Bronchiectasis in rheumatoid arthritis. A clinical appraisial

Bronchiectasis is defined as irreversibly damaged and dilated bronchi and is one of the most common pulmonary manifestations in patients with rheumatoid arthritis (RA). The model of RA-associated autoimmunity induced in some individuals by chronic bacterial infection in bronchiectasis is becoming increasingly acceptable, although a genetic predisposition to RA-associated bronchiectasis has also been demonstrated. Bronchiectasis should be suspected in RA patients with chronic cough and sputum production or frequent respiratory infections and the diagnosis must be confirmed by thoracic high-resolution computed tomography. Management of patients with RA-associated bronchiectasis includes a multimodal treatment approach. Similar to all patients with non-cystic fibrosis bronchiectasis, patients with RA-associated bronchiectasis benefit from a pulmonary rehabilitation program, including an exercise/muscle strengthening program and an education program with a specific session on airway clearance techniques. Prophylactic antibiotics are recommended for patients with frequent (3 or more infective exacerbations per year) or severe infections requiring hospitalization/intravenous antibiotics and inhaled corticosteroids and long-acting β2-agonists should be used in patients with non-cystic fibrosis bronchiectasis and associated airway hyper-responsiveness. In patients with RA-associated bronchiectasis the use of immunomodulatory drugs has to be carefully considered, as they are essential to control disease activity, despite being associated with an increased infectious risk. Pneumococcal and influenza vaccines are advised to all patients with RA-associated bronchiectasis in order to reduce the risk of infection. Patients with RA-associated bronchiectasis have a poorer prognosis than those with either RA or bronchiectasis alone and require regular follow-up, under the joint care of a rheumatologist and a pulmonologist

Complex sacral fracture

We reported a case of a patient with suspected cauda equina syndrome secondary to sacral fracture, after sustaining a fall. The difficulty in early diagnosis of complex sacral fractures and the lack of clearly defined guidelines for treatment are highlighted. Thorough clinical examination is mandatory, in order to make an adequate initial assessment and follow symptoms progression and response to treatment. The threshold for performing CT imaging (or MRI, if advised), when suspecting sacral fracture and neurological compromise, should be low. A multidisciplinary approach, with contributions from orthopaedic and/or neurosurgical surgery and physiatry, should be the gold standard of treatment. In this particular case, conservative management and close follow-up led to a significant improvement of problems and a good final outcome, showing that surgical decompression is not the only valid option and that further prospective studies are needed, regarding patient selection and timing of intervention

AGAP2: modulating TGFβ1-signalling in the regulation of liver fibrosis

AGAP2 (Arf GAP with GTP-binding protein-like domain, Ankyrin repeat and PH domain 2) isoform 2 is a protein that belongs to the Arf GAP (GTPase activating protein) protein family. These proteins act as GTPase switches for Arfs, which are Ras superfamily members, being therefore involved in signaling regulation. Arf GAP proteins have been shown to participate in several cellular functions including membrane trafficking and actin cytoskeleton remodeling. AGAP2 is a multi-tasking Arf GAP that also presents GTPase activity and is involved in several signaling pathways related with apoptosis, cell survival, migration, and receptor trafficking. The increase of AGAP2 levels is associated with pathologies as cancer and fibrosis. Transforming growth factor beta-1 (TGF-β1) is the most potent pro-fibrotic cytokine identified to date, currently accepted as the principal mediator of the fibrotic response in liver, lung, and kidney. Recent literature has described that the expression of AGAP2 modulates some of the pro-fibrotic effects described for TGF-β1 in the liver. The present review is focused on the interrelated molecular effects between AGAP2 and TGFβ1 expression, presenting AGAP2 as a new player in the signaling of this pro-fibrotic cytokine, thereby contributing to the progression of hepatic fibrosis

Intramural Hematoma of the Esophagus After Thrombolysis for Ischemic Stroke

Intramural dissecting hematoma is an unusual esophageal condition with a threatening presentation but excellent prognosis when managed conservatively.We report the case of an 88-year-old woman who developed an intramural hematoma of the esophagus after intravenous thrombolysis for an acute ischemic stroke. Before thrombolysis, nasogastric intubation was attempted unsuccessfully. She was kept on nil by mouth, intravenous hydration, proton pump inhibitor, antiemetics,and an antibiotic initiated 2 days before for periodontal disease. The esophageal hematoma regressed, and she resumed oral diet asymptomatically.To our knowledge, this is the first report of this type of lesion after thrombolysis for an ischemic stroke. A brief discussion and literature review are presented

