Health-related Quality of Life of Patients with Rosacea: A Systematic Review and Meta-analysis of Real-world Data.

Patients with rosacea commonly experience stigmatization, which induces stress and thereby exacerbates their symptoms. Given the strong effects of rosacea on health-related quality of life (HRQoL), addressing the physical and psychosocial aspects of rosacea is essential. To examine the effects of rosacea on HRQoL, we conducted a systematic review and meta-analysis involving real-world data. PubMed, EMBASE, and the Cochrane Library were searched, and randomized controlled trials (RCTs), cross-sectional studies, and case series evaluating the HRQoL of patients with rosacea were included. HRQoL assessment tools such as the Dermatology Life Quality Index (DLQI) and Rosacea-Specific Quality-of-Life Questionnaire (RosaQoL) were used. Data on 13,453 patients were retrieved from 52 eligible studies: 4 RCTs, 15 case series, and 33 cross-sectional studies. Compared with healthy controls, patients with rosacea had significantly lower DLQI scores (standardized mean difference [SMD] = -1.09, 95% confidence interval [CI] = -0.81 to -1.37). The DLQI scores after treatment were higher than those before treatment (SMD = -1.451, 95% CI = -1.091 to -1.810). The pooled estimates for the overall DLQI and RosaQoL scores were 8.61 and 3.06, respectively. In conclusion, patients with rosacea have lower HRQoL compared with healthy individuals, and treatment for rosacea improves their HRQoL.

Risk factors for poor progression of addictive internet use across different COVID-19 periods in China.

BACKGROUND AND OBJECTIVES: Addictive behaviors are serious factors for mental health and usually increase during public crises. We identified the vulnerable characteristics for bad prognosis of addictive internet use across different periods of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Self-reported questionnaires were delivered in three waves through jdh.com during the outbreak (n = 17,960), remission (n = 15,666), and dynamic zero (n = 12,158) periods of COVID-19 pandemic in China. Internet addiction degree was assessed using the Internet Addiction Test. The different progression groups were divided using a latent class growth model among 1679 longitudinal participants. Risk factors for bad progression were identified by two-step logistic regression. RESULTS: A total of 40.16% of participants reported an increase in the addictive degree of internet use compared with prepandemic. Across different COVID-19 periods, the overall trend of addictive internet use was downward among general Chinese study participants (Mslope = -1.56). Childhood traumatic experiences, deterioration of physical health, depression, and anxiety during remission and dynamic periods were the main risk factors for the bad progression of pandemic-induced addictive internet use. DISCUSSION AND CONCLUSIONS: Addictive internet use was remitted following relaxed control policies during the COVID-19 pandemic. Negative childhood experiences and bad mental status during the recovery period were harmful to coping with pandemic-related addictive internet use. SCIENTIFIC SIGNIFICANCE: Our findings profiled the general trend of addictive internet use and the vulnerable characteristics of its bad progression across different periods of the first wave of COVID-19 pandemic in China. Our findings provide valuable insights for preventing the long-term adverse effects of negative public events on Internet addiction.

Effects of probiotics supplementation on skin photoaging and skin barrier function: A systematic review and meta-analysis.

BACKGROUND: Ultraviolet (UV) irradiation is one of the major causes of skin aging. To date, there remains limited evidence on using oral probiotics for skin anti-photoaging. OBJECTIVES: This systematic review and meta-analysis aims to assess the effects of probiotics on skin photoaging. METHODS: We searched the PubMed and Embase databases for studies published until August 31, 2021, and included randomized controlled trials, murine randomized controlled experiments, and in vitro studies. Skin barrier function was compared between UV irradiated probiotics and controls. RESULTS: After given oral probiotics supplements, a significant reduction was shown in all types of measured MMPs in both murine and in vitro studies. Oral probiotics supplementation significantly reversed UV-induced increase of epidermal thickness (standardized mean differences [SMD] = -1.76; 95% confidence interval [CI] = -3.04 to -0.49; p = .007; I2  = 81%), UV-induced increase trans-epidermal water loss (SMD = -1.72; 95% CI = -2.76 to -0.67; p = .001; I2  = 57%), and UV-induced skin dehydration (SMD = 1.85; 95% CI = 1.16 to 2.55; p < .00001; I2  = 4%). CONCLUSIONS: Probiotics are effective against skin photoaging in terms of MMP pathways and reversing skin barrier function from murine randomized data. Further randomized controlled trials on humans are required to warrant these results.

