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1.
J Card Fail ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38065307

RESUMO

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is associated with polyneuropathy, cardiomyopathy, or both. The effects of eplontersen on cardiac structure and function were assessed. METHODS AND RESULTS: NEURO-TTRansform was an open-label trial involving 144 adults with ATTRv polyneuropathy (49 patients [34%] with cardiomyopathy) receiving eplontersen throughout and compared with a historical placebo group (n = 60; 30 patients [50%] with cardiomyopathy) from the NEURO-TTR trial at week 65. Treatment effect (eplontersen vs placebo), presented as mean difference (95% confidence interval) was analyzed after adjusting for age, sex, region, baseline value, ATTRv disease stage, previous ATTRv treatment, and V30M transthyretin variant. There were notable differences at baseline between the eplontersen group and historical placebo. In the cardiomyopathy subgroup, 65 weeks of eplontersen treatment was associated with improvement from baseline relative to placebo in left ventricular ejection fraction of 4.3% (95% confidence interval 1.40-21.01; P = .049) and stroke volume 10.64 mL (95% confidence interval 3.99-17.29; P = .002) while the remainder of echocardiographic parameters remained stable. CONCLUSIONS: Eplontersen was associated with stable or improved measures of cardiac structure and function vs historical placebo in patients with ATTRv polyneuropathy and cardiomyopathy. Further investigation into eplontersen's effect on transthyretin amyloid cardiomyopathy is being conducted in the CARDIO-TTRansform trial.

2.
Gastroenterology ; 161(5): 1526-1539.e9, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34298022

RESUMO

BACKGROUND & AIMS: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. METHODS: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1ß, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. CONCLUSIONS: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.


Assuntos
Proteínas Sanguíneas/análise , Colite Ulcerativa/sangue , Mediadores da Inflamação/sangue , Proteoma , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CCL11/sangue , Quimiocina CCL2/sangue , Quimiocina CXCL11/sangue , Quimiocina CXCL9/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Feminino , Humanos , Masculino , Metaloproteinase 10 da Matriz/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteômica , Reprodutibilidade dos Testes , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/sangue , Regulação para Cima , Adulto Jovem
3.
Neurocrit Care ; 35(3): 845-852, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34173156

RESUMO

BACKGROUND: Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access. METHODS: We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes. RESULTS: We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (- 13 mm Hg [central] vs. - 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration. CONCLUSIONS: Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.


Assuntos
Hipertensão Intracraniana , Cloreto de Sódio , Circulação Cerebrovascular , Humanos , Hipertensão Intracraniana/etiologia , Pressão Intracraniana , Solução Salina Hipertônica/efeitos adversos
4.
Am J Physiol Gastrointest Liver Physiol ; 317(4): G398-G407, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31314571

