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1.
Annu Rev Med ; 72: 243-261, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33052764

RESUMO

Carcinogenesis is a multistep process by which normal cells acquire genetic and epigenetic changes that result in cancer. In combination with host genetic susceptibility and environmental exposures, a prominent procarcinogenic role for the microbiota has recently emerged. In colorectal cancer (CRC), three nefarious microbes have been consistently linked to cancer development: (a) Colibactin-producing Escherichia coli initiates carcinogenic DNA damage, (b) enterotoxigenic Bacteroides fragilis promotes tumorigenesis via toxin-induced cell proliferation and tumor-promoting inflammation, and (c) Fusobacterium nucleatum enhances CRC progression through two adhesins, Fap2 and FadA, that promote proliferation and antitumor immune evasion and may contribute to metastases. Herein, we use these three prominent microbes to discuss the experimental evidence linking microbial activities to carcinogenesis and the specific mechanisms driving this stepwise process. Precisely defining mechanisms by which the microbiota impacts carcinogenesis at each stage is essential for developing microbiota-targeted strategies for the diagnosis, prognosis, and treatment of cancer.


Assuntos
Carcinogênese/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/microbiologia , Microbiota , Neoplasias Colorretais/genética , Progressão da Doença , Humanos
2.
Blood ; 137(25): 3473-3483, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-33754642

RESUMO

Hairy cell leukemia (HCL) is a rare B-cell malignancy, and there is a need for novel treatments for patients who do not benefit from purine analogs. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown, so we conducted a multisite phase 2 study of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate (ORR) at 32 weeks, and we also assessed response at 48 weeks and best response during treatment. Key secondary objectives were characterization of toxicity and determination of progression-free survival (PFS) and overall survival (OS). Thirty-seven patients were enrolled at 2 different doses (24 at 420 mg, 13 at 840 mg). The median duration of follow-up was 3.5 years (range, 0-5.9 years). The ORR at 32 weeks was 24%, which increased to 36% at 48 weeks. The best ORR was 54%. The estimated 36-month PFS was 73% and OS was 85%. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common: anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to patients with HCL with objective responses and results in prolonged disease control. Although the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable PFS suggests that ibrutinib may be beneficial in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01841723.


Assuntos
Adenina/análogos & derivados , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/mortalidade , Piperidinas/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Administração Oral , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Taxa de Sobrevida
3.
J Surg Res ; 284: 42-53, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36535118

RESUMO

A diagnosis of pancreatic cancer carries a 5-y survival rate of less than 10%. Furthermore, the detection of pancreatic cancer occurs most often in later stages of the disease due to its location in the retroperitoneum and lack of symptoms (in most cases) until tumors become more advanced. Once diagnosed, cross-sectional imaging techniques are heavily utilized to determine the tumor stage and the potential for surgical resection. However, a major determinant of resectability is the extent of local vascular involvement of the mesenteric vessels and critical tributaries; current imaging techniques have limited capacity to accurately determine vascular involvement. Surrounding inflammation and fibrosis can be difficult to discriminate from viable tumor, making determination of the degree of vascular involvement unreliable. New innovations in fluorescence and optoacoustic imaging techniques may overcome these limitations and make determination of resectability more accurate. These imaging modalities are able to more clearly discern between viable tumor tissue and non-neoplastic inflammation or desmoplasia, allowing clinicians to more reliably characterize vascular involvement and develop individualized treatment plans for patients. This review will discuss the current imaging techniques used to diagnose pancreatic cancer, the barriers that current techniques raise to accurate staging, and novel fluorescence and optoacoustic imaging techniques that may provide more accurate clinical staging of pancreatic cancer.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Pancreatectomia/métodos , Diagnóstico por Imagem , Estadiamento de Neoplasias , Neoplasias Pancreáticas
4.
J Craniofac Surg ; 34(7): 2040-2045, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37622546

