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1.
World J Surg Oncol ; 22(1): 41, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38303008

RESUMO

BACKGROUND: Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial studies. Hence, this study aimed to comprehensively identify and summarize the prognostic factors associated with IMA. METHODS: A comprehensive search of relevant literature was conducted in the PubMed, Embase, Cochrane, and Web of Science databases from their inception until June 2023. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) of overall survival (OS) and/or disease-free survival (DFS) were obtained to evaluate potential prognostic factors. RESULTS: A total of 1062 patients from 11 studies were included. In univariate analysis, we found that gender, age, TNM stage, smoking history, lymph node metastasis, pleural metastasis, spread through air spaces (STAS), tumor size, pathological grade, computed tomography (CT) findings of consolidative-type morphology, pneumonia type, and well-defined heterogeneous ground-glass opacity (GGO) were risk factors for IMA, and spiculated margin sign was a protective factor. In multivariate analysis, smoking history, lymph node metastasis, pathological grade, STAS, tumor size, and pneumonia type sign were found to be risk factors. There was not enough evidence that epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) mutations, CT signs of lobulated margin, and air bronchogram were related to the prognosis for IMA. CONCLUSION: In this study, we comprehensively analyzed prognostic factors for invasive mucinous adenocarcinoma of the lung in univariate and multivariate analyses of OS and/or DFS. Finally, 12 risk factors and 1 protective factor were identified. These findings may help guide the clinical management of patients with invasive mucinous adenocarcinoma of the lung.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma Mucinoso , Neoplasias Pulmonares , Pneumonia , Humanos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/patologia , Pulmão/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática , Estadiamento de Neoplasias , Pneumonia/patologia , Prognóstico , Estudos Retrospectivos , Masculino , Feminino
2.
Am J Forensic Med Pathol ; 45(1): 20-25, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305298

RESUMO

ABSTRACT: A study was undertaken at Forensic Science SA, Adelaide, South Australia, of all cases of homicide (January 2003-December 2022) where the victims' bodies had been concealed. Three hundred twenty-six homicides were identified, which included 27 cases where bodies had been deliberately hidden (8%) (age range, 2-82 years; ave, 34.9 years; M:F = 1.5:1). Deaths were due to blunt force trauma (n = 11), sharp force trauma (n = 4), asphyxia (n = 4), gunshot wound (n = 2), and a combination of drowning and asphyxia (n = 1). In 5 cases, the cause of death was not determinable. The methods of concealment (which were sometimes overlapping) included the following: dumping at a hidden/isolated location (n = 8), burial (n = 7), dismembering (n = 3), incinerating (n = 3), hiding in a wheeled garbage bin (n = 2), disposing in garbage resulting in the remains being located at waste disposal facilities (n = 2), hiding in a shed (n = 1), under a concrete floor (n = 1), in a suitcase (n = 1), in a river (n = 1), in a mine shaft (n = 1), and in a septic tank (n = 1). Although it has been asserted that concealed homicides are rarely encountered in forensic practice, the current study has demonstrated that the bodies in at least 8% of victims of homicide in South Australia have undergone some form of concealment.


Assuntos
Afogamento , Ferimentos por Arma de Fogo , Ferimentos não Penetrantes , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Distribuição por Idade , Asfixia , Afogamento/diagnóstico , Homicídio , Estudos Retrospectivos , Masculino , Feminino
3.
Eur Rev Med Pharmacol Sci ; 28(2): 534-541, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38305599

RESUMO

OBJECTIVE: Single-organ cutaneous small-vessel vasculitis (SoCSVV) is an inflammatory skin-limited vascular disease affecting the dermal and/or hypodermal vessel wall. Pathogenetically, idiopathic forms are described, as well as the induction from different triggers, such as infections, drugs, and vaccines. Following the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic outbreak, cases of cutaneous vasculitis induced by both COVID-19 and COVID-19 vaccinations have been reported in literature. The aim of this study is to provide the most recent evidence on new etiological factors, clinical features, and management of the SoCSVV. PATIENTS AND METHODS: We included 42 patients (22 women, 20 men) with SoCSVV and no systemic involvement in the study. The mean age of the patients was 57.3 years. Palpable purpura was the most frequent clinical manifestation (38 cases-90.4%). All patients were diagnosed with leukocytoclastic vasculitis by skin biopsy. RESULTS: The etiological factors were as follows: idiopathic in 9 (21%) patients, drug-related in 19 (45%) patients, COVID-19 infection-related in 5 (12%) patients, post-COVID-19 vaccination in 5 (12%) patients, paraneoplastic in 2 (5%) patients, and drug and infection and sepsis in 1 patient each. Among the drug-related cases, 16 (84%) were antibiotic-related, and most of them were beta-lactam antibiotics. Eosinophilia was present in skin biopsy in the cases related to vaccination and drugs, while intense necrosis and vascular damage in the skin were observed in the cases related to COVID-19 infection, unlike the others. A rapid resolution was observed with the cessation of drugs and short-term steroid treatment for the precipitating factors. CONCLUSIONS: SoCSVV is usually associated with drugs, preceding infections, and vaccines. COVID-19 infection and COVID-19 vaccinations have been reported as new etiological factors. SoCSVV indicates that the disease seems to be a mild, self-limiting illness with a good clinical result.


