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1.
Cureus ; 15(8): e44304, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37664362

RESUMO

This comprehensive narrative review delves into the intricate interplay between diet and inflammatory bowel disease (IBD), shedding light on the potential impact of dietary interventions in disease management. By analyzing nutritional interventions, risks, challenges, and future perspectives, this review serves as a vital resource for clinicians, researchers, and patients alike. The amalgamation of evidence underscores the significance of customizing dietary strategies for individual patients, considering disease phenotype and cultural factors. Through an exploration of dietary components' effects on IBD, including exclusive enteral nutrition and omega-3 fatty acids, this review offers pragmatic implementation advice and outlines avenues for further research. Bridging the gap between research findings and clinical applications, the review facilitates informed decision-making and patient-centric care. In the face of escalating IBD prevalence, this review emerges as an indispensable guide for healthcare professionals, empowering them to navigate the complexities of dietary management while enabling patients to actively participate in their care trajectory. Ultimately, this narrative review advances the understanding of diet's pivotal role in IBD management, fostering a more integrated approach to patient care and paving the way for improved research and policy initiatives in the field of inflammatory bowel diseases.

2.
Cureus ; 15(8): e43961, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37753017

RESUMO

Monkeypox, a viral zoonotic ailment originating in the Central and West African regions, has escalated into a global health issue of growing concern. The current analysis offers an exhaustive examination of monkeypox, emphasizing its historical progression, etiology, epidemiological patterns, pathophysiological mechanisms, clinical manifestations, diagnostic methodologies, treatment modalities, and preventive strategies. The worldwide discontinuation of smallpox vaccination has contributed to an increased incidence of monkeypox, driven by the expansion of vulnerable host populations. Significant strides in diagnostic procedures, prospective antiviral treatments, and vaccine development exhibit potential in managing this affliction, yet obstacles remain in terms of disease control, prevention, and treatment. Additionally, the international propagation of monkeypox underscores the need for robust public health initiatives and the significant role played by global health institutions in disease containment. Prospective research endeavors should strive to enhance our comprehension of the natural reservoirs of monkeypox and its transmission dynamics, evaluate sustained immune responses to novel vaccines, and investigate the potential impact of One Health strategies. This analysis underscores the pressing necessity for increased research and synchronized global efforts to tackle this emergent infectious malady.

3.
Matern Child Health J ; 27(10): 1774-1786, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37280462

RESUMO

OBJECTIVE: Approximately one-third of women in the U.S. experience an adverse pregnancy outcome (APO), which are recognized as sex-specific cardiovascular disease (CVD) risk factors. We examine if APOs confer additional CVD risk beyond that of traditional CVD risk factors. METHODS: Women, age 40-79, with a pregnancy history and no pre-existing CVD were identified in the electronic health record of one health system (n = 2306). APOs included any APO, hypertensive disease of pregnancy (HDP), and gestational diabetes (GDM). Hazard ratios of time to CVD event were estimated from survival models using Cox proportional hazard regression. Discrimination, calibration, and net reclassification of re-estimated CVD risk prediction models including APOs were examined. RESULTS: There was no significant association between any APO, HDP, or GDM and time to CVD outcome in survival models (95% confidence intervals all include 1). Including any APO, HDP, GDM in the CVD risk prediction model did not significantly improve discrimination and there were no clinically relevant changes in net reclassification of cases and non-cases. The strongest predictor of time to CVD event in the survival models was Black race, with hazard ratios ranging from 1.59 to 1.62, statistically significant for all three models. CONCLUSION: Women with APOs did not have an additional risk of CVD, controlling for traditional risk factors in the PCE and this sex-specific factor did not improve risk prediction. Black race was consistently a strong predictor of CVD even with data limitations. Further study of APOs can help determine how to best use this information for CVD prevention in women.