RESUMO

PURPOSE: The purpose of this article was to appraise the various methods of reconstruction for meningomyelocele (MMC) defects. METHODS: A systematic review of the literature was performed to evaluate all reconstructions for MMC. The method of reconstruction was categorized by: primary closure with and without fascial flaps, random pattern flaps, VY advancement flaps (VY), perforator flaps, and myocutaneous flaps. Perforator flaps were subsequently subcategorized based on the type of flap. RESULTS: Upon systematic review, 567 articles were screened with 104 articles assessed for eligibility. Twenty-nine articles were further reviewed and included for qualitative synthesis. Two hundred seventy patients underwent MMC repair. The lowest rates of major wound complications (MWC) were associated with myocutaneous and random pattern flaps. A majority of MWC was in the lumbrosacral/sacral region (87.5% of MWC). In this region, random patterns and perforator flaps demonstrated the lowest rate of MWC (4.5, 8.1%). CONCLUSIONS: Plastic surgery consultation should be strongly considered for MMC with defects in the lumbosacral/sacral region. Perforator flaps are excellent options for the reconstruction of these defects.

5.
J Aquat Anim Health ; 35(2): 88-100, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37243311

RESUMO

OBJECTIVE: Viral hemorrhagic septicemia virus (VHSV) is an aquatic rhabdovirus causing severe disease in freshwater and saltwater fish species. The susceptibility of endangered Pallid Sturgeon Scaphirhynchus albus to VHSV genotype IVb (VHSV-IVb) infection was investigated. METHODS: An in vitro assessment using two Pallid Sturgeon cell lines derived from skin and spleen tissue and in vivo evaluation of juvenile Pallid Sturgeon after exposure to VHSV-IVb were performed. RESULT: Plaque assay and RT-PCR results confirmed VHSV-IVb replication in Pallid Sturgeon cell lines. Sturgeon were also susceptible to VHSV-IVb infection after immersion and injection exposures during laboratory experiments. However, after widespread mortality occurred in all treatment groups, including negative control fish, it was determined that the Pallid Sturgeon stock fish were infected with Missouri River sturgeon iridovirus (MRSIV) prior to experimental challenge. Nevertheless, mortalities were equal or higher among VHSV-exposed fish than among negative controls (MRSIV infected), and histopathological assessments indicated reduced hematopoietic cells in spleen and kidney tissues and hemorrhage in the gastrointestinal organs only in fish from the VHSV treatment. CONCLUSION: These results indicate that Pallid Sturgeon is a susceptible host for VHSV-IVb, but the degree of pathogenicity was confounded by the underlying MRSIV infection. Research comparing susceptibility of specific pathogen-free and MRSIV-infected fish to VHSV-IVb is needed to accurately assess the vulnerability of Pallid Sturgeon to VHSV-IVb.


Assuntos
Doenças dos Peixes , Septicemia Hemorrágica Viral , Novirhabdovirus , Animais , Peixes , Genótipo , Água Doce , Novirhabdovirus/genética
6.
Ann Plast Surg ; 88(6): 599-605, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35612533

RESUMO

PURPOSE: Integrated plastic surgery residency programs have increased their social media presence to educate and recruit prospective residents. This study aims to understand the impact of integrated plastic surgery residency program social media on the 2020 to 2021 applicants' evaluation of prospective programs, particularly during the coronavirus disease 2019 pandemic. MATERIALS AND METHODS: An optional 20-item online survey was sent to integrated plastic surgery residency applicants applying to the authors' program. RESULTS: Surveys were sent to 300 integrated plastic surgery residency applicants with an average of 168 responses (56% response rate). Social media resources included official residency program website (87.1%), Instagram (70.2%), and Doximity (46.8%). The most frequently used resource by applicants was the official residency program website (43.9%); Instagram was the second most frequently used (40.2%) followed by Doximity (8.3%). Most respondents agreed that social media was an effective means to inform applicants (66.1%), and it positively impacted their perception of the program (64.8%). The cited benefits were helping the program exhibit its culture and comradery among residents, faculty, and staff (78.4%). Among applicants, 73.6% noted that it had a significant impact on their perceptions of programs. Most respondents truncated their planned plastic surgery subinternships, completing 1 instead of 3 planned subinternships because of coronavirus disease 2019 limitations. CONCLUSIONS: During the 2020 to 2021 plastic surgery application cycle, applicants used social media accounts of plastic surgery residency programs to inform and educate themselves about prospective programs. This study suggests that investing resources into a social media residency accounts is a meaningful pursuit for integrated plastic surgery programs and is an important aspect in today's recruitment.