Assuntos
COVID-19 , Dermatopatias Vasculares , Vasculite Leucocitoclástica Cutânea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Pele/patologia , Dermatopatias Vasculares/diagnóstico , Dermatopatias Vasculares/etiologia , Dermatopatias Vasculares/patologia , Vasculite Leucocitoclástica Cutânea/diagnóstico , Vasculite Leucocitoclástica Cutânea/etiologia , Vasculite Leucocitoclástica Cutânea/patologia
4.
Br J Radiol ; 97(1154): 469-476, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308037

RESUMO

OBJECTIVES: To evaluate radiation doses for all low-dose CT scans performed during the first year of a lung screening trial. METHODS: For all lung screening scans that were performed using a CT protocol that delivered image quality meeting the RSNA QIBA criteria, radiation dose metrics, participant height, weight, gender, and age were recorded. Values of volume CT dose index (CTDIvol) and dose length product (DLP) were evaluated as a function of weight in order to assess the performance of the scan protocol across the participant cohort. Calculated effective doses were used to establish the additional lifetime attributable cancer risks arising from trial scans. RESULTS: Median values of CTDIvol, DLP, and effective dose (IQR) from the 3521 scans were 1.1 mGy (0.70), 42.4 mGycm (24.9), and 1.15 mSv (0.67), whilst for 60-80kg participants the values were 1.0 mGy (0.30), 35.8 mGycm (11.4), and 0.97 mSv (0.31). A statistically significant correlation between CTDIvol and weight was identified for males (r = 0.9123, P < .001) and females (r = 0.9052, P < .001), however, the effect of gender on CTDIvol was not statistically significant (P = .2328) despite notable differences existing at the extremes of the weight range. The additional lifetime attributable cancer risks from a single scan were in the range 0.001%-0.006%. CONCLUSIONS: Low radiation doses can be achieved across a typical lung screening cohort using scan protocols that have been shown to deliver high levels of image quality. The observed dose levels may be considered as typical values for lung screening scans on similar types of scanners for an equivalent participant cohort. ADVANCES IN KNOWLEDGE: Presentation of typical radiation dose levels for CT lung screening examinations in a large UK trial. Effective radiation doses can be of the order of 1 mSv for standard sized participants. Lifetime attributable cancer risks resulting from a single low-dose CT scan did not exceed 0.006%.


Assuntos
Neoplasias Pulmonares , Pulmão , Feminino , Humanos , Masculino , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Doses de Radiação , Tórax , Tomografia Computadorizada por Raios X/métodos , Ensaios Clínicos como Assunto
5.
BMC Ophthalmol ; 24(1): 52, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308203