RESUMO

Initial colonizing bacteria play a critical role in completing the development of the immune system in the gastrointestinal tract of infants. Yet, the interaction of colonizing bacterial organisms with the developing human intestine favors inflammation over immune homeostasis. This characteristic of bacterial-intestinal interaction partially contributes to the pathogenesis of necrotizing enterocolitis (NEC), a devastating premature infant intestinal inflammatory disease. However, paradoxically some unique pioneer bacteria (initial colonizing species) have been shown to have a beneficial effect on the homeostasis of the immature intestine and the prevention of inflammation. We have reported that one such pioneer bacterium, Bacteroides fragilis (B. fragilis), and its surface component polysaccharide A (PSA) inhibit IL-1ß-induced inflammation in a human primary fetal small intestinal cell line (H4 cells). In this study, using transcription profiling of H4 cellular RNA after pretreatment with or without PSA before an inflammatory stimulation of IL-1ß, we have begun to further determine the cellular mechanism for anti-inflammation. We show that a developmentally regulated gene, zona pellucida protein 4 (ZP4), is uniquely elevated after IL-1ß stimulation and reduced with PSA exposure. ZP4 was known as a sperm receptor-mediating species-specific binding protein in the initial life of mammals. However, its intestinal epithelial function is unclear. We found that ZP4 is a developmentally regulated gene involved with immune function and regulated by both Toll-like receptor 2 and 4. Knockdown of ZP4-affected PSA inhibited IL-8 mRNA expression in response to IL-1ß. This represents an initial study of ZP4 innate immune function in immature enterocytes. This study may lead to new opportunity for efficient treatment of NEC.NEW & NOTEWORTHY This study extends previous observations to define the cellular mechanisms of polysaccharide A-induced anti-inflammation in immature enterocytes using transcription profiling of enterocyte genes after preexposure to polysaccharide A before an inflammatory stimulus with IL-1ß.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Bacteroides fragilis/química , Enterócitos/metabolismo , Polissacarídeos/farmacologia , Glicoproteínas da Zona Pelúcida/genética , Glicoproteínas da Zona Pelúcida/metabolismo , Anti-Inflamatórios não Esteroides/química , Linhagem Celular , Quimiocina CXCL5/biossíntese , Quimiocina CXCL5/genética , Enterócitos/efeitos dos fármacos , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/biossíntese , Interleucina-8/biossíntese , Interleucina-8/genética , Polissacarídeos/química , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo
5.
BMC Bioinformatics ; 19(1): 539, 2018 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-30577761

RESUMO

BACKGROUND: Molecular profiles change in response to perturbations. These changes are coordinated into functional modules via regulatory interactions. The genes and their products within a functional module are expected to be differentially expressed in a manner coherent with their regulatory network. This perspective presents a promising approach to increase precision in detecting differential signals as well as for describing differential regulatory signals within the framework of a priori knowledge about the underlying network, and so from a mechanistic point of view. RESULTS: We present Coherent Network Expression (CoNE), an effective procedure for identifying differentially activated functional modules in molecular interaction networks. Differential gene expression is chosen as example, and differential signals coherent with the regulatory nature of the network are identified. We apply our procedure to systematically simulated data, comparing its performance to alternative methods. We then take the example case of a transcription regulatory network in the context of particle-induced pulmonary inflammation, recapitulating and proposing additional candidates to previously obtained results. CoNE is conveniently implemented in an R-package along with simulation utilities. CONCLUSION: Combining coherent interactions with error control on differential gene expression results in uniformly greater specificity in inference than error control alone, ensuring that captured functional modules constitute real findings.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Algoritmos , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Pneumonia/genética , Software , Humanos , Pneumonia/etiologia , Pneumonia/patologia
6.
Ann Emerg Med ; 70(6): 884-890, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28460863

RESUMO

Stress experienced by emergency medical providers during the resuscitation of critically ill or injured patients can cause cognitive and technical performance to deteriorate. Psychological skills training offers a reasonable and easily implemented solution to this problem. In this article, a specific set of 4 performance-enhancing psychological skills is introduced: breathe, talk, see, and focus. These skills comprise breathing techniques, positive self-talk, visualization or mental practice, and implementing a focus "trigger word." The evidence supporting these concepts in various domains is reviewed and specific methods for adapting them to the environment of resuscitation and emergency medicine are provided.


Assuntos
Competência Clínica , Serviços Médicos de Emergência , Estresse Ocupacional/prevenção & controle , Humanos , Ressuscitação/psicologia
7.
Mil Med ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38877890

RESUMO

The 1996 Khobar Towers bombing, a large-scale mass casualty incident (MASCAL) at a coalition forces housing complex, resulted in 519 casualties. Key lessons learned include the importance of MASCAL exercises, self-aid and buddy care, and casualty triage, all critical to preparation for future terrorist attacks or near-peer combat operations MASCALs.