Assuntos
Doenças Cardiovasculares , Diabetes Gestacional , Masculino , Gravidez , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Resultado da Gravidez/epidemiologia , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Diabetes Gestacional/epidemiologia
5.
J Am Acad Dermatol ; 88(3): 560-567, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36228942

RESUMO

BACKGROUND: Despite encouraging trends in survival, sociodemographic inequalities persist among patients with melanoma. OBJECTIVE: We sought to quantify the effect of race/ethnicity, socioeconomic status, and health care systems on melanoma-specific mortality within an insured population of patients. METHODS: Using a retrospective cohort study, we identified insured adults diagnosed with Stage I to IV melanoma from January 1, 2009, to December 31, 2014, followed through 2017, from the California Cancer Registry. We compared melanoma-specific mortality between insured patients diagnosed within the largest vertically integrated health care system in California, Kaiser Permanente Southern California, and insured patients with other private insurance (OPI). RESULTS: Our cohort included 14,614 adults diagnosed with melanoma. Multivariable analyses demonstrated that race/ethnicity was not associated with survival disparities, while socioeconomic status was a strong predictor of melanoma-specific mortality, particularly for those with OPI. For example, hazard ratios demonstrate that the poorest patients with OPI have a 70% increased risk of dying from their melanoma compared to their wealthiest counterparts, while the poorest patients in Kaiser Permanente Southern California have no increased risk. LIMITATIONS: Our main limitation includes inadequate data for certain racial/ethnic groups, such as Native Americans. CONCLUSIONS: Our findings underscore the persistence of socioeconomic disparities within an insured population, specifically among those in non-integrated health care systems.


Assuntos
Prestação Integrada de Cuidados de Saúde , Melanoma , Adulto , Humanos , Etnicidade , Estudos Retrospectivos , Classe Social , Disparidades em Assistência à Saúde , Disparidades nos Níveis de Saúde , Fatores Socioeconômicos , California , Melanoma Maligno Cutâneo
6.
BMC Womens Health ; 22(1): 528, 2022 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-36528580

RESUMO

BACKGROUND: Cardiovascular disease (CVD) guidelines recommend using the Pooled Cohort Equation (PCE) to assess 10-year CVD risk based on traditional risk factors. Pregnancy-related factors have been associated with future CVD. We examined the contribution of two pregnancy-related factors, (1) history of a low birthweight (LBW) infant and (2) breastfeeding to CVD risk accounting for traditional risk factors as assessed by the PCE. METHODS: A nationally representative sample of women, ages 40-79, with a history of pregnancy, but no prior CVD, was identified using NHANES 1999-2006. Outcomes included (1) CVD death and (2) CVD death plus CVD surrogates. We used Cox proportional hazards models to adjust for PCE risk score. RESULTS: Among 3,758 women, 479 had a LBW infant and 1,926 reported breastfeeding. Mean follow-up time was 12.1 years. Survival models showed a consistent reduction in CVD outcomes among women with a history of breastfeeding. In cause-specific survival models, breastfeeding was associated with a 24% reduction in risk of CVD deaths (HR 0.76; 95% CI 0.45─1.27, p = 0.30) and a 33% reduction in risk of CVD deaths + surrogate CVD, though not statistically significant. (HR 0.77; 95% CI 0.52─1.14, p = 0.19). Survival models yielded inconclusive results for LBW with wide confidence intervals (CVD death: HR 0.98; 95% CI 0.47─2.05; p = 0.96 and CVD death + surrogate CVD: HR 1.29; 95% CI 0.74─2.25; p = 0.38). CONCLUSION: Pregnancy-related factors may provide important, relevant information about CVD risk beyond traditional risk factors. While further research with more robust datasets is needed, it may be helpful for clinicians to counsel women about the potential impact of pregnancy-related factors, particularly the positive impact of breastfeeding, on cardiovascular health.


Assuntos
Doenças Cardiovasculares , Gravidez , Recém-Nascido , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Inquéritos Nutricionais , Fatores de Risco , Modelos de Riscos Proporcionais , Recém-Nascido de Baixo Peso
7.
Int J Retina Vitreous ; 8(1): 81, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397121

