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OBJECTIVE: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. METHODS: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard. RESULTS: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-ß2-glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%. CONCLUSION: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.
Assuntos
Síndrome Antifosfolipídica , Reumatologia , Feminino , Gravidez , Humanos , Síndrome Antifosfolipídica/diagnóstico , Autoanticorpos , Imunoglobulina G , Imunoglobulina MRESUMO
Weight of evidence (WoE) approaches are recommended for interpreting various toxicological data, but few systematic and transparent procedures exist. A hypothesis-based WoE framework was recently published focusing on the U.S. EPA's Tier 1 Endocrine Screening Battery (ESB) as an example. The framework recommends weighting each experimental endpoint according to its relevance for deciding eight hypotheses addressed by the ESB. Here we present detailed rationale for weighting the ESB endpoints according to three rank ordered categories and an interpretive process for using the rankings to reach WoE determinations. Rank 1 was assigned to in vivo endpoints that characterize the fundamental physiological actions for androgen, estrogen, and thyroid activities. Rank 1 endpoints are specific and sensitive for the hypothesis, interpretable without ancillary data, and rarely confounded by artifacts or nonspecific activity. Rank 2 endpoints are specific and interpretable for the hypothesis but less informative than Rank 1, often due to oversensitivity, inclusion of narrowly context-dependent components of the hormonal system (e.g., in vitro endpoints), or confounding by nonspecific activity. Rank 3 endpoints are relevant for the hypothesis but only corroborative of Ranks 1 and 2 endpoints. Rank 3 includes many apical in vivo endpoints that can be affected by systemic toxicity and nonhormonal activity. Although these relevance weight rankings (WREL ) necessarily involve professional judgment, their a priori derivation enhances transparency and renders WoE determinations amenable to methodological scrutiny according to basic scientific premises, characteristics that cannot be assured by processes in which the rationale for decisions is provided post hoc.
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Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Determinação de Ponto Final , Testes de Toxicidade/métodos , Androgênios/agonistas , Androgênios/metabolismo , Animais , Estrogênios/agonistas , Estrogênios/metabolismo , Modelos Biológicos , Ratos , Transdução de Sinais/efeitos dos fármacos , Esteroides/biossíntese , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismoRESUMO
BACKGROUND: Infection requiring explantation remains the most devastating complication associated with implant-based breast reconstruction. There are many treatment algorithms to prevent reconstructive failure in face of infection using both oral and intravenous antibiotics. In the absence of patient-specific culture data, antibiotic selection is generally directed toward broad-spectrum coverage based on historical data. We hypothesize that reviewing our institution's microbiology data obtained from explanted implant-based breast reconstructions would provide a rational basis for antibiotic selection in the future. METHODS: A retrospective review of 902 consecutive immediate implant-based breast reconstructions at a single institution from November 2007 to May 2011 was conducted. Implant reconstructions requiring explantation or drainage by interventional radiology were identified. Patient demographics, implant characteristics, presence of skin necrosis, microbiological data, and outcomes were reviewed. RESULTS: Forty-three (4.76%) implant reconstructions requiring explantation or drainage by interventional radiology met the inclusion criteria for this study. Five patients (11.6%) had round, smooth silicone implants, and 36 (88.4%) had textured tissue expanders. Twenty-six implants were explanted because of infection; 3, because of exposure from skin necrosis; and 11, because of the combination of flap necrosis and infection; and 1, secondarily because of cancer invasion into the skin. Reconstruction was salvaged in 21 breasts (51.2%): 12 (57.1%) by implant reconstruction, 5 (23.8%) by pedicled latissimus dorsi flaps, and 4 (19.1%) with a microvascular free flap. Thirty explants had microbiology data available. The most common organism isolated was Staphylococcus epidermidis (10), followed by methicillin-sensitive Staphylococcus aureus (5), Serratia marcescens (5), Pseudomonas aeruginosa (4), enterococcus (3), Escherichia coli (2), Enterobacter (2), group B streptococcus (1), and Morganella morganii (1). Forty percent of the organisms were resistant to cefazolin; however, 86% were sensitive to gentamicin, 80% were sensitive to Levaquin, and 63% were sensitive to ciprofloxacin. CONCLUSIONS: Infection associated with implant-based breast reconstructions continues to threaten explantation and reconstructive failure. Based on our microbiological data, initial cellulitis amenable to oral antibiotics should be treated with oral fluoroquinolones as a first-line treatment. If this regimen fails, intravenous imipenem or gentamicin and vancomycin should be initiated. Obviously, clinical judgment regarding specific patient risk factors and compliance should play a role in decision making, but these data provide an evidence-based rationale for first-line oral antibiotic selection.
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Antibacterianos/uso terapêutico , Implante Mamário , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Administração Oral , Adulto , Idoso , Implantes de Mama , Remoção de Dispositivo , Drenagem , Farmacorresistência Bacteriana , Feminino , Fluoroquinolonas/uso terapêutico , Retalhos de Tecido Biológico/transplante , Gentamicinas/uso terapêutico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/cirurgia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/cirurgia , Humanos , Imipenem/uso terapêutico , Injeções Intravenosas , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Radiografia Intervencionista , Reoperação , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/cirurgia , Dispositivos para Expansão de Tecidos , Resultado do Tratamento , Vancomicina/uso terapêuticoRESUMO
OBJECTIVE: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. METHODS: This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators' consensus as the gold standard. RESULTS: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-ß2 -glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versus 86%, and a sensitivity of 84% versus 99%. CONCLUSION: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.