Assuntos
COVID-19 , Internato e Residência , Mídias Sociais , Cirurgia Plástica , COVID-19/epidemiologia , Humanos , Pandemias , Estudos Prospectivos , Cirurgia Plástica/educação
7.
J Craniofac Surg ; 33(6): 1860-1864, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816753

RESUMO

INTRODUCTION: Nonmelanoma skin cancer is the most common malignancy of the scalp. Of these, squamous cell carcinoma (SCC) is the most troublesome. It poses a challenge to the surgeons caring for these patients as the anatomy of the scalp makes excision and reconstruction difficult. Although more superficial lesions are amenable to Mohs micrographic surgery, more invasive lesions require a different approach. This manuscript is a retrospective review of outer table resection for SCC of the scalp invading to the depth of the pericranium. We include a discussion of full thickness craniectomy for invasive SCC, regardless of depth of invasion, for completeness. METHODS: IRB approval was obtained from St. Joseph's Hospital and Medical Center in Phoenix, Arizona. One hundred four potential cases identified based on ICD codes. Ultimately, 23 cases met study criteria and were included in this analysis. Seventeen cases of outer table resection and 6 cases of full craniectomy were discussed. Additionally, the authors' approach for resection and reconstruction is articulated. RESULTS: Seventeen patients underwent outer table resection at an average age of 79.3 years. All had invasion of the pericranium with a mean surface area of 42.6 cm 2 . Eight patients had prior radiation treatment for SCC of the scalp and 12 patients had at least 1 prior surgery to attempt excision of their lesions. Two patients had local recurrence for a local control rate of 88.2% (15/17). One patient with metastasis prior to presentation, died 6 months after his initial surgery for disease-free survival rate of 94.1% (16/17) at a mean of 15.4months. Thirteen patients were able to achieve immediate reconstruction with local flaps with or without additional skin grafting (76.5%). DISCUSSION: The data in this study supports that in instances of locally invasive primary SCC of the scalp that extends to the pericranium, excision down to the calvarium with complete circumferential and deep peripheral margin assessment, followed by resection of the outer table, is an excellent option. The low rate of local recurrence and high disease-free survival in this study support that this method allows for optimal oncologic outcome while mitigating the significant morbidity associated with the alternative option of a full thickness craniectomy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Estudos Retrospectivos , Couro Cabeludo/patologia , Couro Cabeludo/cirurgia , Neoplasias Cutâneas/patologia , Transplante de Pele/métodos , Crânio/patologia , Crânio/cirurgia
8.
Int J Mol Sci ; 23(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36555749

RESUMO

Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn's disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.


Assuntos
Gastroenteropatias , Neoplasias , Humanos , Inflamação/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Imageamento por Ressonância Magnética/métodos , Gastroenteropatias/diagnóstico por imagem , Endoscopia Gastrointestinal/métodos , Fibrose
9.
Int J Mol Sci ; 22(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803201

RESUMO

Obesity, diabetes, and inflammation increase the risk of breast cancer, the most common malignancy in women. One of the mainstays of breast cancer treatment and improving outcomes is early detection through imaging-based screening. There may be a role for individualized imaging strategies for patients with certain co-morbidities. Herein, we review the literature regarding the accuracy of conventional imaging modalities in obese and diabetic women, the potential role of anti-inflammatory agents to improve detection, and the novel molecular imaging techniques that may have a role for breast cancer screening in these patients. We demonstrate that with conventional imaging modalities, increased sensitivity often comes with a loss of specificity, resulting in unnecessary biopsies and overtreatment. Obese women have body size limitations that impair image quality, and diabetes increases the risk for dense breast tis-sue. Increased density is known to obscure the diagnosis of cancer on routine screening mammography. Novel molecu-lar imaging agents with targets such as estrogen receptor, human epidermal growth factor receptor 2 (HER2), pyrimi-dine analogues, and ligand-targeted receptor probes, among others, have potential to reduce false positive results. They can also improve detection rates with increased resolution and inform therapeutic decision making. These emerg-ing imaging techniques promise to improve breast cancer diagnosis in obese patients with diabetes who have dense breasts, but more work is needed to validate their clinical application.


