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1.
Artigo em Inglês | MEDLINE | ID: mdl-38713291

RESUMO

PURPOSE: Lipoid proteinosis (LP) or Urbach-Wiethe disease (OMIM 247100) is a rare syndrome characterised by early vocal folds infiltration and subsequent multi-organ involvement. LP is often unrecognised and its associated hoarseness is overlooked. The main objective of the study was to investigate hoarseness in LP and implement a diagnosis among otolaryngologists. METHODS: PubMed/MEDLINE and OMIM databases were systematically searched. Authors concentrated the search on published articles starting from the discovery of the pathogenesis of LP by Hamada et al. in 2002. Only cases in which a diagnosis was reported both clinically and through biopsy and/or genetic molecular testing were included. Characteristics of the LP cases were extracted from each included study. Results were obtained through Generalized Estimating Equations. RESULTS: The search strategy yielded 217 articles, of which 74 (34.1%) met the selection criteria. A total of 154 cases were included. Hoarseness was described in all LP cases and clearly stated as the onset symptom in 68.8%. The onset was on average at 19 months of age (CI: 3.00-20.00), while the mean age at diagnosis was 15 years (CI: 10.00-30.00). Therefore, the diagnostic delay amounted to 13.42 years (CI: 8.00-23.83). Hoarseness alone was responsible for an LP diagnosis in only 14.3% of cases. In 43.5% of cases, genetic analysis of the ECM1 gene was performed and exon 6 was the most frequently altered portion. CONCLUSION: Analysing the largest number of published cases, the study underlined that hoarseness is the key symptom for diagnosing LP since early childhood, though frequently overlooked.

2.
Eur Radiol ; 33(9): 5911-5923, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37071163

RESUMO

OBJECTIVES: Acute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis relies on clinical, endoscopic, and pathological investigations. Our purpose is to assess the value of magnetic resonance imaging (MRI) in the diagnosis, staging, and prediction of GI-aGVHD-related mortality. METHODS: Twenty-one hematological patients who underwent MRI for clinical suspicion of acute GI-GVHD were retrospectively selected. Three independent radiologists, blinded to the clinical findings, reanalyzed MRI images. The GI tract was evaluated from stomach to rectum by analyzing fifteen MRI signs suggestive of intestinal and peritoneal inflammation. All selected patients underwent colonoscopy with biopsies. Disease severity was determined on the basis of clinical criteria, identifying 4 stages of increasing severity. Disease-related mortality was also assessed. RESULTS: The diagnosis of GI-aGVHD was histologically confirmed with biopsy in 13 patients (61.9%). Using 6 major signs (diagnostic score), MRI showed 84.6% sensitivity and 100% specificity in identifying GI-aGVHD (AUC = 0.962; 95% confidence interval 0.891-1). The proximal, middle, and distal ileum were the segments most frequently affected by the disease (84.6%). Using all 15 signs of inflammation (severity score), MRI showed 100% sensitivity and 90% specificity for 1-month related mortality. No correlation with the clinical score was found. CONCLUSION: MRI has proved to be an effective tool for diagnosing and scoring GI-aGVHD, with a high prognostic value. If larger studies will confirm these results, MRI could partly replace endoscopy, thus becoming the primary diagnostic tool for GI-aGVHD, being more complete, less invasive, and more easily repeatable. KEY POINTS: • We have developed a new promising MRI diagnostic score for GI-aGVHD with a sensitivity of 84.6% and specificity of 100%; results are to be confirmed by larger multicentric studies. • This MRI diagnostic score is based on the six MRI signs most frequently associated with GI-aGVHD: small-bowel inflammatory involvement, bowel wall stratification on T2-w images, wall stratification on post-contrast T1-w images, ascites, and edema of retroperitoneal fat and declivous soft tissues. • A broader MRI severity score based on 15 MRI signs showed no correlation with clinical staging but high prognostic value (100% sensitivity, 90% specificity for 1-month related mortality); these results also need to be confirmed by larger studies.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Trato Gastrointestinal , Endoscopia Gastrointestinal , Doença Enxerto-Hospedeiro/diagnóstico por imagem , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Doença Aguda
3.
Asian J Androl ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36656177

