RESUMO
Conformational diseases, such as Alzheimer, Parkinson and Huntington diseases, are part of a common class of neurological disorders characterized by the aggregation and progressive accumulation of proteins bearing aberrant conformations. Huntington disease (HD) has autosomal dominant inheritance and is caused by mutations leading to an abnormal expansion in the polyglutamine (polyQ) tract of the huntingtin (HTT) protein, leading to the formation of HTT inclusion bodies in neurons of affected patients. Interestingly, recent experimental evidence is challenging the conventional view by which the disease pathogenesis is solely a consequence of the intracellular accumulation of mutant protein aggregates. These studies reveal that transcellular transfer of mutated huntingtin protein is able to seed oligomers involving even the wild-type (WT) forms of the protein. To date, there is still no successful strategy to treat HD. Here, we describe a novel functional role for the HSPB1-p62/SQSTM1 complex, which acts as a cargo loading platform, allowing the unconventional secretion of mutant HTT by extracellular vesicles. HSPB1 interacts preferentially with polyQ-expanded HTT compared with the WT protein and affects its aggregation. Furthermore, HSPB1 levels correlate with the rate of mutant HTT secretion, which is controlled by the activity of the PI3K/AKT/mTOR signalling pathway. Finally, we show that these HTT-containing vesicular structures are biologically active and able to be internalized by recipient cells, therefore providing an additional mechanism to explain the prion-like spreading properties of mutant HTT. These findings might also have implications for the turn-over of other disease-associated, aggregation-prone proteins.
Assuntos
Proteína Huntingtina , Doença de Huntington , Fosfatidilinositol 3-Quinases , Humanos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Chaperonas Moleculares/genética , Mutação , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteína Sequestossoma-1/genética , Transdução de SinaisRESUMO
BACKGROUND: We aimed at investigating outcome of systemic treatments in advanced breast PT. METHODS: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed. RESULTS: 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months. CONCLUSION: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active.
Assuntos
Neoplasias da Mama , Sarcoma , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Sarcoma/patologiaRESUMO
PRIMARY OBJECTIVE: To examine the convergent validity of the Test of Effort (TOE), a performance validity test (PVT) currently under development that employs a two-subtest (one verbal, one visual), forced-choice recognition memory format. RESEARCH DESIGN: A descriptive, correlational design was employed to describe performance on the TOE and examine the convergent validity between the TOE and comparison measures. METHODS AND PROCEDURES: A sample of 53 individuals with chronic acquired brain injury (ABI) were administered the TOE and three well-validated PVTs (Reliable Digit Span [RDS], Test of Memory Malingering [TOMM] and Dot Counting Test [DCT]). MAIN OUTCOMES AND RESULTS: The TOE appeared more difficult than it actually was, suggesting adequate face validity. Medium-to-large correlations were observed between the TOE and established PVTs, suggesting good convergent validity. Provisional cutoff scores are offered based on performance of a subgroup of participants with "sufficient effort." CONCLUSIONS: Overall, the TOE shows promise as a PVT measure for clinical use. Future studies with larger and more diverse samples are needed to more fully determine the psychometric characteristics of the TOE.
Assuntos
Lesões Encefálicas , Simulação de Doença , Adulto , Lesões Encefálicas/diagnóstico , Humanos , Testes de Memória e Aprendizagem , Testes Neuropsicológicos , Reprodutibilidade dos TestesRESUMO
In humans, studies on the cellular immune response against Trichinella are scarce. Aim of this study was to characterize the cytokine profile of T cells specific for Trichinella britovi in trichinellosis patients. Peripheral blood mononuclear cells (PBMC) were obtained from five patients involved in a trichinellosis outbreak caused by T. britovi, which occurred in 2013 in Tuscany (Italy). All the patients resulted positive for Trichinella-specific IgG, IgE and presented eosinophilia. T cells were investigated for their proliferation to excretory/secretory antigens from Trichinella spiralis muscle larvae (TsES) and for their cytokine profile. A total of 284 CD4+ and 42 CD8+ T-cell clones were obtained from the TsES-specific T-cell lines from PBMC. All T-cell clones proliferated in response to mitogen. Of the 284 CD4+ T-cell clones generated from TsES-specific T-cell lines, 135 (47%) proliferated significantly to TsES; 26% CD8+ T-cell clones showed proliferation to TsES. In the series of the 135 TsES-specific CD4+ clones, 51% expressed a Th2 profile, 30% a Th0 and 19% Th1. In the series of the 11 TsES-specific CD8+ T-cell clones, 18% were Tc2, 45% Tc0 and 36% Tc1. In human trichinellosis, the cellular immune response is, during the chronic phase, mixed Th1/Th2.