RESUMO

BACKGROUND: To investigate whether iris blood flow and iris thickness at the iris smooth muscle region affect the pupil diameter at rest and after drug-induced mydriasis in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: T1DM patients and healthy children were recruited from the SCADE cohort. T2DM patients and healthy adults were recruited from patients undergoing cataract surgery at Shanghai General Hospital. Iris vessel density, pupil diameter (PD) and iris thickness were measured in both the resting and drug-induced mydriasis states. Iris vessel density was measured by optical coherence tomography angiography (OCTA), PD was measured by a pupilometer, and iris thickness at the iris smooth muscle regions were measured using anterior segment optical coherence tomography (AS-OCT). RESULTS: The study included 34 pediatric T1DM patients and 50 adult T2DM patients, both groups without diabetic retinopathy, and age-sex-matched healthy controls. At baseline, T1DM children and healthy children showed no differences in iris blood flow, iris thickness, or PD. However, the adult T2DM group exhibited higher vessel density at the pupil margin, thinner iris thickness at the iris dilator region, and smaller PD compared to healthy adults, with these differences being statistically significant (P < 0.05). After pupil dilation, there were no changes in iris blood flow and PD in the T1DM group compared to healthy children, whereas the T2DM group showed a significantly smaller PD compared to healthy adults. Multivariate regression analysis revealed that in the T2DM group, glycated hemoglobin was an independent factor of PD after dilation (ß=-0.490, p = 0.031), with no such factors identified in the T1DM group. CONCLUSION: The insufficiently dilated pupil diameter after drug-induced mydriasis is correlated to the level of glycated hemoglobin among T2DM patients. TRIAL REGISTRATION: The registration number on the clinical trial website was NCT03631108.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Midríase , Adulto , Criança , Humanos , China , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Dilatação Patológica , Hemoglobinas Glicadas , Pressão Intraocular , Iris , Midríase/induzido quimicamente , Pupila/fisiologia , Tomografia de Coerência Óptica , Masculino , Feminino
6.
BMC Public Health ; 24(1): 355, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308292

RESUMO

BACKGROUND: Healthy Together Victoria (HTV) was a Victorian Government initiative that sought to reduce the prevalence of overweight and obesity through targeting chronic disease risk factors including physical activity, poor diet quality, smoking, and harmful alcohol use. The intervention involved a boosted workforce of > 170 local-level staff in 12 communities; employed to deliver system activation around health and wellbeing for individuals, families and communities. A cluster randomised trial (CRT) of a systems thinking approach to obesity prevention was embedded within HTV. We present the two-year changes in overweight and obesity and associated behaviours among secondary school students across Victoria, Australia. METHODS: Twenty-three geographically bounded areas were randomised to intervention (12 communities) or comparison (11 communities). Randomly selected secondary schools within each community were invited to participate in the trial in 2014 and 2016. Students in Grade 8 (aged approximately 13-15 years) and Grade 10 (aged approximately 15-16 years) at participating schools were recruited using an opt-out approach across July-September 2014 and 2016. Primary outcomes were body mass index (BMI) and waist circumference. Secondary outcomes were physical activity, sedentary behaviour, diet quality, health-related quality of life, and depressive symptoms. Linear mixed models were fit to estimate the intervention effect adjusting for child/school characteristics. RESULTS: There were 4242 intervention children and 2999 control children in the final analysis. For boys, the two-year change showed improvement in intervention versus control for waist circumference (difference in change: - 2.5 cm; 95% confidence interval [CI]: - 4.6, - 0.5) and consumption of sugar-sweetened beverages per day (< 1 serve: 8.5 percentage points; 95% CI: 0.6, 16.5). For girls, there were no statistically significant differences between conditions. CONCLUSIONS: HTV seemed to produce favourable changes in waist circumference and sugar-sweetened beverage consumption for boys, however, no effect on BMI was observed. Although the HTV intervention was cut short, and the period between data collection points was relatively short, the changes observed in HTV contribute to the growing evidence of whole-of-community interventions targeting childhood obesity. TRIAL REGISTRATION: This trial is unregistered. The intervention itself was a policy setting delivered by government and our role was the collection of data to evaluate the effect of this natural experiment. That is, this study was not a trial from the classical point of view and we were not responsible for the intervention.


Assuntos
Obesidade Pediátrica , Feminino , Humanos , Masculino , Sobrepeso/prevenção & controle , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/prevenção & controle , Qualidade de Vida , Instituições Acadêmicas , Estudantes , Análise de Sistemas , Vitória/epidemiologia , Adolescente
7.
Alzheimers Res Ther ; 16(1): 25, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308344

RESUMO

BACKGROUND: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial. METHODS: Data from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status. RESULTS: Increased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status. CONCLUSION: These results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.


