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1.
Artigo em Inglês | MEDLINE | ID: mdl-34597729

RESUMO

BACKGROUND & AIMS: Fistulizing Crohn's disease (CD) is challenging to treat. We report results from ENTERPRISE, a randomized, double-blind, phase 4 trial, evaluating 2 vedolizumab intravenous dosing regimens in patients with fistulizing CD. METHODS: Patients with moderately to severely active CD and 1-3 active perianal fistulae (identified on magnetic resonance imaging [MRI]), received vedolizumab 300 mg intravenously at weeks 0, 2, 6, 14, and 22 (VDZ) or the same regimen plus an additional vedolizumab dose at week 10 (VDZ+wk10). Reduction from baseline in draining perianal fistulae and disease activity, MRI assessments, health-related quality of life (HRQoL), and safety were evaluated. Enrollment was stopped prematurely due to recruitment challenges; analyses are descriptive. RESULTS: Of 32 patients with ≥1 active fistula at baseline per MRI and postbaseline fistulae healing assessment, 28 (14 per dosing regimen) had ≥1 draining fistula at baseline (assessed by gentle finger compression during clinical exam). Rapid and sustained fistula closure was observed: 53.6% (VDZ, 64.3%; VDZ+wk10, 42.9%) and 42.9% (VDZ, 50.0%; VDZ+wk10, 35.7%) of patients achieved ≥50% decrease in draining fistulae and 100% fistulae closure, respectively, at week 30. Mean (standard deviation) CD and Perianal Disease Activity Index scores decreased by 51.1 (78.3) and 4.1 (3.3), respectively, at week 30. HRQoL improved throughout the study. No new safety signals were observed. CONCLUSIONS: Sustained improvements in fistulizing CD were seen with both vedolizumab regimens. An additional dose at week 10 does not appear to alter treatment outcomes. Safety profile was consistent with other vedolizumab studies.

2.
J Youth Adolesc ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34585323

RESUMO

Previous studies have called attention to the fact that popular youth are not immune to peer victimization, suggesting there is heterogeneity in the popularity of victims. Yet, no study to date has determined whether victims with different levels of popularity status can be identified using person-oriented analysis. Such analysis is critically needed to confirm the existence of popular victims. Further, there remains a paucity of research on internalizing indices of such popular victims, especially compared to other victim and non-victim groups. To address this gap in the research literature, the current study used latent profile analysis to identify subgroups of victims based on victimization (self- and peer-report) and popularity (peer-report). This study sought to verify the existence of popular victims and to compare victim subgroups on loneliness and self-esteem. Participants were 804 Dutch adolescents (50.2% boys, Mage = 13.65 years, ranging from 11.29 to 16.75 years). The results revealed six subgroups, including a group of popular self-identified victims. Popular self-identified victims were generally less lonely than other victims, but had higher loneliness and lower self-esteem than non-victims. Implications are discussed for understanding the victimization experiences of high-status youth.

3.
Inflamm Bowel Dis ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525184

RESUMO

BACKGROUND: Perianal fistula (PAF), a complication of Crohn's disease (CD), is associated with substantial economic costs and poor prognosis. We determined prevalence of PAF CD in the United States and compared costs and health care resource utilization (HRU) of PAF CD patients with matched non-PAF CD patients. METHODS: This was a retrospective cohort study of claims data from the IBM MarketScan Commercial Database from October 1, 2015, to September 30, 2018. Eligible patients were aged 18 to 89 years with ≥2 CD diagnoses. Patients with PAF CD had ≥1 PAF diagnosis or procedure code and were matched with non-PAF CD patients. Cumulative prevalence of PAF CD in the US population was calculated across total patients in MarketScan. All-cause and gastrointestinal (GI)-related costs and HRU were compared between groups using a generalized linear model (GLM). RESULTS: Cumulative 3-year prevalence of PAF was 7.70% of patients with CD (N = 81,862) and 0.01% of the US population. Among PAF CD (n = 1218) and matched non-PAF CD (n = 4095) patients, most all-cause costs and HRU were GI-related. Mean total all-cause and GI-related health care costs per patient and per year for PAF CD were $85,233 and $71,612, respectively, vs $40,526 and $29,458 for non-PAF CD (P < .0001). Among PAF CD vs non-PAF CD patients, GLM-adjusted proportions of patients with GI-related inpatient, outpatient, or pharmacy visits, mean GI-related inpatient length of stay, and mean GI-related surgeries were higher (P < .0001 for all comparisons). CONCLUSIONS: Costs and HRU are significantly higher for patients with PAF CD vs non-PAF CD patients, highlighting the economic burden of the disease.