RESUMO

After a huge decline in sperm concentration between 1938 and 1991 was reported, many researchers investigated the possibility of a worsening of human sperm quality. Despite massive efforts, published evidence is still controversial. Similarly, the role of lifestyle factors on semen parameters is debated. We conducted a monocentric Italian study to evaluate the total sperm number trend over the last 10 years (from 2010 to 2019). Additionally, we evaluated the association between lifestyle factors and total sperm number in order to identify possible damaging factors. We performed a retrospective study analyzing subjects aged 18-55 years who had their semen analyzed between 2010 and 2019. A total of 3329 subjects were included: 1655 subjects referred to our department (Department of Experimental Medicine, Sapienza University of Rome, Roma, Italy) for idiopathic infertility and 1674 subjects referred for preconceptional or andrological screening with no confirmed andrological diseases. Semen samples were examined according to World Health Organization (WHO) 2010 criteria by two seminologists with the same training and the same equipment. For statistical evaluations, only total sperm number (×10 6 per ejaculate) was taken into consideration. We detected no significant changes in mean total sperm number during the last decade, in either the entire population or the two subgroups (infertile group and control group). In a multivariate analysis total sperm number was significantly associated with the history of infertility, body mass index (BMI) and cigarette smoking. Our results suggest that infertile men are "vulnerable" subjects, particularly susceptible to several negative factors, many of which still remain unknown. Our study highlights the need for studies addressing men's lifestyle in order to find and reduce deleterious agents.

4.
Oncotarget ; 11(45): 4115-4122, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33227095

RESUMO

CD44v6, the CD44 isoform mostly involved in cancer cell migration and invasion, has been identified as a functional biomarker and therapeutic target in colon cancer stem cells. We here provide evidence that baseline CD44v6-positive CTC predict treatment failure in patients with metastatic colorectal cancer undergoing first-line chemotherapy. We suggest that CD44v6-positive CTC can be used to early detect intrinsic drug resistance in this cancer type.

5.
Thorac Cancer ; 11(7): 1765-1772, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32379396

RESUMO

BACKGROUND: Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy has become a common approach for the treatment of early stage lung cancer. Here, we aimed to establish whether the length of uniportal incision could affect postoperative pain and surgical outcomes in consecutive patients undergoing uniportal VATS lobectomy for early stage lung cancer. METHODS: This was a unicenter Randomized Control Trial (NCT03218098). Consecutive patients undergoing uniportal VATS lobectomy for Stage I lung cancer were randomly assigned to a Small Incision group or Long Incision group in 1:1 ratio based on whether patients received a 4 cm or 8 cm incision. The endpoints were to compare the intergroup difference regarding (i) postoperative pain measured by brief pain inventory (BPI) questionnaire (first endpoint); (ii) operative time; (iii) length of chest drainage; (iv) length of hospital stay; (v) postoperative complications; and (vi) pulmonary functional status (secondary endpoints). RESULTS: A total of 48 patients were eligible for the study. Four patients were excluded; the study population included 44 patients: 23 within the Small Incision group, and 21 within the Long Incision group. The 11 BPI scores between the two groups showed no significant difference. Small Incision group presented higher operative time than Long Incision group (138.69 vs. 112.14 minutes; P = 0.0001) while no significant differences were found regarding length of hospital stay (P = 0.95); respiratory complications (P = 0.92); FEV1% (P = 0.63), and 6-Minute Walking Test (P = 0.77). CONCLUSIONS: A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. KEY POINTS: A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. To perform a larger incision could be a valuable strategy, particularly in nonexpert hands or when the patient's anatomy or tumor size make exposure of anatomic structures through smaller incisions difficult.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Dor Pós-Operatória/epidemiologia , Pneumonectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Cirurgia Torácica Vídeoassistida/efeitos adversos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Tempo de Internação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Prognóstico
6.
Eur Radiol ; 29(9): 5082-5092, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30729332

