Prospective multicentre study on barbed reposition pharyngoplasty standing alone or as a part of multilevel surgery for sleep apnoea.

OBJECTIVES: The aim of this study was to demonstrate in a prospective multicentre study that Barbed Reposition Pharyngoplasty (BRP) procedure is safe and effective in management of obstructive sleep apnoea/hypopnea syndrome (OSAHS) patients. DESIGN: Prospective study. SETTING: Multicentre study. PARTICIPANTS: Patients suffering from obstructive sleep apnoea. MAIN OUTCOMES MEASURES: Values of postoperative apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), epworth sleepiness scale (ESS). RESULTS: 111 Barbed Reposition Pharyngoplasty procedures standing alone or as a part of multilevel surgery for OSAHS, performed between January and September 2016, were analysed in 15 different centres. The average hospitalisation period was 2.5 ± 0.5 days. The mean patient age was 46.3 ± 10.5 years. The average body mass index at the time of the procedure was 27.9 ± 3.2, and the majority of the patients were men (83%). The mean preoperative and postoperative apnoea/hypopnea index was 33.4 ± 19.5 and 13.5 ± 10.3, respectively (P < .001). The mean preoperative and postoperative ESS score was 10.2 ± 4.5 and 6.1 ± 3.6, respectively (P < .001). The mean preoperative and postoperative ODI were 29.6 ± 20.7 and 12.7 ± 10.8, respectively (P < .001). CONCLUSIONS: Patients undergoing BRP standing alone or as part of a multilevel approach for the treatment of OSAHS have a reasonable expectation for success with minimal morbidity.

Fine needle cytology pre-surgical differentiation of parathyroid neoplasms: Is it reliable?

BACKGROUND: Fine needle cytology (FNC) of a parathyroid neoplasia (PN) is reliable, but needs to be confirmed by Parathormone (PTH) and Thyroglobulin (TG) immunoassay on needle washing or by immunocytochemistry (ICC) evaluation. The differentiation between parathyroid adenoma (PA), atypical adenoma (PAA) and carcinoma (PC) is difficult on histology or even impossible on FNC. The aim of this study was to evaluate possible cytological criteria to classify FNC-PN further. METHODS: Twenty-three FNC samples of PN and parathyroid cysts were rather then have been reviewed. The series includes 18 PNs, 4 cysts and 1 Thyr3B (histologically diagnosed as PA). Cytological features were: cellularity, patterns (follicular, solid or papillary), clear, oncocytic, isolated cells, nuclear atypia, cytoplasmic inclusions, nucleoli and mitoses. Data were compared with the histological controls. RESULTS: Seventeen PNs, 2 cysts and 1 Thyr3B FNC samples were histologically diagnosed as PA (16), PAA (2) and PC (2). Two cysts and 1 PN were not confirmed histologically. Cytological features and incidences were: high cellularity (1 PA, 1 PAA, 2 PCs), follicular (8 PAs, 1 PAA), solid (5 PAs, 1 PC), papillary pattern (1PA, 1 PAA, 1 PC), clear cells (4 PAs, 1 PAA, 2 PCs), oncocytic cells (6 PAs, 1 PAA, 2 PCs), isolated cells (5 PAs, 2 PAAs, 2 PCs), nuclear atypia (2 PAs, 1 PAA, 2 PCs), cytoplasmic inclusions (4 PAs, 2 PCs), nucleoli (2 PCs) and mitoses (2 PCs). CONCLUSION: Evident nucleoli and mitoses may suggest the differentiation between PA and PC. However, further investigations are required to confirm these preliminary observations.

NAT2 gene diversity and its evolutionary trajectory in the Americas.

N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.

Association between HLA-DR4 haplotypes and tuberculin skin test response in the Aché population.

