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Observationally, kilonovae are astrophysical transients powered by the radioactive decay of nuclei heavier than iron, thought to be synthesized in the merger of two compact objects1-4. Over the first few days, the kilonova evolution is dominated by a large number of radioactive isotopes contributing to the heating rate2,5. On timescales of weeks to months, its behaviour is predicted to differ depending on the ejecta composition and the merger remnant6-8. Previous work has shown that the kilonova associated with gamma-ray burst 230307A is similar to kilonova AT2017gfo (ref. 9), and mid-infrared spectra revealed an emission line at 2.15 micrometres that was attributed to tellurium. Here we report a multi-wavelength analysis, including publicly available James Webb Space Telescope data9 and our own Hubble Space Telescope data, for the same gamma-ray burst. We model its evolution up to two months after the burst and show that, at these late times, the recession of the photospheric radius and the rapidly decaying bolometric luminosity (Lbol â t-2.7±0.4, where t is time) support the recombination of lanthanide-rich ejecta as they cool.
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The prognostic insights of heart failure (HF) with mid-range (40-49%) ejection fraction (HFmrEF) are not fully elucidated. We investigated whether the six-minutes walking test (6MWT) and brain natriuretic peptide (BNP) are predictive of outcome across the spectrum of LV systolic dysfunction and whether the HFmrEF cut-off impacts the risk stratification abilities of these tests. We studied 538 outpatients, aged 70±12 years, 28% females, with stable chronic HF and EF<50%, 349 with HFmrEF and 189 with HFrEF. End-points were all-cause and cardiac death. HFrEF patients were more often male, with ischemic etiology, severe symptoms, higher BNP levels, and cardiac mortality than HFmrEF subjects. During 32 (15-46) months follow-up, 123 (23%) patients died, 95 (18%) for cardiac causes. Cut-offs of 125 pg/ml for BNP and 360 meters for 6MWT distance were associated with lower all-cause (10% vs 38%, p<0.001 and 10% vs 26%, p<0.001, respectively) and cardiac mortality (6% vs 36%, p<0.001 and 8% vs 23%, p<0.001, respectively). BNP (HR 2.144, 95%CI, 1.403-3.276) and 6MWT walked distance (HR 1.923, 95%CI, 1.195-3.096) independently predicted outcome, after adjustment for age, gender, obesity, kidney dysfunction, ischemic etiology, NYHA class, unlike the 40% LVEF threshold. Model discrimination and survival differences were significant across LVEF strata. Higher BNP levels and shorter walked distance combined identified patients (26% overall) at particularly poor prognosis in both phenotype groups. Despite differences between HFmrEF and HFrEF patients in clinical and biomarker profile, BNP levels and 6MWT walked distance retain prognostic value over the entire spectrum of LV systolic dysfunction.
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Insuficiência Cardíaca/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Teste de CaminhadaRESUMO
OBJECTIVES: To assess the clinical outcome at 1-year follow-up of real-world patients with long coronary lesions treated with the 38 mm Xience Prime (Abbott Vascular) everolimus-eluting stent (EES). BACKGROUND: Long-lesions present special challenges to the interventional cardiologists, including increased risk of restenosis, periprocedural injury, geographical miss, and stent deliverability. Indeed, results obtained with shorter stent in the treatment of simpler lesions are of limited applicability to longer stents. METHODS: Consecutive patients presenting with a long coronary lesion treated by percutaneous coronary intervention with at least one implanted 38 mm EES were enrolled in the study. Their clinical data were prospectively registered. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, nonfatal myocardial infarction (according to the Universal Definition) and target vessel revascularization. Stent thrombosis was defined according to the Academic Research Consortium criteria. RESULTS: Overall, 203 real-world patients (152 men, 68 ± 9 years) were enrolled in the P38 Study. At 1-year follow-up, 6 (3.0%) patients had died from cardiac causes, 7 (3.4%) had a nonfatal myocardial infarction and 8 (3.9%) underwent target vessel revascularization, yielding a 10.3% cumulative rate of MACE. Two patients had a stent thrombosis (one definite and one probable). No significant differences in event rates were found between patients with and without an additional stent implanted overlapping the 38 mm one. CONCLUSIONS: The use of a new-generation polymer-based 38 mm EES in a real-world population with unselected long lesions is associated with excellent procedural results and good clinical outcomes at 12-month follow-up.
