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BACKGROUND: There is limited data on cardiac output in patients with small aortic annuli undergoing trans-catheter aortic valve implantation (TAVI) according to the implanted platform of balloon-expandable (BEV) compared to self-expanding valves (SEV). METHODS: This is a retrospective analysis of consecutive patients with severe aortic stenosis and small annuli who underwent successful TAVI. Cardiac output was measured using echocardiography within 4 weeks following TAVI. Data were recorded and analysed by an experienced operator who was not aware of the type of the implanted valve. RESULTS: 138 patients were included in the analysis, of whom 57 % underwent TAVI with BEV. Clinical and echocardiographic characteristics were comparable between the two platforms, except for more frequent previous cardiac surgery and smaller indexed aortic valve in the BEV group. There was no relationship between computed tomography-derived aortic annulus area and cardiac output post TAVI. When compared to patients who underwent TAVI with BEV, those with SEV had larger cardiac output [mean difference - 0.50 l/min, 95 % CI (-0.99, -0.01)] and cardiac index [mean difference - 0.20 l/min/m2, 95 % CI (-0.47, 0.07)], although the latter did not reach statistical significance. Unlike patients with small body surface area, in those with large body surface area both cardiac output and cardiac index were statistically larger in patients who underwent SEV compared to BEV. CONCLUSION: Cardiac output, as measured by echocardiography, was larger in patients with small annuli who underwent TAVI procedure with SEV compared to BEV. Such difference was more evident in patients with large body surface area.
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INTRODUCTION: Lhermitte's phenomenon (LP) is a transient shock-like sensation that radiates down the spine into the extremities, usually with neck flexion. The potential efficacy and tolerability of various symptomatic therapies in the management of LP have not been systematically reviewed previously. METHOD: A systematic review was conducted using PubMed, EMBASE, and the Cochrane Library from inception to August 2022 for peer-reviewed articles describing the treatment of patients with Lhermitte's phenomenon. The review adheres to the PRISMA guidelines and was registered on PROSPERO. RESULTS: This systematic review included sixty-six articles, which included 450 patients with LP. Treatment of the underlying cause varied by aetiology. Whilst LP is most commonly considered in the context of structural pathology of the cervical cord, medication-induced LP was a common theme in the literature. The most common cause of medication-induced LP was platinum-based chemotherapy agents such as cisplatin and oxaliplatin. In medication-induced LP, symptoms typically resolved with cessation of the causative agent. Non-pharmacological treatment options were associated with mild-moderate symptomatic improvement. The most commonly used agents to treat patients with LP were carbamazepine and gabapentin, which resulted in variable degrees of symptomatic benefit. CONCLUSIONS: No randomised studies currently exist to support the use of symptomatic therapies to treat LP. Observational data suggest that some therapies may yield a symptomatic benefit in the management of LP. However, this systematic review identified a significant paucity of evidence in the literature, which suggests that further controlled studies are needed to investigate the optimal management of this common neurologic phenomenon.
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Antineoplásicos Alquilantes , Medula Cervical , Humanos , Benzodiazepinas , Carbamazepina , CisplatinoRESUMO
BACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.
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Secções Congeladas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Sensibilidade e Especificidade , Curva ROC , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgiaRESUMO
Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants impacted by maternal intake. These nutrients may provide a means for modifying maternal and infant antioxidant capacity. Oxygen radical absorbance capacity (ORAC), alpha-tocopherol, ascorbic acid, and beta-carotene concentrations were measured in breast milk of women with and without GD. Plasma, three-day diet records, and breast milk were collected at 6 to 8 weeks postpartum. Student's t-test was used to compare breast milk ORAC, nutrient antioxidant concentration and plasma ORAC between women with and without GD. Pearson correlations were used to determine associations among antioxidant concentrations in breast milk and dietary antioxidant intake. Breast milk antioxidant concentrations were associated with maternal intake of beta-carotene (r = 0.629, p = 0.005). Breast milk and plasma ORAC and antioxidant vitamin concentrations were not significantly different between GD and NG women. Breast milk ORAC associated with breast milk alpha-tocopherol for NG (r = 0.763, p = 0.010), but not GD women (r = 0.385, p = 0.35), and with breast milk ascorbic acid for GD (r = 0.722, p = 0.043) but not NG women (r = 0.141, p = 0.70; interaction p = 0.041). In GD participants, breast milk ORAC was significantly associated with plasma ORAC (r = 0.780, p = 0.039). ORAC and antioxidant vitamin concentrations in breast milk in women with GD were comparable to women with NG; however, the relationships between breast milk ORAC and vitamin concentrations differed in GD versus NG women for alpha-tocopherol and ascorbic acid.