Assuntos
Doença de Alzheimer , Transtornos Cerebrovasculares , Disfunção Cognitiva , Substância Branca , Idoso , Feminino , Humanos , Masculino , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/patologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/patologia , Cognição , Disfunção Cognitiva/patologia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Substância Branca/patologia , Ensaios Clínicos como Assunto
8.
Rinsho Ketsueki ; 65(1): 18-23, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311384

RESUMO

Aggressive types of adult T-cell leukemia-lymphoma (ATL), namely, the acute type, lymphoma type, and chronic type with poor prognostic factors, have a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (HSCT) may improve prognosis, relapse is common. In June 2021, tucidinostat was approved for relapsed or refractory ATL in Japan. We report a case of a 62-year-old man with relapsed ATL after allogeneic HSCT. In March 2017, he was diagnosed with ATL (acute type) and received two courses of mLSG-15 therapy. ATL cells reappeared in his peripheral blood, so he underwent allogeneic bone marrow transplantation in September 2017. In June 2021, his soluble interleukin-2 receptor (sIL-2R) level increased, and he began experiencing sensory abnormalities in his face and legs. In September, he developed respiratory failure and was diagnosed with relapse of ATL. He was again treated with mLSG-15. His sIL-2R normalized and the sensory abnormalities decreased, but sIL-2R rose again in February 2022. After tucidinostat treatment was initiated, sIL-2R normalized and the patient's general condition improved. Tucidinostat shows promise as an effective treatment for ATL that has relapsed after allogeneic HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva , Receptores de Interleucina-2
9.
Rinsho Ketsueki ; 65(1): 41-46, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311388

RESUMO

The patient was a 21-year-old man who had been diagnosed with Crohn's disease and received infliximab and azathioprine six years earlier. He was admitted with fever and fatigue. Peripheral blood examination showed LDH 2,473 U/l and thrombocytopenia, and contrast-enhanced computed tomography (CT) showed hepatosplenomegaly. Bone marrow biopsy and liver biopsy showed CD4+CD56+TCRγδ+CD8- atypical cells, leading to a diagnosis of hepatosplenic T-cell lymphoma (HSTCL). The patient was refractory to CHOP and DA-EPOCH, and therefore received cord blood transplantation with myeloablative conditioning. CT showed reduced in hepatosplenomegaly and peripheral blood examination showed LDH 165 U/l and plt 180,000/µl, so the patient was discharged on day117. HSTCL is a tumor of immature γδT cells with a Vδ1 mutation in the spleen, and immunodeficiency has been implicated in its pathogenesis. Patients with inflammatory bowel disease treated with azathioprine are known to have an increased risk of lymphoproliferative disease. In this case, use of immunosuppressive drugs for Crohn's disease may have caused malignant transformation of γδ cells in the intestinal epithelium. Although the patient was refractory to chemotherapy, he was able to achieve remission with early cord blood transplantation and long-term survival is expected.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença de Crohn , Neoplasias Hepáticas , Linfoma de Células T , Neoplasias Esplênicas , Masculino , Humanos , Adulto Jovem , Adulto , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Azatioprina/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Imunossupressores/uso terapêutico , Linfoma de Células T/etiologia , Linfoma de Células T/terapia , Linfoma de Células T/diagnóstico , Neoplasias Esplênicas/etiologia
10.
Rinsho Ketsueki ; 65(1): 47-51, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311389

RESUMO

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has a poor prognosis. Nelarabine has recently shown relatively good results in patients with relapsed or refractory T-ALL/LBL, but requires careful monitoring for neurological complications. A 50-year-old man with early recurrence of T-LBL after allogenic peripheral blood stem cell transplantation received nelarabine monotherapy and achieved complete remission after 1 cycle. He then received umbilical cord blood transplantation, and experienced sustained disturbance of consciousness. He later died of multiple organ failure, and autopsy suggested that nelarabine-induced leukoencephalopathy had caused the disturbance of consciousness. This case suggests that physicians should carefully monitor patients for neurological complications and consider imaging follow-up and consultation with a neurologist.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Linfoma de Células T , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Masculino , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Estado de Consciência , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
11.
Rinsho Ketsueki ; 65(1): 1-6, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311382

RESUMO

A 66-year-old man was diagnosed with symptomatic IgG-λ multiple myeloma based on the presence of anemia, thrombocytopenia, renal dysfunction, and a tumor on the right sixth rib. Bone marrow aspiration yielded a dry tap and biopsy revealed myelofibrosis grade 2. Partial response was achieved with Bd (bortezomib and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone). The patient received autologous stem cell transplantation, but the myeloma relapsed 3 months later, and liver tumors developed as well. DKd (daratumumab, carfilzomib, and dexamethasone) was administered, but the patient died due to disease progression. Autopsy revealed multiple extramedullary lesions in the liver, spleen, gallbladder, adrenal glands, kidneys, and multiple lymph nodes, as well as ascites.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Mielofibrose Primária , Masculino , Humanos , Idoso , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Bortezomib/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/terapia , Dexametasona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia , Transplante Autólogo
12.
Rinsho Ketsueki ; 65(1): 13-17, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311383