RESUMO

OBJECTIVES: To identify differences between two cohorts of adult and pediatric patients affected by Crohn's disease (CD), with regard to lesion location in the small intestine and colon-rectum, lesion activity, and prevalence of perianal disease (PD), using MRI as the main diagnostic tool. METHODS: We retrospectively reviewed 350 consecutive MRI examinations performed between 2013 and 2016 in outpatients or inpatients with histologically proven CD, monitored by the Gastroenterology and Pediatric Units of our Hospital. The magnetic resonance enterography (MRE) protocol for adult and pediatric CD patients routinely includes evaluation of nine different intestinal segments (from jejunum to rectum) and of the anal canal. Intestinal activity was also calculated using a validated score. Perianal disease (PD) was staged. Fisher's exact test was used and the odds ratio (OR) was calculated. RESULTS: Two hundred and nineteen out of 350 MRI studies (118 adults and 101 children) were included. The prevalence of PD was 34.6% in children and 16.1% in adults (OR = 2.8; p = 0.0017). Pediatric patients showed more frequent rectal involvement (29.7% vs 13.5%, OR = 2.7; p = 0.0045) and higher risk of PD in the presence of rectal disease (p = 0.043; OR = 4.5). In pediatric patients with severe colorectal disease, the prevalence of PD was twofold (86.7% vs 40%; p = 0.072). Using the clinical Montreal classification for lesion location, no significant differences emerged between the two patient populations. CONCLUSIONS: MRI showed a significantly higher prevalence of rectal involvement and perianal disease in the pediatric population. These results may have a relevant clinical impact and deserve further investigation. KEY POINTS: • To our knowledge, this is the largest morphological comparative study available in the literature using MRI as the main diagnostic tool to compare adult patients and children with Crohn's disease. • Our study showed significant differences between adults and children: a higher prevalence of rectal and perianal fistulous disease (PD) in pediatric patients and an increased prevalence of PD in the presence of severe colon-rectum involvement. • The association of rectal and perianal disease implies a poorer clinical prognosis and a higher risk of disabling complications in pediatric patients.


Assuntos
Canal Anal/patologia , Doença de Crohn/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Criança , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Fenótipo , Prevalência , Estudos Retrospectivos , Adulto Jovem
7.
Front Immunol ; 9: 1747, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105026

RESUMO

Influenza virus replicates intracellularly exploiting several pathways involved in the regulation of host responses. The outcome and the severity of the infection are thus strongly conditioned by multiple host factors, including age, sex, metabolic, and redox conditions of the target cells. Hormones are also important determinants of host immune responses to influenza and are recently proposed in the prophylaxis and treatment. This study shows that female mice are less susceptible than males to mouse-adapted influenza virus (A/PR8/H1N1). Compared with males, PR8-infected females display higher survival rate (+36%), milder clinical disease, and less weight loss. They also have milder histopathological signs, especially free alveolar area is higher than that in males, even if pro-inflammatory cytokine production shows slight differences between sexes; hormone levels, moreover, do not vary significantly with infection in our model. Importantly, viral loads (both in terms of viral M1 RNA copies and tissue culture infectious dose 50%) are lower in PR8-infected females. An analysis of the mechanisms contributing to sex disparities observed during infection reveals that the female animals have higher total antioxidant power in serum and their lungs are characterized by increase in (i) the content and biosynthesis of glutathione, (ii) the expression and activity of antioxidant enzymes (peroxiredoxin 1, catalase, and glutathione peroxidase), and (iii) the expression of the anti-apoptotic protein Bcl-2. By contrast, infected males are characterized by high expression of NADPH oxidase 4 oxidase and phosphorylation of p38 MAPK, both enzymes promoting viral replication. All these factors are critical for cell homeostasis and susceptibility to infection. Reappraisal of the importance of the host cell redox state and sex-related effects may be useful in the attempt to develop more tailored therapeutic interventions in the fight against influenza.