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Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Polímeros , Sirolimo/análogos & derivados , Idoso , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/etiologia , Everolimo , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Prospectivos , Desenho de Prótese , Sistema de Registros , Fatores de Risco , Sirolimo/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (VÌO2) in heart failure (HF) patients. METHODSâANDâRESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakVÌO2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakVÌO2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakVÌO2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakVÌO2. A peakVÌO2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.
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Exercício Físico , Insuficiência Cardíaca , Nefropatias , Consumo de Oxigênio , Volume Sistólico , Adulto , Idoso , Doença Crônica , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Nefropatias/etiologia , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-IdadeAssuntos
Predisposição Genética para Doença , Síndromes Neoplásicas Hereditárias/diagnóstico , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Adulto , Dermoscopia , Feminino , Genótipo , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/cirurgiaRESUMO
BACKGROUND: In the setting of mismatched-hematopoietic stem cells transplantation, the detection of antibodies directed against donor-specific HLA allele(s) or antigen(s) (DSA) represents a barrier for engraftment. It is thus necessary to plan an immunosuppressive strategy, or to select an alternative donor. This prospective study aimed at evaluating the efficacy of our strategy for testing DSAs and the efficacy of the desensitization strategy (DS) employed between November 2017 and November 2020. MATERIALS AND METHODS: The anti-HLA antibody search was performed using the Luminex bead assays (Lifecode ID and LSA I/II-Immucor) and expressed as mean fluorescence intensity (MFI >1,000 positive). If the patient had DSAs and no alternative donors, a DS was employed with rituximab (day -15), 2 single volume plasmaphereses (PP; days -9 and -8), intravenous immunoglobulins (day -7) and infusion of HLA selected platelets, if persistent DSAs were directed against class I HLA. DS was scheduled with or without PP, according to the DSA MFI (>1,000 or <5,000) and FCXM (flow cytometry crossmatch). RESULTS: Twenty-two out of 126 patients (17.46%) showed anti-HLA antibodies, 5 of them DSAs (3.97% of total); 3 patients underwent DS obtaining engraftment. Female gender (p=0.033) and a history of previous pregnancies or miscarriages (p=0.009) showed a statistically significant impact on alloimmunization. Factors associated with a delayed neutrophil engraftment were patient's female gender (p=0.039), stem cell source (p=0.025), and a high HSCT-specific comorbidity index (p=0.028). None of the analyzed variables, including the DSA detection, influenced engraftment. CONCLUSIONS: Our study confirms the importance to test DSAs in mismatched-hematopoietic stem cells transplantation The DS used proved successful in removing DSAs. Prospective multicenter studies are needed to better define and validate consensus strategies on DSA management in HSCT.
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Transplante de Células-Tronco Hematopoéticas , Humanos , Feminino , Estudos Prospectivos , Doadores de Tecidos , Imunoglobulinas Intravenosas , Antígenos HLA , Rejeição de Enxerto/prevenção & controle , Teste de Histocompatibilidade , Estudos RetrospectivosRESUMO
Long-duration gamma-ray bursts (GRBs) are powerful cosmic explosions, signaling the death of massive stars. Among them, GRB 221009A is by far the brightest burst ever observed. Because of its enormous energy (Eiso ≈ 1055 erg) and proximity (z ≈ 0.15), GRB 221009A is an exceptionally rare event that pushes the limits of our theories. We present multiwavelength observations covering the first 3 months of its afterglow evolution. The x-ray brightness decays as a power law with slope ≈t-1.66, which is not consistent with standard predictions for jetted emission. We attribute this behavior to a shallow energy profile of the relativistic jet. A similar trend is observed in other energetic GRBs, suggesting that the most extreme explosions may be powered by structured jets launched by a common central engine.