RESUMO

BACKGROUND: A significant portion of diabetic macular edema (DME) is refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This study investigates morphological and functional outcomes to a single intravitreal bevacizumab (IVB) injection in patients with center-involving DME (ciDME) at 4-6 weeks and compares treatment responders and non-responders based on spectral domain optical coherence tomography (SD-OCT) features. METHODS: IRB approved observational, retrospective chart review of patients with ciDME, identified by ICD-10 code, who received IVB and underwent baseline and 4-6 weeks follow-up SD-OCT imaging between January 1, 2016 and January 19, 2021. Patients who had received previous treatment with anti-VEGF or intraocular steroids within 1 year were excluded. Variables included best-corrected visual acuity (BCVA), central subfield thickness (CST) and total macular volume (TMV). Eyes were classified as responders if CST reduction was greater than 10%. OCT scans were graded qualitatively by two masked graders using Imagivault software. Paired Student's t-tests, Wilcoxon signed rank tests and Chi-Square tests were used for analysis. RESULTS: A total of 334 prospective subjects were identified, and after applying exclusion criteria 52 eyes from 46 patients (mean age 64.22 ± 8.12 years, 58.7% male) were included. Mean BCVA did not significantly change with treatment, 63.9 ETDRS letters (~ 20/50) at baseline and 65.9 ETDRS letters (~ 20/50) post-treatment (p = 0.07). Mean CST decreased from 466 ± 123 µm at baseline to 402 ± 86 µm post-treatment (p < 0.001). 22 (42.3%) of eyes were categorized as responders and 30 (57.7%) as non-responders. Average change in CST from baseline in responders was -164 µm (p < 0.001) and + 9 µm in non-responders (p = 0.47). Vitreomacular adhesion (VMA) was more prevalent in non-responders (28.7% vs. 4.8%, p = 0.03). In addition, cyst location in the inner nuclear layer (INL) was present more frequently in responders (95.5% vs. 73.3%, p = 0.037) as was subretinal fluid (45.5% vs. 13.3%, p = 0.01). CONCLUSION: The short-term response to a single IVB was sub-optimal with structural but no functional improvements. Greater baseline CST, presence of INL cysts and subretinal fluid may represent factors indicative of a better treatment response.

8.
JAMA ; 328(17): 1747-1765, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36318128

RESUMO

Importance: It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022. Study Selection: English-language randomized clinical trials and prospective cohort studies of fair or good quality. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Morbidity and mortality related to chronic conditions; health-related quality of life. Results: Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year. Conclusions and Relevance: Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.


Assuntos
Doença Crônica , Estrogênios , Terapia de Reposição Hormonal , Pós-Menopausa , Progestinas , Feminino , Humanos , Comitês Consultivos/normas , Comitês Consultivos/tendências , Doença Crônica/epidemiologia , Doença Crônica/mortalidade , Doença Crônica/prevenção & controle , Estrogênios/efeitos adversos , Estrogênios/uso terapêutico , Fraturas Ósseas/prevenção & controle , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/métodos , Hormônios/efeitos adversos , Hormônios/uso terapêutico , Prevenção Primária , Progestinas/efeitos adversos , Progestinas/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Medição de Risco , Estados Unidos , Incontinência Urinária/induzido quimicamente , Tromboembolia Venosa/induzido quimicamente
9.
Ophthalmol Retina ; 6(10): 922-929, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35483614

RESUMO

PURPOSE: To evaluate long-term visual acuity (VA) and performance of a monitoring strategy with a self-operated artificial-intelligence-enabled home monitoring system in conjunction with standard care for early detection of neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective review. SUBJECTS: Patients with dry-age-related macular degeneration from 5 referral clinics. METHODS: Clinical data of patients monitored with ForeseeHome (FSH) device from August 2010 to July 2020 were reviewed. MAIN OUTCOME MEASURES: Visual acuity at baseline, VA at diagnosis of nAMD for eyes that converted while monitored, and VA from the final study follow-up, weekly frequency of use, duration of monitoring, modality of conversion diagnosis (system alert vs. detection by other standard care means), and duration and number of treatments since conversion to final study follow-up were collected. RESULTS: We reviewed 3334 eyes of 2123 patients with a mean (standard deviation [SD]) age of 74(8) years, monitored for a mean (SD) duration of 3.1 (2.4) years, with a total of 1 706 433 tests in 10 474 eye-monitoring years. The mean (SD) weekly use per patient was 5.2 (3.4), and it was persistent over the usage period. Two hundred eighty-five eyes converted while monitored at an annual rate of 2.72% and were treated with a mean (SD) 17.3 (16.5) injections over a mean (SD) 2.7 (2.0) years, with 6.4 (3.1) injections per year for eyes treated for > 1 year. The median VAs at baseline and at final follow-up for eyes that did not convert were 20/27 and 20/34 with a median change of 0.0 letters. The median VAs at baseline, conversion, and final follow-up for eyes that converted during the monitoring period were 20/30, 20/39, and 20/32 with a median change from baseline to conversion, baseline to recent, and conversion to recent of -4, -4, and 0 letters, respectively. Fifty-two percent of conversions detected had a system alert before conversion. Forty-eight percent of patients were detected by symptoms or routine visit. Patients experienced a non-nAMD alert on average every 4.6 years. At conversion and at final follow-up, the proportion (95% CI) of eyes that maintained ≥ 20/40 was 84% (78% to 88%) and 82% (76% to 86%), respectively. CONCLUSIONS: Patients in the FSH monitoring program showed excellent long-term VA years after conversion to nAMD.


