The physiological regulation of the immune system encompasses comprehensive anti‐inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent ...studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is also an immunomodulator. In experimental models of inflammatory diseases, vagal nerve stimulation attenuates the production of proinflammatory cytokines and inhibits the inflammatory process. Acetylcholine, the principal neurotransmitter of the vagal nerve, controls immune cell functions via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). From a pharmacological perspective, nicotinic agonists are more efficient than acetylcholine at inhibiting the inflammatory signaling and the production of proinflammatory cytokines. This ‘nicotinic anti‐inflammatory pathway’ may have clinical implications as treatment with nicotinic agonists can modulate the production of proinflammatory cytokines from immune cells. Nicotine has been tested in clinical trials as a treatment for inflammatory diseases such as ulcerative colitis, but the therapeutic potential of this mechanism is limited by the collateral toxicity of nicotine. Here, we review the recent advances that support the design of more specific receptor‐selective nicotinic agonists that have anti‐inflammatory effects while eluding its collateral toxicity.
British Journal of Pharmacology (2007) 151, 915–929; doi:10.1038/sj.bjp.0707264
Objectives
To meta-analyze complication rate in computed tomography (CT)-guided transthoracic lung biopsy and associated risk factors.
Methods
Four databases were searched from 1/2000 to 8/2015 for ...studies reporting complications in CT-guided lung biopsy. Overall and major complication rates were pooled and compared between core biopsy and fine needle aspiration (FNA) using the random-effects model. Risk factors for complications in core biopsy and FNA were identified in meta-regression analysis.
Results
For core biopsy, 32 articles (8,133 procedures) were included and for FNA, 17 (4,620 procedures). Pooled overall complication rates for core biopsy and FNA were 38.8 % (95 % CI: 34.3–43.5 %) and 24.0 % (95 % CI: 18.2–30.8 %), respectively. Major complication rates were 5.7 % (95 % CI: 4.4–7.4 %) and 4.4 % (95 % CI: 2.7–7.0 %), respectively. Overall complication rate was higher for core biopsy compared to FNA (
p
< 0.001). For FNA, larger needle diameter was a risk factor for overall complications, and increased traversed lung parenchyma and smaller lesion size were risk factors for major complications. For core biopsy, no significant risk factors were identified.
Conclusions
In CT-guided lung biopsy, minor complications were common and occurred more often in core biopsy than FNA. Major complication rate was low. For FNA, smaller nodule diameter, larger needle diameter and increased traversed lung parenchyma were risk factors for complications.
Key Points
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Minor complications are common in CT-guided lung biopsy
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Major complication rate is low in CT-guided lung biopsy
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CT-guided lung biopsy complications occur more often in core biopsy than FNA
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Major complication rate is similar in core biopsy and FNA
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Risk factors for FNA are larger needle diameter, smaller lesion size
Necrotizing enterocolitis (NEC) is a severe multifactorial disease in preterm neonates associated with high morbidity and mortality. Better insight into prognostic values of the many reported factors ...associated with NEC is needed to enable identification of neonates at risk for NEC. The aim was to systematically review the literature to identify independent risk factors for NEC from the literature.
Medline, Cochrane, Embase, Pubmed and Google Scholar were searched systematically for cohort studies reporting prognostic factors for NEC in neonates using multivariable analysis. Studies were scored with the Quality In Prognosis Studies tool (QUIPS).
From 5154 initial hits, 14 prognostic studies were included, with various designs. Study quality was rated high in three studies, moderate or low in the 11 others. Significant prognostic factors for NEC reported in at least two studies were: low birth weight, small for gestational age, low gestational age, assisted ventilation, premature rupture of membranes, black ethnicity, sepsis, outborn, hypotension (all increased risk), surfactant therapy (conflicting results) and cesarean section (lower risk). Meta-analysis was considered not feasible.
High quality studies on prognostic factors for NEC are rare. Several prognostic factors, that are not necessarily causal, are associated with NEC. High quality prognostic research is necessary to establish the predictive values of these factors.
