nd R0 resections disappeared (HR, 1.05; 95% CI, 0.54-2.01). Conclusions and Relevance The difference in OS by quality of surgery with or without imatinib was associated with the presence of tumor rupture. When the latter was excluded, the presence of R1 margins was not associated with worse OS. Trial Registration ClinicalTrials.gov Identifier NCT00103168.Importance Prospective studies of the disease course in patients with morphea are lacking, particularly those comparing adults and children. Objective To investigate the disease course in patients with morphea treated with standard-of-care therapy using validated clinical outcome measures. Design, Setting, and Participants Prospective cohort study of 130 adults and children from the Morphea in Adults and Children cohort with at least 2 years of clinical follow-up and Localized Scleroderma Cutaneous Assessment Tool scores recorded at each study visit. Study patients were seen at a tertiary referral center (UT Southwestern Medical Center, Dallas, Texas) from November 1, 2008, through April 1, 2016. The dates of analysis were May 2016 through July 2019. Exposures All patients received standard-of-care therapy. Main Outcomes and Measures Patterns in disease activity and recurrence were examined. The time to recurrence of morphea disease activity from the first visit with inactive disease was assessed using survivappeared to improve in most patients with morphea over 6 to 12 months using previously published treatment plans, underscoring their effectiveness. Sclerosis improved more slowly (over 2-5 years), often after discontinuation of treatment, but atrophy increased slightly as sclerosis subsided. Standard-of-care therapy appears to improve disease activity, which allows sclerosis to improve, and provides relative stability of other features of disease damage. A substantial number of patients, particularly those with generalized subtype, have a relapsing-remitting course over many years. Patients with morphea should be monitored for recurrent disease activity over extended periods.Importance Mental health problems are associated with considerable occupational, medical, social, and economic burdens. Psychosocial stressors at work have been associated with a higher risk of mental disorders, but the risk of sickness absence due to a diagnosed mental disorder, indicating a more severe condition, has never been investigated in a systematic review and meta-analysis. Objective To synthesize the evidence of the association of psychosocial stressors at work with sickness absence due to a diagnosed mental disorder among adult workers. Data Sources Seven electronic databases (MEDLINE, Embase, PsycInfo, Web of Science, CINAHL, Sociological Abstracts, and International Bibliography of the Social Sciences), 3 gray literature databases (Grey Literature Report, WHO-IRIS and Open Grey), and the reference lists of all eligible studies and reviews were searched in January 2017 and updated in February 2019. Study Selection Only original prospective studies evaluating the association of at least 1 psychosoness absence due to a diagnosed mental disorder compared with nonexposed workers (pooled risk ratio [RR], 1.76 [95% CI, 1.49-2.08]), as were those exposed to effort-reward imbalance (pooled RR, 1.66 [95% CI, 1.37-2.00]), job strain (pooled RR, 1.47 [95% CI, 1.24-1.74]), low job control (pooled RR, 1.25 [95% CI, 1.02-1.53]), and high psychological demands (pooled RR, 1.23 [95% CI, 1.04-1.45]). Conclusions and Relevance This meta-analysis found that workers exposed to psychosocial stressors at work were associated with a higher risk of sickness absence due to a mental disorder. A better understanding of the importance of these stressors could help physicians when evaluating their patients' mental health and work capacity.Importance First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)-referred to herein as mycophenolate-is recommended; however, evidence to support this recommendation remains weak. Objective To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate. Main Outcomes and Measures The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea. Results There were 61 female patients (79%) and 16 male patients (21%) in the study, with a medits had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. Conclusions and Relevance This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.Prostate cancer is a slow-growing disease, but not always. A highly rare and lethal form of the disease shows survival rates of less than a year. It is called squamous cell prostate carcinoma. In this issue of JEM, Hermanova et al. (https//doi.org/10.1084/jem.20191787) provide new findings in mouse demonstrating a strong genetic handle on both the reasons behind the rarity and the aggressiveness. © 2020 Mathew and Trotman.Importance Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease with high heritability; however, the bone morphogenetic protein receptor 2 (BMPR2) gene only accounts for 17% of IPAH. https://www.selleckchem.com/btk.html The genetic basis of IPAH needs further investigation. Objective To identify novel IPAH susceptibility genes other than BMPR2. Design, Setting, and Participants This 2-stage, case-control genetic association study enrolled 230 patients with IPAH from 2 referral pulmonary hypertension centers in China. Eligible patients had no BMPR2 variants and were compared with 968 healthy control participants. Data were collected from January 1, 2000, to July 31, 2015, and analyzed from August 1, 2015, to May 30, 2018. Exposures PTGIS rare variants. Main Outcomes and Measures Whole-genome sequencing was performed to identify putative IPAH genes in a discovery cohort, with validation in an independent referral cohort. Correlation of genotype and hemodynamic characteristics was then evaluated at baseline and after pulmonary vasodilator testing.