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Millions of abandoned oil and gas wells are scattered across the United States, causing methane emissions and other environmental hazards. Governments are increasingly interested in decommissioning these wells but want to do so efficiently. However, information on the costs of decommissioning wells is very limited. In this analysis, we provide new cost estimates for decommissioning oil and gas wells and key cost drivers. We analyze data from up to 19,500 wells and find median decommissioning costs are roughly $20,000 for plugging only and $76,000 for plugging and surface reclamation. In rare cases, costs exceed $1 million per well. Each additional 1,000 feet of well depth increases costs by 20%, older wells are more costly than newer ones, natural gas wells are 9% more expensive than wells that produce oil, and costs vary widely by state. Surface characteristics also matter: each additional 10 feet of elevation change in the 5-acre area surrounding the well raises costs by 3%. Finally, we find that contracting in bulk pays: each additional well per contract reduces decommissioning costs by 3% per well. These findings suggest that regulators can adjust bonding requirements to better match the characteristics of each well.
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Campos de Petróleo e Gás , Poços de Água , Meio Ambiente , Metano , Gás Natural , Estados UnidosRESUMO
BACKGROUND: Inadvertent perioperative hypothermia is a common complication of surgery, and active body surface warming (ABSW) systems are used to prevent adverse clinical outcomes. Prior data on certain outcomes are equivocal (ie, blood loss) or limited (ie, pain and opioid consumption). The objective of this study was to provide an updated review on the effect of ABSW on clinical outcomes and temperature maintenance. METHODS: We conducted a systematic review of randomized controlled trials evaluating ABSW systems compared to nonactive warming controls in noncardiac surgeries. Outcomes studied included postoperative pain scores and opioid consumption (primary outcomes) and other perioperative clinical variables such as temperature changes, blood loss, and wound infection (secondary outcomes). We searched Ovid MEDLINE daily, Ovid MEDLINE, EMBASE, CINHAL, Cochrane CENTRAL, and Web of Science from inception to June 2019. Quality of evidence (QoE) was rated according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Subgroup analysis sought to determine the effect of preoperative + intraoperative warming versus intraoperative warming alone. Metaregression evaluated the effect of year of publication, use of neuromuscular blockers, anesthesia, and surgery type on outcomes. RESULTS: Fifty-four articles (3976 patients) were included. Pooled results demonstrated that ABSW maintained normothermia compared to controls, during surgery (30 minutes postinduction [mean difference {MD}: 0.3°C, 95% confidence interval {CI}, 0.2-0.4, moderate QoE]), end of surgery (MD: 1.1°C, 95% CI, 0.9-1.3, high QoE), and up to 4 hours postoperatively (MD: 0.3°C, 95% CI, 0.2-0.5, high QoE). ABSW was not associated with difference in pain scores (<24 hours postoperatively, moderate to low QoE) or perioperative opioid consumption (very low QoE). ABSW increased patient satisfaction (MD: 2.2 points, 95% CI, 0.9-3.6, moderate QoE), reduced blood transfusions (odds ratio [OR] = 0.6, 95% CI, 0.4-1.0, moderate QoE), shivering (OR = 0.2, 95% CI, 0.1-0.4, high QoE), and wound infections (OR = 0.3, 95% CI, 0.2-0.7, high QoE). No significant differences were found for fluid administration (low QoE), blood loss (very low QoE), major adverse cardiovascular events (very low QoE), or mortality (very low QoE). Subgroup analysis and metaregression suggested increased temperature benefit with pre + intraoperative warming, use of neuromuscular blockers, and recent publication year. ABSW seemed to confer less temperature benefit in cesarean deliveries and neurosurgical/spinal cases compared to abdominal surgeries. CONCLUSIONS: ABSW is effective in maintaining physiological normothermia, decreasing wound infections, shivering, blood transfusions, and increasing patient satisfaction but does not appear to affect postoperative pain and opioid use.