Assuntos
Interações Hospedeiro-Patógeno , Vírus da Influenza A , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/virologia , Oxirredução , Animais , Antioxidantes/metabolismo , Biomarcadores , Citocinas/metabolismo , Resistência à Doença , Suscetibilidade a Doenças , Feminino , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos , Infecções por Orthomyxoviridae/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores Sexuais
8.
Arthritis Res Ther ; 19(1): 39, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28245863

RESUMO

BACKGROUND: Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc. METHODS: Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion. Circulating monocytes from SSc and healthy donors (HDs) were infected with EBV. Gene expression of innate immune mediators were evaluated in EBV-infected monocytes from SSc and HDs. Involvement of Toll-like receptor (TLR)8 in viral-mediated TLR8 response was investigated by comparing the TLR8 expression induced by infectious EBV to the expression stimulated by CL075/TLR8/agonist-ligand in the presence of TLR8 inhibitor in THP-1 cells. RESULTS: Infectious EBV strongly induced TLR8 expression in infected SSc and HD monocytes in vitro. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were upregulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally induced TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral mRNA and proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes. CONCLUSION: This study provides the first evidence of infectious EBV in monocytes from patients with SSc and links EBV to the activation of TLR8 and IFN innate immune response in freshly isolated SSc monocytes. This study provides the first evidence of EBV replication activating the TLR8 molecular pathway in primary monocytes. Immunogenicity of infectious EBV suggests a novel mechanism mediating monocyte inflammation in SSc, by which EBV triggers the innate immune response in infected cells.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Imunidade Inata/imunologia , Monócitos/imunologia , Escleroderma Sistêmico/imunologia , Receptor 8 Toll-Like/imunologia , Adulto , Idoso , Western Blotting , Linhagem Celular Tumoral , Células Cultivadas , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Perfilação da Expressão Gênica/métodos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/genética , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/virologia , Quinolinas/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/metabolismo , Tiazóis/farmacologia , Receptor 8 Toll-Like/genética , Receptor 8 Toll-Like/metabolismo , Replicação Viral/genética , Replicação Viral/imunologia , Replicação Viral/fisiologia , Adulto Jovem
9.
Oncoimmunology ; 5(7): e1175800, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27622025

RESUMO

Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helios(high) and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression.

10.
Am J Dent ; 29(4): 197-200, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29178747

RESUMO

PURPOSE: To assess correlations between periodontal status, maternal age and adverse pregnancy outcomes, such as pre-term and low birth weight in a sample of pregnant women. METHODS: Study population was represented by outpatient pregnant women, gestational age > 26 weeks. Medical history questionnaires were administered to all participants who underwent clinical evaluation; clinical obstetric outcome records were collected after delivery. A questionnaire was administered regarding personal information, socio-economic status, oral hygiene habits, and oral health conditions. A clinical oral examination was performed to collect Simplified Oral Hygiene Index (OHI-S) and Community Periodontal Index (CPI). Pregnancy outcome records included: delivery week, kind and causes of delivery, any relevant complications, and birth weight. Descriptive statistics were used to depict the data from the questionnaire while the relationship between delivery week, birth weight, maternal age and periodontal status was evaluated through multivariate tests of significance. RESULTS: 88 pregnant women were enrolled in the study. The results showed a statistically significant correlation (P< 0.001) among participants older than 40 years of age, between periodontal disease and adverse pregnancy outcomes. No statistical correlation was found among pre-term and low birth weight, smoking, ethnicity and educational level of mothers. The results highlight the importance of including a routine oral and periodontal health examination in pregnant women older than 40 years of age. CLINICAL SIGNIFICANCE: The correlation between periodontal status and adverse pregnancy outcomes in older mothers indicates the need for routine oral health examination and periodontal status assessment and care in pregnant women older than 40 years of age.


Assuntos
Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Idade Materna , Saúde Bucal , Doenças Periodontais/complicações , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Índice Periodontal , Gravidez , Resultado da Gravidez , Fatores de Risco , Inquéritos e Questionários
11.
Am J Gastroenterol ; 110(10): 1485-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26372508

RESUMO

OBJECTIVES: In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients. METHODS: We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh-Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers. RESULTS: A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD ("high-titer" symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic ("high-titer" asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between "high-titer" symptomatic and "high-titer" asymptomatic children (Fisher exact test, P=1.000). CONCLUSIONS: If confirmed in large multicenter prospective studies, the "biopsy-sparing" protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.