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To assess the effectiveness of the search for an unrelated donor on the outcome of patients with high-risk acute lymphoblastic leukemia, we analyzed prospectively 136 patients who underwent a search for cord blood (CB) and an unrelated volunteer donor (UD) at the same time. The probability of finding a donor was 58.2%, 70.3%, and 75.7% at 3, 6, and 12 months, respectively. The median time to find a donor was 1.8 months for CB and 3.5 months for UD. Of the 99 patients with a donor, 38.4% failed to undergo the transplant because of a relapse observed at a median of 4 months from the start of the search. In univariate analysis, absence of relapse during the search (p < 0.0001) and transplant (p = 0.004) showed a positive impact on long-term survival. In multivariate analysis, relapse during the search remained the key factor affecting survival (p < 0.0001). Since an extension of the search beyond 3 months enables only a slight increase in the probability of finding a donor compared to the increased risk of relapse, the time of the search should not exceed the 3-month time point. The simultaneous search for CB and UD increases the likelihood of performing a timely transplant.
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Doadores de Sangue , Teste de Histocompatibilidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doadores não Relacionados , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sangue Fetal/citologia , Teste de Histocompatibilidade/métodos , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Recidiva , Indução de Remissão , Fatores de Risco , Análise de Sobrevida , Voluntários , Adulto JovemRESUMO
BACKGROUND: The impact of ABO incompatibility on the outcome of hematopoietic stem cell transplantation (HSCT) is still debated. We report the results of a prospective, single-center study evaluating the impact of ABO mismatch on the development of immediate and late immuno-hematological complications, and the efficacy of the protocol used at the "Sapienza" University (Rome, Italy) to manage ABO incompatibility in patients undergoing HSCT. MATERIALS AND METHODS: From January 2013 to December 2016, we prospectively analyzed all patients undergoing HSCT. Graft manipulation or desensitization strategies were used according to ABO incompatibility, donor sex and donor transfusion history. Red blood cell and platelet transfusions were given based on immunohematological features. RESULTS: From January 2013 to December 2016, 104 consecutive patients underwent HSCT from a matched related donor (29.81%), matched unrelated donor (53.58%), cord blood (1.9%) or haploidentical donor (14.42%). Forty-nine patients (47%) were ABO-identical and 55 (53%) ABO-incompatible (23 major, 25 minor, 7 bidirectional). Donor engraftment, graft failure or other complications did not differ between ABO compatible or incompatible patients. ABO incompatibility did not show a significant impact on graft-versus-host disease, overall survival or disease-free survival. Factors associated with the need for prolonged red blood cell support were ABO incompatibility (p=0.0395), HLA disparity between donor and recipient (p=0.004) and the onset of hemorrhagic cystitis (p=0.015). In multivariate analysis HLA disparity was the only statistically significant condition (p=0.004). DISCUSSION: ABO incompatibility does not represent a barrier to allogeneic HSCT. It is, however, associated with prolonged transfusion requirements. Close immunohematological monitoring, as a shared standard procedure, allows appropriate transfusion support to be provided and limits post-HSCT immuno-hematological complications.
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Transplante de Células-Tronco Hematopoéticas , Reação Transfusional , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
Polypoid Spitz nevus represents a spitzoid melanocytic neoplasm that frequently has worrying and challenging histopathological details. Distinction from polypoid melanoma may not be straightforward. Two cases of polypoid Spitz nevus with striking histopathological features were studied. One case had prolonged follow up (Case 1) and one patient had undergone sentinel lymph node biopsy (Case 2), and fluorescence in situ hybridization (FISH) analysis was also completed (both cases). Follow up and genetic analysis of three control cases of polypoid melanoma is also presented. Our clinical and genetic results suggest that both the polypoid Spitz nevi were benign. The patients are alive with no evidence of disease. FISH analysis did not show abnormalities with probes tested. This is in sharp contrast with the control cases of polypoid melanoma, wherein genomic alterations were detectable. Our data indicate that the two polypoid lesions presented here are most probably benign, despite their worrying histopathological features. More cases with long-term follow up and greater numbers of DNA probes are necessary to extend this conclusion to other ambiguous melanocytic tumors.