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Analgésicos/uso terapêutico , Anestesia/métodos , Reaquecimento , Temperatura Corporal , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Introduction: The coronavirus disease 19 (COVID-19) pandemic has placed significant strains on healthcare resources including staff, theatre, high dependency and intensive care availability. Surgery remains the optimal treatment for the majority of oral malignancies, and primary reconstruction is often necessary to avoid significant morbidity as a result of ablative procedures. Description: The supraclavicular artery island flap (SCAIF) is increasingly finding a place as an alternative to free flap reconstruction of soft-tissue defects and has several specific advantages when compared to use of a soft-tissue free flap during the COVID-19 pandemic. It can be used for a range of head and neck defects. Results: We describe our experience with the SCAIF during the pandemic in five patients with a variety of tumour types and locations. All five patients had a successful outcome with none requiring further reconstruction and all had a functional swallow postoperatively, including a patient who underwent a total pharyngeal reconstruction with a SCAIF. Discussion: The use of a SCAIF during the current COVID-19 pandemic has significant advantages and is a reliable alternative to a soft tissue free flap.
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The glycemic index (GI) has been included in the Canadian clinical practice guidelines for type 2 diabetes (T2D) management since 2003, and even longer in other parts of the world (e.g., Australia). Despite this, dietitians have reported that GI is "too difficult for patients to understand and apply." They have called for diverse GI-utility data and evidence-informed education materials. To address these concerns, we developed and evaluated a GI education workshop and supporting materials, using the Kirkpatrick Model, for a T2D population. Participants (n = 29) with T2D attended a dietitian-facilitated workshop and received education materials. A mixed-form questionnaire (GIQ) and 3-day-diet-record were used to capture patient demographics, satisfaction, knowledge, and application, prior to and immediately after the workshop, 1-week, and 4-weeks post-education. Dietary GI was significantly lower at 1 and 4 weeks post-education (mean ± SEM; both 54 ± 1), compared to pre-education (58 ± 1; p ≤ 0.001). Participants (28/29) were satisfied with the intervention. The GI knowledge score was significantly higher post-education at baseline (83.5 ± 3.4%; p ≤ 0.001), week one (87.5 ± 2.6%; p = 0.035), and week four (87.6 ± 3.8%; p = 0.011) when compared to pre-education (53.6 ± 5.1%). A significant reduction in dietary GI was achieved by participants living with T2D, after completing the workshop, and they were able to acquire and apply GI knowledge in a relatively short period.
