Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-38761275

RESUMO

PURPOSE: Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard. METHODS: The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined. RESULTS: Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT. CONCLUSION: This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care.

2.
Brain Behav Immun ; 117: 493-509, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38307446

RESUMO

In the last years, the hypothesis that elevated levels of proinflammatory cytokines contribute to the pathogenesis of neurodevelopmental diseases has gained popularity. IL-1 is one of the main cytokines found to be elevated in Autism spectrum disorder (ASD), a complex neurodevelopmental condition characterized by defects in social communication and cognitive impairments. In this study, we demonstrate that mice lacking IL-1 signaling display autistic-like defects associated with an excessive number of synapses. We also show that microglia lacking IL-1 signaling at early neurodevelopmental stages are unable to properly perform the process of synapse engulfment and display excessive activation of mammalian target of rapamycin (mTOR) signaling. Notably, even the acute inhibition of IL-1R1 by IL-1Ra is sufficient to enhance mTOR signaling and reduce synaptosome phagocytosis in WT microglia. Finally, we demonstrate that rapamycin treatment rescues the defects in IL-1R deficient mice. These data unveil an exclusive role of microglial IL-1 in synapse refinement via mTOR signaling and indicate a novel mechanism possibly involved in neurodevelopmental disorders associated with defects in the IL-1 pathway.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Camundongos , Microglia , Serina-Treonina Quinases TOR , Citocinas , Sirolimo/farmacologia , Sinapses , Interleucina-1 , Mamíferos
3.
Eur Arch Otorhinolaryngol ; 279(9): 4247-4255, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35505113

RESUMO

PURPOSE: Transoral laser microsurgery (TOLMS) with carbon dioxide is a safe approach for laryngeal carcinoma. In literature there are three main methods for evaluating speech outcomes: acoustic and aerodynamics analysis, perceptual evaluation and patient-reported outcomes (PROs). The aim of this study was to systematically review the literature about the voice quality outcomes of TOLMS according to type of cordectomy. METHODS: A systematic literature review was performed and all the results until December 2021 were extrapolated. We evaluated the acoustic and aerodynamics parameters (fundamental frequency, harmonics to noise ratio, jitter, shimmer and maximum phonation time), perceptual data (GRBAS scale) and patient-related outcomes (VHI scale). RESULTS: 24 studies met the inclusion criteria for a total number of 1207 patients enrolled. The number for each type of cordectomy are: 287 type I (23.78%), 311 type II (25.78%), 328 type III (27.14%), 129 type 4 (10.69%) and 152 type V (12.60%). Patients are grouped according to the type of cordectomy in: limited cordectomy (type I and II) and extended cordectomy (types III-IV-V). The difference between two groups is statistically significative in terms of acoustic analysis, perceptual data and patient-related outcomes (p < 0.05). CONCLUSIONS: Patients who underwent type I or II cordectomy have significantly better quality of voice in terms of VHI, perceptual voice quality evaluations and acoustic parameters compared to type III, IV and V cordectomies. The effect of TOLMS on the voice should depend from the extent of the resection and in particular from the scar of the vocal muscle.


Assuntos
Neoplasias Laríngeas , Terapia a Laser , Lasers de Gás , Dióxido de Carbono , Glote/cirurgia , Humanos , Neoplasias Laríngeas/cirurgia , Terapia a Laser/métodos , Lasers de Gás/uso terapêutico , Microcirurgia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Qualidade da Voz
4.
J Hepatol ; 76(1): 107-114, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34530063