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DNA de Neoplasias/metabolismo , Nevo de Células Epitelioides e Fusiformes/metabolismo , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Adulto , DNA de Neoplasias/genética , Seguimentos , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/genética , Sondas de Oligonucleotídeos/química , Sondas de Oligonucleotídeos/genética , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/genéticaRESUMO
Melanoma progression is favoured by prevalence, within the micro-environment of primary cutaneous melanoma, of suppressive forces, e.g. exerted by CD4(+) CD25(+) FOXP3(+) regulatory T lymphocytes, over anti-melanoma immunity, e.g. exerted by CD8(+) cytolytic T lymphocytes. The CD27 glycoprotein is crucial because it is able to identify regulatory T cells endowed with strong suppressive ability, whilst CD8(+) T cells endowed with actual cytolytic ability become CD27(-). The present in situ quantitative immunohistochemical study, including a series of double labelling experiments and morphometrical cell analyses, shows that the vast majority of lymphocytes infiltrating primary cutaneous melanoma express CD27. Specifically, virtually the entire CD4(+) CD25(+) FOXP3(+) T subset infiltrating primary cutaneous melanoma also co-expressed CD27; CD27 was, moreover, co-expressed even by the vast majority of the CD8(+) T cells, and, conversely, effector/cytotoxic CD8(+)CD27(-) cells were very scarcely represented. The overwhelming CD27 co-expression may confer on the CD4(+)CD25(+)FOXP3(+) T subset a consistent capacity to suppress anti-melanoma immunity, whereas the too low CD8(+) CD27(-) cell proportion may presumably be insufficient to confer on the CD8(+) T subset a satisfactory anti-melanoma cytotoxic activity. We therefore propose that these CD27-discriminated pathways may trigger a functional imbalance within the microenvironment of primary cutaneous melanoma, thus favouring melanoma progression.
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Progressão da Doença , Linfócitos do Interstício Tumoral/metabolismo , Melanoma/patologia , Neoplasias Cutâneas/patologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Dermatite/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Subpopulações de Linfócitos/metabolismo , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Linfócitos T Reguladores/metabolismoRESUMO
We introduce CIGNOweb.it, a database of oncology resources for patients, the general public and healthcare professionals. It builds on the previous Italian cancer resource Azaleaweb and offers quality-evaluated content. It meets international bibliographic and technical standards such as the Open Archives Initiative (OAI) for web content interoperability and the Functional Requirements for Bibliographic Records (FRBR) for bibliographic description with respect to the different media, applications, and user needs. Database content is supplied in collaboration with non-profit associations, libraries and the network of Cancer Information Points that is currently being established all over Italy. Expert and customer evaluation and feedback are provided for in the system. The graphic layout has been painstakingly designed to be user-friendly for a non-expert public. CIGNOweb.it is multicentric and will in time offer health information outside the field of oncology. It is designed to become a multilingual tool to organize, optimize and access patient information produced in the languages of the "newer" European countries. It is hoped that CIGNOweb.it will support other European nations in enhancing the structure and organization of their own-language patient health information and will contribute towards making a common health information portal of the European Union a reality.
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Bases de Dados Factuais , Disseminação de Informação/métodos , Internet , Oncologia , Bases de Dados Factuais/normas , Bases de Dados Factuais/tendências , Humanos , ItáliaRESUMO
Elastosis perforans serpiginosa (EPS) can occur in patients with an underlying connective tissue disorder. Down syndrome, osteogenesis imperfecta, acrogeria, Ehlers-Danlos syndrome type IV, Marfan syndrome, pseudoxanthoma elasticum, Rothmund-Thomson syndrome, and scleroderma have all been associated with EPS. The clinical appearance exhibits umbilicated papules arranged in a typical serpiginous pattern, usually located around the neck. Less frequently, lesions may be seen on the face, abdomen, and extremities with a symmetrical distribution, as in our case. The clinical course may be variable with a spontaneous resolution in a few months or years, but frequently new lesions develop leading to persistence and progression of the disorder. We describe a 12-year-old girl affected by Down syndrome who presented a localized form of EPS, which involved only the extremities. Strangely, it resolved spontaneously after biopsy with no recurrence, without therapy.