Assuntos
Neoplasias da Mama , Diabetes Mellitus , Mamografia , Obesidade , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Diabetes Mellitus/diagnóstico por imagem , Diabetes Mellitus/metabolismo , Feminino , Humanos , Obesidade/diagnóstico por imagem , Obesidade/metabolismo
10.
Aesthet Surg J ; 41(7): NP914-NP920, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33491085

RESUMO

BACKGROUND: During the past decade, a growing number of women have pursued medical careers, including in plastic surgery. However, female physicians have tended to be underrepresented in a variety of leadership roles in their respective specialties. OBJECTIVES: The authors sought to evaluate the representation of female plastic surgeons on the editorial boards of high-impact plastic surgery journals. METHODS: The gender of editorial board members on 3 high-impact plastic surgery journals was evaluated from 2009 and 2018. The number of women on each editorial board was then compared with the number of board-certified female plastic surgeons (BCFPS) and board-certified female academic plastic surgeons (BCFAPS), a subgroup of BCFPS. RESULTS: There were 555 unique editorial board members from Plastic and Reconstructive Surgery, Aesthetic Surgery Journal, and Annals of Plastic Surgery from 2009 to 2018. During that period, 72 editors (13.0%) were women. At the beginning of the study, there were significantly fewer female editors than expected based on proportionate representation of BCFPS and BCFAPS to all board-certified plastic surgeons (P = 0.007 and 0.007, respectively). During the study, there was a 177% increase in women holding editorial board positions. At study end, women were adequately represented on all 3 editorial boards compared with their population data (BCFPS and BCFAPS). CONCLUSIONS: During the 10 years of this study (2009-2018), editorial boards have overcome the underrepresentation of women on, and female plastic surgeons are currently adequately represented on the top 3 high-impact journal editorial boards.


Assuntos
Médicas , Procedimentos de Cirurgia Plástica , Cirurgiões , Cirurgia Plástica , Feminino , Humanos , Estados Unidos
11.
Biol Reprod ; 102(1): 133-144, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31436294

RESUMO

Radiation induces ovarian damage and accelerates reproductive aging. Inbred mouse strains exhibit differential sensitivity to lethality induced by total body irradiation (TBI), with the BALB/cAnNCrl (BALB/c) strain being more sensitive than the 129S2/SvPasCrl (129) strain. However, whether TBI-induced ovarian damage follows a similar pattern of strain sensitivity is unknown. To examine this possibility, female BALB/c and 129 mice were exposed to a single dose of 1 Gy (cesium-137 γ) TBI at 5 weeks of age, and ovarian tissue was harvested for histological and gene expression analyses 2 weeks post exposure. Sham-treated mice served as controls. 1 Gy radiation nearly eradicated the primordial follicles and dramatically decreased the primary follicles in both strains. In contrast, larger growing follicles were less affected in the 129 relative to BALB/c strain. Although this TBI paradigm did not induce detectable ovarian fibrosis in either of the strains, we did observe strain-dependent changes in osteopontin (Spp1) expression, a gene involved in wound healing, inflammation, and fibrosis. Ovaries from BALB/c mice exhibited higher baseline Spp1 expression that underwent a significant decrease in response to radiation relative to ovaries from the 129 strain. A correspondingly greater change in the ovarian matrix, as evidenced by reduced ovarian hyaluronan content, was also observed following TBI in BALB/c mice relative to 129 mice. These early changes in the ovary may predispose BALB/c mice to more pronounced late effects of TBI. Taken together, our results demonstrate that aspects of ovarian damage mirror other organ systems with respect to overall strain-dependent radiation sensitivity.