RESUMO

BACKGROUND & AIMS: Decompensated cirrhosis (DC) is associated with high mortality, mainly owing to the development of acute-on-chronic liver failure (ACLF). Identifying the patients with DC who are at high risk of mortality and ACLF development is an unmet clinical need. Liver fatty acid-binding protein (L-FABP) is expressed in several organs and correlates with liver and systemic inflammation. Herein, we aimed to assess the prognostic value of L-FABP in patients with DC. METHODS: A prospective series of 444 patients hospitalized for DC was divided into 2 cohorts: study cohort (305 patients) and validation cohort (139 patients). L-FABP was measured in urine and plasma samples collected at admission. Neutrophil gelatinase-associated lipocalin (NGAL) was also measured in urine samples for comparison. RESULTS: Urine but not plasma L-FABP correlated with 3-month survival on univariate analysis. On multivariate analysis, urine L-FABP and model for end-stage liver disease (MELD)-Na were the only independent predictors of prognosis. Urine L-FABP levels were higher in patients with ACLF than in those without and also predicted the development of ACLF, together with MELD-Na, during follow-up. In patients with ACLF, urine L-FABP correlated with liver, coagulation, and circulatory failure. Urine L-FABP levels were also increased in patients with acute kidney injury, particularly in those with acute tubular necrosis. The ability of urinary L-FABP to predict survival and ACLF development was confirmed in the validation cohort. Urine NGAL predicted outcome on univariate but not multivariate analysis. CONCLUSIONS: Urinary L-FABP levels are independently associated with the 3-month clinical course in patients with DC, in terms of mortality and ACLF development. Urinary L-FABP is a promising prognostic biomarker for patients with DC. LAY SUMMARY: Increased levels of liver fatty acid-binding protein (L-FABP), a protein related to lipid metabolism, have been associated with liver-related diseases. The present study analyzed urinary L-FABP levels in 2 independent groups of patients with decompensated cirrhosis and showed that higher urinary L-FABP levels correlated with increased mortality and risk of acute-on-chronic liver failure development. Therefore, urinary L-FABP levels could be useful as a new tool to predict complications in patients with decompensated cirrhosis.


Assuntos
Insuficiência Hepática Crônica Agudizada/diagnóstico , Proteínas de Ligação a Ácido Graxo/análise , Proteínas de Ligação a Ácido Graxo/urina , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/urina , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/urina , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estatísticas não Paramétricas
5.
J Hepatol ; 74(2): 340-349, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32853747

RESUMO

BACKGROUND & AIMS: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. METHODS: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. RESULTS: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5-4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. CONCLUSION: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin - 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. LAY SUMMARY: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.


Assuntos
Ascite , Cirrose Hepática , Assistência de Longa Duração/métodos , Albumina Sérica Humana/administração & dosagem , Albumina Sérica/análise , Ascite/etiologia , Ascite/terapia , Produtos Biológicos/administração & dosagem , Biomarcadores Farmacológicos/análise , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Análise de Intenção de Tratamento , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Sobrevida , Resultado do Tratamento
6.
Ann Ital Chir ; 92020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32876052

RESUMO

INTRODUCTION: Fungus ball (FB) represents a granulomatous mass due to a fungal colonization which may disseminate and potentially lead to a systemic infection. Maxillary fungus ball is considered to be a complication of dental treatment and, according to relevant literature, it often stems from improper endodontic therapies. MATERIAL AND METHODS: The authors report the case of a 69-year-old caucasian woman with nasal respiratory distress and frequent sinusitis symptoms. According to clinical and radiological evidence, FESS surgery was planned, thus validating FB diagnostic hypothesis. CONCLUSIONS: Fungal infection should always be considered in patients with sinusitis and previous root canal theraphy. Misdiagnosis can lead to severe complications. Surgical removal seems to be effective and resolutive. KEY WORDS: Endoscopic surgery, Fungus Ball, Maxillary sinusitiss.


Assuntos
Aspergillus flavus/isolamento & purificação , Complicações do Diabetes , Seio Maxilar , Sinusite , Idoso , Aspergilose/complicações , Aspergilose/diagnóstico por imagem , Aspergilose/cirurgia , Endoscopia , Feminino , Humanos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/microbiologia , Seio Maxilar/cirurgia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Sinusite/diagnóstico por imagem , Sinusite/microbiologia , Sinusite/cirurgia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Superinfecção/tratamento farmacológico , Superinfecção/microbiologia
7.
Hepatol Commun ; 4(9): 1257-1262, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32838102