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Síndrome de Down/complicações , Dermatopatias/diagnóstico , Criança , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipopituitarismo/complicações , Hipopituitarismo/tratamento farmacológico , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Joelho , Remissão Espontânea , Dermatopatias/etiologia , Dermatopatias/patologia , Tiroxina/uso terapêuticoRESUMO
We evaluated the effectiveness of natural organic surfactants such as humic acids (HA) from lignite to simultaneously wash heavy metals (HM) and polychlorobiphenyls (PCB) from a heavily contaminated industrial soil of northern Italy. Supramolecular HA promote in solution a micelle-like structure, where recalcitrant apolar organic xenobiotics are repartitioned from surfaces of soil particles during soil washing process. Concomitantly, the HA acidic functional groups enable a simultaneous complexation of HM. A single soil washing with HA removed 68 and 75% of PCB congeners for 1:1 and 10:1 solution/soil ratios, respectively. The same HA washing simultaneously and efficiently removed a cumulative average of 47% of total HM, with a maximum of 57 and 67% for Hg and Cu, respectively. We showed that washing a highly polluted soil with HA solution not only is an effective and rapid soil remediation technique but also simultaneously removes both HM and persistent organic pollutants (POP). Soil washing by humic biosurfactants is also a sustainable and eco-friendly technology, since, contrary to synthetic surfactants and solvents used in conventional washing techniques, it preserves soil biodiversity, promotes natural attenuation of unextracted POP, and accelerates further soil reclamation techniques such as bio- or phytoremediation.
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Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Itália , Metais Pesados/análise , Solo , Poluentes do Solo/análise , TensoativosRESUMO
In Operating Theatres (OT), the ventilation system plays an important role in controlling airborne contamination and reducing the risks of Surgical Site Infections (SSIs). The air cleanliness is really crucial in this field and different measurements are used in order to characterize the situation in terms of both airborne microbiological pollutants and particle size and concentration. Although the ventilation systems and airborne contamination are strictly linked, different air diffusion schemes (in particular, the Partial Unidirectional Airflow, P-UDAF, and the Mixing Airflow, MAF) and various design parameters are used, and there is still no consensus on real performance and optimum solutions. This study presents measurements procedures and results obtained during Inspection and Periodic Performance Testing (1228 observations) in a large sample of Italian OTs (175 OTs in 31 Italian hospitals) in their operative life (period from 2010 to 2018). The inspections were made after a cleaning procedure, both in "at-rest" conditions and "in operation" state. Inert and microbial contamination data (in air and on surfaces) are analyzed and commented according to four relevant air diffusion schemes and design classes. Related data on Recovery Time (RT) and personnel presence were picked up and are commented. The results confirm that the ventilation systems are able to maintain the targeted performance levels in the OT operative life. However, they attest that significant differences in real OT contamination control capabilities do exist and could be ascribed to various design choices and to different operation and maintenance practices. The study shows and confirms that the air diffusion scheme and the design airflow rate are critical factors. Beside large variations in measurements, the performance values, in terms of control of airborne particle and microbial contamination (in air and on surfaces), for P-UDAF systems are better than those that were assessed for the MAF air diffusion solution. The average performances do increase with increasing airflows, and the results offer a better insight on this relationship leading to some possible optimization.
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Microbiologia do Ar , Salas Cirúrgicas , Ventilação , Ar Condicionado , ItáliaRESUMO
Eccrine porocarcinoma is a rare skin cancer that originates from the acrosyringium of eccrine sweat glands. From the clinical point of view the differential diagnosis with other skin cancers such as basal cell carcinoma and squamous cell carcinoma it is often impossible, only the histopathologic features can lead to the definitive diagnosis. Eccrine porocarcinoma can arise from a previous poroma or de novo, it may recur after surgical excision and cause lymph node and visceral metastasis. There are no international guidelines for treatment or follow-up of patients. The aim of this work was to present a rare case of eccrine porocarcinoma of the scalp successfully treated in our clinic and to extrapolate from the international literature the main clinical and histopathological features of eccrine porocarcinoma and the various experiences regarding the types of treatment.