Assuntos
Expressão Gênica/efeitos da radiação , Ovário/efeitos da radiação , Irradiação Corporal Total , Animais , Feminino , Ácido Hialurônico/metabolismo , Camundongos Endogâmicos , Osteopontina/genética , Osteopontina/metabolismo , Ovário/metabolismo , Especificidade da Espécie
12.
Bioconjug Chem ; 31(2): 194-213, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31365819

RESUMO

Squaraine dyes are a class of organic dyes with strong and narrow absorption bands in the near-infrared. Despite high molar absorptivities and fluorescence quantum yields, these dyes have been less explored than other dye scaffolds due to their susceptibility to nucleophilic attack. Recent strategies in probe design including encapsulation, conjugation to biomolecules, and new synthetic modifications have seen squaraine dyes emerging into the forefront of biomedical imaging and other applications. Herein, we provide a concise overview of (1) the synthesis of symmetrical and unsymmetrical squaraine dyes, (2) the relationship between structure and photophysical properties of squaraine dyes, and (3) current applications of squaraine dyes in the literature. Given the recent successes at overcoming the limitations of squaraine dyes, they show high potential in biological imaging, in photodynamic and photothermal therapies, and as molecular sensors.


Assuntos
Ciclobutanos/química , Corantes Fluorescentes/química , Fenóis/química , Animais , Técnicas de Química Sintética/métodos , Ciclobutanos/síntese química , Ciclobutanos/uso terapêutico , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/uso terapêutico , Humanos , Imagem Óptica/métodos , Fenóis/síntese química , Fenóis/uso terapêutico , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos
13.
J Intensive Care Med ; 35(8): 738-744, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29886788

RESUMO

INTRODUCTION: Early removal of urinary catheters is an effective strategy for catheter-associated urinary tract infection (CAUTI) prevention. We hypothesized that a nurse-directed catheter removal protocol would result in decreased catheter utilization and CAUTI rates in a surgical trauma intensive care unit (STICU). METHODS: We performed a retrospective, cohort study following implementation of a multimodal CAUTI prevention bundle in the STICU of a large tertiary care center. Data from a 19-month historical control were compared to data from a 15-month intervention period. Pre- and postintervention indwelling catheter utilization and CAUTI rates were compared. RESULTS: Catheter utilization decreased significantly with implementation of the nurse-driven protocol from 0.78 in the preintervention period to 0.70 in the postintervention period (P < .05). As a result of the bundle, the CAUTI rate declined significantly, from 5.1 to 2.0 infections per 1000 catheter-days in the pre- vs postimplementation period (Incident Rate Ratio [IRR]: 0.38, 95% confidence interval: 0.21-0.65). CONCLUSIONS: Implementation of a nurse-driven protocol for early urinary catheter removal as part of a multimodal CAUTI intervention strategy can result in measurable decreases in both catheter utilization and CAUTI rates.


Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Enfermagem de Cuidados Críticos/métodos , Remoção de Dispositivo/enfermagem , Controle de Infecções/métodos , Cateterismo Urinário/enfermagem , Infecções Urinárias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Relacionadas a Cateter/etiologia , Cateteres de Demora/efeitos adversos , Protocolos Clínicos , Resultados de Cuidados Críticos , Infecção Hospitalar/etiologia , Infecção Hospitalar/prevenção & controle , Remoção de Dispositivo/efeitos adversos , Feminino , Implementação de Plano de Saúde , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Cateterismo Urinário/efeitos adversos , Cateteres Urinários/efeitos adversos , Infecções Urinárias/etiologia , Adulto Jovem
14.
J Public Health (Oxf) ; 42(4): e428-e434, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-31774535