nd R0 resections disappeared (HR, 1.05; 95% CI, 0.54-2.01). Conclusions and Relevance The difference in OS by quality of surgery with or without imatinib was associated with the presence of tumor rupture. When the latter was excluded, the presence of R1 margins was not associated with worse OS. Trial Registration ClinicalTrials.gov Identifier NCT00103168.Importance Prospective studies of the disease course in patients with morphea are lacking, particularly those comparing adults and children. Objective To investigate the disease course in patients with morphea treated with standard-of-care therapy using validated clinical outcome measures. Design, Setting, and Participants Prospective cohort study of 130 adults and children from the Morphea in Adults and Children cohort with at least 2 years of clinical follow-up and Localized Scleroderma Cutaneous Assessment Tool scores recorded at each study visit. Study patients were seen at a tertiary referral center (UT Southwestern Medical Center, Dallas, Texas) from November 1, 2008, through April 1, 2016. The dates of analysis were May 2016 through July 2019. Exposures All patients received standard-of-care therapy. Main Outcomes and Measures Patterns in disease activity and recurrence were examined. The time to recurrence of morphea disease activity from the first visit with inactive disease was assessed using survivappeared to improve in most patients with morphea over 6 to 12 months using previously published treatment plans, underscoring their effectiveness. Sclerosis improved more slowly (over 2-5 years), often after discontinuation of treatment, but atrophy increased slightly as sclerosis subsided. Standard-of-care therapy appears to improve disease activity, which allows sclerosis to improve, and provides relative stability of other features of disease damage. A substantial number of patients, particularly those with generalized subtype, have a relapsing-remitting course over many years. Patients with morphea should be monitored for recurrent disease activity over extended periods.Importance Mental health problems are associated with considerable occupational, medical, social, and economic burdens. Psychosocial stressors at work have been associated with a higher risk of mental disorders, but the risk of sickness absence due to a diagnosed mental disorder, indicating a more severe condition, has never been investigated in a systematic review and meta-analysis. Objective To synthesize the evidence of the association of psychosocial stressors at work with sickness absence due to a diagnosed mental disorder among adult workers. Data Sources Seven electronic databases (MEDLINE, Embase, PsycInfo, Web of Science, CINAHL, Sociological Abstracts, and International Bibliography of the Social Sciences), 3 gray literature databases (Grey Literature Report, WHO-IRIS and Open Grey), and the reference lists of all eligible studies and reviews were searched in January 2017 and updated in February 2019. Study Selection Only original prospective studies evaluating the association of at least 1 psychosoness absence due to a diagnosed mental disorder compared with nonexposed workers (pooled risk ratio [RR], 1.76 [95% CI, 1.49-2.08]), as were those exposed to effort-reward imbalance (pooled RR, 1.66 [95% CI, 1.37-2.00]), job strain (pooled RR, 1.47 [95% CI, 1.24-1.74]), low job control (pooled RR, 1.25 [95% CI, 1.02-1.53]), and high psychological demands (pooled RR, 1.23 [95% CI, 1.04-1.45]). Conclusions and Relevance This meta-analysis found that workers exposed to psychosocial stressors at work were associated with a higher risk of sickness absence due to a mental disorder. A better understanding of the importance of these stressors could help physicians when evaluating their patients' mental health and work capacity.Importance First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)-referred to herein as mycophenolate-is recommended; however, evidence to support this recommendation remains weak. Objective To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate. Main Outcomes and Measures The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea. Results There were 61 female patients (79%) and 16 male patients (21%) in the study, with a medits had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. Conclusions and Relevance This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.Prostate cancer is a slow-growing disease, but not always. A highly rare and lethal form of the disease shows survival rates of less than a year. It is called squamous cell prostate carcinoma. In this issue of JEM, Hermanova et al. (https//doi.org/10.1084/jem.20191787) provide new findings in mouse demonstrating a strong genetic handle on both the reasons behind the rarity and the aggressiveness. © 2020 Mathew and Trotman.Importance Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease with high heritability; however, the bone morphogenetic protein receptor 2 (BMPR2) gene only accounts for 17% of IPAH. https://www.selleckchem.com/btk.html The genetic basis of IPAH needs further investigation. Objective To identify novel IPAH susceptibility genes other than BMPR2. Design, Setting, and Participants This 2-stage, case-control genetic association study enrolled 230 patients with IPAH from 2 referral pulmonary hypertension centers in China. Eligible patients had no BMPR2 variants and were compared with 968 healthy control participants. Data were collected from January 1, 2000, to July 31, 2015, and analyzed from August 1, 2015, to May 30, 2018. Exposures PTGIS rare variants. Main Outcomes and Measures Whole-genome sequencing was performed to identify putative IPAH genes in a discovery cohort, with validation in an independent referral cohort. Correlation of genotype and hemodynamic characteristics was then evaluated at baseline and after pulmonary vasodilator testing.
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