RESUMO

Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our aim was to describe the clinical course of patients with immunosuppressed autoimmune hepatitis (AIH) during coronavirus disease 2019 (COVID-19) infection in Italy. Our study is a case series of patients with AIH treated with immunosuppression, who tested positive for SARS-CoV-2 in March 2020 during the outbreak of COVID-19. Ten patients from seven different hospitals in Italy were diagnosed with COVID-19 during the outbreak of SARS-CoV-2 in March 2020. Seven subjects were female (70%), and age ranged from 27 to 73 years. Before the onset of SARS-CoV-2 infection, all patients were taking immunosuppressive therapy for AIH, and eight of them were on biochemical remission. Two other patients had recent acute onset of their AIH, and consequently started high-dose steroids, as per induction protocol. All patients had a respiratory syndrome and a positive nasal swab for SARS-CoV-2. Five patients developed a computed tomography-confirmed COVID-19 pneumonia. Six subjects received a combination of antiretroviral and antimalarial drugs. In seven patients, the dosage of immunosuppressive medication was changed. Liver enzymes were repeated during SARS-CoV-2 infection in all hospitalized cases; they remained within the normal range in all cases, and improved in the two acute cases treated with high-dose steroids. The clinical outcome was comparable to the reported cases occurring in non-immunosuppressed subjects. Conclusion: Patients under immunosuppressive therapy for AIH developing COVID-19 show a disease course presumptively similar to that reported in the non-immunosuppressed population. These data might aid in medical decisions when dealing with SARS-CoV-2 infection in immunocompromised patients.

8.
Stem Cells Transl Med ; 9(9): 1068-1084, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32496649

RESUMO

The critical role of neuroinflammation in favoring and accelerating the pathogenic process in Alzheimer's disease (AD) increased the need to target the cerebral innate immune cells as a potential therapeutic strategy to slow down the disease progression. In this scenario, mesenchymal stem cells (MSCs) have risen considerable interest thanks to their immunomodulatory properties, which have been largely ascribed to the release of extracellular vesicles (EVs), namely exosomes and microvesicles. Indeed, the beneficial effects of MSC-EVs in regulating the inflammatory response have been reported in different AD mouse models, upon chronic intravenous or intracerebroventricular administration. In this study, we use the triple-transgenic 3xTg mice showing for the first time that the intranasal route of administration of EVs, derived from cytokine-preconditioned MSCs, was able to induce immunomodulatory and neuroprotective effects in AD. MSC-EVs reached the brain, where they dampened the activation of microglia cells and increased dendritic spine density. MSC-EVs polarized in vitro murine primary microglia toward an anti-inflammatory phenotype suggesting that the neuroprotective effects observed in transgenic mice could result from a positive modulation of the inflammatory status. The possibility to administer MSC-EVs through a noninvasive route and the demonstration of their anti-inflammatory efficacy might accelerate the chance of a translational exploitation of MSC-EVs in AD.


Assuntos
Doença de Alzheimer/terapia , Vesículas Extracelulares/transplante , Imunomodulação , Células-Tronco Mesenquimais/metabolismo , Neuroproteção , Administração Intranasal , Doença de Alzheimer/patologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Polaridade Celular , Células Cultivadas , Citocinas/metabolismo , Espinhas Dendríticas/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Microglia/patologia , Fenótipo
10.
Minerva Gastroenterol Dietol ; 66(1): 11-16, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31760736

RESUMO

BACKGROUND: The water load test is a simple, cheap and standardized method to evaluate gastric distension and gastric motility responses. We have previously shown that in patients with mild erosive or non-erosive esophagitis this test is frequently abnormal, suggesting an altered gastric function. The aim was to evaluate the water load test score before and after Nissen fundoplication in reflux patients. METHODS: Thirty-one patients (16 men, 15 women, mean age 46.5 y) were studied before and 3 months after Nissen fundoplication by stationary esophageal manometry, wireless Bravo pH system monitoring (48 hours), and water load test. A dyspepsia symptom questionnaire was also completed before and after surgery. Data were compared with those of 35 controls. RESULTS: All patients had pH-monitoring positive for pathological acid exposure and/or related-reflux symptoms in the absence of motility disorders. Basal symptoms scores were higher in patients compared to controls and improved after surgery, except than postprandial fullness, early satiation, and bloating, that were significantly increased. At baseline, all patients ingested significantly lower water volumes than controls, with a tendency to early onset of fullness and nausea, respectively. After surgery, the water volumes were significantly lower than presurgery. CONCLUSIONS: In patients with reflux-related symptoms, with or without esophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. Nissen fundoplication is associated with a relatively higher incidence of bloating, epigastric pain and fullness. These preliminary data could explain the incomplete resolution of symptoms after surgery in some patients, and suggest the use of additional studies to explore the gastric function in presurgical evaluation.