8.
J Spec Oper Med ; 24(2): 67-71, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38865655

RESUMO

BACKGROUND: Medical training and evaluation are important for mission readiness in the pararescue career field. Because evaluation methods are not standardized, evaluation methods must align with training objectives. We propose an alternative evaluation method and discuss relevant factors when designing military medical evaluation metrics. METHODS: We compared two evaluation methods, the traditional checklist (TC) method used in the pararescue apprentice course and an alternative weighted checklist (AWC) method like that used at the U.S. Army static line jumpmaster course. The AWC allows up to two minor errors, while critical task errors result in autofailure. We recorded 168 medical scenarios during two Apprentice course classes and retroactively compared the two evaluation methods. RESULTS: Despite the possibility of auto-failure with the AWC, there was no significant difference between the two evaluation methods, and both showed similar overall pass rates (TC=50% pass, AWC=48.8% pass, p=.41). The two evaluation methods yielded the same result for 147 out of 168 scenarios (87.5%). CONCLUSIONS: The AWC method strongly emphasizes critical tasks without significantly increasing failures. It may provide additional benefits by being more closely aligned with our training objectives while providing quantifiable data for a longitudinal review of student performance.


Assuntos
Lista de Checagem , Medicina Militar , Militares , Humanos , Avaliação Educacional/métodos , Competência Clínica
9.
Adv Ther ; 41(3): 1168-1183, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280066

RESUMO

INTRODUCTION: Anemia of chronic kidney disease (CKD) has a high incidence and is associated with many disease conditions. Iron dysmetabolism is an important contributor to anemia in CKD patients. METHODS: ALTAI, a randomized, active-controlled, phase 4 trial, investigated the efficacy of roxadustat versus recombinant human erythropoietin (rHuEPO) on gastrointestinal iron absorption in patients with anemia of CKD (stage 4/5). The primary endpoint was change from baseline to day 15 in gastrointestinal iron absorption (serum iron area under the concentration-time curve; AUC0-3h) following single-dose oral iron. RESULTS: Twenty-five patients with a mean age of 55.1 years were randomized 1:1 to roxadustat (n = 13) or rHuEPO (n = 12). Baseline iron profiles were similar between treatment groups. Change from baseline to day 15 in serum iron AUC0-3h was not statistically significantly different between the roxadustat and rHuEPO groups. Mean (SD) change from baseline in serum iron AUC0-3h was 11.3 (28.2) g × 3 h/dl in the roxadustat group and - 0.3 (9.7) g × 3 h/dl in the rHuEPO group. Roxadustat treatment was associated with decreased hepcidin and also increased transferrin, soluble transferrin receptor, and total iron-binding capacity (TIBC), with nominal significance. The proportion of patients experiencing one or more adverse events was 38.5% when treated with roxadustat and 16.7% with rHuEPO. CONCLUSIONS: The study showed no significant difference between roxadustat and rHuEPO in iron absorption but was underpowered because of recruitment challenges. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04655027.


Assuntos
Anemia , Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Anemia/tratamento farmacológico , Anemia/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Ferro/uso terapêutico , Glicina/efeitos adversos , Isoquinolinas/efeitos adversos , China , Hemoglobinas/análise
10.
J Spec Oper Med ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39172917

RESUMO

INTRODUCTION: Mass casualty events (MASCALs) in the combat environment, which involve large numbers of casualties that overwhelm immediately available resources, are fundamentally chaotic and dynamic and inherently dangerous. Formal triage systems use diagnostic algorithms, colored markers, and four or more named categories. We hypothesized that formal triage systems are inadequately trained and practiced and too complex to successfully implement in true MASCAL events. This retrospective analysis evaluates the real-world application of triage systems in prehospital military MASCALs and other aspects of MASCAL management. METHODS: We surveyed Special Operations Forces (SOF) medics known to us who have participated in military prehospital MASCALs and analyzed them. Aggregated data describing the scope of the incidents, the use of formal triage algorithms and colored markers, the number of categories, and the interventions on scene were analyzed using descriptive statistics, and lessons learned were consolidated. RESULTS: From 1996 to 2022 we identified 29 MASCALs that were managed by military medics in the prehospital setting. There was a median of three providers (range 1-85) and 15 casualties (range 6-519) per event. Four or more formal triage categories were used in only one event. Colored markers and formal algorithms were not used. Life-saving interventions were performed in 27 of 29 (93%) missions and blood transfusions were performed in four (17%) MASCALs. The top lessons learned were: 1) security and accountability are cornerstones of MASCAL management; 2) casualty movement is a priority; 3) intuitive triage categories are the default; 4)life-saving interventions are performed as time and tacticspermit. CONCLUSION: Formal triage systems requiring the use ofdiagnostic algorithms, colored tags, and four or five categories are seldom implemented in real-world military prehospitalMASCAL management. The training of field triage should besimplified and pragmatic, as exemplified by these instances.

