Undergoing head and neck cancer surgery: A grounded theory

Surgery is the treatment of choice in most head and neck cancers. Very often, the surgery is radical with high impact on the psychosocial, functional and aesthetic fields. The aim of this study is to gain a deeper understanding of the patient's, clinician's and key informant's point of view when surgery is proposed, to improve the quality of pathways in terms of patients' practical, psychological and relational needs. We followed a Grounded Theory approach with semi-structured interviews. Seventeen participants (six patients, nine healthcare professionals and two volunteers) were interviewed immediately before surgery. The study generated a process of "persuading the patient of an obligation" as the core category. The other principal categories that emerged highlighted the patients' doubts and fears regarding the surgery consequences and, in parallel, strategies employed by the healthcare professionals to rebut hindering issues impeding surgery. In particular, healthcare professionals involved patients in an affiliation process through simplified communication to sustain the choice of surgery; the family plays a supportive role in this process. The interplay between the organisational process and patients' experience results in "I will let you convince me" at the end of the decision-making process, where the main aim was to save and be saved

FDG-PET/CT imaging for staging and target volume delineation in conformal radiotherapy of anal carcinoma

Background: FDG-PET/CT imaging has an emerging role in staging and treatment planning of various tumor locations and a number of literature studies show that also the carcinoma of the anal canal may benefit from this diagnostic approach. We analyzed the potential impact of FDG-PET/CT in stage definition and target volume delineation of patients affected by carcinoma of the anal canal and candidates for curative radiotherapy. Methods: Twenty seven patients with biopsy proven anal carcinoma were enrolled. Pathology was squamous cell carcinoma in 20 cases, cloacogenic carcinoma in 3, adenocarcinoma in 2, and basal cell carcinoma in 2. Simulation was performed by PET/CT imaging with patient in treatment position. Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) were drawn on CT and on PET/CT fused images. PET-GTV and PET-CTV were respectively compared to CT-GTV and CT-CTV by Wilcoxon rank test for paired data. Results: PET/CT fused images led to change the stage in 5/27 cases (18.5%): 3 cases from N0 to N2 and 2 from M0 to M1 leading to change the treatment intent from curative to palliative in a case. Based on PET/CT imaging, GTV and CTV contours changed in 15/27 (55.6%) and in 10/27 cases (37.0%) respectively. PET-GTV and PET-CTV resulted significantly smaller than CT-GTV (p = 1.2 7 10-4) and CT-CTV (p = 2.9 7 10-4). PET/CT-GTV and PET/CT-CTV, that were used for clinical purposes, were significantly greater than CT-GTV (p = 6 7 10-5) and CT-CTV (p = 6 7 10-5). Conclusions: FDG-PET/CT has a potential relevant impact in staging and target volume delineation of the carcinoma of the anal canal. Clinical stage variation occurred in 18.5% of cases with change of treatment intent in 3.7%. The GTV and the CTV changed in shape and in size based on PET/CT imaging

The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells

The protein product of the ocular albinism type 1 gene, named OA1, is a pigment cell-specific G protein-coupled receptor exclusively localized to intracellular organelles, namely lysosomes and melanosomes. Loss of OA1 function leads to the formation of macromelanosomes, suggesting that this receptor is implicated in organelle biogenesis, however the mechanism involved in the pathogenesis of the disease remains obscure. We report here the identification of an unexpected abnormality in melanosome distribution both in retinal pigment epithelium (RPE) and skin melanocytes of Oa1-knock-out (KO) mice, consisting in a displacement of the organelles from the central cytoplasm towards the cell periphery. Despite their depletion from the microtubule (MT)-enriched perinuclear region, Oa1-KO melanosomes were able to aggregate at the centrosome upon disruption of the actin cytoskeleton or expression of a dominant-negative construct of myosin Va. Consistently, quantification of organelle transport in living cells revealed that Oa1-KO melanosomes displayed a severe reduction in MT-based motility; however, this defect was rescued to normal following inhibition of actin-dependent capture at the cell periphery. Together, these data point to a defective regulation of organelle transport in the absence of OA1 and imply that the cytoskeleton might represent a downstream effector of this receptor. Furthermore, our results enlighten a novel function for OA1 in pigment cells and suggest that ocular albinism type 1 might result from a different pathogenetic mechanism than previously thought, based on an organelle-autonomous signalling pathway implicated in the regulation of both membrane traffic and transport

Cellular and Molecular Immune Response to Chikungunya Virus Infection

Chikungunya virus (CHIKV) is a re-emergent arthropod-borne virus (arbovirus) that causes a disease characterized primarily by fever, rash and severe persistent polyarthralgia. In the last decade, CHIKV has become a serious public health problem causing several outbreaks around the world. Despite the fact that CHIKV has been around since 1952, our knowledge about immunopathology, innate and adaptive immune response involved in this infectious disease is incomplete. In this review, we provide an updated summary of the current knowledge about immune response to CHIKV and about soluble immunological markers associated with the morbidity, prognosis and chronicity of this arbovirus disease. In addition, we discuss the progress in the research of new vaccines for preventing CHIKV infection and the use of monoclonal antibodies as a promising therapeutic strategy

Dengue Virus Type 4 Phylogenetics in Brazil 2011: Looking beyond the Veil

Dengue Fever and Dengue Hemorrhagic Fever are diseases affecting approximately 100 million people/year and are a major concern in developing countries. In the present study, the phylogenetic relationship of six strains of the first autochthonous cases of DENV-4 infection occurred in Sao Paulo State, Parana State and Rio Grande do Sul State, Brazil, 2011 were studied. Nucleotide sequences of the envelope gene were determined and compared with sequences representative of the genotypes I, II, III and Sylvatic for DEN4 retrieved from GenBank. We employed a Bayesian phylogenetic approach to reconstruct the phylogenetic relationships of Brazilian DENV-4 and we estimated evolutionary rates and dates of divergence for DENV-4 found in Brazil in 2011. All samples sequenced in this study were located in Genotype II. The studied strains are monophyletic and our data suggest that they have been evolving separately for at least 4 to 6 years. Our data suggest that the virus might have been present in the region for some time, without being noticed by Health Surveillance Services due to a low level of circulation and a higher prevalence of DENV-1 and DENV- 2

Severe asthma: One disease and multiple definitions

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU