Robotic and Laparoscopic Adrenalectomy for Pheochromocytoma: An International Multicenter Study.

Background And Objective: Robotic adrenalectomy (RA) has attracted interest as an alternative to laparoscopic adrenalectomy (LA) for patients with pheochromocytoma, although its beneficial effects are uncertain. Our aim was to compare RA and LA outcomes for these patients.

Methods: Data for patients who underwent RA or LA for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed.

Bi-national Review of Phaeochromocytoma Care: Is ICU Admission Always Necessary?

Background: Post-operative management after phaeochromocytoma resection includes monitoring of blood pressure and blood sugar, and vigilance for haemorrhage. Guidelines recommend 24 h of continuous blood pressure monitoring, usually necessitating HDU/ICU admission. We hypothesised that most patients undergoing phaeochromocytoma resection do not require post-operative HDU/ICU admission.

Transcriptome analysis of IPF fibroblastic foci identifies key pathways involved in fibrogenesis.

Introduction: Fibroblastic foci represent the cardinal pathogenic lesion in idiopathic pulmonary fibrosis (IPF) and comprise activated fibroblasts and myofibroblasts, the key effector cells responsible for dysregulated extracellular matrix deposition in multiple fibrotic conditions. The aim of this study was to define the major transcriptional programmes involved in fibrogenesis in IPF by profiling unmanipulated myofibroblasts within fibrotic foci in situ by laser capture microdissection.

Methods: The challenges associated with deriving gene calls from low amounts of RNA and the absence of a meaningful comparator cell type were overcome by adopting novel data mining strategies and by using weighted gene co-expression network analysis (WGCNA), as well as an -based approach to identify transcriptional signatures, which correlate with fibrillar collagen gene expression.

Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis.

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points.

Author Correction: The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Profile and generalist physician knowledge about neurology in emergency department: headache management.

Background: Neurological complaints are frequent in emergency department routine. Among them, headache is a common disorder, which requires a certain degree of knowledge on Neurology because of its extensive differential diagnosis.

Objective: To assess general practice physicians' level of knowledge about headaches, in addition to outlining the profile of professionals who attend in emergency departments, as well as the profile of their respective workplaces in terms of neurological approach.

The circadian clock protein REVERBα inhibits pulmonary fibrosis development.

Pulmonary inflammatory responses lie under circadian control; however, the importance of circadian mechanisms in the underlying fibrotic phenotype is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of amplitude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis.

The patient with epilepsy and medicolegal aspects: a view for the neurologist.

Patients with epilepsy face innumerable obstacles in daily life, related to work, permission to drive and interpersonal relationships, which require medical guidance. This paper reports a literature review based on scientific articles and civil and traffic system, as a way to resolve doubts about medical obligations in the patient's permission to drive and work. An employment agreement requires the contractor to guarantee safety conditions as well as requiring the patient, at the pre-employment medical examination, to let the physician know previous medical conditions, including epilepsy.

Olfactory impairment in frontotemporal dementia: A systematic review and meta-analysis.

Unlabelled: Frontotemporal dementia (FTD) presents clinically in three variants: one behavioral and two with progressive primary aphasia - non-fluent/agrammatic and semantic. Defined by the degenerative process and cerebral atrophy, olfactory dysfunction occurs in up to 96% of previous FTD case series.

Objective: the present study aims to critically synthesize data about the relationship between FTD and olfactory impairment to analyze the usefulness of olfactory evaluation tests as a complementary element in early diagnosis.

mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β-induced collagen biosynthesis.

The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)-producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue repair is complete, lead to pathological fibrosis and are also features of the stromal response in cancer. Myofibroblast differentiation is accompanied by changes in cellular metabolism, including increased glycolysis, to meet the biosynthetic demands of enhanced ECM production.

A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis.

Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR.A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics and pharmacodynamics.

The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis.

Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluation in IPF. Here we demonstrate that rapamycin-insensitive mTORC1 signaling via 4E-BP1 is a critical pathway for TGF-β stimulated collagen synthesis in human lung fibroblasts, whereas canonical PI3K/Akt signaling is not required.

Restless legs syndrome in Parkinson's disease and increased cardiovascular risk.

Objective: Restless legs syndrome (RLS) is a disorder commonly found in patients with Parkinson's disease, with descriptions for both conditions impairing dopaminergic transmission in central nervous system. Previous studies in varied populations indicate an association between the presence of RLS and increased cardiovascular risk and, so far, there are no consistent studies of this association in Parkinson's disease. To analyze the influence of RLS on cardiovascular risk in patients with Parkinson's disease.

Olfactory dysfunction in Alzheimer's disease Systematic review and meta-analysis.

Unlabelled: Alzheimer's disease (AD), a neurodegenerative condition, is one of the most prevalent kinds of dementia, whose frequency doubles for every 5 years of age in elderly.

Objective: To determine the correlation between AD and olfactory alterations, identifying the most affected domains and exploring the utility of olfactory tests for complementing early diagnosis.

Methods: Databases were searched using the terms "olfactory OR smell OR olfaction AND alzheimer" for articles related to the proposed theme.

Evidence for chemokine synergy during neutrophil migration in ARDS.

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space.

Objectives: The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete.

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF.

Rationale: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting.

The anti-fibrotic effect of inhibition of TGFβ-ALK5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent γ-herpesvirus infection.

TGFβ-ALK5 pro-fibrotic signalling and herpesvirus infections have been implicated in the pathogenesis and exacerbation of pulmonary fibrosis. In this study we addressed the role of TGFβ-ALK5 signalling during the progression of fibrosis in a two-hit mouse model of murine γ-herpesvirus 68 (MHV-68) infection on the background of pre-existing bleomycin-induced pulmonary fibrosis. Assessment of total lung collagen levels in combination with ex vivo micro-computed tomography (µCT) analysis of whole lungs demonstrated that MHV-68 infection did not enhance lung collagen deposition in this two-hit model but led to a persistent and exacerbated inflammatory response.

Regulation of neutrophilic inflammation by proteinase-activated receptor 1 during bacterial pulmonary infection.

Neutrophils are key effector cells of the innate immune response to pathogenic bacteria, but excessive neutrophilic inflammation can be associated with bystander tissue damage. The mechanisms responsible for neutrophil recruitment to the lungs during bacterial pneumonia are poorly defined. In this study, we focus on the potential role of the major high-affinity thrombin receptor, proteinase-activated receptor 1 (PAR-1), during the development of pneumonia to the common lung pathogen Streptococcus pneumoniae.

Mechanisms of alveolar epithelial injury, repair, and fibrosis.

The challenge facing many fibrotic lung diseases is that these conditions usually present late, often after several decades of repetitive alveolar epithelial injury, during which functional alveolar units are gradually obliterated and replaced with nonfunctional connective tissue. The resulting fibrosis is often progressive and, in the case of idiopathic pulmonary fibrosis (IPF), invariably leads to respiratory insufficiency and, ultimately, the premature death of affected individuals. Recent years have seen a greater appreciation of the relative importance of chronic inflammation as a driver of fibrotic responses.

Translational models of lung disease.

The 2nd Cross Company Respiratory Symposium (CCRS), held in Horsham, U.K. in 2012, brought together representatives from across the pharmaceutical industry with expert academics, in the common interest of improving the design and translational predictiveness of in vivo models of respiratory disease.