Assuntos
Células Th1/imunologia , Células Th2/imunologia , Trichinella/imunologia , Triquinelose/imunologia , Adulto , Animais , Células Clonais/imunologia , Citocinas , Feminino , Humanos , Imunidade Celular , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Trichinella spiralis/imunologiaRESUMO
BACKGROUND: Liver involvement is a common manifestation of hereditary haemorrhagic telangiectasia (HHT). Although a number of studies have been carried out in adult patients, no study has ever been focused on investigating HHT-related hepatic involvement in paediatric patients. The present study aimed for the first time to systematically estimate the prevalence of HHT-associated liver involvement and to characterize HHT-associated hepatic angiodynamic features in paediatric age. PATIENTS AND METHODS: The study was designed as a cross-sectional survey in an HHT paediatric cohort, subclassified as HHT1 and HHT2 according to the mutated gene. The evaluation of the angiodynamic profile was performed by duplex ultrasound examination. Investigation by multi-slice computed tomography (MSCT) or magnetic resonance angiography (MRA) was performed in patients >12 years. RESULTS: MSCT/MRA examination disclosed silent hepatic involvement in 7/20 (35.0 %) children, and nodular regenerative hyperplasia in two cases. Diameter of common hepatic artery was significantly larger in HHT2 (0.45 ± 0.15 cm) compared to HHT1 (0.33 ± 0.09, p < 0.01) and control children (0.32 ± 0.08, p < 0.05). None of the patients had clinical manifestations of liver involvement. Angiodynamic profiles were different between paediatric and adult HHT patients. CONCLUSIONS: Liver involvement can be detected in paediatric HHT patients, albeit with a lower frequency compared to adults. Paediatric HHT2 children show a higher frequency of liver involvement and a trend to hepatic artery dilation when compared to HHT1 children.
Assuntos
Artéria Hepática/anormalidades , Fígado/irrigação sanguínea , Receptores de Activinas Tipo II/genética , Adolescente , Fatores Etários , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/epidemiologia , Malformações Arteriovenosas/genética , Doenças Assintomáticas , Estudos de Casos e Controles , Criança , Pré-Escolar , Angiografia por Tomografia Computadorizada/métodos , Estudos Transversais , Dilatação Patológica , Progressão da Doença , Endoglina/genética , Feminino , Predisposição Genética para Doença , Artéria Hepática/diagnóstico por imagem , Humanos , Itália/epidemiologia , Angiografia por Ressonância Magnética , Masculino , Tomografia Computadorizada Multidetectores , Mutação , Fenótipo , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagem , Valor Preditivo dos Testes , Prevalência , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/epidemiologia , Telangiectasia Hemorrágica Hereditária/genética , Fatores de Tempo , Ultrassonografia Doppler DuplaRESUMO
BACKGROUND: A 17-year-old boy was referred to our center with a history of brain abscess (BA) recurring after 9 years. The patient reported 2 previous treatments for pulmonary arteriovenous malformations, sporadic nosebleeds, and familial history for epistaxis. Clinical investigations revealed arteriovenous malformations in lung, brain, and liver, as well as mucocutaneous telangiectases. A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis. This is the first report of BA recurrence at the end of pediatric age. CONCLUSIONS: The present case and the literature review of all cases of BA thus far reported highlight the need to raise the suspicion of a pulmonary arteriovenous malformations, both isolated and in the context of a possible hereditary hemorrhagic telangiectasia, for any case of BA of unexplained etiology, in children as well as in adults.