Assuntos
Degeneração Macular , Ranibizumab , Idoso , Inibidores da Angiogênese , Hormônio Foliculoestimulante/uso terapêutico , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
10.
JAMA ; 327(11): 1068-1082, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35289875

RESUMO

Importance: Eating disorders are associated with adverse health and social outcomes. Objective: To review the evidence on screening for eating disorders in adolescents and adults to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, PsycINFO, and trial registries through December 19, 2020; surveillance through January 1, 2022. Study Selection: English-language studies of screening test accuracy, randomized clinical trials (RCTs) of screening or interventions for eating disorders in populations with screen-detected or previously untreated eating disorders (trials limited to populations who are underweight were ineligible). Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. Meta-analysis of test accuracy studies and intervention trials. Main Outcomes and Measures: Test accuracy, eating disorder symptom severity, quality of life, depression, and harms. Results: Fifty-seven studies were included (N = 10 773); 3 (n = 1073) limited to adolescents (mean or median age, 14-15 years). No study directly evaluated the benefits and harms of screening. Seventeen studies (n = 6804) evaluated screening test accuracy. The SCOFF questionnaire (cut point ≥2) had a pooled sensitivity of 84% (95% CI, 74% to 90%) and pooled specificity of 80% (95% CI, 65% to 89%) in adults (10 studies, n = 3684). Forty RCTs (n = 3969) evaluated interventions for eating disorders; none enrolled a screen-detected population. Lisdexamfetamine for binge eating disorder (4 RCTs; n = 900) was associated with larger reductions in eating disorder symptom severity on the Yale-Brown Obsessive Compulsive Scale modified for binge eating (YBOCS-BE) than placebo (pooled mean difference, -5.75 [95% CI, -8.32 to -3.17]). Two RCTs (n = 465) of topiramate for binge eating disorder found larger reductions in YBOCS-BE scores associated with topiramate than placebo, from -6.40 (95% CI, -8.16 to -4.64) to -2.55 (95% CI, -4.22 to -0.88). Nine pharmacotherapy trials (n = 2006) reported on harms. Compared with placebo, lisdexamfetamine was associated with higher rates of dry mouth, headache, and insomnia, and topiramate was associated with higher rates of paresthesia, taste perversion, confusion, and concentration difficulty. Twenty-four trials (n = 1644) assessed psychological interventions. Guided self-help for binge eating disorder improved eating disorder symptom severity more than control (pooled standardized mean difference, -0.96 [95% CI, -1.26 to -0.67]) (5 studies, n = 391). Evidence on other interventions was limited. Conclusions and Relevance: No studies directly assessed the benefits and harms of screening. The SCOFF questionnaire had adequate accuracy for detecting eating disorders among adults. No treatment trials enrolled screen-detected populations; guided self-help, lisdexamfetamine, and topiramate were effective for reducing eating disorder symptom severity among referred populations with binge eating disorder, but pharmacotherapies were also associated with harms.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Adolescente , Adulto , Comitês Consultivos , Humanos , Serviços Preventivos de Saúde , Estados Unidos
11.
J Cardiol Cases ; 25(3): 123-125, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35261692

RESUMO

Cysticercosis is a parasitic infection that is caused by the tapeworm Taenia solium and is prevalent in Latin America, southern Africa, and parts of Asia. Cysticercosis normally affects the central nervous system, but rare cases of cardiac cysticercosis have been reported in the literature. We report a case of asymptomatic cardiac cysticercosis in a 54-year-old Afro-Brazilian man with a history of hemicolectomy and chemotherapy, who demonstrated characteristic intramyocardial lesions on transthoracic echocardiogram and cardiac magnetic resonance imaging, and responded well to subsequent treatment with albendazole and prednisone. .