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Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos/psicologia , Índice Glicêmico , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto/métodos , Satisfação do Paciente/estatística & dados numéricos , Adulto , Canadá , Diabetes Mellitus Tipo 2/psicologia , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The encapsulation of water-soluble therapeutics and biologics into nanocarriers to produce novel therapeutics has been envisioned for decades, but clinical translation has been hampered by complex synthesis strategies. The methods that have been developed are often limited by poor encapsulation efficiency/loading or complex processing to achieve therapeutic loadings high enough to be medically relevant. To address this unmet need, we introduce a solubility-driven self-assembly process to form polymeric nanocarriers comprising a biologic in a hydrophilic core, encapsulated by a poly(lactic acid) shell, and stabilized by a poly(ethylene glycol) brush. Called "inverse Flash NanoPrecipitation (iFNP)," the technique achieves biologic loadings (wt% of total formulation) that are 5-15× higher than typical values (9-27% versus < 2%). In contrast to liposomes and polymersomes, we sequentially assemble the polymer layers to form the final nanocarrier. Installation of the poly(lactic acid) shell before water exposure sequesters the biologic in the core and results in the improved loadings that are achieved. We demonstrate the broad applicability of the process and illustrate its implementation by formulating over a dozen different oligosaccharides, antibiotics, peptides, proteins, and RNA into nanocarriers with narrow size distributions, at high loadings, and with high reproducibility. Lysozyme and horseradish peroxidase are shown to retain 99% activity after processing. These results demonstrate the potential for commercial implementation of this technology, enabling the translation of novel treatments in immunology, oncology, or enzyme therapies.
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Produtos Biológicos/química , Portadores de Fármacos , Nanopartículas , Nanotecnologia , Poliésteres/síntese química , Polietilenoglicóis/síntese química , Precipitação Química , Composição de Medicamentos , Estabilidade de Medicamentos , Tamanho da Partícula , Solubilidade , Água/químicaRESUMO
The present study describes the knowledge about smoking and nicotine among a sample of current Iraq-/Afghanistan-era veterans who smoke (N = 117). A majority of participants had knowledge regarding general risks of smoking and benefits of nicotine replacement therapy. However, many participants underestimated their personal cardiovascular and cancer risk as a smoker. Many participants also inaccurately believed that nicotine causes cancer and that nicotine medications work by making one physically sick if used while smoking. These beliefs could lead to reluctance to use nicotine replacement therapy. Discussion of findings offers potential solutions in the form of patient education as well as emphasis on training healthcare providers training on best practices for patient education (beyond simple advice to quit). More nuance and detail in patient education may facilitate increased knowledge about smoking and nicotine among U.S. military veterans with the ultimate goal of increasing cessation rates.
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The objective of this study was to use qualitative methodology to tailor and refine an existing smoking cessation intervention for the population of people who use cigarettes and are diagnosed with schizophrenia, schizoaffective, or psychotic disorder. Successive cohort design methodology was used to iteratively modify the treatment in response to qualitative participant, therapist, and consultant feedback on the intervention. Qualitative methodology for participant feedback included analysis of semistructured interviews with participants, visualization of app utilization data, and stakeholder feedback from study therapists and consultants. Using the successive cohort design, a tailored multicomponent mobile health smoking cessation intervention was developed. The intervention included mobile contingency management (i.e., financial compensation for confirmed abstinence from smoking), pharmacotherapy for smoking cessation, cognitive-behavioral counseling sessions, and the Stay Quit app for relapse prevention. Two cohorts (N = 13) were completed in the study; after each cohort, the treatment protocol was revised. The intervention is described, as well as the qualitative findings from each cohort and subsequent changes made to the intervention based upon patient and provider feedback. Metrics of patient engagement included treatment adherence (40% in Cohort 1 and 63% in Cohort 2). Both participants and therapists reported that the intervention was helpful. Over one third of participants self-reported abstinence at posttreatment. Since qualitative methodology is often underutilized in mental health treatment development, this study demonstrates the utility of the successive cohort design for treatment development of behavior change interventions for at-risk, vulnerable populations.
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Esquizofrenia/terapia , Psicologia do Esquizofrênico , Smartphone , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Telemedicina/métodos , Adulto , Bupropiona/uso terapêutico , Terapia Cognitivo-Comportamental/métodos , Terapia Cognitivo-Comportamental/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente/métodos , Participação do Paciente/tendências , Esquizofrenia/epidemiologia , Prevenção Secundária/métodos , Prevenção Secundária/tendências , Smartphone/tendências , Fumar/epidemiologia , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Telemedicina/tendênciasRESUMO
BACKGROUND: The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown. METHODS: In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes. RESULTS: Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery. CONCLUSIONS: Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.