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Porocarcinoma Écrino/diagnóstico , Couro Cabeludo/patologia , Neoplasias das Glândulas Sudoríparas/diagnóstico , Idoso de 80 Anos ou mais , Porocarcinoma Écrino/patologia , Porocarcinoma Écrino/terapia , Humanos , Masculino , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/terapiaRESUMO
BACKGROUND: The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors-ticagrelor and prasugrel-currently recommended by the guidelines. STUDY DESIGN: DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. CONCLUSIONS: The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618837 . Registered on 1 December 2015.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem , Síndrome Coronariana Aguda/tratamento farmacológico , Esquema de Medicação , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
To date, the role of CPET (cardiopulmonary exercise testing) for risk stratification in elderly patients with HF (heart failure) with depressed or preserved ventricular function has not been evaluated. In the present study, we analysed whether CPET is useful in predicting outcome in this population. A total of 220 NYHA (New York Heart Association) class I-III patients with HF > or =70 years of age [median age, 75 years; 23% had NYHA class III; and 59% had preserved ventricular systolic function (left ventricular ejection fraction > or =40%)] performed maximal CPET (peak expiratory exchange ratio >1.00). Median peak oxygen uptake was 11.9 ml.kg(-1) of body weight.min(-1), median VE/VCO(2) slope (slope of the minute ventilation/carbon dioxide production ratio) was 33.2 and 45% had an EVR (enhanced ventilatory response) to exercise (VE/VCO(2) slope > or =34). During 19 months of follow-up, 94 patients (43%) met the combined end point of death and hospital admission for worsening HF, arrhythmias or acute coronary syndromes. By Cox multivariable analysis, a creatinine clearance of <50 ml/min {HR (hazard ratio), 1.657 [95% CI (confidence interval), 1.055-2.602]} and EVR [HR, 1.965 (95% CI, 1.195-3.231)] were the best predictors of outcome, while ventricular function had no influence on prognosis. In conclusion, in elderly patients with HF, a steeper VE/VCO(2) slope provides additional information for risk stratification across the spectrum of ventricular function and identifies a high-risk population, commonly not considered in exercise testing guidelines.
Assuntos
Teste de Esforço/métodos , Insuficiência Cardíaca/diagnóstico , Idoso , Limiar Anaeróbio , Dióxido de Carbono/fisiologia , Métodos Epidemiológicos , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Masculino , Peptídeo Natriurético Encefálico/sangue , Consumo de Oxigênio/fisiologia , Prognóstico , Troca Gasosa Pulmonar/fisiologia , Volume Sistólico/fisiologia , UltrassonografiaRESUMO
We observed 5 patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) who were unusual, in that they also exhibited features of lupus erythematosus (LE). This observation is in keeping with a recent study that reported an increased rate of autoimmune disease, including systemic lupus erythematosus (SLE), among patients with SPTCL. In all cases, attributes indicating SPTCL included an infiltrate of lymphocytes with pleomorphic nuclei involving subcutaneous lobules exhibiting a cytotoxic T-cell (CD3/CD8/betaF1) immunophenotype. Additionally, a high proliferation rate and a monoclonal T-cell receptor-gamma gene rearrangement were observed in most cases. The manifestations of LE in these patients included a spectrum of clinical and histopathological abnormalities. Clinical manifestations of LE included, in some patients, morphologic evidence of lupus erythematosus panniculitis (LEP) with subcutaneous nodules that healed with lipoatrophy on the face. In addition, all the patients exhibited serologic and/or extracutaneous end-organ abnormalities seen in patients with SLE, with 2 patients having sufficient findings to meet American College of Rheumatology criteria for SLE. Histopathological evidence of LE included vacuolar change at the dermal-epidermal interface in 3 patients, 2 of whom also showed interstitial deposition of mucin in the reticular dermis. One of these patients also had findings of LEP in the subcutaneous lobules with clusters of CD20 B cells partially arranged within germinal centers. In 2 patients in which neither the epidermis nor dermis was available for review, histopathological features of LE included, in one patient, a few small clusters of CD123 plasmacytoid dendritic cells within the adipose tissue and, in the other patient, a positive direct immunofluorescence test (lupus band) on clinically uninvolved and lesional skin. Our study shows that some patients show overlap between SPTCL and LE. We suspect that these patients may suffer from both diseases concomitantly. Furthermore, patients with LE, particularly LEP, should be monitored for evolution into SPTCL with biopsy of any subcutaneous lesion that is not typical of LEP. Additionally, screening for cutaneous LE and SLE could be considered in patients with SPTCL.