Can Heart Rate Variability be Viewed as a Biomarker of Problematic Internet Use? A Systematic Review and Meta-Analysis.

Heart rate variability (HRV) has been used to explore the parasympathetic activity of individuals with problematic Internet use (PIU), but the results are controversial. We conducted a systematic review and meta-analysis of studies comparing HRV in PIU individuals and healthy participants from several databases. HRV was analyzed according to the parasympathetic activity in hierarchical order (primary analysis), and the total variability (secondary analysis). The baseline HRV and HRV reactivity were both considered. Of the 106 studies screened, 12 were included in the quantitative analysis. Significant differences were observed for baseline HRV in PIU individuals compared to the controls. Regarding HRV reactivity, PIU individuals did not have a significantly lower HRV value during pleasant or unpleasant stimuli. In summary, PIU individuals and healthy subjects had significantly different resting state parasympathetic activity. The finding of HRV reactivity in PIU individuals awaits further investigation.

Continuous use of metformin in patients receiving contrast medium: what is the evidence? A systematic review and meta-analysis.

OBJECTIVES: Substantial inconsistencies exist in current guidelines regarding recommendations of metformin usage with the administration of a contrast medium. We aimed to perform a meta-analysis to determine whether the risks of contrast-induced acute kidney injury (CI-AKI) and lactic acidosis increase with metformin use in diabetic patients receiving a contrast medium. METHODS: Studies were retrieved from databases from inception to May 15, 2021. Studies that compared the outcomes of using metformin with not using metformin during contrast medium administration were included. The primary outcomes were incidence of CI-AKI and lactic acidosis. The secondary outcomes were renal function changes from baseline. Data analysis was using risk ratio (RR) for dichotomous outcomes and mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes. RESULTS: Analyses of two randomized controlled trials and four retrospective cohorts examining a total of 1459 patients revealed no significant differences in the incidence of CI-AKI (RR = 1.08; 95% CI, 0.72 to 1.63) and in changes in renal function measurements (serum creatinine: MD = 0.00 mg/dL, 95% CI, - 0.05 to 0.05; estimated glomerular filtration rate: MD = 0.22, 95% CI, - 2.47 to 2.91) after contrast medium administration between patients using and not using metformin. CONCLUSIONS: There is no evidence that continuing metformin during contrast medium administration is associated with a higher risk of CI-AKI, lactic acidosis, or renal function deterioration compared to patients who discontinued metformin or who were not metformin users. The limited quality of the included studies may compromise the strength of evidence provided in this meta-analysis. KEY POINTS: There is no need to discontinue metformin either before or after intravenous contrast medium exposure in patients with eGFR > 30 mL/min/1.73 m2. In patients receiving intra-arterial contrast medium with first-pass renal exposure, there is no need to withhold metformin if eGFR is above 60 mL/min/1.73 m2. For patients who have an eGFR level between 30 and 60 mL/min/1.73 m2 and are receiving intra-arterial contrast medium with first-pass renal exposure, no case of lactic acidosis was observed based on present data, but further evidence is needed to make a strong suggestion regarding its safety.

Dehydroepiandrosterone status and efficacy of dehydroepiandrosterone supplementation for bone health in anorexia nervosa: A systematic review and meta-analysis.