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Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Complicações Intraoperatórias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Estudos de Coortes , Feminino , Humanos , Hipotensão/epidemiologia , Internacionalidade , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Hepatocellular carcinoma (HCC) represents the second most common cause of cancer-related death worldwide, and is increasing in incidence. Currently, our therapeutic repertoire for the treatment of HCC is severely limited, and therefore effective new therapies are urgently required. Recently, there has been increasing interest focusing on the cellular and molecular interactions between cancer cells and their microenvironment. HCC represents a unique opportunity to study the relationship between a diseased stroma and promotion of carcinogenesis, as 90% of HCCs arise in a cirrhotic liver. Hepatic stellate cells (HSC) are the major source of extracellular proteins during fibrogenesis, and may directly, or via secreted products, contribute to tumour initiation and progression. In this review we explore the complex cellular and molecular interplay between HSC biology and hepatocarcinogenesis. We focus on the molecular mechanisms by which HSC modulate HCC growth, immune cell evasion and angiogenesis. This is followed by a discussion of recent progress in the field in understanding the mechanistic crosstalk between HSC and HCC, and the pathways that are potentially amenable to therapeutic intervention. Furthermore, we summarise the exciting recent developments in strategies to target HSC specifically, and novel techniques to deliver pharmaceutical agents directly to HSC, potentially allowing tailored, cell-specific therapy for HCC.
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Carcinogênese/metabolismo , Carcinoma Hepatocelular/metabolismo , Células Estreladas do Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral/fisiologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Transdução de SinaisRESUMO
OBJECTIVE: Gestational diabetes mellitus (GDM) has been associated with inflammation as well as Vitamin D insufficiency. While Vitamin D has anti-inflammatory properties, relationships between Vitamin D and inflammatory markers remain unexplored in GDM. Therefore, this case--control study investigated adipocytokine and Vitamin D [25(OH)D] concentrations and correlations in GDM and control women, as well as their neonates. DESIGN/PARTICIPANTS/MEASUREMENTS: seventy-three women participated: 36 GDM and 37 controls. Maternal samples were drawn at 31 weeks. Umbilical arterial and venous samples were collected at birth. 25(OH)D and adipocytokine concentrations were compared for GDM vs control maternal, umbilical arterial and venous samples. Correlations were explored between biochemical results, maternal and neonatal demographics. RESULTS: Compared with age- and weight-matched control participants, GDM women had significantly lower concentrations of 25(OH)D (77·3 ± 24·3 vs 93·2 ± 19·2 nm/l; P = 0·009); adiponectin (17·5 ± 11·8 vs 34·1 ± 20·3 µg/ml, P < 0·001); resistin (25·4 ± 9·1 vs 31·9 ± 12·1 ng/ml, P = 0·045); and plasminogen activator inhibitor-1 (PAI-1) 13·9 ± 10·0 vs 21·0 ± 12·6 ng/ml, P = 0·038), while delivering 1 week earlier (38·2 ± 1·2 vs 39·5 ± 0·9 weeks, P < 0·001). GDM maternal 25(OH)D concentrations positively correlated with PAI-1, IL-8 and TNF-α concentrations. Umbilical 25(OH)D concentrations were not significantly different in GDM vs control offspring, whereas adiponectin, resistin and PAI-1 concentrations were significantly lower in GDM offspring. CONCLUSIONS: GDM women had lower 25(OH)D concentrations than controls, while neonatal umbilical concentrations of 25(OH)D did not differ. GDM maternal and GDM offspring had lower adiponectin, resistin and PAI-1 concentrations compared with controls. Results suggest that both GDM women and their offspring demonstrate abnormal adipocytokine patterns.