Assuntos
Fístula Arteriovenosa/complicações , Abscesso Encefálico/etiologia , Abscesso Encefálico/patologia , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Telangiectasia Hemorrágica Hereditária/complicações , Adolescente , Adulto , Fístula Arteriovenosa/terapia , Abscesso Encefálico/cirurgia , Embolização Terapêutica , Humanos , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Recidiva , Telangiectasia Hemorrágica Hereditária/terapiaRESUMO
PURPOSE: Epididymo-orchitis (EO) is infrequently reported in anorectal malformation (ARM) cases. Therefore, it is difficult to assess its risk factors. METHODS: A total of 110 male patients who were operated on for ARM at the same Institution over a period of 13 years were contacted. Association was assessed between EO and the following: spinal dysraphism (SD), symptomatic VUR (VUR), and bowel management (BM) requiring enemas. The data were analyzed with the Chi-square test. RESULTS: A total of 89 patients were contacted. Ten cases of EO were found, and all occurred in patients with recto-urethral (RU) fistula after reconstruction. The patients' age at first episode ranged between 4 and 11 years. RU fistula patients experiencing EO (Group A, 10 patients) were compared with those without EO (Group B, 33 patients). VUR occurred in 9/10 cases in Group A and in 13/33 cases in group B (Chi-square 7.8658, p = 0.005038). SD was present in 4/10 cases in group A and in 13/33 cases in Group B (Chi-square 0.0434, p = 0.83491). A total of 8/10 cases in Group A and 12/33 cases in Group B were on BM (Chi-square 5.87, p = 0.0015). CONCLUSIONS: EO occurs in approximately in 20 % of male cases with ARM, and recto-urinary communication and should be considered the primary diagnosis in the presence of testicular pain. This could avoid unnecessary surgical exploration, and the family should be counseled about this subject.
Assuntos
Anormalidades Múltiplas/cirurgia , Canal Anal/anormalidades , Epididimite/complicações , Orquite/complicações , Procedimentos de Cirurgia Plástica/métodos , Reto/anormalidades , Canal Anal/cirurgia , Criança , Pré-Escolar , Epididimite/cirurgia , Humanos , Masculino , Orquite/cirurgia , Reto/cirurgia , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Over the past few decades, advances in medical research and diagnostic tools have shed light on some aspects of pyoderma gangrenosum (PG). Nevertheless, the multifactorial etiology, pathogenesis, and optimal management strategies for PG need to be further investigated. To address these knowledge gaps and contribute to a better understanding of this complex dermatological disorder, we collected epidemiological, clinical, and therapeutic aspects of a case series of PG patients occurring in our department over the past 10 years. METHODS: We performed a single-centered, retrospective, observational study analyzing all cases with a diagnosis of PG observed at the Dermatology clinic of the Fondazione Policlinico A. Gemelli IRCCS Catholic University from January 1, 2013, to January 1, 2023. For each case, we retrieved demographic data, the presence of other skin and systemic conditions, and the histopathological and clinical characteristics of PG, such as clinical variant, number of lesions, disease localization, previous therapy, response to treatment, and occurrence of relapse. RESULTS: We included 35 patients, 22 females and 13 males with a mean age of 40.0 years. Twenty patients (57.1%) had multiple localizations of disease, and the most commonly involved site was the lower limbs (85.7%). The lesions were mainly associated with inflammatory bowel diseases (51.4%) and hidradenitis suppurativa (37.1%). Clinical resolution with complete re-epithelialization was achieved in 25 patients (71.4%) with an average time of 20.8 months. On average, patients who underwent therapy with biological drugs had better outcomes. CONCLUSIONS: PG is a severe, rare, and pleomorphic disease associated with a broad spectrum of conditions. Corticosteroids remain the primary first-line approach for severe forms, but using biological immunosuppressants is promising.
Assuntos
Pioderma Gangrenoso , Humanos , Pioderma Gangrenoso/epidemiologia , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Adolescente , Recidiva , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologiaRESUMO
BACKGROUND: We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers. MATERIALS AND METHODS: We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out. RESULTS: Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% [95% confidence interval (CI) 43% to 68%] and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS [hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89] with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results. CONCLUSIONS: This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted.
Assuntos
Neoplasias da Mama , Hemangiossarcoma , Neoplasias Induzidas por Radiação , Humanos , Hemangiossarcoma/etiologia , Hemangiossarcoma/terapia , Hemangiossarcoma/tratamento farmacológico , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/radioterapia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Idoso , Neoplasias Induzidas por Radiação/etiologia , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician's Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.