OBJECTIVE: This study was designed to determine the status of dehydroepiandrosterone (DHEA) in women with anorexia nervosa (AN) and to assess the efficacy of DHEA supplementation as a treatment for bone health in women with AN. METHOD: Studies were retrieved from the PubMed, Embase, Cochrane Library, MEDLINE, and Scopus databases from inception to February 14, 2022. Observational studies that compared serum DHEA levels between women with AN and healthy controls were included for meta-analysis, and randomized controlled trials (RCTs) that evaluated the effects of DHEA supplementation on bone mass were reviewed. RESULTS: Meta-analysis of 15 cross-sectional studies revealed that patients with AN had significantly elevated serum DHEA levels (mean difference (MD) = 311.63 ng/dl; 95% confidence interval (CI), 78.01-545.25) and reduced DHEAS levels (MD = -24.90 µg/dl; 95% CI, -41.72 to -8.07) compared with healthy controls. A systematic review of seven RCTs found that DHEA monotherapy does not improve bone mineral density (BMD) compared with placebo after adjusting for weight gain. While the combination of DHEA and conjugated oral contraceptives has led to increased bone strength and decreased bone loss, the beneficial effect appears to be limited to older adolescents and adults with closed physes. Potential detrimental effects on BMD were identified in younger adolescents with open physes in one study. DISCUSSION: Due to the lack of apparent benefit of DHEA in women with AN and its potential detrimental effect on BMD in young patients with AN, current evidence does not support the use of DHEA. PUBLIC SIGNIFICANCE: This study demonstrates that women with anorexia nervosa have abnormal levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), which have been suggested by previous studies to play a role in the development of low bone density in this condition. However, current evidence does not support the use of DHEA as a treatment to preserve bone health in patients with anorexia nervosa given the lack of clear benefit following its use and also because of a potential detrimental effect on bone mineral density in young patients with anorexia nervosa.

OBJETIVO: Este estudio fue diseñado para determinar el estado de la dehidroepiandrosterona (DHEA) en mujeres con anorexia nerviosa (AN) y para evaluar la eficacia de la suplementación con DHEA como tratamiento para la salud ósea en mujeres con AN. MÉTODO: Los estudios se obtuvieron de las bases de datos PubMed, Embase, Cochrane library, MEDLINE y Scopus desde su inicio hasta el 14 de febrero de 2022. Se incluyeron estudios observacionales que compararon los niveles séricos de DHEA entre mujeres que padecen AN y controles sanos para el metanálisis, y se revisaron los ensayos controlados aleatorios (ECA) que evaluaron los efectos de la suplementación con DHEA sobre la masa ósea. RESULTADOS: El metanálisis de 15 estudios transversales reveló que los pacientes que padecen AN tenían niveles séricos significativamente elevados de DHEA (diferencia de medias [DM] = 311,63 ng/dL; intervalo de confianza [IC] del 95%, 78,01-545,25) y niveles reducidos de DHEAS (DM = -24,90 µg/dL; IC del 95%, -41,72 a -8,07) en comparación con los controles sanos. La revisión sistemática de siete ECA encontró que la monoterapia con DHEA no mejora la densidad mineral ósea (DMO) en comparación con placebo después de ajustar el aumento de peso. Si bien la combinación de DHEA y anticonceptivos orales conjugados ha llevado a un aumento de la fuerza ósea y una disminución de la pérdida ósea, el efecto beneficioso parece limitarse a adolescentes mayores y adultos con placas de crecimiento cerradas. En un estudio se identificaron posibles efectos perjudiciales sobre la DMO en adolescentes más jóvenes con placas de crecimiento abiertas. DISCUSIÓN: Debido a la falta de beneficio aparente de la DHEA en mujeres que padecen AN y su posible efecto perjudicial sobre la DMO en pacientes jóvenes que padecen AN, la evidencia actual no apoya el uso de la DHEA.

Serum vitamin D levels in females with urinary incontinence: a meta-analysis of observational trials.