Assuntos
Dispepsia/complicações , Fundoplicatura , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/cirurgia , Água , Adulto , Idoso , Técnicas de Diagnóstico do Sistema Digestório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Água/administração & dosagem
11.
Cells ; 8(9)2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510042

RESUMO

Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect ß-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer's disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the Aß plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct ß-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.


Assuntos
Vesículas Extracelulares/transplante , Células-Tronco Mesenquimais/metabolismo , Placa Amiloide/terapia , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Vesículas Extracelulares/metabolismo , Feminino , Hipocampo/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neuritos/metabolismo
12.
Int J Oral Implantol (Berl) ; 12(2): 209-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31090751

RESUMO

PURPOSE: To test a minimally invasive flap in the lateral approach for maxillary sinus floor elevation when compared to a trapezoidal flap. MATERIALS AND METHODS: Each patient received a bilateral sinus elevation procedure based on two different randomly allocated surgical approaches according to a split-mouth design: in the test side, a horizontal incision at mucogingival line was realised; in the control side, a trapezoidal flap was elevated to prepare the lateral window. Each sinus was filled using deproteinised bovine bone and the window covered with a collagen membrane. Implants were inserted according to a two-stage technique 6 months after sinus elevation procedures, submerged and then loaded after 6 months with definitive screw-retained metal-ceramic prostheses. Patients were followed up to 4 months post-loading. Outcome measures included: implant and prosthesis failures, complications, peri-implant marginal bone level changes, residual bone height and width, recorded before sinus augmentation and 180 days post-intervention by computed tomography (CT) scans, surgical times and patient discomfort data, assessed using a visual analogue scale (VAS) diagram for each treated side at 1, 7, 14 and 30 days of follow-up. RESULTS: Seventeen patients were enrolled in this trial and none dropped out. Five completely edentulous patients were treated with full-arch prosthetic restorations (Toronto dental prosthesis) and 12 patients with partial metal-ceramic screw-retained prostheses. In total 72 implants were inserted, 37 in the test group and 35 in the control group. No prosthesis or implant failures occurred. A total of seven patients showed complications: five of them had complications in both test and control sides. Eight complications were detected in each group. During maxillary sinus elevation procedures, nine interventions (four from the test group and five from the control group) were affected by intrasurgical complications (six membrane perforations and three severe bleedings); post-surgical complications occurred to three patients (one submucosal emphysema in a patient from the test group, one wound dehiscence and a graft infection both recorded in the control group); a total of four implants in two patients in the test group, versus three implants from one patient in the control group showed peri-implant mucositis. There were no statistically significant differences in complications between the two groups (P = 1.00; 95% confidence interval [CI]: 0.15-3.11). Patients from the control group, at 4 months after loading, lost on average 0.53 mm (standard deviation [SD] 0.27; 95% CI: 0.40-0.65), and patients from the test group lost on average 0.66 mm (SD 0.27; 95% CI: 0.53-0.78); the difference was not statistically significant (mean difference: 0.07 mm; SD 0.34; 95% CI: -0.03-0.17; P = 0.102). Significant values for bone augmentation in height, 9.26 mm (SD 1.46; 95% CI: 8.56-9.95) in the test group and 9.38 mm (SD 1.95; 95% CI: 8.45-10.30) in the control group, and width, 1.68 mm (SD 1.04; 95% CI: 1.18-2.20) in the test group and 1.60 mm (SD 1.27; 95% CI: 0.99-2.20) in the control group, were found from the 180-day CT scans. No statistically significant differences were detected between the two groups, either for the bone augmentation data (difference: 0.27 mm; 95% CI: 0.15-0.38; P = 0.60) or for the bone width values (difference: 0.02 mm; 95% CI: 0.07-0.11; P = 0.67). A significant reduction in the total surgical time was found in the test group (mean difference: 6.64 minutes; SD 4.32; 95% CI: 4.58-8.69), with the difference being statistically significant (P = 0.009). Evaluation of patients' postoperative discomfort showed a significant preference for the test procedure: at 1 day the VAS value was 4 (interquartile range [IQR] 2 to 5) in the test group; in the control group the VAS score was 5 (IQR 4 to 8). The intergroup difference was statistically significant (P = 0.002). At the 7-day follow-up, the VAS value was 1 in the test group (IQR 0 to 3) and 3 in the control group (IQR 0 to 7), this difference was statistically significant (P = 0.003). No differences were detected at 14 and 30 days (P > 0.05). CONCLUSIONS: A minimally invasive approach to access the sinus cavity can be as successful as a conventional trapezoidal flap in maxillary sinus floor elevations.