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Adipocinas/sangue , Diabetes Gestacional/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adiponectina/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Inflamação , Inibidor 1 de Ativador de Plasminogênio/sangue , Gravidez , Resultado da Gravidez , Resistina/sangue , Artérias Umbilicais/química , Veias Umbilicais/química , Vitamina D/sangueAssuntos
Anticorpos Monoclonais/efeitos adversos , Doenças da Córnea/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Acuidade Visual/efeitos dos fármacos , Adolescente , Doenças da Córnea/patologia , Ceratócitos da Córnea/efeitos dos fármacos , Ceratócitos da Córnea/patologia , Doença de Crohn/complicações , Humanos , Infliximab , Masculino , PrognósticoRESUMO
Ulcerative colitis (UC) and Crohn's disease (CD) are related polygenic inflammatory bowel diseases (IBDs), with distinct and overlapping susceptibility loci. Recently, hypothesis-free genome-wide association (GWA) studies have revolutionized the field of complex disease genetics. Substantial advances have been achieved in defining the genetic architecture of IBD. To date, over 60 published IBD susceptibility loci have been discovered and replicated, of which approximately a third are associated with both UC and CD, although 21 are specific to UC and 23 to CD. In CD, the breakthrough identification of NOD2 as a susceptibility gene was followed by a rapid phase of gene discovery from GWA studies between 2006 and 2008. Progress in UC was slower; however, by initially testing hits for CD in UC, and later scanning larger UC cohorts, significant new loci for UC have been discovered, with exciting novel insights into disease pathogenesis. Notably, genes implicated in mucosal barrier function (ECM1, CDH1, HNF4α, and laminin B1) confer risk of UC; furthermore, E-cadherin is the first genetic correlation between colorectal cancer and UC. Impaired IL10 signaling has reemerged as a key pathway in intestinal inflammation, and is perhaps the most amenable to therapeutic intervention in UC. Collaborative international efforts with large meta-analyses of GWA studies and replication will yield many new UC genes. Furthermore, a large effort is required to characterize the loci found. Fine-mapping, deep resequencing, and functional studies will be critical to translating these gene discoveries into pathogenic insights, and ultimately into clinical insights and novel therapeutics.
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Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Estudo de Associação Genômica Ampla , HumanosRESUMO
OBJECTIVE: Although widely adopted, there is lack of immediate and long-term follow-up data for patients undergoing video-assisted thoracoscopic surgery (VATS) management of pneumothorax. Therefore, we have reviewed our experience with both primary (PSP) and secondary (SSP) spontaneous pneumothorax to assess the perioperative outcomes and long-term efficacy associated with different VATS operative strategies. METHODS: A retrospective case series review was undertaken on all patients undergoing VATS procedures for PSP or SSP over a 17-year period. RESULTS: A total of 644 VATS pneumothorax procedures were performed between 1992 and 2008 on 569 patients, of which 550 procedures were performed for PSP and 94 for SSP. Mean age for PSP and SSP groups were 28.4 ± 10.4 and 58.2 ± 14.2 years, respectively. Surgical technique used bullectomy in combination with abrasion (273), poudrage (246) and pleurectomy (46). Isolated poudrage was used in 72 cases. Median postoperative stay was 3 and 4 days, respectively. Major complications occurred in 25 (4.6%) PSP and 18 (19.2%) SSP patients. Two patients in the SSP group died (2.1%). Median follow-up was 73 months. Freedom from further surgery for the two populations was PSP: 98.1% at 5 years (confidence interval (C.I.): 96.9-99.4) and 97.8% at 10 years (C.I.: 96.5-99.2); SSP: 96.1% at 5 years (C.I.: 91.5-1.006) and 96.1% at 10 years (C.I.: 91.5-1.006). Freedom from further operation at 10 years was independent of the pleurodesis technique employed: abrasion 96.4%, poudrage 98.9% and pleurectomy 97.5% (p=0.22). CONCLUSIONS: VATS management of both PSP and SSP offers good short-term results and excellent long-term freedom from repeat surgery. In combination with bullectomy, results of abrasion and poudrage do not significantly differ from pleurectomy. We recommend abrasion for pleurodesis in young patients reserving poudrage for the elderly. Pleurectomy may not be necessary.