RESUMO

BACKGROUND: The Global Burden of Disease reports indicate that musculoskeletal conditions are important causes of disability worldwide. Such conditions may originate in childhood, but studies investigating changes longitudinally and from childhood to adulthood are infrequent. METHODS: Nine birth cohorts of children (starting at ages 7-15 years) were followed. Participants were identified from Consultations in Primary Care Archive, an electronic health record database of 11 English general practices. Musculoskeletal consultation prevalence figures were calculated, and reasons for consultation evaluated. RESULTS: Annual musculoskeletal consultation prevalence was similar across cohorts for each age. Prevalence increased from 6 to 16% between ages 7 and 22 and was higher in males until age 15, after which prevalence was higher in females. Pain was the most common reason for consultation. Back pain consultations increased from 1 consultation/1000 7 year olds to 84 consultations/1000 22 year olds. Lower limb pain consultations increased from 21 consultations/1000 7 year olds to 56 consultations/1000 22 year olds. CONCLUSIONS: This study shows that from childhood, individuals are more likely to seek healthcare for musculoskeletal consultations as they age, but rates are not increasing over time. Changes in consultation rates by age, gender and pain region may inform studies on the development of chronic musculoskeletal pain over the life-course.


Assuntos
Medicina Geral , Doenças Musculoesqueléticas , Encaminhamento e Consulta , Adolescente , Adulto , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência , Atenção Primária à Saúde , Adulto Jovem
15.
Infect Immun ; 87(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31481410

RESUMO

Fibrosis is a significant complication of intestinal disorders associated with microbial dysbiosis and pathobiont expansion, notably Crohn's disease (CD). Mechanisms that favor fibrosis are not well understood, and therapeutic strategies are limited. Here we demonstrate that colitis-susceptible Il10-deficient mice develop inflammation-associated fibrosis when monoassociated with adherent/invasive Escherichia coli (AIEC) that harbors the yersiniabactin (Ybt) pathogenicity island. Inactivation of Ybt siderophore production in AIEC nearly abrogated fibrosis development in inflamed mice. In contrast, inactivation of Ybt import through its cognate receptor FyuA enhanced fibrosis severity. This corresponded with increased colonic expression of profibrogenic genes prior to the development of histological disease, therefore suggesting causality. fyuA-deficient AIEC also exhibited greater localization within subepithelial tissues and fibrotic lesions that was dependent on Ybt biosynthesis and corresponded with increased fibroblast activation in vitro Together, these findings suggest that Ybt establishes a profibrotic environment in the host in the absence of binding to its cognate receptor and indicate a direct link between intestinal AIEC and the induction of inflammation-associated fibrosis.


Assuntos
Colite/microbiologia , Escherichia coli/metabolismo , Fibrose/etiologia , Inflamação/microbiologia , Interleucina-10/metabolismo , Fenóis/metabolismo , Tiazóis/metabolismo , Animais , Aderência Bacteriana , Colite/complicações , Colite/patologia , Regulação Bacteriana da Expressão Gênica , Vida Livre de Germes , Humanos , Inflamação/patologia , Interleucina-10/genética , Camundongos , Camundongos Knockout , Mutação
16.
J Gen Intern Med ; 34(11): 2592-2601, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31385216

RESUMO

BACKGROUND: Professionalism standards encourage physicians to participate in public advocacy on behalf of societal health and well-being. While the number of publications of advocacy curricula for GME-level trainees has increased, there has been no formal effort to catalog them. OBJECTIVE: To systematically review the existing literature on curricula for teaching advocacy to GME-level trainees and synthesize the results to provide a resource for programs interested in developing advocacy curricula. METHODS: A systematic literature review was conducted to identify articles published in English that describe advocacy curricula for graduate medical education trainees in the USA and Canada current to September 2017. Two reviewers independently screened titles, abstracts, and full texts to identify articles meeting our inclusion and exclusion criteria, with disagreements resolved by a third reviewer. We abstracted information and themes on curriculum development, implementation, and sustainability. Learning objectives, educational content, teaching methods, and evaluations for each curriculum were also extracted. RESULTS: After reviewing 884 articles, we identified 38 articles meeting our inclusion and exclusion criteria. Curricula were offered across a variety of specialties, with 84% offered in primary care specialties. There was considerable heterogeneity in the educational content of included advocacy curriculum, ranging from community partnership to legislative advocacy. Common facilitators of curriculum implementation included the American Council for Graduate Medical Education requirements, institutional support, and preexisting faculty experience. Common barriers were competing curricular demands, time constraints, and turnover in volunteer faculty and community partners. Formal evaluation revealed that advocacy curricula were acceptable to trainees and improved knowledge, attitudes, and reported self-efficacy around advocacy. DISCUSSION: Our systematic review of the medical education literature identified several advocacy curricula for graduate medical education trainees. These curricula provide templates for integrating advocacy education into GME-level training programs across specialties, but more work needs to be done to define standards and expectations around GME training for this professional activity.


