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Autoimmune hepatitis (AIH) is relatively rare in children. Herein, our case demonstrates a unique presentation of AIH in a previously healthy 18-year-old female presenting with a mild cough, fatigue, and severe anemia (hemoglobin 2.9 g/dL). Initial evaluation revealed jaundice and scleral icterus, prompting transfer of care and further testing, which demonstrated severe microcytic anemia, pancytopenia, elevated liver enzymes, direct hyperbilirubinemia, and marked splenomegaly. Concern for autoimmune hemolytic anemia resulted in a delayed diagnosis. The combination of triple antibody positivity (anti-nuclear antibodies, anti-actin, and anti-liver-kidney microsomal-1) and liver histology findings confirmed the diagnosis of AIH. Intravenous methylprednisolone was initiated to induce remission. Due to pancytopenia and persistently elevated international normalized ratio, tacrolimus was chosen as the maintenance immunosuppression instead of azathioprine. This case highlights several significant considerations for clinicians, including the importance of a timely clinicopathologic diagnosis, the severe anemia presentation secondary to hypersplenism, and the rare finding of triple autoantibody-positive AIH.
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OBJECTIVE: We sought to evaluate the quality and timeliness of patient-reported outcome (PRO) measure reporting, which have not been previously studied. METHODS: Clinical trials that informed new US Food and Drug Administration (FDA) approvals for the first rheumatological indication between 1995 and 2021 were identified. Data were recorded to determine whether collected PROs were published, met minimum clinically important difference (MCID) or statistical significance (P < 0.05) thresholds, and were consistent with Consolidated Standards of Reporting Trials (CONSORT)-PRO standards. Hazard ratios and Kaplan-Meier estimate were used to assess the time from FDA approval to PRO publication. RESULTS: Thirty-one FDA approvals corresponded with 110 pivotal trials and 262 reported PROs. Of the 90 included studies, 1 (1.1%) met all 5 recommended items, 10 (11.1%) met 4 items, 17 (18.9%) met 3 items, 21 (23.3%) met 2 items, 26 (28.9%) met 1 item, and 15 (16.7%) met none of the reporting standards. Most PROs met MCID thresholds (149/262; 56.9%) and were statistically significant (223/262; 85.1%). Of our subset analysis, one-third of PROs were not published upfront (70/212; 33%) and 1 of 9 (22/212; 10.4%) remained unpublished ≥ 4 years after initial trial reporting. Publication rates were highest for the Health Assessment Questionnaire-Disability Index (97.4%) and lowest for the 36-item Short Form Health Survey (81.8%). Less than half of these published PROs met MCID and statistical significance thresholds (94/212; 44.3%). CONCLUSION: One in 9 PROs remained unpublished for ≥ 4 years after initial trial reporting, and compliance with CONSORT-PRO reporting guidelines was poor. Efforts should be made to ensure PROs are adequately reported and expeditiously published.
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Extracellular cytochrome filaments are proposed to serve as conduits for long-range extracellular electron transfer. The primary functional physiological evidence has been the reported inhibition of Geobacter sulfurreducens Fe(III) oxide reduction when the gene for the filament-forming cytochrome OmcS is deleted. Here we report that the OmcS-deficient strain from that original report reduces Fe(III) oxide as well as the wild-type, as does a triple mutant in which the genes for the other known filament-forming cytochromes were also deleted. The triple cytochrome mutant displayed filaments with the same 3 nm diameter morphology and conductance as those produced by Escherichia coli heterologously expressing the G. sulfurreducens PilA pilin gene. Fe(III) oxide reduction was inhibited when the pilin gene in cytochrome-deficient mutants was modified to yield poorly conductive 3 nm diameter filaments. The results are consistent with the concept that 3 nm diameter electrically conductive pili (e-pili) are required for G. sulfurreducens long-range extracellular electron transfer. In contrast, rigorous physiological functional evidence is lacking for cytochrome filaments serving as conduits for long-range electron transport. IMPORTANCE: Unraveling microbial extracellular electron transfer mechanisms has profound implications for environmental processes and advancing biological applications. This study on Geobacter sulfurreducens challenges prevailing beliefs on cytochrome filaments as crucial components thought to facilitate long-range electron transport. The discovery of an OmcS-deficient strain's unexpected effectiveness in Fe(III) oxide reduction prompted a reevaluation of the key conduits for extracellular electron transfer. By exploring the impact of genetic modifications on G. sulfurreducens' performance, this research sheds light on the importance of 3-nm diameter electrically conductive pili in Fe(III) oxide reduction. Reassessing these mechanisms is essential for uncovering the true drivers of extracellular electron transfer in microbial systems, offering insights that could revolutionize applications across diverse fields.