Assuntos
Síndrome Antifosfolipídica , Reumatologia , Feminino , Gravidez , Humanos , Estados Unidos , beta 2-Glicoproteína I , Autoanticorpos , Imunoglobulina G , Imunoglobulina MRESUMO
INTRODUCTION: The profunda artery perforator (PAP) flap is a new addition to our reconstructive armamentarium. In effort to better understand patient candidacy for the PAP flap we characterized the profunda artery perforators on preoperative imaging. METHODS: A retrospective review was completed of 40 preoperative posterior thigh computed tomography angiographies and magnetic resonance angiographies by four plastic surgeons. The positioning of the patient, type of study, number of perforators, and size of perforators were documented. The location was documented on an x-y-axis. Perforator course and surrounding musculature was documented. RESULTS: In 98.8% of posterior thighs suitable profunda artery perforators were identified. The average number and size of perforators was 3.3 and 1.9 mm. The most common perforator was medial (present in 85.6% of thighs); found near the adductor magnus at 3.8 cm from midline and 5.0 cm below the gluteal fold. The second most common perforator was lateral (present in 65.4% of thighs); found near the biceps femoris and vastus lateralis at 12.0 cm from midline and 5.0 cm below the gluteal fold. Nearly 48.3% were purely septocutaneous. And 51.7% had an intramuscular course (average length 5.7 cm). Preoperative imaging corresponded to suitable perforators at the time of dissection of all PAP flaps. Thirty five PAP flaps (18 patients) were performed with 100% flap survival. CONCLUSION: Analysis of preoperative posterior thigh imaging confirms our intraoperative findings that a considerable number of suitable posterior thigh profunda perforators are present, emerge from the fascia in a common pattern, and are of sufficient caliber to provide adequate flap perfusion and recipient vessel size match.
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Retalhos de Tecido Biológico/irrigação sanguínea , Angiografia por Ressonância Magnética , Mamoplastia/métodos , Retalho Perfurante/irrigação sanguínea , Cuidados Pré-Operatórios , Coxa da Perna/irrigação sanguínea , Tomografia Computadorizada por Raios X , Adulto , Feminino , Retalhos de Tecido Biológico/transplante , Sobrevivência de Enxerto , Humanos , Pessoa de Meia-Idade , Retalho Perfurante/transplante , Estudos Retrospectivos , Coxa da Perna/diagnóstico por imagemRESUMO
The United States Environmental Protection Agency (USEPA) has long required both avian sub-acute dietary and acute oral studies to inform risk assessments for pesticides. Recently, the USEPA collaborated with People for the Ethical Treatment of Animals to determine whether the results of the acute oral avian toxicity test or the sub-acute dietary toxicity test consistently generated the greatest risk predictions in USEPA tier 1 assessments for pesticides first registered between 1998 and 2017. Their study concluded that in 99% of the cases, risk conclusions were driven by the acute oral study (OPPTS 850.2100, OCSPP 850.2100, or similar) because using these data results in higher risk quotients than sub-acute dietary data. Shortly after publishing these results, the USEPA released a formal memorandum providing guidance for waiving the sub-acute dietary study for most pesticides. The USEPA will, however, retain the option to require sub-acute dietary studies for pesticides with certain chemical properties. However, as the avian sub-acute dietary study has an exposure regimen that is often more representative of how birds are exposed to pesticides under actual use conditions than does the acute oral study (i.e., as part of a dietary item eaten over the course of a day and not a bolus dose), this study can provide useful context for risk assessment on a case-by-case basis. Decision criteria are needed to determine a path forward that both minimizes vertebrate animal testing and positions the avian sub-acute dietary data as an option for risk refinement. Decision criteria are proposed here with recommendations for refining the design of avian sub-acute dietary studies to ensure that the data generated are optimized to support a science-based acute avian risk assessment, supported by a case study demonstrating when and how sub-acute dietary studies may be used in a higher-tier risk assessment. Integr Environ Assess Manag 2022;18:1629-1638. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
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Praguicidas , Animais , Estados Unidos , Testes de Toxicidade Aguda , Praguicidas/toxicidade , Medição de Risco/métodos , Aves , EcotoxicologiaRESUMO
About two years ago, Michael Metzner, MD, took a break from his San Antonio surgical residency program for what was supposed to be a year-long gig in the bright lights of Hollywood. He hasn't come back. He says he will just not quite yet.
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Cirurgia Geral , Internato e Residência , Filmes Cinematográficos , Televisão , HumanosRESUMO
There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its 'oxidative immune-metabolic' physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population.
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COVID-19/patologia , Deficiência de Glucosefosfato Desidrogenase/genética , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Deficiência de Vitamina D/genética , Negro ou Afro-Americano/estatística & dados numéricos , COVID-19/mortalidade , Síndrome da Liberação de Citocina/patologia , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Glutationa/metabolismo , Humanos , SARS-CoV-2 , Vitamina D/análogos & derivados , Vitamina D/metabolismoRESUMO
After 151 years of all-male leadership at the American Medical Association, a family physician from Texas broke through the glass ceiling on June 17, 1998. Twenty-one years later, another Texas physician is set to become the AMA's sixth woman president - and its third in a row.
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American Medical Association/organização & administração , Liderança , Médicas , Feminino , Humanos , Texas , Estados UnidosRESUMO
Call it fate, karma, destiny. It was written in his stars, in his professional DNA. It had to happen. Houston pediatrician and microbiologist Peter Hotez, MD, PhD, just had to write Vaccines Did Not Cause Rachel's Autism.
RESUMO
San Antonio surgical resident Michael Metzner, MD, blends his passions for the arts and medicine as a Grey's Anatomy consultant.
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Anatomia Artística , Televisão , Humanos , Cirurgiões , TexasRESUMO
The Texas Medical Association has made recommendations to improve the Centers for Medicare & Medicaid Services' proposed rule to implement the Medicare Access and CHIP Reauthorization Act (MACRA), which results in numerous compliance and administrative hassles.