LMWH versus UFH, and one compared LMWH versus no LMWH. The mean age of participants ranged from 24.5 to 37.6 years. In the studies reporting the sex of participants, there were a total of 145 men and 59 women. The certainty of the evidence was downgraded to low or very low because all studies were at high risk of performance or reporting bias (or both) and there was imprecision in the results due to the small numbers of participants. The three studies comparing LMWH versus UFH reported the success rate of replantation using different units of analysis (participant or digit), so we were unable to combine data from all three studies (one study reported results for both participants and digits). No evidence of a benefit in success of replantation was seen in the LMWH group when compared with UFH, regardless of whether the outcomes were reported by number of participants (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.87 to 1.10; 130 participants, 2 studies; very low-certainty evidence); or by number of digits (RR 0.97, 95% CI 0.90 to 1.04; 200 digits, 2 studies; low-certainty evidence). No studies reported the incidence of compromised microcirculation requiring surgical or non-surgical therapy, or any systemic/other causes of microvascular insufficiency. There was no evidence of a clear difference between the LMWH and UFH groups in occurrence of arterial occlusion (RR 1.08, 95% CI 0.16 to 7.10; 54 participants, 1 study; very low-certainty evidence) or venous occlusion (RR 0.81, 95% CI 0.20 to 3.27; 54 participants, 1 study; very low-certainty evidence). Two studies reported adverse effects. The LMWH and UFH groups showed no evidence of a difference in wound bleeding (RR 0.53, 95% CI 0.23 to 1.23; 130 participants, 2 studies; low-certainty evidence), haematuria (RR 0.43, 95% CI 0.09 to 2.11; 130 participants, 2 studies; very low-certainty evidence), ecchymoses (RR 0.82, 95% CI 0.21 to 3.19; 130 participants, 2 studies; very low-certainty evidence), epistaxis (RR 0.27, 95% CI 0.03 to 2.32; 130 participants, 2 studies; very low-certainty evidence), gingival bleeding (RR 0.18, 95% CI 0.02 to 1.43; 130 participants, 2 studies; very low-certainty evidence), and faecal occult blood (RR 0.27, 95% CI 0.03 to 2.31; 130 participants, 2 studies; very low-certainty evidence). We could not pool data on coagulation abnormalities as varying definitions and tests were used in the three studies. One study compared LMWH versus no LMWH. The success rate of replantation, when analysed by digits, was reported as 91.2% success in the LMWH group and 82.1% in the control group (RR 1.11, 95% CI 0.93 to 1.33; 73 digits, 1 study; very low-certainty evidence). Compromised microcirculation requiring surgical re-exploration, analysed by digits, was 11.8% in the LMWH group and 17.9% in the control group (RR 0.86, 95% CI 0.21 to 3.58; 73 digits, 1 study; very low-certainty evidence). Compromised microcirculation requiring incision occurred in five out of 34 digits (14.7%) in the LMWH group and eight out of 39 digits (20.5%) in the control group (RR 0.72, 95% CI 0.26 to 1.98; 73 digits; very low-certainty evidence). Microvascular insufficiency due to arterial occlusion, analysed by digits, was 11.8% in the LMWH group and 17.9% in the control group (RR 0.66, 95% CI 0.21 to 2.05; 73 digits, 1 study; very low-certainty evidence), and venous occlusion was 14.7% in the LMWH group and 20.5% in the control (RR 0.72, 95% CI 0.26 to 1.98; 73 digits, 1 study; very low-certainty evidence). The study did not report complications or adverse effects. AUTHORS' CONCLUSIONS: There is currently low to very low-certainty evidence, based on four RCTs, suggesting no evidence of a benefit from LMWH when compared to UFH on the success rates of replantation or affect microvascular insufficiency due to vessel occlusion (analysed by digit or participant). LMWH had similar success rates of replantation; and the incidence rate of venous and arterial microvascular insufficiency showed no evidence of a difference between groups when LMWH was compared to no LMWH (analysed by digit). Similar rates of complications and adverse effects were seen between UFH and LMWH. There was insufficient evidence to draw conclusions on any effect on coagulation when comparing LMWH to UFH or no LMWH. The certainty of the evidence was downgraded due to performance and reporting bias, as well as imprecision in the results. Further adequately powered studies are warranted to provide high-certainty evidence.

Correction to: DNMT3b/OCT4 expression confers sorafenib resistance and poor prognosis of hepatocellular carcinoma through IL-6/STAT3 regulation.

In the original publication of this article [1], labelling within Fig. 7a was incorrect. The updated figure is shown below, with 'DMT1' now corrected to read 'DNMT1'.

Change in body weight and body mass index in psoriasis patients receiving biologics: A systematic review and network meta-analysis.

BACKGROUND: Previous studies have suggested that biologic therapy for psoriasis might relate to body weight gain. OBJECTIVE: To assess the changes in body weight and body mass index (BMI) in psoriasis patients after receiving various biologics. METHODS: We conducted a systematic review and network meta-analysis to evaluate the changes in body weight and BMI in psoriasis patients receiving biologics. On March 1, 2019, we searched Medline, Embase, and Cochrane Central Register of Controlled Trials for relevant studies. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS: We included 6 studies with 862 psoriasis patients. Compared with conventional systemic treatments, treatment with tumor necrosis factor α inhibitors was associated with a significant increase in body weight (mean difference 1.40 kg, 95% confidence interval 0.88-1.93 kg) and BMI (0.39 kg/m2, 95% confidence interval 0.24-0.54 kg/m2). In contrast, no significant increase in body weight or BMI was found among patients receiving anti-interleukin (IL)-12/23 or anti-IL-17 biologics. LIMITATIONS: Only 1 study reported body weight and BMI for patients receiving the anti-IL-17 biologic. CONCLUSION: Tumor necrosis factor α inhibitor treatment appears to be associated with an increase in body weight and BMI, and treatment with anti-IL-12/23 and anti-IL-17 biologics do not. This association should be considered before initiating biologics for overweight and obese patients.