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Citocromos , Compostos Férricos , Geobacter , Oxirredução , Transporte de Elétrons , Geobacter/genética , Geobacter/metabolismo , Citocromos/metabolismo , Citocromos/genética , Compostos Férricos/metabolismo , Fímbrias Bacterianas/metabolismo , Fímbrias Bacterianas/genética , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismoRESUMO
The field of rheumatology has experienced dozens of novel drug approvals in the past two and a half decades, but the regulatory mechanisms underpinning these decisions are not well understood. In the USA, the Food and Drug Administration (FDA) evaluates the safety and efficacy of novel drugs through the New Drug Application (NDA) process. When additional content expertise is required to evaluate scientific or technical matters, the FDA may convene Human Drug Advisory Committees. To better understand the landscape of rheumatology NDAs and the FDA use of advisory committees, we performed a review of all rheumatic disease drug applications from 1996 to 2021 that were granted approval by the FDA. Our review identified 31 NDAs, seven of which utilized an advisory committee. The indications for using advisory committees and their influence on ultimate approvals was not clear. Recommendations to improve transparency and increase public trust in FDA decisions are provided.
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Aprovação de Drogas , Reumatologia , Estados Unidos , Humanos , United States Food and Drug Administration , Comitês ConsultivosRESUMO
OBJECTIVES: Randomized controlled trials (RCTs) provide high-quality evidence for treatment efficacy, but many RCTs remain unpublished. The objective of this study was to describe the proportion of unpublished RCTs in five rheumatic diseases and to identify factors associated with publication. METHODS: Registered RCTs for five rheumatic diseases (SLE, vasculitis, spondyloarthritis, SS and PsA) with over 30 months since study completion were identified using ClinicalTrials.gov. Index publications were identified by NCT ID numbers and structured text searches of publication databases. The results of unpublished studies were identified in abstracts and press releases; reasons for non-publication were assessed by surveying corresponding authors. RESULTS: Out of 203 studies that met eligibility criteria, 17.2% remained unpublished, representing data from 4281 trial participants. Higher proportions of published trials were phase 3 RCTs (57.1% vs 28.6% unpublished, P < 0.05) or had a positive primary outcome measure (64.9% vs 25.7% unpublished, P < 0.001). In a multivariable Cox proportional hazards model, a positive outcome was independently associated with publication (hazard ratio 1.55; 95% CI: 1.09, 2.22). Corresponding authors of 10 unpublished trials cited ongoing preparation of the manuscript (50.0%), sponsor/funder issues (40.0%) and unimportant/negative result (20.0%) as reasons for lack of publication. CONCLUSIONS: Nearly one in five RCTs in rheumatology remain unpublished 2 years after trial completion, and publication is associated with positive primary outcome measures. Efforts to encourage universal publication of rheumatology RCTs and reanalysis of previously unpublished trials should be undertaken.
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Artrite Psoriásica , Doenças Reumáticas , Humanos , Sistema de Registros , Doenças Reumáticas/tratamento farmacológicoRESUMO
Bilateral thalamic infarctions are uncommon and often lead to more severe and long-lasting symptoms than unilateral thalamic infarctions. This article describes a patient with bilateral thalamic infarction caused by occlusion in the artery of Percheron, an anatomic variant thought to be present in 4% to 12% of the population.