11.
PLoS One ; 18(3): e0283102, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36920959

RESUMO

Within the direct-to-consumer (DTC) genetic test industry, attracting customers can be difficult especially due to the highly sensitive nature of these products. How these tests are communicated to consumers may be one avenue in which companies can impact customer purchase intentions. A 2 (message sidedness: one-way vs. two-way refutational) x 2 (hedging: present vs. absent) between-subjects experiment was conducted to understand how message features and prior product use influence information processing, risk and trust perceptions, and attitude toward the genetic test, which in turn, may influence direct-to-consumer (DTC) genetic test purchase intentions. Results demonstrated that having used a genetic test in the past predicted participants' trust in the company, information processing, and risk judgments; however, among those who used a genetic test, viewing a message that included hedging tended to increase their trust in the message. Trust in the message and company, information processing, and risk judgments significantly predicted participants' attitudes toward genetic testing, which in turn predicted their purchase intentions. The results suggest that in the context of DTC genetic test messaging, practitioners should strive to increase consumer trust in the message and the company and facilitate information processing, and they should work to diminish perceived risk. These results suggest opportunities for identifying other message features that may influence message and company trust, information processing, risk judgments, and attitudes related to DTC genetic testing.


Assuntos
Intenção , Confiança , Humanos , Atitude , Testes Genéticos , Cognição
12.
J Spec Oper Med ; 23(1): 59-66, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36853853

RESUMO

Mass casualty incidents (MCIs) can rapidly exhaust available resources and demand the prioritization of medical response efforts and materials. Principles of triage (i.e., sorting) from the 18th century have evolved into a number of modern-day triage algorithms designed to systematically train responders managing these chaotic events. We reviewed reports and studies of MCIs to determine the use and efficacy of triage algorithms. Despite efforts to standardize MCI responses and improve the triage process, studies and recent experience demonstrate that these methods have limited accuracy and are infrequently used.


Assuntos
Planejamento em Desastres , Serviços Médicos de Emergência , Incidentes com Feridos em Massa , Humanos , Triagem , Serviços Médicos de Emergência/métodos , Planejamento em Desastres/métodos , Algoritmos
13.
Cells ; 13(1)2023 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-38201264

RESUMO

Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn's disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGFß superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD.


Assuntos
Doença de Crohn , Humanos , Inflamação , Meios de Cultivo Condicionados/farmacologia , Progressão da Doença , Fibroblastos
14.
J Spec Oper Med ; 23(1): 18-22, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36764287

RESUMO

BACKGROUND: Research among military personnel and veterans indicates that subjective appraisal of warzone stressors explains the relation of combat exposure to posttraumatic stress disorder (PTSD), but not the relation of exposure to injury and death to PTSD. Studies have primarily been limited to conventional forces using aggregate measures of warzone stressor exposure. Threat appraisal may play a different role in the emergence of PTSD among military personnel for whom dangerous deployment experiences are more closely associated with exposure to injury and death, such as US Air Force Pararescuemen and Combat Rescue officers. MATERIALS AND METHODS: In a sample of 207 rescue personnel, correlations among various types of warzone stressor exposure, threat appraisal, and postdeployment PTSD symptoms were examined. RESULTS: The relative strongest correlates of threat appraisal were stressors related to injury, death, and human remains. Although exposure to these stressors was also correlated with PTSD symptom severity, partial correlations of stressor exposure and PTSD symptoms were no longer significant when adjusting for threat appraisal. CONCLUSION: Results support the contributing role of threat appraisal to PTSD among military personnel whose primary duties entail exposure to injury and death under hostile and dangerous conditions.