Assuntos
Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Animais , Bovinos , Implantação Dentária Endóssea , Humanos , Seio Maxilar , Boca
13.
Bioessays ; 41(4): e1800199, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30919493

RESUMO

No cure yet exists for devastating Alzheimer's disease (AD), despite many years and humongous efforts to find efficacious pharmacological treatments. So far, neither designing drugs to disaggregate amyloid plaques nor tackling solely inflammation turned out to be decisive. Mesenchymal stem cells (MSCs) and, in particular, extracellular vesicles (EVs) originating from them could be proposed as an alternative, strategic approach to attack the pathology. Indeed, MSC-EVs-owing to their ability to deliver lipids/proteins/enzymes/microRNAs endowed with anti-inflammatory, amyloid-ß degrading, and neurotrophic activities-may be exploited as therapeutic tools to restore synaptic function, prevent neuronal death, and slow down memory impairment in AD. Herein the results presented in the most recently published studies on this topic are critically evaluated, providing a strong rationale for possible employment of MSC-EVs in AD. Also see the video abstract here https://youtu.be/tBtDbnlRUhg.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Vesículas Extracelulares/metabolismo , Inflamação/patologia , Células-Tronco Mesenquimais/metabolismo , Regeneração , Animais , Humanos
14.
Hepatology ; 70(1): 319-333, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30810244

RESUMO

Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS-AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase-associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin-18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia-induced AKI (48%), 93 were HRS-AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28-day mortality together with Model for End-Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis.


Assuntos
Injúria Renal Aguda/diagnóstico , Lipocalina-2/urina , Cirrose Hepática/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/urina , Idoso , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia
15.
Lancet ; 391(10138): 2417-2429, 2018 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-29861076

RESUMO

BACKGROUND: Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS: We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS: From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION: In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING: Italian Medicine Agency.


Assuntos
Albuminas/uso terapêutico , Ascite/terapia , Cirrose Hepática/tratamento farmacológico , Idoso , Ascite/etiologia , Diuréticos/administração & dosagem , Diuréticos/efeitos adversos , Quimioterapia Combinada , Feminino , Furosemida/administração & dosagem , Furosemida/efeitos adversos , Humanos , Hiperpotassemia/induzido quimicamente , Hiponatremia/induzido quimicamente , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Paracentese , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Taxa de Sobrevida , Fatores de Tempo
16.
Medicine (Baltimore) ; 97(19): e0628, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29742700