Assuntos
Anticorpos Monoclonais Humanizados , Psoríase , Idoso , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Índice de Gravidade de Doença , Psoríase/tratamento farmacológicoRESUMO
OBJECTIVE: To evaluate the clinical features in a large cohort of pediatric patients with genetically confirmed hereditary hemorrhagic telangiectasia (HHT) and to identify possible predictors of arteriovenous malformation (AVM) onset or clinical significance. STUDY DESIGN: Prospective cross-sectional survey of all children subjected to screening for AVMs in the multidisciplinary HHT center. All patients proved to be carriers of endoglin mutations or activin A receptor type-II-like kinase 1 mutations, defined as HHT1 and HHT2, respectively. A full clinical-radiological protocol for AVM detection was adopted, independent from presence or absence of AVM-related symptoms. RESULTS: Forty-four children (mean age, 10.3 years; range, 1-18) were subjected to a comprehensive clinical-radiologic evaluation. This investigation disclosed cerebrovascular malformations in 7 of 44 cases, pulmonary AVMs in 20 of 44 cases, and liver AVMs in 23 of 44 cases. Large visceral AVMs were found in 12 of 44 children and were significantly more frequent in patients with HHT1. Only large AVMs were associated with symptoms and complications. CONCLUSIONS: Children with HHT have a high prevalence of AVMs; therefore, an appropriate clinical and radiological screening protocol is advisable. Large AVMs can be associated with complications in childhood, whereas small AVMs probably have no clinical risk.
Assuntos
Malformações Arteriovenosas/etiologia , Telangiectasia Hemorrágica Hereditária/complicações , Adolescente , Malformações Arteriovenosas/epidemiologia , Malformações Arteriovenosas/genética , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Prevalência , Estudos Prospectivos , Telangiectasia Hemorrágica Hereditária/genéticaRESUMO
OBJECTIVE: To present the results of the first 2 years of a human papillomavirus (HPV) test-based screening programme outside the research context. DESIGN: Population-based cohort study. SETTING: A cervical service screening programme in Italy. POPULATION: Women aged 25-64 years invited to screening from April 2009 to April 2011. METHODS: Eligible women were invited to undergo an HPV test: those with a negative HPV test went on to the next screening episode; those with a positive HPV went on to triage with a Pap smear. Women with positive cytology (i.e. positive for atypical squamous cells of undetermined significance or worse, ASC-US+) were referred to colposcopy, whereas those with negative cytology were referred to repeat HPV testing 1 year later. MAIN OUTCOME MEASURES: Participation rate, positivity at HPV and at triage, referral rate to colposcopy, positive predictive value for cervical intraepithelial neoplasia grade 2+ (CIN2+) at colposcopy, and detection rate for CIN2+. RESULTS: Participation increased compared with the previous Pap programme (60.6 versus 43.9%). The HPV positivity rate was 7.0; 39.6% of Pap smears were scored as positive, and therefore 2.8% of the women screened were referred for immediate colposcopy. The compliance of women who scored positive for HPV and negative for Pap for repeat HPV testing at 12 months was 78.6%, and the HPV positivity rate was 56.6%. The overall referral rate to colposcopy was 4.6%. The overall detection rate for CIN2+ was 4.5 versus 1.5% of the Pap programme (25-34 years, 8.2%; 35+ years, 3.6%). CONCLUSIONS: Compared with the traditional Pap test, the HPV programme recorded a higher response to invitation and an increased DR for CIN2+. The most critical aspects were the reading of cytology in women that were positive for HPV and the increased workload at colposcopy.