Assuntos
Distúrbios de Guerra , Militares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Distúrbios de Guerra/complicações , Distúrbios de Guerra/diagnóstico , Guerra do Iraque 2003-2011 , Campanha Afegã de 2001-
15.
Data Brief ; 41: 107858, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35128009

RESUMO

This data set contains rolling conditional correlation networks estimated from stock returns and the volume synchronized probability of informed trading. Only the largest 104 financial firms are included for the period of 1996 through 2012. The data was used to analyze banking sector systemic risk in Borochin and Rush (2022)[1].

16.
J Trauma Acute Care Surg ; 93(2S Suppl 1): S160-S164, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35583968

RESUMO

BACKGROUND: The overall approach to massive casualty triage has changed little in the past 200 years. As the military and civilian organizations prepare for the possibility of future large-scale combat operations, terrorist attacks and natural disasters, potentially involving hundreds or even thousands of casualties, a modified approach is needed to conduct effective triage, initiate treatment, and save as many lives as possible. METHODS: Military experience and review of analyses from the Department of Defense Trauma Registry are combined to introduce new concepts in triage and initial casualty management. RESULTS: The classification of the scale of massive casualty (MASCAL) incidents, timeline of life-saving interventions, immediate first pass actions prior to formal triage decisions during the first hour after injury, simplification of triage decisions, and the understanding that ultra-MASCAL will primarily require casualty movement and survival needs with few prehospital life-saving medical interventions are discussed. CONCLUSION: Self aid, bystander, and first responder interventions are paramount and should be trained and planned extensively. Military and disaster planning should not only train these concepts, but should seek innovations to extend the timelines of effectiveness and to deliver novel capabilities within the timelines to the greatest extent possible.


Assuntos
Planejamento em Desastres , Serviços Médicos de Emergência , Socorristas , Incidentes com Feridos em Massa , Terrorismo , Humanos , Triagem
17.
Inflammation ; 45(4): 1631-1650, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35190924

RESUMO

Inflammasomes are intracellular protein complexes whose activation results in proinflammatory cytokines. Inflammasomes are implicated in Crohn´s disease (CD) pathogenesis, yet the contribution of inflammasomes in intestinal epithelial cells (IECs) versus lamina propria (LP) macrophages is poorly understood. Whether inflammasome expression in intestinal tissue reflects the serum inflammatory protein profile of patients is also not known. We aimed to determine the intestinal cell types where inflammasome expression is increased in CD and if they correlate with the serum protein profile. RT-PCR and NanoString nCounter technology were used to characterize inflammasome gene expression in CD patients and controls. The mucosa, LP and IEC cell fractions and FACS-sorted cells were analyzed. Proximity extension assay with a 92-protein panel was used to determine the serum inflammatory protein profile. Compositional analysis was used to correlate ileum inflammasome gene expression with intestinal mononuclear phagocyte populations. We show that NLRP3 and MEFV inflammasome sensors and downstream effector expression including IL-1ß are increased in inflamed mucosa of IBD patients and correlate with disease activity. Inflammasome gene expression increased with the abundance of immature intestinal macrophages, and increased IL-1ß released by CD LP cells correlated with immature macrophage frequency. Inflammasome gene expression was also increased in circulating monocytes, the precursors of immature intestinal macrophages. Finally, the serum inflammatory profile of CD patients correlates with ileal expression of genes related to NLRP3 and MEFV inflammasomes. Overall, we show that MEFV and NLRP3 inflammasome expression in CD intestine is attributed to the accumulation of immature macrophages and correlates with serum inflammatory proteins.