4.
Transl Res ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34547499

RESUMO

While the coronavirus disease 19 (COVID-19) pandemic has transformed the medical and scientific communites since it was first reported in late 2019, we are only beginning to understand the chronic health burdens associated with this disease. Although COVID-19 is a multi-systemic disease, the lungs are the primary source of infection and injury, resulting in pneumonia and, in severe cases, acute respiratory distress syndrome (ARDS). Given that pulmonary fibrosis is a well-recognized sequela of ARDS, many have questioned whether COVID-19 survivors will face long-term pulmonary consequences. This review is aimed at integrating our understanding of the pathophysiologic mechanisms underlying fibroproliferative ARDS with our current knowledge of the pulmonary consequences of COVID-19 disease.

5.
Ann Clin Microbiol Antimicrob ; 20(1): 61, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481497

RESUMO

BACKGROUND: It is essential to detect carriers of carbapenemase-producing Enterobacterales in order to implement infection control measures. The objectives of this study was to evaluate the NG-Test® CARBA 5 (CARBA 5) assay for detection of five carbapenemases and to assess the cross reactivity of other OXA-type carbapenemases with the OXA-48-like specific antibodies. METHODS: A total of 197 Enterobacterales isolates were tested. To evaluate the cross reactivity, 73 carbapenem-resistant A. baumannii, harboring OXA-type variants, were tested. Polymerase chain reaction (PCR) served as gold standard for carbapenemase identification. RESULTS: Excellent agreement was found between PCR and CARBA 5, for all but one isolate. The single false positive result (a blaSME positive S. marcescens isolate) was incorrectly positive for blaOXA-48 by CARBA 5. No cross reactivity was observed. The sensitivity and specificity were 100.0% and 98.0%, respectively. CONCLUSIONS: The CARBA 5 assay is highly sensitive and specific and is recommended as a tool for the detection of the main carbapenemases of interest in clinical microbiology laboratories.

6.
Lancet Gastroenterol Hepatol ; 6(10): 826-849, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34416186

RESUMO

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.


Assuntos
Polipose Adenomatosa do Colo/complicações , Colectomia/efeitos adversos , Colite Ulcerativa/complicações , Bolsas Cólicas/efeitos adversos , Pouchite/diagnóstico , Proctocolectomia Restauradora/efeitos adversos , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/cirurgia , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/patologia , Colectomia/métodos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Consenso , Progressão da Doença , Feminino , Guias como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Pouchite/classificação , Proctocolectomia Restauradora/métodos , Qualidade de Vida
7.
Semin Arthritis Rheum ; 51(5): 996-1004, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411838

RESUMO

BACKGROUND: The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. METHODS: Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. RESULTS: Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. CONCLUSION: In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

8.
J Dev Biol ; 9(3)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34449643

RESUMO

A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together-chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.

11.
Methods Mol Biol ; 2350: 267-287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34331291

RESUMO

The UltraPlex method for multiplexed two-dimensional fluorescent immunohistochemistry is described, in which hapten tags conjugated to primary antibodies facilitate multiplexed imaging of four or more antigens per tissue section at once. Anti-hapten secondary antibodies labeled with fluorophores provide amplified signal for detection, which is accomplished using a standard fluorescent microscope or digital slide scanner. The protocol is rapid and straightforward and utilizes conventionally prepared tissue samples. The resulting staining is highly sensitive and specific, enabling high-resolution imaging of multiple cellular subtypes within tissue samples. Tumor cells and tumor-infiltrating lymphocytes are presented as examples. Multiple 4-plex-stained tissue samples can be digitally overlaid to create 8-plex (or more) high-content images, enabling visualization of distribution of complex cellular subtypes across tissues.


Assuntos
Imunofluorescência , Haptenos , Imuno-Histoquímica/métodos , Biomarcadores , Biomarcadores Tumorais , Análise de Dados , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/metabolismo , Neoplasias/patologia , Coloração e Rotulagem
12.
Nat Commun ; 12(1): 4566, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315881

RESUMO

The airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.


Assuntos
Epitélio/fisiopatologia , Fibrose Pulmonar Idiopática/fisiopatologia , Pulmão/fisiopatologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Anfirregulina/genética , Anfirregulina/metabolismo , Fenômenos Biofísicos/efeitos dos fármacos , Epitélio/efeitos dos fármacos , Receptores ErbB/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Predisposição Genética para Doença , Humanos , Fibrose Pulmonar Idiopática/genética , Queratina-5/genética , Queratina-5/metabolismo , Pulmão/efeitos dos fármacos , Mucina-5B/genética , Mucina-5B/metabolismo , Quinazolinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Tirfostinas/farmacologia , Verteporfina/farmacologia
13.
BMC Health Serv Res ; 21(1): 689, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253212

RESUMO

BACKGROUND: It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients' awareness and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages. METHODS: A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher's exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher's test. Post-hoc hospital-wise analyses were performed using Fisher's exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3). RESULTS: 6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105, p < 0.001) while the fewest patients were in H-SE (1 %, N = 1/100, p = 0.001). In addition, 82.5 %, (N = 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional. CONCLUSIONS: Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust.