RESUMO

A 24-year-old man was found to have an ileocecal ulcer by colonoscopy. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) with diffuse positive reaction of Epstein-Barr encoding region (EBER) by in situ hybridization was made based on analysis of the specimen. Acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis jirovecii pneumonia was also diagnosed. As no other significant lymphomatous lesions were identified by further examination, a clinical diagnosis of EBV-positive mucocutaneous ulcer (EBVMCU) was made. Rather than performing systemic chemotherapy, the lesion was closely monitored and antiretroviral therapy (ART) for AIDS was started with the hope of treating the lesion through immune reconstitution. The lesion had completely disappeared by day 79 after starting ART, and has not recurred for over 3 years. EBVMCU is known to develop secondary to various immunosuppressive states including AIDS. Here we report a rare case of EBVMCU detected at diagnosis of AIDS that entered complete remission after immune reconstitution by ART.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por Vírus Epstein-Barr , Infecções por HIV , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Adulto Jovem , Adulto , Úlcera/etiologia , Herpesvirus Humano 4 , Remissão Espontânea , Síndrome de Imunodeficiência Adquirida/complicações , Recidiva Local de Neoplasia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico
13.
Rinsho Ketsueki ; 65(1): 7-12, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38311391

RESUMO

An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Falência Renal Crônica , Transplante de Rim , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Adolescente , Cromossomo Filadélfia , Transplante Homólogo , Transplante de Medula Óssea , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
14.
Psychother Psychosom Med Psychol ; 74(2): 85-93, 2024 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-38316437

RESUMO

OBJECTIVE: To date the relationships between rape myths and other psychological constructs within males who have committed rape have not been explored sufficiently. Considered as a risk factor for the perpetration of rape it seems significant to examine their association to individual behavioral and personality characteristics more in detail. METHODS: Therefore, we analyzed the relations between self-reported rape myth acceptance and the self-evaluation of aggressiveness, assertiveness, hypersexuality, social anxiety, sexual anxiety, SCID personality characteristics and the external assessment of psychopathy within a sample of N=569 males convicted of rape. RESULTS: The results showed significant correlations with all constructs except sexual anxiety, antisocial personality and psychopathy. Furthermore, findings indicated the assignment of the relevant variables to two principal components: rape myths, aggressiveness, hypersexuality, paranoid and narcissistic personality (K1) on the one hand and psychopathy and antisocial personality (K2) on the other hand. DISCUSSION: Following the results, rape myths are contextualized within the investigated psychological constructs and their potential differentiation from psychopathy and antisocial personality is discussed.


Assuntos
Estupro , Masculino , Humanos , Estupro/psicologia , Comportamento Sexual , Fatores de Risco , Personalidade
15.
NEJM Evid ; 3(1): EVIDoa2300171, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38320513

RESUMO

Targeted Inhibition of CYP11A1 in Prostate CancerIn this single-arm, multicenter, combined phase 1 and phase 2 study, patients with metastatic prostate adenocarcinoma with progression on prior androgen receptor pathway inhibitors and taxane-based chemotherapy were treated with ODM-208. A decrease in prostate-specific antigen levels of 50% or more occurred in 16/42 (38.1%) and 24/45 (53.3%) in phase 1 and 2 respectively. Responses mainly occurred in patients with androgen receptor mutations. Adrenal insufficiency was the dose-limiting toxicity.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Enzima de Clivagem da Cadeia Lateral do Colesterol , Antígeno Prostático Específico/uso terapêutico , Resultado do Tratamento , Antagonistas de Receptores de Andrógenos/farmacologia
16.
FASEB J ; 38(3): e23447, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38329326