Tuberculous Meningitis: The Important Role of Imaging

Tuberculous meningitis is the most severe form of tuberculosis, and the diagnosis continues to be challenging for clinicians. Indeed, many cases of tuberculous meningitis cannot be confirmed based on clinical findings, and laboratory techniques are largely insensitive or slow. Clinical presentation can be nonspecific and suggest alternative conditions. The difficulty in diagnosis often leads to a delay in treatment and subsequent morbidity and mortality. We present the case of a 4-year-old Indian girl with meningitis that presented neurological deterioration while taking antibiotics. The epidemiological history and neuroimaging findings of incipient hydrocephalus, infarcts, and probable tuberculomas were essential to evoking the diagnosis of tuberculous meningitis. Diagnosis of tuberculous meningitis is difficult mainly in these rare cases with acute presentation that clinically present similarly to other forms of meningitis. The recognition of this entity involves a high index of suspicion based on the previous referred findings and is essential to prevent morbidity and mortality.info:eu-repo/semantics/publishedVersio

Introductions to the Community: Early-Career Researchers in the Time of COVID-19

COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers

Invasive Meningococcal Disease Unraveling a Novel Mutation in the C5 Gene in a Portuguese Family

Although bacterial meningitis is a rare presentation of a congenital immunodeficiency, invasive meningococcal disease is classically associated with complement deficiencies. We report a patient from a consanguineous kindred presenting with an invasive meningococcal disease caused by serogroup B meningococcus that revealed an underlying C5 deficiency caused by a novel mutation in the C5 gene.info:eu-repo/semantics/publishedVersio

Role of AGAP2 in the profibrogenic effects induced by TGFβ in LX-2 hepatic stellate cells

Liver damage induces hepatic stellate cells (HSC) activation, characterised by a fibrogenic, proliferative and migratory phenotype. Activated HSC are mainly regulated by transforming growth factor β 1 (TGFβ1), which increases the production of extracellular matrix proteins (e.g. collagen-I) promoting the progression of hepatic fibrosis. AGAP2 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2) is a GTPase/GTP-activating protein involved in the actin remodelling system and receptor recycling. In the present work the role of AGAP2 in human HSC in response to TGFβ1 was investigated. LX-2 HSC were transfected with AGAP2 siRNA and treated with TGFβ1. AGAP2 knockdown prevented to some extent the proliferative and migratory TGFβ1-induced capacities of LX-2 cells. An array focused on human fibrosis revealed that AGAP2 knockdown partially prevented TGFβ1-mediated gene expression of the fibrogenic genes ACTA2, COL1A2, EDN1, INHBE, LOX, PDGFB, TGFΒ12, while favored the expression of CXCR4, IL1A, MMP1, MMP3 and MMP9 genes. Furthermore, TGFβ1 induced AGAP2 promoter activation and its protein expression in LX-2. In addition, AGAP2 silencing affected TGFβ1-receptor 2 (TGFR2) trafficking in U2OS cells, blocking its effective recycling to the membrane. AGAP2 silencing in LX-2 cells prevented the TGFβ1-induced increase of collagen-I protein levels, while its over-expression enhanced collagen I protein expression in the presence or absence of the cytokine. AGAP2 overexpression also increased focal adhesion kinase (FAK) phosphorylated levels in LX-2 cells. FAK and MEK1 inhibitors prevented the increase of collagen-I expression caused by TGFβ1 in LX-2 overexpressing AGAP2. In summary, the present work shows for the first time, that AGAP2 is a potential new target involved in TGFβ1 signalling, contributing to the progression of hepatic fibrosis

Screening of Dementia in Portuguese Primary Care: Methodology, Assessment Tools, and Main Results

The objectives of this article are as follows: (1) to describe the assessment protocol used to outline people with probable dementia in Primary Health Care; (2) to show the methodological design and procedure to obtain a representative sample of patients with probable dementia; and (3) to report the main characteristics of the sample collected in the context of the study “Characteristics and needs of people with probable dementia.” The study protocol was based on the “Community Assessment of Risk and Treatment Strategies (CARTS) Program” and is composed by a set of instruments that allow the assessment of older adults with probable dementia in several areas (health, psychological, functionality, and other). Descriptive analysis was used to characterize the final sample (n = 436). The study protocol as well as the methodological procedure to obtain the referral of research participants and data collection on the condition of people with probable dementia in Primary Health Care proved to be a valuable tool to obtain a sample of patients distributed by the full range of probable dementia in a large geographical area. Results may allocate the design of care pathways for old people with cognitive disorders to prevent, delay impairment, and/or optimize quality of life of patients