Assuntos
Doença de Crohn , Inflamassomos , Macrófagos , Proteínas Sanguíneas/metabolismo , Doença de Crohn/metabolismo , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pirina/genética , Pirina/metabolismo
18.
J Spec Oper Med ; 21(4): 90-93, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34969134

RESUMO

Low-titer cold-stored O-positive whole blood (LTCSO+WB) resuscitation therapy is the cornerstone of military hemorrhagic shock resuscitation. During the past 19 years, improved patient outcomes have shown the importance of this intervention in shock treatment. Iliac crest intraosseous (IO) placement is an alternative when peripheral sites such as the humeral head and tibia are not available options. To date, no study has explored the administration of LTCSO+WB through an iliac crest IO in the military prehospital setting. Contingency procedures for vascular access are necessary for casualties with severe trauma to all four extremities, and the iliac crest is a viable option. The literature supports situational advantages over other peripheral IO sites.


Assuntos
Serviços Médicos de Emergência , Choque Hemorrágico , Humanos , Ílio , Infusões Intraósseas , Ressuscitação , Choque Hemorrágico/terapia
19.
J Spec Oper Med ; 21(1): 25-29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33721302

RESUMO

BACKGROUND: The Air Force Special Warfare Medical Officer Course was created to address the lack of operationally focused, job-specific clinical training for medical officers (MOs). This course addresses the gap in knowledge, skill, and application of operational medicine, as well as the behavioral health, human performance, education, and medical oversight of Operators. METHODS: The course was designed around the senior author's decade of experience piecing together training for his own role as a pararescue flight surgeon and informed by 5 years of flight surgeon courses, lessons learned from case studies of ill-prepared deployed physicians, and input from prehospital medicine subject matter experts. RESULTS: Air Force pararescue and special tactics flight surgeons, physician assistants, and an independent duty medical technician (IDMT) attended. The course consisted of 10 full weekdays of didactics and skills sessions covering theory and application of operational medicine, human performance optimization, behavioral health for Operators, adult education theory, principles of prehospital clinical oversight, and other expeditionary concepts. The course culminated with combat casualty care scenario-based exercises, in which the providers performed operational medicine in full kit with weapons and simulation rounds. DISCUSSION: For many logistical and practical reasons, civilian medical experience, traditional military medical training, existing special operations medical courses, and "merit badge" card classes are not adequate preparation for this specialized role. Focused, job-specific training should be provided to Special Operations Forces Medical Officers (SOFMO) and, ultimately, to any MO deploying in support of medics or combatants. The goal is to maximize the success of military medical operations while reducing the morbidity and mortality of combat and training casualties. CONCLUSION: This operationally focused MO course can serve as a model for the future training of SOFMO and has stimulated discussion for consideration of a joint approach to prehospital medical training.


Assuntos
Medicina Militar , Militares , Pessoal de Saúde , Humanos , Guerra
20.
J Spec Oper Med ; 21(1): 44-48, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33721306

RESUMO

Uncontrolled hemorrhage secondary to unstable pelvic fractures is a preventable cause of prehospital death in the military and civilian sectors. Because the mortality rate associated with unstable pelvic ring injuries exceeds 50%, the use of external compression devices for associated hemorrhage control is paramount. During mass casualty incidents and in austere settings, the need for multiple external compression devices may arise. In assessing the efficacy of these devices, the magnitude of applied force has been offered as a surrogate measure of pubic symphysis diastasis reduction and subsequent hemostasis. This study offers a sensor-circuit assessment of applied force for a convenience sample of pelvic compression devices. The SAM® (structural aluminum malleable) Pelvic Sling II (SAM Medical) and improvised compression devices, including a SAM Splint tightened by a Combat Application Tourniquet® (C-A-T; North American Rescue) and a SAM® Splint tightened by a cravat, as well as two joined cravats and a standard-issue military belt, were assessed in male and female subjects. As hypothesized, compressive forces applied to the pelvis did not vary significantly based on device operator, subject sex, and subject body fat percentage. The use of the military belt as an improvised method to obtain pelvic stabilization is not advised.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Feminino , Fraturas Ósseas/terapia , Hemorragia/prevenção & controle , Humanos , Masculino , Pelve , Torniquetes
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