12.
Cell Rep ; 37(5): 109953, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731630

RESUMO

Receptor clustering is the first and critical step to activate apoptosis by death receptor-5 (DR5). The recent discovery of the autoinhibitory DR5 ectodomain has challenged the long-standing view of its mechanistic activation by the natural ligand Apo2L. Because the autoinhibitory residues have remained unknown, here we characterize a crucial patch of positively charged residues (PPCR) in the highly variable domain of DR5. The PPCR electrostatically separates DR5 receptors to autoinhibit their clustering in the absence of ligand and antibody binding. Mutational substitution and antibody-mediated PPCR interference resulted in increased apoptotic cytotoxic function. A dually specific antibody that enables sustained tampering with PPCR function exceptionally enhanced DR5 clustering and apoptotic activation and distinctively improved the survival of animals bearing aggressive metastatic and recurrent tumors, whereas clinically tested DR5 antibodies without PPCR blockade function were largely ineffective. Our study provides mechanistic insights into DR5 activation and a therapeutic analytical design for potential clinical success.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidores , Células A549 , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/metabolismo , Anticorpos Monoclonais Humanizados/farmacologia , Especificidade de Anticorpos , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/metabolismo , Epitopos , Humanos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/imunologia , Neoplasias/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
mBio ; 12(5): e0273521, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34663092

RESUMO

Aspergillus fumigatus is a human-pathogenic mold that extracts nutrients from the environment or from host tissues by secreting hydrolytic enzymes. The ability of A. fumigatus to adjust secretion levels in proportion to demand relies on the assistance of the unfolded protein response (UPR), an adaptive stress response pathway that regulates the unique protein-folding environment of the endoplasmic reticulum (ER). The P5-type ATPase Spf1 has recently been implicated in a novel mechanism of ER homeostasis that involves correcting errors in ER-membrane protein targeting. However, the contribution of this protein to the biology of A. fumigatus is unknown. Here, we employed a gene knockout and RNA sequencing strategy to determine the functional role of the A. fumigatus gene coding for the orthologous P5 ATPase SpfA. The data reveal that the spfA gene is induced by ER stress in a UPR-dependent manner. In the absence of spfA, the A. fumigatus transcriptome shifts toward a profile of altered redox and lipid balance, in addition to a signature of ER stress that includes srcA, encoding a second P-type ATPase in the ER. A ΔspfA deletion mutant showed increased sensitivity to ER stress, oxidative stress, and antifungal drugs that target the cell wall or plasma membrane. The combined loss of spfA and srcA exacerbated these phenotypes and attenuated virulence in two animal infection models. These findings demonstrate that the ER-resident ATPases SpfA and SrcA act jointly to support diverse adaptive functions of the ER that are necessary for fitness in the host environment. IMPORTANCE The fungal UPR is an adaptive signaling pathway in the ER that buffers fluctuations in ER stress but also serves as a virulence regulatory hub in species of pathogenic fungi that rely on secretory pathway homeostasis for pathogenicity. This study demonstrates that the gene encoding the ER-localized P5-type ATPase SpfA is a downstream target of the UPR in the pathogenic mold A. fumigatus and that it works together with a second ER-localized P-type ATPase, SrcA, to support ER homeostasis, oxidative stress resistance, susceptibility to antifungal drugs, and virulence of A. fumigatus.