Assuntos
Medicamentos Genéricos , Hospitais , Estudos Transversais , Alemanha , Grécia , Humanos , Polônia , Estudos Retrospectivos
14.
Dig Dis Sci ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34268660

RESUMO

BACKGROUND: Vedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population. AIMS: Here, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD. METHODS: This retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes. RESULTS: 212 cases were identified-108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p < 0.001). CONCLUSIONS: In a cohort of IBD patients over age 60, vedolizumab showed no statistically significant differences in infection, hospitalization, or surgical intervention-free survival as compared to anti-TNF. Vedolizumab was discontinued less frequently than anti-TNF. Patients on vedolizumab had higher rates of endoscopic remission and response.

15.
Arch Pathol Lab Med ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297794

RESUMO

CONTEXT: - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARSCoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases including HIV and Zika virus, but their involvement in SARS-CoV-2 in unknown. OBJECTIVE: - To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium and other villous stromal cells in infected placentas of liveborn and stillborn infants. DESIGN: - Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast and other fetal-derived cells. RESULTS: - Chronic histiocytic intervillositis and trophoblast necrosis was present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4/22 placentas (18%). Villous capillary endothelial staining was positive in 2/22 cases (9%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21/22 placentas (95%). Hofbauer cell hyperplasia was present in 3/22 placentas (14%). In the 7 cases having documented transplacental infection of the fetus, 2 occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. CONCLUSIONS: - SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.

16.
Emerg Infect Dis ; 27(8): 2127-2134, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34287121

RESUMO

We performed a spatial and mixed ecologic study of community-onset Enterobacteriaceae isolates collected from a public healthcare system in Cook County, Illinois, USA. Individual-level data were collected from the electronic medical record and census tract-level data from the US Census Bureau. Associations between individual- and population-level characteristics and presence of ceftriaxone resistance were determined by logistic regression analysis. Spatial analysis confirmed nonrandom distribution of ceftriaxone resistance across census tracts, which was associated with higher percentages of Hispanic, foreign-born, and uninsured residents. Individual-level analysis showed that ceftriaxone resistance was associated with male sex, an age range of 35-85 years, race or ethnicity other than non-Hispanic Black, inpatient encounter, and percentage of foreign-born residents in the census tract of isolate provenance. Our findings suggest that the likelihood of community-onset ceftriaxone resistance in Enterobacteriaceae is influenced by geographic and population-level variables. The development of effective mitigation strategies might depend on better accounting for these factors.


Assuntos
Ceftriaxona , Enterobacteriaceae , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Hispano-Americanos , Humanos , Illinois/epidemiologia , Masculino , Pessoa de Meia-Idade
17.
Am J Physiol Lung Cell Mol Physiol ; 321(2): L440-L450, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34160296

RESUMO

Idiopathic pulmonary fibrosis (IPF) is an incurable genetic disease that affects 5 million people worldwide. The gain-of-function MUC5B promoter variant rs35705950 is the dominant genetic risk factor for IPF, yet has a low penetrance. This raises the possibility that other genes and transcripts affect the penetrance of MUC5B. Previously, we have shown that the concentration of Muc5b in bronchoalveolar epithelia is directly associated with the extent and persistence of bleomycin-induced lung fibrosis in mice. In this study, we investigated whether bleomycin-induced lung injury is Muc5b dependent in genetically divergent strains of mice. Specifically, mice from the eight Diversity Outbred (DO) founders were phenotyped for Muc5b expression and lung fibrosis 3 wk after intratracheal bleomycin administration. Although we identified strains with low Muc5b expression and minimal lung fibrosis (CAST/EiJ and PWK/PhJ) and strains with high Muc5b expression and extensive lung fibrosis (NZO/H1LtJ and WSB/EiJ), there also were strains that did not demonstrate a clear relationship between Muc5b expression and lung fibrosis (129S1/SvlmJ, NOD/ShiLtJ, and C57BL/6J, A/J). Hierarchical clustering suggests that other factors may work in concert with or potentially independent of Muc5b to promote bleomycin-induced lung injury and fibrosis. This study suggests that these strains and their recombinant inbred crosses may prove helpful in identifying the genes and transcripts that interact with Muc5b and cause lung fibrosis.