Assuntos
Doenças Assintomáticas , Autoanticorpos/imunologia , Doença Celíaca/diagnóstico , Duodeno/patologia , Guias de Prática Clínica como Assunto , Adolescente , Biomarcadores , Biópsia/métodos , Doença Celíaca/genética , Doença Celíaca/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Endoscopia do Sistema Digestório , Feminino , Proteínas de Ligação ao GTP/imunologia , Antígenos HLA-DQ/genética , Haplótipos , Humanos , Lactente , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Reprodutibilidade dos Testes , Estudos Retrospectivos , Transglutaminases/imunologia
12.
PLoS One ; 10(6): e0128607, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26061065

RESUMO

CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes) represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factor-α inhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control). The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factor-α inhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factor-α inhibitor therapy to validate in a larger cohort of patients.


Assuntos
Antígenos/imunologia , Apoptose/imunologia , Artrite Reumatoide/tratamento farmacológico , Linfócitos T CD8-Positivos/imunologia , Etanercepte/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Humanos
13.
BMC Surg ; 15: 54, 2015 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-25935155

RESUMO

BACKGROUND: The rising interest towards minimally invasive surgery has led to the introduction of laparo-endoscopic single site (LESS) surgery as the natural evolution of conventional multiport laparoscopy. However, this new surgical approach is hampered with peculiar technical difficulties. The SPIDER surgical system has been developed in the attempt to overcome some of these challenges. Our study aimed to compare standard laparoscopy and SPIDER technical performance on a surgical simulator, using standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS). METHODS: Twenty participants were divided into two groups based on their surgical laparoscopic experience: 10 PGY1 residents were included in the inexperienced group and 10 laparoscopists in the experienced group. Participants performed the FLS pegboard transfers task and pattern cutting task on a laparoscopic box trainer. Objective task scores and subjective questionnaire rating scales were used to compare conventional laparoscopy and SPIDER surgical system. RESULTS: Both groups performed significantly better in the FLS scores on the standard laparoscopic simulator compared to the SPIDER. Inexperienced group: Task 1 scores (median 252.5 vs. 228.5; p = 0.007); Task 2 scores (median 270.5 vs. 219.0; p = 0.005). Experienced group: Task 1 scores (median 411.5 vs. 309.5; p = 0.005); Task 2 scores (median 418.0 vs. 331.5; p = 0.007). Same aspects were highlighted for the subjective evaluations, except for the inexperienced surgeons who found both devices equivalent in terms of ease of use only in the peg transfer task. CONCLUSIONS: Even though the SPIDER is an innovative and promising device, our study proved that it is more challenging than conventional laparoscopy in a population with different degrees of surgical experience. We presume that a possible way to overcome such challenges could be the development of tailored training programs through simulation methods. This may represent an effective way to deliver training, achieve mastery and skills and prepare surgeons for their future clinical experience.


Assuntos
Competência Clínica , Laparoscopia/instrumentação , Treinamento por Simulação , Adulto , Humanos , Laparoscopia/educação , Laparoscopia/métodos , Cidade de Roma
14.
Ann Otol Rhinol Laryngol ; 124(4): 312-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25358610

RESUMO

OBJECTIVE: The aim of this study was to assess pre- and postoperative taste ability in patients undergoing middle ear surgery for otosclerosis or chronic otitis media. Olfactory function was also evaluated to rule out taste deficits due to concomitant nasal pathology. METHODS: All patients underwent ear, nose, and throat examination, otomicroscopy, nasal endoscopy, anterior rhinomanometry, taste testing, and olfactory testing. Patients were evaluated at 1 to 5 days preoperatively (T0), and at 1 (T1), 6 (T6), and 12 (T12) months postoperatively. RESULTS: Both groups of patients experienced worsening of the mean taste threshold postoperatively. This phenomenon was more serious in poststapedotomy patients. Follow-up showed progressive improvement in both groups. All values of olfactory testing were within the normal range for otosclerosis patients. Patients with chronic otitis media showed variable postoperative findings. CONCLUSION: Chorda tympani function can be negatively affected by middle ear surgery. Deficits may be more marked in stapedotomy patients than in those undergoing tympanoplasty. Postoperative recovery of taste is satisfactory, although with different timelines for the 2 types of pathology.