Assuntos
Colo do Útero/virologia , DNA Viral/análise , Detecção Precoce de Câncer/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Estudos de Coortes , Colposcopia/estatística & dados numéricos , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Cooperação do Paciente , Valor Preditivo dos Testes , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/estatística & dados numéricos , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
Acute basilar artery occlusion has a poor prognosis and best treatment has not been assessed yet; as for intra-arterial treatment, no "gold standard" exists. We evaluated a series of ten patients treated with intra-arterial combination of recombinant tissue plasminogen activator (rtPA) and abciximab. Partial/complete recanalisation was achieved in all patients and good outcome (1 month Modified Rankin Scale 0-2) in eight cases, while one patient had symptomatic intracranial haemorrhage and died. Such outcome appears significantly better if compared with the results of Basilar Artery International Cooperation Study, suggesting that intra-arterial administration of rtPA and abciximab may be a promising option in patients with acute basilar artery occlusion undergoing endovascular treatment.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Fibrinolíticos/administração & dosagem , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Ativador de Plasminogênio Tecidual/administração & dosagem , Insuficiência Vertebrobasilar/tratamento farmacológico , Abciximab , Adulto , Idoso , Feminino , Seguimentos , Humanos , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de SaúdeRESUMO
OBJECTIVES: To estimate the association between safety perception on vaccine acceptance and adoptions of risk mitigation strategies among dental health care workers (DHCWs). METHODS: A survey was emailed to DHCWs in the New Jersey area from December 2020 to January 2021. Perceived safety from regular SARS-CoV-2 testing of self, coworkers, and patients and its association with vaccine hesitancy and risk mitigation were ascertained. Risk Mitigation Strategy (RiMS) scores were computed from groupings of office measures: 1) physical distancing (reduced occupancy, traffic flow, donning of masks, minimal room crowding), 2) personal protective equipment (fitted for N95; donning N95 masks; use of face shields; coverings for head, body, and feet), and 3) environmental disinfection (suction, air filtration, ultraviolet, surface wiping). RESULTS: SARS-CoV-2 testing of dental professionals, coworkers, and patients were perceived to provide safety at 49%, 55%, and 68%, respectively. While dentists were least likely to feel safe with regular self-testing for SARS-CoV-2 (P < 0.001) as compared with hygienists and assistants, they were more willing than hygienists (P = 0.004; odds ratio, 1.79 [95% CI, 1.21 to 2.66]) and assistants (P < 0.001; odds ratio, 3.32 [95% CI, 1.93 to 5.71]) to receive the vaccine. RiMS scores ranged from 0 to 19 for 467 participants (mean [SD], 10.9 [2.9]). RiMS scores did not significantly differ among groups of DHCWs; however, mean RiMS scores were higher among those who received or planned to receive the COVID-19 vaccine than those with who did not (P = 0.004). DHCWs who felt safer with regular testing had greater RiMS scores than those who did not (11.0 vs. 10.3, P = 0.01). CONCLUSIONS: Understanding DHCWs' perception of risk and safety is crucial, as it likely influences attitudes toward testing and implementation of office risk mitigation policies. Clinical studies that correlate risk perception and RiMS with SARS-CoV-2 testing are needed to demonstrate the effectiveness of RiMS in dental care settings. KNOWLEDGE TRANSFER STATEMENT: Educators, clinicians, and policy makers can use the results of this study when improving attitudes toward testing and implementation of risk mitigation policies within dental offices, for current and future pandemics.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Teste para COVID-19 , Atenção à Saúde , PercepçãoRESUMO
Vascular contribution to cognitive impairment and dementia (VCID) is a clinical label encompassing a wide range of cognitive disorders progressing from mild to major vascular cognitive impairment (VCI), which is also defined as vascular dementia (VaD). VaD diagnosis is mainly based on clinical and imaging findings. Earlier biomarkers are needed to identify subjects at risk to develop mild VCI and VaD. In the present meta-analysis, we comprehensively evaluated the role of inflammatory biomarkers in differential diagnosis between VaD and Alzheimer's disease (AD), and assessed their prognostic value on predicting VaD incidence. We collected literature until January 31, 2021, assessing three inflammatory markers [interleukin(IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α] from blood or cerebrospinal fluid (CSF) samples. Thirteen cross-sectional and seven prospective studies were included. Blood IL-6 levels were cross-sectionally significantly higher in people with VaD compared to AD patients (SMD: 0.40, 95% CI: 0.18 to 0.62) with low heterogeneity (I2: 41%, p = 0.13). Higher IL-6 levels were also associated to higher risk of incident VaD (relative risk: 1.28, 95% CI: 1.03 to 1.59, I2: 0%). IL-6 in CSF was significantly higher in people with VaD compared to healthy subjects (SMD: 0.77, 95% CI: 0.17 to 1.37, I2: 70%), and not compared to AD patients, but due to limited evidence and high inconsistency across studies, we could not draw definite conclusion. Higher blood IL-6 levels might represent a useful biomarker able to differentiate people with VaD from those with AD and might be correlated with higher risk of future VaD.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Demência Vascular , Doença de Alzheimer/diagnóstico , Biomarcadores , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Demência Vascular/diagnóstico , Humanos , Interleucina-6 , Estudos ProspectivosRESUMO