The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Evidence for association with tuberculosis (TB) is more consistent for class II than for class I HLA genes. TB is important among indigenous peoples in South America, not only because of its historical role in regional depopulation, but also because it is still widespread. The aim of this study was to evaluate the association of HLA class II alleles, haplotypes and genotypes and tuberculin skin test response (TST) in 76 individuals of the Aché population. Poisson Regression was employed to assess risk genotypes. DRB1*04, DQA1*03 and DQB1*03:02 were associated with TST response in this population.

Distribution patterns of variability for 18 immune system genes in Amerindians--relationship with history and epidemiology.

Native American populations generally have a higher prevalence of infectious diseases than non-Native populations and this fact can induce different pressures in their immune system. We investigated the patterns of population differentiation (FST ) of 32 polymorphisms related to adaptive immune response in four Native American populations (Aché, Guarani-Kaiowá, Guarani-Ñandeva and Kaingang), and the results were compared with the three major world population data [Yoruba of Ibadan, Nigeria (YRI), Utah residents with northern and Western Europe ancestry (CEU) and Han Chinese of Beijing, China (CHB)] available in the HapMap database. The Aché clearly differentiated from the other Amerindians, but when all Native Americans were compared with the samples of other ethnic groups the lowest difference (0.08) was found with CHB (Asians), the second lowest (0.15) with YRI (Africans) and the most marked with CEU (European-derived). The considerable intra and interethnic differences found can be explained both in terms of diverse evolutionary distances and more recent environmental pathogen exposures; and they should be appropriately considered prior to any specific public health action.

Detection of new mutations and molecular pathology of mild and moderate haemophilia A patients from southern Brazil.

A total of 76 unrelated male patients with mild (n = 55) or moderate (n = 21) haemophilia A living in the southern Brazilian state of Rio Grande do Sul were studied by direct sequencing of all F8 26 exons, the 5' UTR and 3' UTR, intron-exon junctions and the promoter region. When no mutation was found, a multiplex ligation-dependent probe amplification analysis was performed. We identified the disease-causing mutations in 69 patients, who showed 33 different mutations: 27 missense, one small deletion, two small duplications and three splice site mutations. Seven missense and two splice site mutations were not previously reported in HAMSTeRS and were not identified in any current literature search. Nine recurrent mutations were found, one of them never described before (p.Tyr1786Phe). Haplotype analysis indicated that this mutation had originated in the Brazilian population as a single event in a common ancestor. The possible influence of these mutations in the determination of the disease was carefully considered, including bioinformatic tools. These data add to the general knowledge of the disease and can also be useful for HA diagnosis and detection of carriers in the southern Brazilian population.

Nasal Vestibulitis and Vestibular Furunculosis: a systematic review about two common nasal infections and considerations about correct diagnosis and management.

Background: Nasal vestibulitis (NV) and nasal vestibular furunculosis (NVF) are two infectious processes of the nasal vestibule, sharing common etiology, the same risk of complications, and similar treatment while remaining two different pathological entities. Methods: We performed a comprehensive literature research on NV and NVF in PubMed, Cochrane, and Google Scholar databases, with the aim to review the evidence on these two conditions and discuss the therapeutic approaches. Results: We identified a total of 248 records; according to our inclusion/exclusion criteria, 27 of them, published over a period of 59 years (1962-2021), were included in this review. Conclusion: NV and NVF are reported to be common conditions, with well-known etiological agents and risk factors. The diagnosis is clinical and topical antibiotics are the mainstay of treatment. Complications appear to be infrequent. Further studies are necessary to clarify the pathogenetic mechanisms and the exact prevalence of both conditions.

Electrochemotherapy as palliative treatment in patients with recurrent and/or metastatic head and neck tumours: features analysis for an early determination of the partial responsive patients.

OBJECTIVE: The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurrent and/or metastatic head and neck (H&N) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies. PATIENTS AND METHODS: 131 patients (186 treatment sessions) with recurrent and/or metastatic H&N neoplasm were subjected to ECT. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR. RESULTS: In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A difference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the median current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%. CONCLUSIONS: The study confirmed that ECT is an interesting antitumoral therapy in advanced chemo- and radio-refractory H&N neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.