Assuntos
Transtornos do Olfato/fisiopatologia , Otite Média/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Olfato/fisiologia , Distúrbios do Paladar/fisiopatologia , Paladar/fisiologia , Timpanoplastia/efeitos adversos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Distúrbios do Paladar/etiologia , Limiar Gustativo/fisiologia
15.
Surg Endosc ; 28(1): 242-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23996341

RESUMO

BACKGROUND: Construct validity of virtual laparoscopic simulators for basic laparoscopic skills has been proposed; however, it is not yet clear whether the simulators can identify the actual experience of surgeons in more complex procedures such as laparoscopic Roux-en-Y gastric bypass. This study tested the ability of the Lap Mentor simulator to recognize the experience in advanced laparoscopic procedures and to assess its role in the certification of bariatric surgeons. METHODS: Twenty surgeons were divided into two groups according to their experience in laparoscopic and bariatric surgery. The general group included 10 general surgeons performing between 75 and 100 nonbariatric laparoscopic procedures. The bariatric group included 10 bariatric surgeons performing between 50 and 100 laparoscopic bariatric procedures. Participants were tested on the simulator in one basic task (task 1: eye-hand coordination) and in two tasks of the gastric bypass module (task 2: creation of the gastric pouch; task 3: gastrojejunal anastomosis). RESULTS: Comparing the groups, no significant differences were found in task 1. Analyzing the results from the gastric bypass module (bariatric vs. general), in task 2, significant differences (p < 0.05) were found in the median volume of the gastric pouch (21 vs. 48 cm(3)), in the percentage of fundus included in the pouch (8.4 vs. 29.4 %), in the complete dissection at the angle of His (10 vs. 3), and in safety parameters. In task 3, significant differences were found in the size and position of enterotomies. CONCLUSIONS: The Lap Mentor may be proposed as a certification tool for bariatric surgeons because it also recognizes their specific skills in the technical details of the procedure that affect long-term results. Furthermore, the possibility of analyzing the performance in detail can help define areas where the surgeon is lacking. These findings indicate a potential role of the Lap Mentor in tailoring the training to maximize improvement.


Assuntos
Cirurgia Bariátrica/educação , Certificação , Simulação por Computador , Educação Médica Continuada/normas , Terapia de Exposição à Realidade Virtual/educação , Adulto , Anastomose Cirúrgica/educação , Competência Clínica , Dissecação/educação , Feminino , Humanos , Itália , Laparoscopia/educação , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor , Análise e Desempenho de Tarefas , Interface Usuário-Computador , Terapia de Exposição à Realidade Virtual/normas
16.
Intern Emerg Med ; 9(6): 641-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24146110

RESUMO

The occurrence of heart failure during the whole pre-discharge course of coronary revascularization, as far as its influence on subsequent prognosis, is poorly understood. The present study examined the effect of transient heart failure (THF) developing in the acute and rehabilitative phase on survival after coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI). Patients in the Italian survey on cardiac rehabilitation and secondary prevention after cardiac revascularization (ICAROS) were analyzed for THF, the latter being defined either as signs and symptoms consistent with decompensation or cardiogenic shock. ICAROS was a prospective, multicenter registry of 1,262 consecutive patients discharged from 62 cardiac rehabilitation (CR) facilities, providing data on risk factors, lifestyle habits, drug treatments, and major cardiovascular events (MACE) during a 1-year follow-up. Records were linked to the official website of the Italian Association of Cardiovascular Prevention and Rehabilitation (GICR-IACPR). The overall prevalence of pre-discharge THF was 7.6%, with 69.8% of cases in acute wards, 22.9% during CR, and 7.3% in both settings. THF affected more frequently patients with chronic cardiac condition (42.7 vs. 30.6%; p < 0.05), age ≥75 years (33.3 vs. 23.1%; p < 0.005), COPD (19.8 vs. 12.3%; p < 0.05), and chronic kidney disease (17.7 vs. 7%; p < 0.001). After discharge, THF patients showed good maintenance rates of RAAS modulators (90.6%) and beta-blockers (83.3%), while statin therapy significantly decreased from 81.3 to 64.6% (p < 0.05). The pursuit of secondary prevention targets, as far as self-reported drug adherence, was not different among groups. Patients with THF had increased 1-year mortality (8.3 vs. 1.6%, p < 0.001). Moreover, THF independently predicted adverse outcome with OR for recurrent events (mainly further episodes of decompensation) of 2.4 (CI 1.4-4.3). Patients who experienced THF after coronary revascularization had increased post-discharge mortality and cardiovascular events. Hemodynamic instability, rather than recurrent myocardial ischemia, seems to be linked with worse prognosis.