INTRODUCTION AND HYPOTHESIS: The association of vitamin D deficiency with female urinary incontinence is unclear. METHODS: A systematic review of English and non-English articles was conducted. All observational studies in databases including PubMed, EMBASE, the Cochrane Library Trials Register, and Google Scholar were searched until 5 October 2020. Additional studies were identified by contacting clinical experts and searching the bibliographies and abstracts of the compiled articles. Search terms included urinary incontinence and vitamin D. Article data, including study quality indicators, were independently extracted by two authors using predefined data fields. RESULTS: Two cohort studies, four case-control studies and five cross-sectional studies were included in the qualitative synthesis. Two cohort studies and one cross-sectional study, with a total of 2501 females, were included in the meta-analysis. Heterogeneity among the three studies was not observed (I2 = 0.0%, P = 0.69). All pooled analyses were based on fixed-effects models. No difference in vitamin D level was observed between the urinary incontinence group and the control group (mean difference 0.07 ng/ml; 95% confidence interval [CI] -0.57-0.72, P = 0.81, I2 = 0%). CONCLUSIONS: Our meta-analysis revealed that adult females with urinary incontinence did not have lower serum vitamin D levels than control females.

The Efficacy of Pulsed Dye Laser Treatment for Acne Vulgaris: A Systemic Review and Meta-Analysis.

BACKGROUND: Previous reports have shown that pulsed dye laser (PDL) is promising for the treatment of acne; however, results provide conflicting evidence. OBJECTIVE: To determine the efficacy of PDL in treating acne vulgaris. METHODS: A systematic review and meta-analysis of studies published before March 31, 2020 was conducted. Randomized controlled trials and case series were analyzed. The meta-analysis estimated the standardized mean difference (SMD) in acne severity score changes in patients treated by PDL versus control and also the SMD of the acne severity scores and comedone counts changes before and after PDL treatment. RESULTS: Eleven studies were included in this systematic review. Six studies were included in the meta-analysis. Pulsed dye laser treatment was not found to be superior to the control group in treating acne vulgaris (SMD: -0.285; 95% confidence interval [CI], -0.886 to 0.317). However, single-arm studies revealed a significantly improved acne severity score after PDL therapy (SMD, -1.321; 95% CI, -2.057 to -0.586), especially when a multiple-session treatment and a longer pulse duration were employed. The comedone counts were significantly decreased after PDL therapy (SMD, -0.596; 95% CI, -1.137 to -0.054). CONCLUSION: When treatment consisted of 4 or more sessions or longer pulse duration, PDL could significantly decrease the acne severity score.

Heart rate variability in patients with dementia or neurocognitive disorders: A systematic review and meta-analysis.

OBJECTIVE: Heart rate variability, a quantitative measure of mainly parasympathetic activity, has been applied in evaluating many types of psychiatric and neurological disorders, including dementia (or neurocognitive disorders). However, although dementia patients often showed significantly lower heart rate variability (various indices) than healthy controls, and different types of dementia had distinct heart rate variability features, the results were not identical across studies. We designed a systematic review and meta-analysis for incorporating data from different studies. METHODS: We gathered studies comparing heart rate variability in patients with dementia and in healthy controls. Heart rate variability was analysed in several ways: parasympathetic function in hierarchical order (main analysis), total variability, comparison of heart rate variability between different subtypes of dementia, specific indices of heart rate variability and heart rate variability reactivity. RESULTS: In the initial search, we found 3425 relevant articles, from which 24 studies with a total of 1107 dementia patients and 1017 control participants finally entered the main meta-analysis. The dementia patients had a significantly lower resting heart rate variability for parasympathetic function (Hedges' g = -0.3596, p = 0.0002) and total variability (Hedges' g = -0.3059, p = 0.0002) than the controls. For diagnostic subgroup analysis relative to the controls, heart rate variability was significantly lower in patients with mild cognitive impairment (Hedges' g = -0.3060) and in patients with dementia with Lewy bodies (Hedges' g = -1.4154, p < 0.0001). Relative to patients with Alzheimer's disease, heart rate variability in patients with dementia with Lewy bodies was significantly lower (Hedges' g = -1.5465, p = 0.0381). Meta-regression revealed that gender proportion was significantly associated with effect size. CONCLUSION: Our results show that dementia patients (especially those with dementia with Lewy bodies and mild cognitive impairment) have lower parasympathetic activity than healthy people. The influence of gender on the results should be carefully interpreted.