Joint Species Distribution Modelling (JSDM) is becoming an increasingly popular statistical method for analysing data in community ecology. Hierarchical Modelling of Species Communities (HMSC) is a ...general and flexible framework for fitting JSDMs. HMSC allows the integration of community ecology data with data on environmental covariates, species traits, phylogenetic relationships and the spatio‐temporal context of the study, providing predictive insights into community assembly processes from non‐manipulative observational data of species communities.
The full range of functionality of HMSC has remained restricted to Matlab users only. To make HMSC accessible to the wider community of ecologists, we introduce Hmsc 3.0, a user‐friendly r implementation.
We illustrate the use of the package by applying Hmsc 3.0 to a range of case studies on real and simulated data. The real data consist of bird counts in a spatio‐temporally structured dataset, environmental covariates, species traits and phylogenetic relationships. Vignettes on simulated data involve single‐species models, models of small communities, models of large species communities and models for large spatial data. We demonstrate the estimation of species responses to environmental covariates and how these depend on species traits, as well as the estimation of residual species associations. We demonstrate how to construct and fit models with different types of random effects, how to examine MCMC convergence, how to examine the explanatory and predictive powers of the models, how to assess parameter estimates and how to make predictions. We further demonstrate how Hmsc 3.0 can be applied to normally distributed data, count data and presence–absence data.
The package, along with the extended vignettes, makes JSDM fitting and post‐processing easily accessible to ecologists familiar with r.
The monoamine serotonin, 5-hydroxytryptamine (5-HT), is a remarkable molecule with conserved production in prokaryotes and eukaryotes and a wide range of functions. In the gastrointestinal tract, ...enterochromaffin cells are the most important source for 5-HT production. Some intestinal bacterial species are also able to produce 5-HT. Besides its role as a neurotransmitter, 5-HT acts on immune cells to regulate their activation. Several lines of evidence indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. In this review, we discuss the current knowledge on the production, secretion, and signaling of 5-HT in the intestine. We present an inventory of intestinal immune and epithelial cells that respond to 5-HT and describe the effects of these signaling processes on intestinal homeostasis. Further, we detail the mechanisms by which 5-HT could affect inflammatory bowel disease course and describe the effects of interventions that target intestinal 5-HT signaling.
Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of ...global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.
The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.
Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.
Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?
This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility.
Scenario‐based biodiversity modelling is a powerful approach to evaluate how possible future socio‐economic developments may affect biodiversity. Here, we evaluated the changes in terrestrial ...biodiversity intactness, expressed by the mean species abundance (MSA) metric, resulting from three of the shared socio‐economic pathways (SSPs) combined with different levels of climate change (according to representative concentration pathways RCPs): a future oriented towards sustainability (SSP1xRCP2.6), a future determined by a politically divided world (SSP3xRCP6.0) and a future with continued global dependency on fossil fuels (SSP5xRCP8.5). To this end, we first updated the GLOBIO model, which now runs at a spatial resolution of 10 arc‐seconds (~300 m), contains new modules for downscaling land use and for quantifying impacts of hunting in the tropics, and updated modules to quantify impacts of climate change, land use, habitat fragmentation and nitrogen pollution. We then used the updated model to project terrestrial biodiversity intactness from 2015 to 2050 as a function of land use and climate changes corresponding with the selected scenarios. We estimated a global area‐weighted mean MSA of 0.56 for 2015. Biodiversity intactness declined in all three scenarios, yet the decline was smaller in the sustainability scenario (−0.02) than the regional rivalry and fossil‐fuelled development scenarios (−0.06 and −0.05 respectively). We further found considerable variation in projected biodiversity change among different world regions, with large future losses particularly for sub‐Saharan Africa. In some scenario‐region combinations, we projected future biodiversity recovery due to reduced demands for agricultural land, yet this recovery was counteracted by increased impacts of other pressures (notably climate change and road disturbance). Effective measures to halt or reverse the decline of terrestrial biodiversity should not only reduce land demand (e.g. by increasing agricultural productivity and dietary changes) but also focus on reducing or mitigating the impacts of other pressures.