Assuntos
Ponte de Artéria Coronária , Insuficiência Cardíaca/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Humanos , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Tempo
17.
Ann Ital Chir ; 84(2): 171-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23697994

RESUMO

BACKGROUND: Evidence-based criteria in the therapeutic choice for sigmoid acute diverticulitis (AD) are lacking. It is necessary to differentiate an acute episode of diverticular disease, not complicated (NCAD) and complicated (CAD) because these stages of diverticular disease needs different approach. METHODS: In a prospective study on 377 consecutive patients admitted for AD, 265 had NCAD and 112 CAD diagnosed with CT scan. Thirty-six of 265 with NCAD were operated on due to two or more previous episodes of AD. On 188 patients with NCAD followed-up, 35 had further episodes of NCAD and 2 had CAD. On 112 CAD patients, 61 had Hinchey I and were submitted to colonic resection. Twenty-three of 24 patients with Hinchey II were treated with percutaneous drainage. All Hinchey II patients were operated on. All the 13 patients with Hinchey III and IV had emergency surgery. RESULTS: We had no mortality and respectively 9.8% and 30% morbidity in Hinchey I and II patients. In Hinchey II patients percutaneous drainage was successful in 21 on 23 (91.3%). In 13 Hinchey III and IV patients the mortality rate was 25%. The comparison of CT findings and pathological results showed a sensitivity of 100% and predictive positive value of respectively 94.4, 96.7, 100 and 100% for NCAD, Hinchey I, Hinchey II and Hinchey III-IV. CONCLUSIONS: The therapeutic approach of diverticular disease needs to differentiate among an acute episode, NCAD and CAD. Evidence-based therapeutic choices can be reached only by homogeneous diagnostic criteria obtained by CT scan.


Assuntos
Colo Sigmoide , Diverticulite , Diverticulite/cirurgia , Doença Diverticular do Colo , Drenagem , Humanos , Estudos Prospectivos
18.
PLoS One ; 8(2): e57372, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23460845

RESUMO

BACKGROUND: Video-games have become an integral part of the new multimedia culture. Several studies assessed video-gaming enhancement of spatial attention and eye-hand coordination. Considering the technical difficulty of laparoscopic procedures, legal issues and time limitations, the validation of appropriate training even outside of the operating rooms is ongoing. We investigated the influence of a four-week structured Nintendo® Wii™ training on laparoscopic skills by analyzing performance metrics with a validated simulator (Lap Mentor™, Simbionix™). METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective randomized study on 42 post-graduate I-II year residents in General, Vascular and Endoscopic Surgery. All participants were tested on a validated laparoscopic simulator and then randomized to group 1 (Controls, no training with the Nintendo® Wii™), and group 2 (training with the Nintendo® Wii™) with 21 subjects in each group, according to a computer-generated list. After four weeks, all residents underwent a testing session on the laparoscopic simulator of the same tasks as in the first session. All 42 subjects in both groups improved significantly from session 1 to session 2. Compared to controls, the Wii group showed a significant improvement in performance (p<0.05) for 13 of the 16 considered performance metrics. CONCLUSIONS/SIGNIFICANCE: The Nintendo® Wii™ might be helpful, inexpensive and entertaining part of the training of young laparoscopists, in addition to a standard surgical education based on simulators and the operating room.