Assuntos
Defesa do Consumidor/normas , Currículo , Internato e Residência/organização & administração , Canadá , Humanos , Papel do Médico , Estados Unidos
17.
BMC Health Serv Res ; 19(1): 527, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357993

RESUMO

BACKGROUND: The PRagmatic trial Of Video Education in Nursing homes (PROVEN) aims to test the effectiveness of an advance care planning (ACP) video intervention. Relatively little is known about the challenges associated with implementing ACP interventions in the nursing home (NH) setting, especially within a pragmatic trial. To address this research gap, this report sought to identify facilitators of and barriers to implementing PROVEN from the perspective of the Champions charged with introducing the ACP video program delivery to patients and families. METHODS: In semi-structured telephone interviews at 4 and 15 months of the 18-month implementation period, ACP Champions at all PROVEN intervention facilities (N = 119) were asked about their perceptions of program implementation. Forty interviews were purposively sampled, transcribed, and analyzed using a hybrid deductive/inductive approach to thematic analysis incorporating the Consolidated Framework for Implementation Research's domains: Intervention Characteristics (IC), Inner Setting (IS), Characteristics of Individuals (CI), Outer Setting (OS), and Process (P). RESULTS: Implementation facilitators identified by Champions included: the intervention's adaptable mode of presentation and minimal time burden (IC) as well as the program's customizable delivery to patients and families and opportunity for group reflection on implementation among ACP Champions (P). Barriers included mandated protocol-driven aspects of the program (OS), limited time to deliver the intervention (IS), and lack of perceived relevance and emotional readiness for ACP amongst stakeholders (CI). CONCLUSIONS: Despite the promise of PROVEN's intervention for improving ACP in nursing homes, unchangeable setting and characteristics of Champions, patients, and family members presented implementation barriers. Researchers need to engage all program participants (i.e., facility staff, patients, and families), in addition to corporate-level stakeholders, in early pragmatic trial design to minimize such obstacles. Further, despite the facilitating nature of PROVEN's implementation processes, the study encountered tension between scientific rigor and real-world demands. Researchers need to optimize the real-world authenticity of pragmatic trial design while avoiding excessive implementation protocol deviations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02612688. Registered 19 November 2015.


Assuntos
Planejamento Antecipado de Cuidados , Casas de Saúde , Educação de Pacientes como Assunto , Gravação em Vídeo , Atitude do Pessoal de Saúde , Feminino , Pessoal de Saúde/educação , Humanos , Capacitação em Serviço , Entrevistas como Assunto , Masculino , Educação de Pacientes como Assunto/métodos , Assistentes Sociais/educação
18.
Int J Mol Sci ; 21(1)2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31905812

RESUMO

A variety of seemingly non-specific symptoms manifest within the gastrointestinal (GI) tract, particularly in the colon, in response to inflammation, infection, or a combination thereof. Differentiation between symptom sources can often be achieved using various radiologic studies. Although it is not possible to provide a comprehensive survey of imaging gastrointestinal GI tract infections in a single article, the purpose of this review is to survey several topics on imaging of GI tract inflammation and infections. The review discusses such modalities as computed tomography, positron emission tomography, ultrasound, endoscopy, and magnetic resonance imaging while looking at up-an-coming technologies that could improve diagnoses and patient comfort. The discussion is accomplished through examining a combination of organ-based and organism-based approaches, with accompanying selected case examples. Specific focus is placed on the bacterial infections caused by Shigella spp., Escherichia coli, Clostridium difficile, Salmonella, and inflammatory conditions of diverticulitis and irritable bowel disease. These infectious and inflammatory diseases and their detection via molecular imaging will be compared including the appropriate differential diagnostic considerations.