RESUMO

Pyogenic liver abscess (PLA) are space-occupying lesions in the liver associated with high morbidity and mortality. The aim of this study is to review an Italian hospital experience in epidemiological, clinical patterns, and management of PLA.We performed a retrospective, descriptive case series at a single center assessing demographic characteristics, presentation patterns, etiological factors, microbiological etiology, and management for patients treated for PLA between 2000 and 2016.Around 109 patients were identified. The majority of patients presented with fever (73%); right upper abdominal pain in 63.3%, vomiting and nausea in 28.4%. The most common laboratory abnormality among included items was increased C-reactive protein and fibrinogen blood levels, respectively, in 98% and 93.9% of cases. Abdominal ultrasound was the diagnostic investigation in 42.4% of cases; CT scan and MR imaging were performed in 51.1% and 3.3% of cases respectively. We observed blood or pus culture study in 99 cases of which only 53.5% came with positive microbial reports. The most common organism identified was Escherichia coli (26.5%), followed by Streptococcus spp (13.2%). Early antibiotic treatment started on all patients and 66.7% of cases required different approaches, Ultrasound or CT-guided needle aspiration of PLA was performed in 13 patients (11%) and percutaneous abscess drainage was performed on 72 patients (67%).PLA is a diagnostically challenging problem due to nonspecific presenting characteristics. The microbiological yield identified was a typical European spectrum with a preponderance of Escherichia coli infections. Once recognized, percutaneous drainage and antibiotic treatment are the mainstay of management for PLA.


Assuntos
Antibacterianos/administração & dosagem , Fístula Biliar , Drenagem , Abscesso Hepático Piogênico , Fígado , Pneumotórax , Complicações Pós-Operatórias , Adulto , Fístula Biliar/diagnóstico , Fístula Biliar/etiologia , Fístula Biliar/cirurgia , Drenagem/efeitos adversos , Drenagem/métodos , Escherichia coli/isolamento & purificação , Feminino , Humanos , Itália/epidemiologia , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Abscesso Hepático Piogênico/diagnóstico , Abscesso Hepático Piogênico/microbiologia , Abscesso Hepático Piogênico/mortalidade , Abscesso Hepático Piogênico/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Pneumotórax/diagnóstico , Pneumotórax/etiologia , Pneumotórax/terapia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Streptococcus/isolamento & purificação , Tomografia Computadorizada por Raios X/métodos
17.
Sci Rep ; 7(1): 1829, 2017 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-28500294

RESUMO

Fatty-acid-binding proteins (FABPs) are small intracellular proteins that coordinate lipid-mediated processes by targeting metabolic and immune response pathways. The aim of the study was to investigate plasma FABPs levels and their relationship with clinical outcomes in cirrhosis. Plasma levels of L-FABP1(liver and kidney), I-FABP2(intestine), and A-FABP4(adipocyte and macrophages) were measured in 274 patients with decompensated cirrhosis. Hepatic gene expression of FABPs was assessed in liver biopsies from patients with decompensated cirrhosis and in liver cell types from mice with cirrhosis. Immunohistochemistry of A-FABP4 in human liver biopsy was also performed. Plasma levels of FABPs were increased in patients with decompensated cirrhosis compared to those of healthy subjects (L-FABP1: 25 (17-39) vs 10 (9-17) ng/mL p = 0.001, I-FABP2: 1.1 (0.5-2.1) vs 0.6 (0.4-1) ng/mL p = 0.04 and A-FABP4: 37 (20-68) vs 16 (11-33) ng/mL p = 0.002), respectively. Increased A-FABP4 levels were associated with complications of cirrhosis, acute-on-chronic liver failure and poor survival. Hepatic A-FABP4 gene expression was upregulated in decompensated cirrhosis. Macrophages were the main liver cell that over-expressed A-FABP4 in experimental cirrhosis and increased A-FABP4 was found in macrophages of human biopsies by immunohistochemistry. A-FABP4 levels are increased in decompensated cirrhosis and correlate with poor outcomes. Liver macrophages appear to be the main source of A-FABP4 in decompensated cirrhosis.


Assuntos
Adipócitos/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Expressão Gênica , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Idoso , Infecções Bacterianas/etiologia , Biomarcadores , Comorbidade , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Modelos de Riscos Proporcionais
18.
Artigo em Inglês | MEDLINE | ID: mdl-28402353

RESUMO

The purpose of the present study was to compare two different surgical procedures, connective tissue graft and guided bone regeneration, when applied in conjunction with implant placement. Probing pocket depth and the recession depth were recorded at the implant site after crown placement (T1) and at the 1-year follow-up (T2), while the keratinized tissue height and the buccal mucosa thickness were recorded at three different time points: at the time of implant surgery (T0), after crown placement, and at the 1-year follow-up. No statistically significant differences in peri-implant mucosa thickness, recession, or other periodontal parameters were recorded at adjacent teeth.