Assuntos
Competência Clínica , Educação Médica , Laparoscopia/educação , Médicos , Jogos e Brinquedos , Jogos de Vídeo , Adulto , Colecistectomia Laparoscópica , Feminino , Humanos , Masculino
19.
Clin Nucl Med ; 38(5): 349-53, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23531770

RESUMO

PURPOSE OF THE REPORT: Autonomous functioning thyroid nodules (AFTN), defined as "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim of our study was to investigate the long-term outcome in patients treated with an 131I calculated dose, to identify a possible "size-tailored" dose, and to simplify follow-up procedures. PATIENTS AND METHODS: Retrospective analysis was carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an 131I calculated dose. Our study focused on nodular size and mean administered dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from treatment was considered. RESULTS: A single 131I dose was effective for the vast majority of patients (93%). The outcome was influenced by nodular size. On the basis of the Italian dose limit for outpatient treatment, our population was divided into subgroups according to administered doses (more or less than 16 mCi) and nodular dimensions: no differences in outcome were observed for each class of nodule size. A dose ≤10 mCi was effective on the smaller nodules (50.1% of our population). The agreement between TSH and scan after treatment was 90.3% at 3 months and 94.5% at 6 months. CONCLUSIONS: 131I therapy with a calculated dose is an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often resolutive and for nodules <3 cm a dose of 10 mCi can suffice. Nodules >5 cm are eligible for surgery. TSH is the only parameter required to evaluate the outcome.


Assuntos
Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Pessoa de Meia-Idade , Cintilografia , Dosagem Radioterapêutica , Estudos Retrospectivos , Nódulo da Glândula Tireoide/patologia , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
20.
Int J Cardiol ; 167(4): 1390-5, 2013 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-22575623

RESUMO

BACKGROUND AND AIM: Secondary prevention is a priority after coronary revascularization. We investigate the impact of a cardiac rehabilitation (CR) program on lifestyle, risk factors and medication modifications and analyze predictors of poor behavioral changes and events in patients after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). METHODS: Multicenter (n=62), prospective, longitudinal survey in post-CABG or -PCI consecutive patients after a comprehensive CR program. Cardiac risk factors, lifestyle habits, medication and 1 year cardiovascular events were collected. Logistic regression analyzed the association between risk factors, events and predictors of non-adherence to treatment and lifestyle. RESULTS: At 1 year, of the 1262 patients (66 ± 10 years, CABG 69%, PCI 31%), 94% were taking antiplatelet agents (vs. 91.8% at CR admission and 91.7% at CR discharge, p=ns), 87% statins (vs. 67.5%, p<.0001, and 86.3%, p=ns), 80.7% beta-blockers (vs. 67.4%, p<.0001, and 88.8%, p=ns), and 81.1% ACE inhibitors (vs. 57.5% p<.0001, and 77.7%, p=ns). 89.9% of the patients showed good adherence to treatment, 72% adhered to diet and 51% to exercise recommendations; 74% of smokers stopped smoking. Younger age was predictive of smoking resumption (OR 8.9, CI 3.5-22.8). Pre-event sedentary lifestyle (OR 3.3, CI 1.3-8.7) was predictive of poor diet. Older patients with comorbidity (OR 3.1; CI, 1.8-5.2) tended to persist in sedentary lifestyle and discontinue therapy and diet recommendations. Age, diabetes, smoking and PCI indication were predictors of recurrent CV events which occurred in 142 patients. CONCLUSION: Participation in CR results in excellent treatment after revascularization, as well as a good lifestyle and medication adherence at 1 year and provides further confirmation of the benefit of secondary prevention. Several clinical characteristics may predict poor behavioral changes.


Assuntos
Reabilitação Cardíaca , Fármacos Cardiovasculares/uso terapêutico , Cooperação do Paciente , Intervenção Coronária Percutânea/métodos , Comportamento de Redução do Risco , Prevenção Secundária/métodos , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Estudos Transversais/métodos , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento
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