We project the changes in terrestrial biodiversity intactness from 2015 to 2050 corresponding with three of the shared socio‐economic pathways combined with different levels of climate change, using an updated version of the GLOBIO model. Biodiversity intactness declined in all three scenarios, with large losses particularly for sub‐Saharan Africa. Effective measures to halt or reverse the decline of terrestrial biodiversity should not only reduce land demand but also reduce or mitigate the impacts of other pressures.
The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of ...the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated.
The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table 1) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.
This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. (Figure 1)
The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.
Diagnóstico y tratamiento de la infertilidad masculina: guía de la AUA/ ASRM parte 1.
El resumen representa la Parte I de una serie de dos partes dedicada al diagnóstico y tratamiento de la infertilidad masculina: Guía de la AUA/ASRM. La primera parte describe la evaluación apropiada del hombre en una pareja infértil. Las recomendaciones pasan por la realización de una historia y un examen físico apropiados (Apéndice I), así como pruebas de diagnóstico, cuando esté resulte indicado.
El equipo del Centro de Práctica Basada en la Evidencia del Instituto de Investigación de Cuidados de Emergencia buscó en PubMed, Embase y Medline desde enero de 2000 hasta mayo de 2019. Cuando existían pruebas suficientes, se asignaba al conjunto de pruebas una calificación de A (alta), B (moderada) o C (baja) para el apoyo de las recomendaciones fuertes, moderadas o condicionales. En ausencia de pruebas suficientes, se proporciona información adicional en forma de Principios Clínicos y Opiniones de Expertos. (Cuadro 1). Este resumen se publica simultáneamente en Fertility and Sterility y The Journal of Urology.
Esta guía proporciona recomendaciones actualizadas y basadas en la evidencia sobre la evaluación de la infertilidad masculina, así como la asociación de la infertilidad masculina con otras condiciones de salud importantes. La detección de la infertilidad masculina aumenta el riesgo de posterior desarrollo de los problemas de salud de los hombres. Además, determinadas afecciones médicas se asocian con algunas causas de la infertilidad masculina. La evaluación y las recomendaciones de tratamiento se resumen en el algoritmo asociado. (Figura 1)
La presencia de la infertilidad masculina es crucial para la salud de los pacientes y sus efectos deben ser considerados para el bienestar de sociedad. Este documento se actualizará a medida que continúe el conocimiento sobre los tratamientos actuales y las opciones de tratamiento futuras para expandirse.
BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK ...inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 .
Reported incidence rates of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus (BO) vary widely. As the effectiveness of BO surveillance is crucially dependent on this rate, its clarification ...is essential.
To estimate the rate of malignant progression in patients with BO, all patients with a first diagnosis of BO with no dysplasia (ND) or low-grade dysplasia (LGD) between 1991 and 2006 were identified in the Dutch nationwide registry of histopathology (PALGA). Follow-up data were evaluated up to November 2007.
42 207 patients with BO were included; 4132 (8%) of them had LGD. Re-evaluation endoscopies at least 6 months after initial diagnosis were performed in 16 365 patients (39%), who were significantly younger than those not re-examined (58+/-13 vs 63+/-16 years, p<0.001). These patients were followed-up for a total of 78 131 person-years, during which 666 (4%) high-grade dysplasia (HGD)/OACs occurred, affecting 4% of the surveillance patient population (mean age: 69+/-12 years, 76% male). After excluding HGD/OAC cases detected within 1 year after BO diagnosis (n=212, 32%), incidence rates per 1000 person-years were 4.3 (95% CI 3.4 to 5.5) for OAC and 5.8 (95% CI 4.6 to 7.0) for HGD/OAC combined. Risk factors for HGD/OAC were increased age (eg, >75 years HR 12; 95% CI 8.0 to 18), male sex (2.01; 1.68 to 2.60) and presence of LGD at baseline (1.91; 1.53 to 2.40).
In this largest reported cohort of unselected patients with BO, the annual risk of OAC was 0.4%. Male sex, older age and LGD at diagnosis are independent predictors of malignant progression, and should enable an improved risk assessment in BO.
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