BACKGROUND: Mammographic density (MD) is a risk factor for breast cancer (BC) development, and recurrence. However, its predictive value has been less studied. Herein, we challenged MD as a biomarker associated with response in patients treated with neoadjuvant therapy (NAT). METHODS: Data on all NAT treated BC patients prospectively collected in the registry of Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy (2009-2019) were identified. Diagnostic mammograms were used to evaluate and score MD as categorized by the Breast Imaging-Reporting and Data System (BI-RADS), which identifies 4 levels of MD in keeping with relative increase of fibro-glandular over fat tissue. Each case was classified according to the following categories a (MD < 25%), b (26-50%), c (51-75%), and d (> 75%). The association between MD and pathological complete response (pCR), i.e., absence of BC cells in surgical specimens, was analyzed in multivariable setting used logistic regression models with adjustment for clinical and pathological variables. RESULTS: A total of 442 patients were analyzed, 120 of which (27.1%) attained a pCR. BI-RADS categories a, b, c, and d accounted for 10.0%, 37.8%, 37.1% and 15.2% of cases. Corresponding pCR were 20.5%, 26.9%, 30.5%, 23.9%, respectively. At multivariable analysis, when compared to cases classified as BI-RADS a, those with denser breast showed an increased likelihood of pCR with odds ratio (OR) of 1.70, 2.79, and 1.47 for b, c and d categories, respectively (p = 0.0996), independently of age, BMI [OR underweight versus (vs) normal = 3.76], clinical nodal and tumor status (OR T1/Tx vs T4 = 3.87), molecular subtype (HER2-positive vs luminal = 10.74; triple-negative vs luminal = 8.19). In subgroup analyses, the association of MD with pCR was remarkable in triple-negative (ORs of b, c and d versus a: 1.85, 2.49 and 1.55, respectively) and HER2-positive BC cases (ORs 2.70, 3.23, and 1.16). CONCLUSION: Patients with dense breast are more likely to attain a pCR at net of other predictive factors. The potential of MD to assist decisions on BC management and as a stratification factor in neoadjuvant clinical trials should be considered.
Assuntos
Densidade da Mama , Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Mamografia , Terapia Neoadjuvante , Razão de Chances , Receptor ErbB-2RESUMO
BACKGROUND: Left atrial appendage (LAA) closure represents a novel therapeutic chance for patients with contraindications to long-term anticoagulation therapy, such as those affected by hereditary hemorrhagic telangiectasia (HHT) and atrial fibrillation (AF). Nevertheless, current experts' indications suggest the postprocedural administration of antithrombotic therapies to minimize the residual thromboembolic risk due to AF and to the need for device endothelialization. The aim of our study was to investigate the safety and effectiveness of LAA closure in preventing arterial thromboembolism in a very high-bleeding risk group, such as HHT patients, who are at risk not to tolerate even the mild postprocedural antithrombotic therapy usually recommended. METHODS: Eight HHT-affected patients with non-valvular AF, high-bleeding risk and/or known intolerance to antiplatelet and anticoagulant therapy were treated with interventional LAA occlusion with the Amplatzer™ Cardiac Plug™ and Amplatzer™ Amulet™ devices. Device implantation was successful in all patients. RESULTS: Postprocedural antiplatelet/anticoagulation therapy was attempted in seven patients: adherence to therapy exceeded 6 months only for one, while four patients suspended all antithrombotic medications within 30 days from the procedure due to an increase in bleeding frequency and/or severity and the other two discontinued treatment within 6 months; a single patient was not prescribed any antithrombotic therapy. At a medium follow-up of 22.4±14.3 months no thromboembolic episodes attributable to AF or device related thrombosis were reported. Two deaths were recorded 1231 and 783 days after the procedure which were classified as unrelated to any cerebral or cardiovascular accident. CONCLUSIONS: Our study suggests that the percutaneous LAA closure in HHT patients with AF could be safe and effective in preventing arterial systemic thromboembolism, also in the presence of reduced or absent postinterventional antithrombotic treatment. LAA occluder implantation can represent a valid and potentially life-saving alternative to lifelong anticoagulant therapy in HHT, as in other very high-bleeding risk patients.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Telangiectasia Hemorrágica Hereditária , Tromboembolia , Anticoagulantes/efeitos adversos , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/terapia , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Resultado do TratamentoRESUMO
Hereditary haemorrhagic telangiectasia (HHT) is a rare vascular multisystemic disease that leads to epistaxis, anaemia due to blood loss, and arteriovenous malformations (AVMs) in organs such as the lungs, liver and brain. HHT prevalence is estimated at 1/6000, i.e. around 85,000 European citizens, and is served by the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN). HHT treatments depend on clinical manifestations, and span multiple different medical, surgical and interventional disciplines. Separate to local treatments in the nose, in severe settings, intravenous bevacizumab has been proposed as treatment option, and the purpose of the current article is to assess the use of intravenous bevacizumab in patients with HHT in 2022 according to available data.