Heart rate variability in patients with anxiety disorders: A systematic review and meta-analysis.

AIMS: Patients with anxiety disorders (AD) have been found to have lower heart rate variability (HRV) than healthy individuals in some studies, but this was inconsistent. Furthermore, the influence of distinct diagnoses, study design, and demographic factors on the results was not comprehensively examined. METHODS: We gathered studies comparing HRV in patients with AD and in healthy controls. The parasympathetic activity in the hierarchical order principle was adopted in the main analysis. We adopted the random effects model to calculate the standardized mean difference. RESULTS: Of the 7805 screened studies, 99 were included in the quantitative analysis, with a total of 4897 AD patients and 5559 controls finally entered the meta-analysis. AD patients had a significantly lower resting-state HRV for parasympathetic activity compared to control (Hedges' g = -0.3897). For the diagnostic subgroup analysis relative to the controls, resting-state HRV was significantly lower in post-traumatic stress disorder, panic disorder, generalized anxiety disorder, and social anxiety disorder patients. HRV reactivity (all reactivity data, data on physiological challenge, and psychological challenge) did not show significant inter-group differences between AD patients and healthy subjects. CONCLUSIONS: The results supported that patients with AD had significantly lower resting-state HRV than the healthy population, but no alterations were found for HRV reactivity.

Tumor Suppressor miRNA-503 Inhibits Cell Invasion in Head and Neck Cancer through the Wnt Signaling Pathway via the WNT3A/MMP Molecular Axis.

Head and neck cancer (HNC) is the fifth most common cancer worldwide, and its incidence and death rates have been consistently high throughout the past decades. MicroRNAs (miRNAs) have recently gained significant attention because of their role in the regulation of a variety of biological processes via post-transcriptional silencing mechanisms. Previously, we determined a specific profile of miRNAs associated with HNC using a miRNA microarray analysis. Of the 23 miRNAs with highly altered expression in HNC cells, miR-503 was the most significantly downregulated miRNA. In this study, we confirmed that miR-503 acts as a tumor suppressor, as our results showed decreased levels of miR-503 in cancer cells and patients with HNC. We further characterized the role of miR-503 in the malignant functions of HNC. Although there was a minimal effect on cell growth, miR-503 was found to inhibit cellular invasion significantly. Algorithm-based studies identified multiple potential target genes and pathways associated with oncogenic mechanisms. The candidate target gene, WNT3A, was confirmed to be downregulated by miR-503 at both the mRNA and protein levels and validated by a reporter assay. Furthermore, miR-503 modulated multiple invasion-associated genes, including matrix metalloproteinases (MMPs), through the Wnt downstream signaling pathway. Overall, this study demonstrates that miR-503 suppresses HNC malignancy by inhibiting cell invasion through the Wnt signaling pathway via the WNT3A/MMP molecular axis. The modulation of miR-503 may be a novel therapeutic approach to intervene in cancer invasion.

Association between bullous pemphigoid and psychiatric disorders: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Despite the well-established association between bullous pemphigoid (BP) and neurological diseases, the association between BP and psychiatric disorders remains unclear. In this study, we aimed to investigate the association between BP and various psychiatric disorders. PATIENTS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched for the identification of eligible cohort and case-control studies until May 30, 2021. Meta-analyses of crude estimates and adjusted estimates of odds ratio (OR) for case-control studies and hazard ratio (HR) cohort studies were then conducted. RESULTS: Sixteen studies involving 637,285 patients were included for the qualitative synthesis. In the meta-analysis of adjusted estimates for case-control studies, patients with BP exhibited a significantly higher prevalence of psychiatric disorders (OR 1.77, 95 % confidence interval (CI) 1.07-2.92) and schizophrenia (OR 2.63, 95 % CI 2.03-3.39). Regarding the analysis of adjusted estimates of cohort studies, BP presented no significantly higher risk of depression (HR 1.09, 95 % CI 0.94-1.26) and schizophrenia (HR 1.35, 95 % CI 0.76-2.39). CONCLUSIONS: Psychiatric disorders, especially schizophrenia, have a significantly higher risk of preceding BP.