RESUMO

We aimed to analyze sex-related differences in galectin-1 (Gal-1), a ß-galactoside-binding lectin, in aortic stenosis (AS) and its association with the inflammatory and fibrocalcific progression of AS. Gal-1 was determined in serum and aortic valves (AVs) from control and AS donors by western blot and immunohistochemistry. Differences were validated by ELISA and qPCR in AS samples. In vitro experiments were conducted in primary cultured valve interstitial cells (VICs). Serum Gal-1 was not different neither between control and AS nor between men and women. There was no association between circulating and valvular Gal-1 levels. The expression of Gal-1 in stenotic AVs was higher in men than women, even after adjusting for confounding factors, and was associated with inflammation, oxidative stress, extracellular matrix remodeling, fibrosis, and osteogenesis. Gal-1 (LGALS1) mRNA was enhanced within fibrocalcific areas of stenotic AVs, especially in men. Secretion of Gal-1 was up-regulated over a time course of 2, 4, and 8 days in men's calcifying VICs, only peaking at day 4 in women's VICs. In vitro, Gal-1 was associated with similar mechanisms to those in our clinical cohort. ß-estradiol significantly up-regulated the activity of an LGALS1 promoter vector and the secretion of Gal-1, only in women's VICs. Supplementation with rGal-1 prevented the effects elicited by calcific challenge including the metabolic shift to glycolysis. In conclusion, Gal-1 is up-regulated in stenotic AVs and VICs from men in association with inflammation, oxidative stress, matrix remodeling, and osteogenesis. Estrogens can regulate Gal-1 expression with potential implications in post-menopause women. Exogenous rGal-1 can diminish calcific phenotypes in both women and men.


Assuntos
Estenose da Valva Aórtica , Calcinose , Galectina 1 , Feminino , Humanos , Masculino , Estenose da Valva Aórtica/metabolismo , Células Cultivadas , Galectina 1/genética , Galectina 1/metabolismo , Inflamação/metabolismo
17.
Radiol Cardiothorac Imaging ; 6(1): e230250, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38329405

RESUMO

Purpose To assess periaortic adipose tissue attenuation at CT angiography in different abdominal aortic aneurysm disease states. Materials and Methods In a retrospective observational study from January 2018 to December 2022, periaortic adipose tissue attenuation was assessed at CT angiography in patients with asymptomatic or symptomatic (including rupture) abdominal aortic aneurysms and controls without aneurysms. Adipose tissue attenuation was measured using semiautomated software in periaortic aneurysmal and nonaneurysmal segments of the abdominal aorta and in subcutaneous and visceral adipose tissue. Periaortic adipose tissue attenuation values between the three groups were assessed using Student t tests and Wilcoxon rank sum tests followed by a multiregression model. Results Eighty-eight individuals (median age, 70 years [IQR, 65-78]; 78 male and 10 female patients) were included: 70 patients with abdominal aortic aneurysms (40 asymptomatic and 30 symptomatic, including 24 with rupture) and 18 controls. There was no evidence of differences in the periaortic adipose tissue attenuation in the aneurysmal segment in asymptomatic patients versus controls (-81.44 HU ± 7 [SD] vs -83.27 HU ± 9; P = .43) and attenuation in nonaneurysmal segments between asymptomatic patients versus controls (-75.43 HU ± 8 vs -78.81 HU ± 6; P = .08). However, symptomatic patients demonstrated higher periaortic adipose tissue attenuation in both aneurysmal (-57.85 HU ± 7; P < .0001) and nonaneurysmal segments (-58.16 HU ± 8; P < .0001) when compared with the other two groups. Conclusion Periaortic adipose tissue CT attenuation was not increased in stable abdominal aortic aneurysm disease. There was a generalized increase in attenuation in patients with symptomatic disease, likely reflecting the systemic consequences of acute rupture. Keywords: Abdominal Aortic Aneurysm, Periaortic Adipose Tissue Attenuation, CT Angiography ClinicalTrials.gov registration no. NCT02229006 © RSNA, 2024.


Assuntos
Aneurisma da Aorta Abdominal , Idoso , Feminino , Humanos , Masculino , Tecido Adiposo/diagnóstico por imagem , Adiposidade , Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Obesidade , Estudos Retrospectivos
18.
Pediatrics ; 153(Suppl 2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300010

RESUMO

Using multiple metrics, the diversity of the pediatric population in the United States is increasing. However, recent data suggest significant disparities in both the prevalence and management of child health conditions cared for by pediatric subspecialists. These inequities occur across multiple dimensions of diversity, including race and ethnicity, country of origin, socioeconomic status, sex and gender, and disability. Research also suggests that attending to diversity, equity, and inclusion in the medical workforce may positively affect health outcomes. High-quality pediatric subspecialty care thus requires knowledge of these data, attention to the effects of social drivers, including racism and discrimination, on health and wellbeing, and interventions to improve pediatric health equity through educational, practice, policy, and research innovations. In this article, we review data on the diversity of the pediatric population and pediatric subspecialty workforce, suggest potential strengths, weaknesses, opportunities, and threats of current diversity, equity, and inclusion initiatives in academic pediatrics, and provide recommendations across 4 domains: education and training, practice, policy, and future research. The ultimate goal of pediatrics is to improve health equity for all infants, children, adolescents, and young adults cared for in the United States by pediatric subspecialists.