Assuntos
Malformações Arteriovenosas , Telangiectasia Hemorrágica Hereditária , Bevacizumab/uso terapêutico , Epistaxe/tratamento farmacológico , Humanos , Doenças Raras , Telangiectasia Hemorrágica Hereditária/tratamento farmacológicoRESUMO
OBJECTIVE: Prenatal diagnosis of urinomas has long been established with underlying obstructive uropathy generally responsible for urinary extravasation. Because urinoma formation represents a pop-off mechanism in cases of posterior urethral valves, the number of affected males greatly exceeds the number of females. Fetal urinoma has rarely been reported without obstruction and in females it has only been described as a consequence of a complicated amniocentesis. METHODS: Three cases of fetal urinoma in female fetuses without any dilatation of the urinary tract are described. Since the fetus remained healthy, they were all conservatively managed. RESULTS: Two urinomas resolved after birth and 1 exhibited significant regression. In the second case, a compressed kidney was visualized with fetal MRI. Renal function was impaired in cases 1 and 3 and absent in case 2 (the kidney was no longer visualized). CONCLUSIONS: Fetal urinomas can occur even in the absence of urinary tract obstruction and in a low-pressure system as is found in female fetuses. Fetal MRI may help both visualize the ipsilateral kidney and differentiate the mass from other conditions. In a healthy fetus, fetal urinomas can be conservatively managed, but renal function after birth is often absent or impaired. Whether or not in utero aspiration may be beneficial for the preservation of renal function remains unclear.
Assuntos
Doenças Fetais/diagnóstico , Diagnóstico Pré-Natal , Urinoma/diagnóstico , Urinoma/embriologia , Doenças Urológicas/embriologia , Adulto , Feminino , Idade Gestacional , Humanos , Imageamento por Ressonância Magnética , Masculino , Gravidez , Ultrassonografia Pré-Natal , Urinoma/terapiaRESUMO
AIM: Can the tension-free suturless technique, used in the surgical treatment of inguinal hernia, to be the gold standard for treatment of inguinal hernia? METHODS: The tension-free suturless technique is often criticized as a fundamental principle: do not have suture. The criticism stems from concern that the mesh can migrate and cause damage to important anatomical structures. We conducted a study on the mobility of prosthesis on 33 patients, by using titanium clips that we have fixed on the meshes corner, X-rays over time, done at last, a follow-up of ten years. RESULTS: The study shows that the prosthesis moves together with the anatomical space in which there is the forces present in the inguinal canal: gravity, intra-abdominal pressure, reactive force ascending gait. Across thirty-three patients have relapsed in the first six months and two recurrences in ten years, in the reconstitution of the neo-orifice, through which passes the cord. In the remaining patients the mesh were relocated upward and medially (as identified by the clips of the increase of 10-15%). CONCLUSION: Our study shows that the mesh migrates upwards and medially. Migration is more or less, depending on the patient's age and quality of its tissue. Fix the prosthesis is good practice to secure at the flag on the inguinal ligament leads to two advantages: not to frustrate the principle tension-free, since the fixed prosthesis on one side does not create moments of tension, and prevent the prosthesis returns to the opening road to relapse.