Zusammenhang zwischen bullösem Pemphigoid und psychiatrischen Erkrankungen: Eine systematische Übersicht und Metaanalyse.

HINTERGRUND UND ZIELE: Trotz des wohlbekannten Zusammenhangs zwischen bullösem Pemphigoid (BP) und neurologischen Erkrankungen ist der Zusammenhang zwischen BP und psychiatrischen Erkrankungen nach wie vor ungeklärt. In dieser Studie war es unser Ziel, den Zusammenhang zwischen BP und verschiedenen psychischen Störungen zu untersuchen. PATIENTEN UND METHODEN: Die Datenbanken PubMed, Embase und Cochrane Library wurden bis zum 30. Mai 2021 hinsichtlich der Identifizierung geeigneter Kohorten- und Fall-Kontroll-Studien durchsucht. Anschließend wurden Metaanalysen der rohen Schätzwerte sowie der bereinigten Schätzwerte der Odds-Ratio (OR) für Fall-Kontroll-Studien und der Hazard-Ratio (HR) für Kohortenstudien durchgeführt. ERGEBNISSE: Es wurden 16 Studien mit 637 285 Patienten in die qualitative Synthese eingeschlossen. In der Metaanalyse der bereinigten Schätzwerte für Fall-Kontroll-Studien zeigten Patienten mit BP eine signifikant höhere Prävalenz psychischer Störungen (OR 1,77, 95 %-Konfidenzintervall (KI) 1,07-2,92) und Schizophrenie (OR 2,63, 95 %-KI 2,03-3,39). Hinsichtlich der Analyse der bereinigten Schätzwerte für Kohortenstudien stellte BP kein signifikant höheres Risiko für Depression (HR 1,09, 95 %-KI 0,94-1,26) und Schizophrenie (HR 1,35, 95 %-KI 0,76-2,39) dar. SCHLUSSFOLGERUNGEN: Bei psychiatrischen Erkrankungen, insbesondere Schizophrenie, besteht ein signifikant höheres Risiko, dass sie einem BP vorausgehen.

Serum Homocysteine, Folate, and Vitamin B12 Levels in Patients with Systemic Lupus Erythematosus: A Meta-Analysis and Meta-Regression.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) have elevated cardiovascular risk. Hyperhomocysteinemia may be one of the contributing factors to this phenomenon. This study therefore aimed to compare the serum homocysteine levels and the levels of folate and vitamin B12, cofactors for homocysteine metabolism, between individuals with and without SLE. METHODS: A literature search was performed in PubMed, Embase, and the Cochrane library (from inception to March 31, 2019). Studies comparing serum homocysteine, folate or vitamin B12 levels between individuals with and without SLE were selected. Of the 1040 screened studies, 50 studies met the inclusion criteria. RESULTS: A total of 50 studies involving 4396 patients with SLE were included. Patients with SLE had a significantly higher serum level of homocysteine (standardized mean difference [SMD], 1.134; 95% CI, 0.795-1.474) and lower level of vitamin B12 (SMD, -0.359; 95% CI, -0.638 to -0.080) than controls. The folate level didn't differ markedly between SLE patients and the control group (SMD, -0.276; 95% CI, -0.674-0.123). Subgroup analysis showed consistent results in adult SLE patients. A random effects meta-regression analysis revealed a significantly inverse correlation between the SMD of homocysteine levels and C3 levels (coefficient, -0.0356, 95% CI, -0.054 to -0.0171; P < .001) and C4 levels (coefficient, -0.0876, 95% CI, -0.1407 to -0.0345; P = .0012). CONCLUSIONS: Serum homocysteine levels were higher and vitamin B12 levels were lower among individuals with SLE than those without SLE. Physicians are encouraged to monitor these parameters and offer timely interventions for patients with SLE.