Role(s) of formyl-peptide receptors expressed in nasal epithelial cells.

Chronic rhinosinusitis is one of the most frequent chronic diseases in humans. Little is known about stimuli initiating tissue remodeling process that determines the morphological expression of the disease. N-formyl peptide receptors (FPRs) are innate immunity receptors important in tissue remodeling of gastric and intestinal epithelium. The expression and functions of FPRs in nasal epithelial cells were examined to evaluate whether they could be important in the remodeling of nasal mucosa. The aim of this study is to examine FPR expression in a nasal epithelial cell line (RPMI-2650) at mRNA and protein levels. To determine whether FPRs were functional, chemotaxis experiments were carried out. In addition the effects of FPRs agonists on the expression (PCR and ELISA) of VEGF-A and TGF-beta, two key mediators of tissue remodelling, were examined. Here we demonstrate that RPMI-2650 express FPR and FPRL2, but not FPRL1. fMLP, a bacterial product active on FPR, and uPAR(84-95), an inflammatory mediator agonist for FPRL2, stimulated migration of nasal epithelial cells. fMLP and uPAR(84-95) induce expression and secretion of VEGF-A and TGF-beta. Our results suggest a possible mechanisms initiating tissue remodeling observed during chronic rhinosinusitis. This study provides further evidence that FPRs play a more complex role in human pathophysiology than bacterial recognition.

Six-month smell and taste recovery rates in coronavirus disease 2019 patients: a prospective psychophysical study.

BACKGROUND: The long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified. METHODS: Olfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation. RESULTS: A total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent. CONCLUSION: Six months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.

Genomics and evolution - a personal appraisal.

After a brief introduction about present approaches in evolutionary thinking and systems biology, I present a review about the most recent research of our group, with special reference to the genomics of Amerindians. This information was integrated with the present knowledge and concepts in this area. Human microevolutionary approaches are faced with special challenges, and proper interpretation demands the consideration of our unique specificity: culture.

The effect of habitat fragmentation on the genetic structure of a top predator: loss of diversity and high differentiation among remnant populations of Atlantic Forest jaguars (Panthera onca).

Habitat fragmentation may disrupt original patterns of gene flow and lead to drift-induced differentiation among local population units. Top predators such as the jaguar may be particularly susceptible to this effect, given their low population densities, leading to small effective sizes in local fragments. On the other hand, the jaguar's high dispersal capabilities and relatively long generation time might counteract this process, slowing the effect of drift on local populations over the time frame of decades or centuries. In this study, we have addressed this issue by investigating the genetic structure of jaguars in a recently fragmented Atlantic Forest region, aiming to test whether loss of diversity and differentiation among local populations are detectable, and whether they can be attributed to the recent effect of drift. We used 13 microsatellite loci to characterize the genetic diversity present in four remnant populations, and observed marked differentiation among them, with evidence of recent allelic loss in local areas. Although some migrant and admixed individuals were identified, our results indicate that recent large-scale habitat removal and fragmentation among these areas has been sufficiently strong to promote differentiation induced by drift and loss of alleles at each site. Low estimated effective sizes supported the inference that genetic drift could have caused this effect within a short time frame. These results indicate that jaguars' ability to effectively disperse across the human-dominated landscapes that separate the fragments is currently very limited, and that each fragment contains a small, isolated population that is already suffering from the effects of genetic drift.

Smell and taste recovery in coronavirus disease 2019 patients: a 60-day objective and prospective study.