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Variação Anatômica , Arteriopatias Oclusivas/etiologia , Artérias Cerebrais/anatomia & histologia , Infarto Cerebral/etiologia , Tálamo/irrigação sanguínea , Arteriopatias Oclusivas/diagnóstico , Infarto Cerebral/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Massive acetaminophen (N-acetyl-p-aminophenol; APAP) ingestion is characterized by a rapid onset of mitochondrial dysfunction, including metabolic acidosis, lactemia, and altered mental status without hepatotoxicity which may not respond to the standard doses of N-acetylcysteine (NAC). A 64-year-old woman without medical history presented comatose after an ingestion of 208 tablets of Tylenol PM™ (APAP 500 mg and diphenhydramine 25 mg). The initial APAP concentration measured 1,017 µg/mL (therapeutic range 10-30 µg/mL), and elevated anion gap metabolic acidosis, lactemia, and 5-oxoprolinemia were detected. High-dose intravenous (IV) NAC, 4-methylpyrazole (4-MP), and hemodialysis (HD) were initiated. She was transferred to a liver transplant center and continued both NAC and HD therapies until complete resolution of metabolic acidosis and coma without developing hepatitis. She was discharged without sequelae. This is the fourth highest APAP concentration recorded in a surviving patient. Moreover, this is the first report of a novel "triple therapy" using NAC, 4-MP, and HD in the setting of massive APAP ingestion that presents with coma, elevated anion gap metabolic acidosis, and lactemia. Emergency physicians should recognize these critically ill patients and consider high-dose NAC, 4-MP, and HD to be initiated in the emergency department (ED).
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PURPOSE: This study aimed to determine the current attitudes, perceptions, and practices of emergency medicine providers and nurses (RNs) regarding the discharge of adult patients from the emergency department (ED) after administration of opioid analgesics. METHODS: A cross-sectional survey was administered at 3 hospital sites with a combined annual ED census of >180,000 visits per year. All 59 attending emergency physicians (EPs), 233 RNs, and 23 advanced practice clinicians (APCs) who worked at these sites were eligible to participate. FINDINGS: Thirty-five EPs (59.3%), 88 RNs (37.8%), and 14 APCs (60.9%) completed the survey for an overall response rate of 51.75%. Most respondents were female (95 [69.9%]). The factor ranked most important to consider when discharging a patient from the ED after administration of opioids was the patient's functional status and vital signs (median, 2.00; interquartile range, 2.00-3.50). More RNs (84 [96.6%]) than EPs (29 [82.9%]) reported that developing an ED policy or guideline for safe discharge after administration of opioids is important to clinical practice (P = 0.02). Only 8 physicians (23.5%) reported that they did not prescribe intramuscular morphine, and 15 (42.9%) reported that they did not prescribe intramuscular hydromorphone. EPs (7 [20.0%]) and RNs (3 [3.4%]) differed in regard to whether they were aware if any patients to whom they administered an opioid had experienced an adverse drug-related event (P = 0.01). Most EPs (24 [68.6%]) and RNs (54 [61.4%]) believed that the decision for patient discharge should be left to both the emergency medicine provider and the RN. IMPLICATIONS: Most study participants believed that developing a policy or guideline for safe discharge after administration opioids in the ED is important to clinical practice. Only a few physicians reported that they did not prescribe intramuscular hydromorphone or morphine. Most participants believed the discharge decision after administration of opioids in the ED should be primarily determined by both the emergency medicine provider and the RN.