Small molecule inhibitors and biologics in treating nail psoriasis: A systematic review and network meta-analysis.

BACKGROUND: Various systemic immunomodulating therapies have been investigated to treat nail psoriasis, but the efficacy remains unclear. OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. METHODS: Eligible studies in online databases were identified until March 10, 2020. To assess the efficacy of small molecule inhibitors and biologics, network meta-analyses with surface under the cumulative ranking curve of improvement in nail score at 10 to 16 and at 24 to 26 weeks, as well as 100% improvement of Nail Psoriasis Severity Index (NAPSI), were performed. RESULTS: Thirty-nine studies with a total of 13 treatment arms involving 15,673 patients with nail psoriasis were included. An network meta-analysis showed that tofacitinib (weighted mean difference, 56.67; 95% confidence interval [CI], 35.87-77.48) and ixekizumab (weighted mean difference, 59.40; 95% CI, 45.87-72.93) presented the most improvement of nail score at 10 to 16 weeks and 24 to 26 weeks, respectively. For 100% improvement of the Nail Psoriasis Severity Index, ixekizumab showed the best efficacy among all treatments (odds ratio, 2.98; 95% CI, 1.74-5.10). LIMITATIONS: Insufficiency of eligible data and no long-term follow-up data. CONCLUSION: Tofacitinib and ixekizumab presented the best efficacy for treating nail psoriasis in 10 to 16 weeks and 24 to 26 weeks, respectively.

Treating toxic epidermal necrolysis with systemic immunomodulating therapies: A systematic review and network meta-analysis.

BACKGROUND: Various systemic immunomodulating therapies have been used to treat toxic epidermal necrolysis (TEN), but their efficacy remains unclear. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) evaluating the effects of systemic immunomodulating therapies on mortality for Stevens-Johnson syndrome (SJS)/TEN overlap and TEN. METHODS: A literature search was performed in online databases (from inception to October 31, 2019). Outcomes were mortality rates and Score of Toxic Epidermal Necrolysis (SCORTEN)-based standardized mortality ratio (SMR). A frequentist random-effects model was adopted. RESULTS: Sixty-seven studies involving 2079 patients were included. An NMA of 10 treatments showed that none was superior to supportive care in reducing mortality rates and that thalidomide was associated with a significantly higher mortality rate (odds ratio, 11.67; 95% confidence interval [CI], 1.42-95.96). For SMR, an NMA of 11 treatment arms showed that corticosteroids and intravenous immunoglobulin combination therapy was the only treatment with significant survival benefits (SMR, 0.53; 95% CI, 0.31-0.93). LIMITATIONS: Heterogeneity and a paucity of eligible randomized controlled trials. CONCLUSIONS: Combination therapy with corticosteroids and IVIg may reduce mortality risks in patients with SJS/TEN overlap and TEN. Cyclosporine and etanercept are promising therapies, but more studies are required to provide clearer evidence.

Cardiorespiratory coupling is associated with exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. METHODS: This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). RESULTS: The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64-0.97), n = 43) and a desynchronized group (median 0.23 (0.02-0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. CONCLUSION: This is the first result studying the heart-lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Enmein Decreases Synaptic Glutamate Release and Protects against Kainic Acid-Induced Brain Injury in Rats.