Assuntos
Gastroenteropatias/diagnóstico por imagem , Trato Gastrointestinal/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Imagem Molecular/métodos , Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/microbiologia , Clostridioides difficile , Infecções por Clostridium/diagnóstico por imagem , Disenteria Bacilar/diagnóstico por imagem , Endoscopia , Escherichia coli , Infecções por Escherichia coli/diagnóstico por imagem , Trato Gastrointestinal/microbiologia , Humanos , Síndrome do Intestino Irritável/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Salmonella , Infecções por Salmonella/diagnóstico por imagem , Sensibilidade e Especificidade , Shigella , Tomografia Computadorizada por Raios X , Ultrassonografia
19.
J Craniofac Surg ; 29(1): 96-98, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29194278

RESUMO

Consensus does not exist regarding the best dosage regimen for using tranexamic acid (TXA) for patients undergoing open calvarial vault remodeling in craniosynostosis surgery. The purpose of this study was to evaluate 2 dosing protocols, as well as the cost of using TXA. Previously, the institutional protocol was to give patients undergoing open calvarial vault remodeling a loading infusion of TXA (10 mg/kg) at the start of their procedure, after which intravenous TXA (5 mg/kg/h) was given throughout surgery and for 24 hours postoperatively. In July 2015, the protocol changed to a reduced postoperative infusion time of 4 hours. A retrospective review was conducted of records of 30 patients who had surgery before the protocol change (24-hour group) and 23 patients whose surgery occurred after the protocol change (4-hour group). The following data were collected: blood volume transfused, hemoglobin levels, estimated blood loss, and intensive care days; and costs of TXA and blood transfusion. Results showed a 4-hour infusion was as effective as a 24-hour infusion for reducing blood loss in patients undergoing craniosynostosis. Transfusion requirements, hemoglobin and hematocrit levels, and estimated blood loss were not significantly different for the groups. The cost of TXA and transfusion in the 4-hour group was significantly less (P < 0.001) than in the 24-hour group. No significant difference in cost existed for patients who received blood transfusion alone versus patients who received the 4-hour TXA infusion.


Assuntos
Antifibrinolíticos/administração & dosagem , Craniossinostoses/cirurgia , Procedimentos de Cirurgia Plástica , Ácido Tranexâmico/administração & dosagem , Antifibrinolíticos/economia , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Volume Sanguíneo , Custos de Medicamentos , Hematócrito , Hemoglobinas/metabolismo , Humanos , Lactente , Unidades de Terapia Intensiva , Tempo de Internação , Período Pós-Operatório , Estudos Retrospectivos , Ácido Tranexâmico/economia
20.
Molecules ; 23(11)2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30366395

RESUMO

Almost every variety of medical imaging technique relies heavily on exogenous contrast agents to generate high-resolution images of biological structures. Organic small molecule contrast agents, in particular, are well suited for biomedical imaging applications due to their favorable biocompatibility and amenability to structural modification. PET/SPECT, MRI, and fluorescence imaging all have a large host of small molecule contrast agents developed for them, and there exists an academic understanding of how these compounds can be developed. Optoacoustic imaging is a relatively newer imaging technique and, as such, lacks well-established small molecule contrast agents; many of the contrast agents used are the same ones which have found use in fluorescence imaging applications. Many commonly-used fluorescent dyes have found successful application in optoacoustic imaging, but others generate no detectable signal. Moreover, the structural features that either enable a molecule to generate a detectable optoacoustic signal or prevent it from doing so are poorly understood, so design of new contrast agents lacks direction. This review aims to compile the small molecule optoacoustic contrast agents that have been successfully employed in the literature to bridge the information gap between molecular design and optoacoustic signal generation. The information contained within will help to provide direction for the future synthesis of optoacoustic contrast agents.


Assuntos
Meios de Contraste/química , Fluorescência , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Espectroscopia de Luz Próxima ao Infravermelho
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