Assuntos
Bleomicina/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Fibrose Pulmonar Idiopática , Mucina-5B , Mucosa Respiratória , Animais , Bleomicina/farmacologia , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/genética , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , Mucina-5B/biossíntese , Mucina-5B/genética , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia
18.
Clin Microbiol Infect ; 27(10): 1518.e1-1518.e3, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34111587

RESUMO

OBJECTIVES: The Israeli national policy for containing carbapenemase-producing Enterobacterales (CPE) includes a protocol allowing for discontinuation of carrier status following spontaneous decolonization. We examined the strategy's effectiveness based on carbapenemase type. METHODS: We performed a retrospective cohort study comparing individuals colonized with KPC- or NDM-producing Enterobacterales who underwent the process of isolation discontinuation. The primary outcome was reversion of carrier status, i.e. re-identification of the same CPE species following isolation discontinuation. We used survival analysis to estimate overall hazard ratio and performed competing-risks analysis using a Fine-Gray subdistribution hazard model and cause-specific hazard ratios. RESULTS: Between 1 January 2006 and 1 January 2019 we identified 1694 individuals who met inclusion criteria, including 1337 (78.9%) carriers of KPC-producing Enterobacterales, 305 (18.0%) carriers of NDM-producing Enterobacterales and 52 (3.1%) carriers of dual KPC-/NDM-producing Enterobacterales. A total of 134 individuals (7.9%) had reversion of carrier status: 9.1% (121/1337) and 4.3% (13/305) of individuals with KPC- and NDM-producing Enterobacterales, respectively. The subdistribution hazard ratio of status reversion was not increased among carriers of NDM producers compared with KPC producers (0.567, 95% CI 0.320-1.000], p 0.052). Cause-specific hazard ratios yielded similar results (0.522, 95% CI 0.291-0.937, p 0.029. CONCLUSIONS: Carriage of NDM-producing Enterobacterales was not associated with higher rates of reversion to carrier status following spontaneous decolonization than was carriage of KPC-producing Enterobacterales.

19.
Head Neck ; 43(10): 3165-3176, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34165221

RESUMO

BACKGROUND: Surgery with adjuvant radiotherapy is the accepted standard for treatment of advanced oral cavity squamous cell carcinoma (OCSCC); however, alternative evidence suggests that definitive (chemo)radiotherapy may have similar outcomes. METHODS: Systematic review was performed to assess the therapeutic value of radiotherapy or chemoradiotherapy as a primary modality for treating OCSCC. Meta-analysis of outcomes was performed between articles comparing radiotherapy and primary surgical treatment. RESULTS: Meta-analysis showed less favorable results of radiotherapy compared to surgery: overall survival at 3-years (odds ratio [OR] = 0.51; 95% confidence interval [CI] = 0.34-0.77) and 5-years (OR = 0.42; 95% CI = 0.29-0.60); disease-specific survival at 3-years (OR = 0.55; 95% CI = 0.32-0.96) and 5-years (OR = 0.55; 95% CI = 0.32-0.96). Odds of feeding tube dependency were higher in primary radiotherapy group (OR = 2.67; 95% CI = 1.27-5.64). CONCLUSIONS: Results of this study support the current perspective favoring primary surgical treatment for OCSCC in the absence of surgical contraindications.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço
20.
Artigo em Inglês | MEDLINE | ID: mdl-34133376

RESUMO

PURPOSE: The majority of childhood cancer survivors do not follow-up for long-term risk-based screening for recurrent illness and treatment late effects, despite a high prevalence of secondary morbidities. The primary aim of this study was to investigate factors that influence long-term follow-up for survivorship care, from the perspectives of providers, patients, and caregivers. MATERIALS AND METHODS: A semistructured interview was designed to elicit stakeholder perspectives on factors that facilitate or impede routine clinic visits after completion of cancer therapy. Results were analyzed using a qualitative framework method. RESULTS: Providers, patients, and caregivers identified a wide range of factors that might influence long-term follow-up for care. All respondents noted the importance of efficient clinical operations, resources such as parking, provider behaviors, rapport/attachment, and patient/family logistics. Compared with patients/caregivers, providers more frequently mentioned institutional operations, their own education and skills, patient/family understanding and motivation, and interpersonal processes such as communication style. Families more frequently mentioned clinic environment, and patients more frequently noted the importance of having a family member present, something neither providers nor caregivers reported. CONCLUSIONS: Providers, patients, and patient caregivers have different perspectives regarding factors that may influence follow-up for long-term survivorship care. Understanding these differences can help inform efforts to improve follow-up.

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