Assuntos
Aspergillus fumigatus/genética , Aspergillus fumigatus/patogenicidade , Estresse do Retículo Endoplasmático , Proteínas Fúngicas/genética , Transdução de Sinais , Adenosina Trifosfatases , Animais , Aspergillus fumigatus/enzimologia , Retículo Endoplasmático/metabolismo , Feminino , Proteínas Fúngicas/metabolismo , Técnicas de Inativação de Genes , Homeostase , Larva/microbiologia , Masculino , Camundongos , Mariposas/microbiologia , Dobramento de Proteína , Análise de Sequência de RNA , Virulência/genética
14.
JAMA ; 325(10): 971-987, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687468

RESUMO

Importance: Lung cancer is the leading cause of cancer-related death in the US. Objective: To review the evidence on screening for lung cancer with low-dose computed tomography (LDCT) to inform the US Preventive Services Task Force (USPSTF). Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2019; references; experts; and literature surveillance through November 20, 2020. Study Selection: English-language studies of screening with LDCT, accuracy of LDCT, risk prediction models, or treatment for early-stage lung cancer. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled because of heterogeneity of populations and screening protocols. Main Outcomes and Measures: Lung cancer incidence, lung cancer mortality, all-cause mortality, test accuracy, and harms. Results: This review included 223 publications. Seven randomized clinical trials (RCTs) (N = 86 486) evaluated lung cancer screening with LDCT; the National Lung Screening Trial (NLST, N = 53 454) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON, N = 15 792) were the largest RCTs. Participants were more likely to benefit than the US screening-eligible population (eg, based on life expectancy). The NLST found a reduction in lung cancer mortality (incidence rate ratio [IRR], 0.85 [95% CI, 0.75-0.96]; number needed to screen [NNS] to prevent 1 lung cancer death, 323 over 6.5 years of follow-up) with 3 rounds of annual LDCT screening compared with chest radiograph for high-risk current and former smokers aged 55 to 74 years. NELSON found a reduction in lung cancer mortality (IRR, 0.75 [95% CI, 0.61-0.90]; NNS to prevent 1 lung cancer death of 130 over 10 years of follow-up) with 4 rounds of LDCT screening with increasing intervals compared with no screening for high-risk current and former smokers aged 50 to 74 years. Harms of screening included radiation-induced cancer, false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, and increases in distress. For every 1000 persons screened in the NLST, false-positive results led to 17 invasive procedures (number needed to harm, 59) and fewer than 1 person having a major complication. Overdiagnosis estimates varied greatly (0%-67% chance that a lung cancer was overdiagnosed). Incidental findings were common, and estimates varied widely (4.4%-40.7% of persons screened). Conclusions and Relevance: Screening high-risk persons with LDCT can reduce lung cancer mortality but also causes false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, increases in distress, and, rarely, radiation-induced cancers. Most studies reviewed did not use current nodule evaluation protocols, which might reduce false-positive results and invasive procedures for false-positive results.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Detecção Precoce de Câncer/efeitos adversos , Reações Falso-Positivas , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/mortalidade , Uso Excessivo dos Serviços de Saúde , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Fatores de Risco , Sensibilidade e Especificidade , Fumar/efeitos adversos , Procedimentos Desnecessários
15.
J Cutan Pathol ; 48(1): 147-150, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32974961

RESUMO

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare disease typically characterized by a histiocytic proliferation within lymph nodes, which is due to an unknown etiology. Extranodal involvement can occur, and it more rarely can involve the skin. RDD generally presents with an indolent nature and follows a benign disease course, although more aggressive cases have been reported. The condition predominately affects children and young adults. It is classically characterized by massive, bilateral painless lymphadenopathy and accumulation of CD68-positive, S100-positive, CD1a-negative histiocytes, with the presence of emperipolesis as a hallmark. Herein, we present an aggressive case in a 76-year-old male with past medical history significant for prostate cancer, who presented with a 7-month history of lymphadenopathy and new onset of multiple large abdominal wall, cutaneous, lymph node, liver, and lung masses, all of which were histopathologically atypical, but showed features consistent with RDD, including emperipolesis and strong S100 positivity. Molecular studies showed a KRAS 117N mutation, which has been recently reported in RDD. While most cases present as a benign tumor, this case demonstrated aggressive features clinically, showed partial response to MEK inhibitor immunotherapy in the setting of a KRAS mutation, and demonstrated atypical cytologic features on histopathology.