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Analgésicos Opioides/administração & dosagem , Serviço Hospitalar de Emergência/estatística & dados numéricos , Alta do Paciente , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Medicina de Emergência , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Hidromorfona/administração & dosagem , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Percepção , Inquéritos e Questionários , Adulto JovemRESUMO
Eosinophilic gastrointestinal disorders are a rare and complex group of disorders that are characterized by eosinophilic infiltration of the gastrointestinal tract. Patients often present with a wide range of signs and symptoms as any length or layer of the GI tract can be involved such as mucosal, muscular, or serosal. As a part of the workup, patients frequently undergo computed tomography scans and multiple endoscopies before the diagnosis is finally made as was true in our case of a 59-year-old male patient presenting with 2 months of nausea, abdominal pain, and weight loss. He underwent esophagogastroduodenoscopies, colonoscopies, video capsule study, and balloon enteroscopy before the diagnosis was confirmed histologically. Endoscopic and radiographic findings can be variable and are usually unpredictable. The diagnosis is confirmed on histopathological examination of biopsies that must show >15-50 eosinophils/high-power field based on the location in the GI tract. In our patient, erythema, scalloping, whitish exudate, and patches of villous blunting were noted in the duodenum to proximal ileum endoscopically with >50 eosinophils/high-power field confirming the diagnosis of eosinophilic enteritis. This class of diseases is often found in patients with a history of allergic disorders suggestive of hypersensitivity in the etiology of the disease although our patient had no such known history. Elimination diets and steroids are the mainstay of therapy and often lead to complete resolution of symptoms as well as endoscopic and radiographic findings in up to 90% of patients as was seen in our patient, although some patients have a chronic remitting course.
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BACKGROUND: The way in which women and their babies transition from maternity services to the care of child and family health nurses differs across Australia. The aim of the study was to understand the transition of care from one service to another and how to promote collaboration in the first few weeks after the birth. METHOD: A descriptive study was undertaken. All midwifery, child and family health and Families NSW managers in NSW were invited to participate by completing a questionnaire. RESULTS: There was a wide range of transition of care models. These varied by setting, geography, context and history. Three main models emerged from the analysis. These were as follows: DISCUSSION: There were a range of different models of transition of care identified in NSW depending on local context, expertise, interests and policies. Some are very structured and others have developed and evolved over time. Many models seem to be dependant on the goodwill and enthusiasm of individual clinicians. CONCLUSION: A more coordinated and systematised approach needs to be developed. Collaboration and communication between midwives and child and family health nurses is essential if the needs of families are to be addressed during this transition period.
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Continuidade da Assistência ao Paciente , Serviços de Saúde Materna , Tocologia , Enfermeiras e Enfermeiros , Assistência Centrada no Paciente , Saúde da Família , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , New South Wales , GravidezRESUMO
PURPOSE: To examine the effects of moderate intensity chronic exercise on tumor necrosis factor-alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) responses to endotoxin in female Sprague-Dawley rats. METHODS: Rats were divided into two groups, exercise (n=17) and sedentary (n=24). Exercise (Ex) rats completed 12 weeks of motorized treadmill running 3 days/week for 15-25 min at 22-25 m/min, while sedentary (Sed) rats remained in their cages. Twenty-four hrs after the last exercise session, animals were subdivided into three groups. One subgroup served as baseline controls. These rats received an injection of saline (s) and were killed immediately (Sed-s and Ex-s), while the other groups received an injection of lipopolysaccharide (LPS). LPS animals were killed 2 h (Sed-L2 and Ex-L2) or 4 h after the LPS injection (Sed-L4 and Ex-L4). RESULTS: Serum TNFalpha was elevated 2 h after LPS injection in both Sed and Ex groups, but was significantly higher in the chronic exercise group (Ex-L2 versus. Sed-L2). Similarly, serum beta glucuronidase activity, an indicator of tissue damage, was elevated 2 and 4 h after LPS injection, and was significantly higher in the exercise groups. Post-treatment left ventricular TNFalpha and iNOS activity, as well as stable nitric oxide derivatives in the serum (NOx), were significantly higher in LPS-injected groups compared to saline groups, but no difference in LPS effect was observed between sedentary and exercise groups. CONCLUSIONS: Moderate intensity chronic exercise stress caused an exaggerated serum TNFalpha response to endotoxin and an elevation in a serum marker of LPS-induced tissue damage.