BACKGROUND: The long-term recovery rate of chemosensitive functions in coronavirus disease 2019 patients has not yet been determined. METHOD: A multicentre prospective study on 138 coronavirus disease 2019 patients was conducted. Olfactory and gustatory functions were prospectively evaluated for 60 days. RESULTS: Within the first 4 days of coronavirus disease 2019, 84.8 per cent of patients had chemosensitive dysfunction that gradually improved over the observation period. The most significant increase in chemosensitive scores occurred in the first 10 days for taste and between 10 and 20 days for smell. At the end of the observation period (60 days after symptom onset), 7.2 per cent of the patients still had severe dysfunctions. The risk of developing a long-lasting disorder becomes significant at 10 days for taste (odds ratio = 40.2, 95 per cent confidence interval = 2.204-733.2, p = 0.013) and 20 days for smell (odds ratio = 58.5, 95 per cent confidence interval = 3.278-1043.5, p = 0.005). CONCLUSION: Chemosensitive disturbances persisted in 7.2 per cent of patients 60 days after clinical onset. Specific therapies should be initiated in patients with severe olfactory and gustatory disturbances 20 days after disease onset.

The role of cytokines in head and neck squamous cell carcinoma: A review.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for approximately 6% of all cancer cases and responsible for an estimated 1-2% of all cancer deaths. Much research evidence has accumulated in the recent years on the changes in the expression of pro-inflammatory and, to a lesser extent, anti-inflammatory cytokines, that (i) may have a role in the malignant transformation of HNSCC, (ii) may be used as diagnostic markers in the sera of patients because of their excessive production by the tumor cells and (iii) may act as possible immunotherapeutic targets. Among pro-inflammatory cytokines, interleukin-8 (IL--8) has been reported to have an important role in cancer invasion, angiogenesis and metastasis. Recent studies have shown an increased concentration of IL--8 in patients with HNSCC and a positive association with lymph node metastasis and tumor classification, although IL--8 was not significantly associated with shorter overall survival and cancer progression-free survival. Additional evidence on the pathological mechanism of origin, invasion, and metastasis of HNSCC, as well as a better understanding of the implications of cytokines, chemokines and growth factors, are of paramount importance for the advancement of research in head and neck oncology.

Remote psychophysical evaluation of olfactory and gustatory functions in early-stage coronavirus disease 2019 patients: the Bologna experience of 300 cases.

BACKGROUND: An objective evaluation of coronavirus disease 2019 in the first days of infection is almost impossible, as affected individuals are generally in home quarantine, and there is limited accessibility for the operator who should perform the test. To overcome this limitation, a recently validated psychophysical self-administered test was used, which can be performed remotely in the assessment of early-stage coronavirus disease 2019 patients. METHODS: Olfactory and gustatory functions were objectively assessed in 300 patients in the first 7 days from coronavirus disease 2019 symptom onset. RESULTS: Seventy per cent of the patients presented olfactory and/or gustatory disorders. The dysfunctions detected were mainly complete anosmia (47 per cent) or ageusia (38 per cent). A significant correlation was found between taste dysfunction and female gender (odds ratio = 1.936, p = 0.014) and fever (odds ratio = 2.132, p = 0.003). CONCLUSION: The psychophysical evaluation protocol proposed is an effective tool for the fast and objective evaluation of patients in the early stages of coronavirus disease 2019. Chemosensitive disorders have been confirmed to be frequent and early symptoms of the coronavirus infection, and, in a significant number of cases, they are the first or only manifestation of coronavirus disease 2019.

Introns 1 and 22 inversions and factor VIII inhibitors in patients with severe haemophilia A in southern Brazil.

A total of 107 unrelated severe haemophilia A patients living in the southern Brazilian state of Rio Grande do Sul were studied in relation to the prevalence of inversions present in introns 22 and 1 and a subsample of them (95) tested for the presence of Factor VIII inhibitors. These data were then incorporated with those from 15 other countries and 3871 patients. The frequencies of these two inversions show a remarkable homogeneity in series collected in different continents, from people with diverse ethnic extraction. The prevalence of inhibitors among patients with inversion 22, on the other hand, varies widely (5-51%; seven countries, 1482 patients), the value observed by us being the highest. The importance of obtaining data from patients throughout the world to clarify the aetiology of this important complicating factor in the therapeutics of the disease is emphasized.