Assuntos
Regeneração Óssea , Tecido Conjuntivo/transplante , Implantes Dentários , Reparação de Restauração Dentária/métodos , Regeneração Tecidual Guiada , Peri-Implantite/diagnóstico , Peri-Implantite/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Transplantes/cirurgia , Transplantes/transplante
19.
Liver Transpl ; 23(5): 583-593, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28318147

RESUMO

The alfapump system has been proposed as a new treatment for the management of refractory ascites. The system removes ascites from the peritoneal cavity to urinary bladder, producing a continuous low-volume paracentesis. The aim of the study is to investigate the effects of treatment with the alfapump™ system on kidney and circulatory function in patients with cirrhosis and refractory ascites. This was a prospective study including 10 patients with cirrhosis and refractory ascites. Primary outcomes were changes in glomerular filtration rate (GFR), as assessed by isotopic techniques, and changes in circulatory function assessed by arterial pressure, cardiac output, and activity of vasoconstrictor systems. Secondary outcomes were the need for large-volume paracentesis and adverse events. Follow-up was 1 year. GFR decreased significantly from 67 mL/minute/1.73 m2 (41-90 mL/minute/1.73 m2 ) at baseline to 45 mL/minute/1.73 m2 (36-74 mL/minute/1.73 m2 ) at month 6 (P = 0.04). Mean arterial pressure and cardiac output did not change significantly; however, there was a marked increase in plasma renin activity and norepinephrine concentration (median percent increase with respect to baseline +191% and 59%, respectively). There were 68 episodes of complications of cirrhosis in 8 patients during follow-up, the most frequent being acute kidney injury. In conclusion, treatment with alfapump™ system was associated with marked activation of endogenous vasoconstrictor systems and impairment of kidney function. The chronological relationship observed between kidney impairment and vasoconstrictor systems activation after device insertion suggests a cause-effect relationship, raising the possibility that treatment with alfapump impairs effective arterial blood volume mimicking a postparacentesis circulatory dysfunction syndrome. In this context, the potential role of albumin in counteracting these effects should be investigated in future studies. Liver Transplantation 23 583-593 2017 AASLD.


Assuntos
Ascite/terapia , Drenagem/efeitos adversos , Drenagem/instrumentação , Cirrose Hepática/complicações , Idoso , Ascite/etiologia , Volume Sanguíneo , Feminino , Humanos , Testes de Função Renal , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos , Espanha/epidemiologia , Vasoconstrição
20.
Dig Liver Dis ; 49(6): 651-656, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28233684

RESUMO

BACKGROUND: Success of colonoscopy is linked to the adequacy of bowel cleansing. Polyethylene glycol 4L (PEG 4L) solutions are widely used for colonic cleansing but with limitations concerning tolerability and acceptability. AIM: To demonstrate the equivalence of a new low-volume PEG containing citrates and simeticone (Clensia) versus a standard PEG 4L. METHODS: In this, multicentre, randomised, observer-blind trial, patients received either Clensia 2L or PEG 4L solution. Primary endpoint was the proportion of patients with colon cleansing evaluated as excellent or good. RESULTS: 422 patients received Clensia (n=213) or PEG 4L (n=209). Rate of excellent/good bowel cleansing was 73.6% and 72.3% in Clensia and PEG 4L group respectively. Clensia was demonstrated to be equivalent to PEG 4L. No SAEs were observed. Clensia showed better gastrointestinal tolerability (37.0% vs 25.4%). The acceptability was significantly better with Clensia in terms of proportion of subjects who felt no distress (Clensia 72.8% vs PEG 4L 63%, P=0.0314) and willingness-to-repeat (93.9% vs 82.2%, P=0.0002). The rate of optimal compliance was similar with both formulations (91.1% for Clensia vs 90.9% for PEG 4L, P=0.9388). CONCLUSIONS: The low-volume Clensia is equally effective and safe in bowel cleansing compared to the standard PEG 4L, with better gastrointestinal tolerability and acceptability.


Assuntos
Catárticos/administração & dosagem , Citratos/administração & dosagem , Colonoscopia , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...