This study investigated the effects of enmein, an active constituent of Isodon japonicus Hara, on glutamate release in rat cerebrocortical nerve terminals (synaptosomes) and evaluated its neuroprotective potential in a rat model of kainic acid (KA)-induced glutamate excitotoxicity. Enmein inhibited depolarization-induced glutamate release, FM1-43 release, and Ca2+ elevation in cortical nerve terminals but had no effect on the membrane potential. Removing extracellular Ca2+ and blocking vesicular glutamate transporters, N- and P/Q-type Ca2+ channels, or protein kinase C (PKC) prevented the inhibition of glutamate release by enmein. Enmein also decreased the phosphorylation of PKC, PKC-α, and myristoylated alanine-rich C kinase substrates in synaptosomes. In the KA rat model, intraperitoneal administration of enmein 30 min before intraperitoneal injection of KA reduced neuronal cell death, glial cell activation, and glutamate elevation in the hippocampus. Furthermore, in the hippocampi of KA rats, enmein increased the expression of synaptic markers (synaptophysin and postsynaptic density protein 95) and excitatory amino acid transporters 2 and 3, which are responsible for glutamate clearance, whereas enmein decreased the expression of glial fibrillary acidic protein (GFAP) and CD11b. These results indicate that enmein not only inhibited glutamate release from cortical synaptosomes by suppressing Ca2+ influx and PKC but also increased KA-induced hippocampal neuronal death by suppressing gliosis and decreasing glutamate levels by increasing glutamate uptake.

Topical calcineurin inhibitors and risk of lymphoma: a systematic review and meta-analysis.

The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus have been used widely as corticosteroid-sparing agents in treating various cutaneous diseases. However, the association between TCIs and risk of malignancy remains controversial. By systematic review and meta-analysis, we aimed to investigate the association between TCIs and lymphoma. Eligible studies in online databases were identified from the date of inception to August 30, 2020. To assess the outcome of TCI-related risk of lymphoma, analysis of cohort studies comparing the incidence of lymphoma with and without treatment with TCIs was performed. Furthermore, the subgroup analyses of Hodgkin lymphoma and non-Hodgkin lymphoma were also conducted. The pooled results revealed that using topical tacrolimus (RR 1.68, 95 % CI 1.39-2.04) or pimecrolimus (RR 1.40, 95 % CI 1.13-1.74) significantly increased the risk of lymphoma. TCI users also showed higher incidence of lymphoma in the range of 0.02-0.09 %, compared to that of 0.02-0.06 % in the control group. Additionally, subgroup analyses showed both tacrolimus (RR 1.89; 95 % CI 1.53-2.32) and pimecrolimus (RR 1.38; 95 % CI 1.09-1.74) had significantly higher risk of non-Hodgkin lymphoma, but no increased risk of Hodgkin lymphoma. In conclusion, TCI-exposed patients have a significantly increased risk of lymphoma, especially non-Hodgkin lymphoma.

Emphysema-Predominant COPD Had a Greater 5-Year Mortality and a Worse Annual Decline in Lung Function Than Airway Obstruction-Predominant COPD or Asthma at Initial Same Degree of Airflow Obstruction.

Background and Objectives: We studied whether the extent of exertional oxygen desaturation and emphysema could cause greater mortality in COPD and asthma independent of airflow obstruction. Materials and Methods: We performed a 5-year longitudinal observational study in COPD and asthma patients who matched for airflow obstruction severity. All subjects performed a 6-min walk test (6MWT) and high-resolution computed tomography (HRCT) and followed spirometry and oxygen saturation (SpO2) during the 6MWT every 3-6 months. Overall survival was recorded. Cumulative survival curves were performed according to the Kaplan-Meier method and compared with the log-rank test. Results: The COPD group had higher emphysema scores, higher Δinspiratory capacities (ICs) and lower SpO2 during the 6MWT, which showed a greater yearly decline in FEV1 (40.6 mL) and forced vital capacity (FVC) (28 mL) than the asthma group (FEV1, 9.6 mL; FVC, 1.2 mL; p < 0.05). The emphysema-predominant COPD group had an accelerated annual decline in lung function and worse survival. The nadir SpO2 ≤ 80% and a higher emphysema score were the strong risk factors for mortality in COPD patients. Conclusions: The greater structural changes with a higher emphysema score and greater desaturation during the 6MWT in COPD may contribute to worse yearly decline in FEV1 and higher five-year mortality than in asthma patients with a similar airflow obstruction. The lowest SpO2 ≤ 80% during the 6MWT and emphysema-predominant COPD were the strong independent factors for mortality in chronic obstructive airway disease patients.