Assuntos
Histiocitose Sinusal/genética , Histiocitose Sinusal/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Humanos , Masculino , Mutação
16.
Syst Rev ; 9(1): 243, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076975

RESUMO

BACKGROUND: The exponential growth of the biomedical literature necessitates investigating strategies to reduce systematic reviewer burden while maintaining the high standards of systematic review validity and comprehensiveness. METHODS: We compared the traditional systematic review screening process with (1) a review-of-reviews (ROR) screening approach and (2) a semi-automation screening approach using two publicly available tools (RobotAnalyst and AbstrackR) and different types of training sets (randomly selected citations subjected to dual-review at the title-abstract stage, highly curated citations dually reviewed at the full-text stage, and a combination of the two). We evaluated performance measures of sensitivity, specificity, missed citations, and workload burden RESULTS: The ROR approach for treatments of early-stage prostate cancer had a poor sensitivity (0.54) and studies missed by the ROR approach tended to be of head-to-head comparisons of active treatments, observational studies, and outcomes of physical harms and quality of life. Title and abstract screening incorporating semi-automation only resulted in a sensitivity of 100% at high levels of reviewer burden (review of 99% of citations). A highly curated, smaller-sized, training set (n = 125) performed similarly to a larger training set of random citations (n = 938). CONCLUSION: Two approaches to rapidly update SRs-review-of-reviews and semi-automation-failed to demonstrate reduced workload burden while maintaining an acceptable level of sensitivity. We suggest careful evaluation of the ROR approach through comparison of inclusion criteria and targeted searches to fill evidence gaps as well as further research of semi-automation use, including more study of highly curated training sets.


Assuntos
Publicações , Revisões Sistemáticas como Assunto , Automação , Programas de Rastreamento , Carga de Trabalho
17.
J Cosmet Laser Ther ; 22(6-8): 226-229, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33794721

RESUMO

Soft tissue augmentation with injectable fillers is increasingly being performed, and providers must be prepared to understand and treat complications. Periorbital skin presents unique challenges due to its thin nature, easily evident pigmentary and textural irregularities, and anatomical considerations including vasculature and subcutaneous layers. The most common complications of infraorbital filler include ecchymosis, malar edema, blue-gray hue, and contour irregularities. Uncommon complications include infection and biofilm formation, skin necrosis, and blindness. This purpose of this review is to highlight the infraorbital anatomy, complications of filler injection in this region, and techniques to avoid these complications.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Edema , Face , Humanos , Ácido Hialurônico/efeitos adversos
18.
J Cosmet Laser Ther ; 22(4-5): 171-173, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-33709866

RESUMO

Non-surgical rhinoplasty is becoming an increasingly common procedure to alter the appearance and cosmesis of the nose. Although rare, complications with this procedure do exist, some of which can be devastating. Major complications include infection, vascular compromise, skin necrosis, and blindness. Here we discuss the nasal anatomy, complications associated with non-surgical rhinoplasty, and techniques to prevent these complications.


Assuntos
Preenchedores Dérmicos , Rinoplastia , Preenchedores Dérmicos/efeitos adversos , Humanos , Nariz/anatomia & histologia , Rinoplastia/efeitos adversos
20.
Med Care ; 57(7): 536-543, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31194701

RESUMO

OBJECTIVE: To examine factors associated with HIV screening among women veterans receiving health care in the Department of Veterans Affairs. MATERIALS AND METHODS: Cross-sectional study of women veterans receiving Veterans Affairs care between 2001 and 2014 derived from the Women Veteran's Cohort Study. Descriptive and bivariate statistics were calculated comparing patients with and without an HIV screen. Generalized estimating equations were conducted to estimate the odds of HIV screening among women screened for military sexual trauma (MST) and the subset with a positive MST screen. Multivariable analyses were adjusted for demographic characteristics, mental health diagnoses, pregnancy, HIV risk factors, and facility level clustering. RESULTS: Among the 113,796 women veterans in the sample, 84.3% were screened for MST and 13.2% were screened for HIV. Women screened for MST were over twice as likely to be tested for HIV (odds ratio, 2.8; 95% confidence interval, 2.2-3.5). A history of MST was inversely associated with HIV screening (odds ratio, 0.9; 95% confidence interval, 0.8-0.9). CONCLUSIONS: Women veterans screened for sexual trauma received more comprehensive preventive health care in the form of increased HIV screening.


Assuntos
Infecções por HIV/diagnóstico , Programas de Rastreamento , Militares/psicologia , Delitos Sexuais , Veteranos/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Estados Unidos , United States Department of Veterans Affairs
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