Assuntos
Saúde da Criança , Diversidade, Equidade, Inclusão , Adolescente , Lactente , Feminino , Masculino , Adulto Jovem , Humanos , Criança , Escolaridade , Benchmarking , Recursos Humanos
19.
Lancet Haematol ; 11(2): e101-e113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38302221

RESUMO

BACKGROUND: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma. METHODS: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups. Induction therapy consisted of four 21-day cycles of RVd (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11]; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1-2) or, RVd induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, and on days 1 and 11 for cycles 3-4; E-RVd). Autologous haematopoietic stem-cell transplantation was followed by two 21-day cycles of either RVd consolidation (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus RVd consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15) followed by maintenance with either lenalidomide (10 mg orally on days 1-28 for cycles 1-3; thereafter, up to 15 mg orally on days 1-28; RVd/R or E-RVd/R group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1-6, and on day 1 for cycles 7-26; RVd/E-R or E-RVd/E-R group) for 2 years. The primary endpoint was progression-free survival analysed in a modified intention-to-treat (ITT) population. Safety was analysed in all patients who received at least one dose of trial medication. This trial is registered with ClinicalTrials.gov, NCT02495922, and is completed. FINDINGS: Between June 29, 2015, and on Sept 11, 2017, 564 patients were included in the trial. The modified ITT population comprised 559 (243 [43%] females and 316 [57%] males) patients and the safety population 555 patients. After a median follow-up of 49·8 months (IQR 43·7-55·5), there was no difference in progression-free survival between the four treatment groups (adjusted log-rank p value, p=0·86), and 3-year progression-free survival rates were 69% (95% CI 61-77), 69% (61-76), 66% (58-74), and 67% (59-75) for patients treated with RVd/R, RVd/E-R, E-RVd/R, and E-RVd/E-R, respectively. Infections (grade 3 or worse) were the most frequently observed adverse event in all treatment groups (28 [20%] of 137 for RVd/R; 32 [23%] of 138 for RVd/E-R; 35 [25%] of 138 for E-RVd/R; and 48 [34%] of 142 for E-RVd/E-R). Serious adverse events (grade 3 or worse) were observed in 68 (48%) of 142 participants in the E-RVd/E-R group, 53 (39%) of 137 in the RVd/R, 53 (38%) of 138 in the RVd/E-R, and 50 (36%) of 138 in the E-RVd/R (36%) group. There were nine treatment-related deaths during the study. Two deaths (one sepsis and one toxic colitis) in the RVd/R group were considered lenalidomide-related. One death in the RVd/E-R group due to meningoencephalitis was considered lenalidomide and elotuzumab-related. Four deaths (one pulmonary embolism, one septic shock, one atypical pneumonia, and one cardiovascular failure) in the E-RVd/R group and two deaths (one sepsis and one pneumonia and pulmonary fibrosis) in the E-RVd/E-R group were considered related to lenalidomide or elotuzumab, or both. INTERPRETATION: Addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed multiple myeloma did not provide clinical benefit. Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory multiple myeloma. FUNDING: Bristol Myers Squibb/Celgene and Chugai.


Assuntos
Anticorpos Monoclonais Humanizados , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Pneumonia , Sepse , Adulto , Masculino , Feminino , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Lenalidomida/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo , Pneumonia/etiologia , Sepse/induzido quimicamente , Sepse/tratamento farmacológico
20.
Nat Commun ; 15(1): 1124, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321058

RESUMO

The recovery of mitochondrial quality control (MQC) may bring innovative solutions for neuroprotection, while imposing a significant challenge given the need of holistic approaches to restore mitochondrial dynamics (fusion/fission) and turnover (mitophagy and biogenesis). In diabetic retinopathy, this is compounded by our lack of understanding of human retinal neurodegeneration, but also how MQC processes interact during disease progression. Here, we show that mitochondria hyperfusion is characteristic of retinal neurodegeneration in human and murine diabetes, blunting the homeostatic turnover of mitochondria and causing metabolic and neuro-inflammatory stress. By mimicking this mitochondrial remodelling in vitro, we ascertain that N6-furfuryladenosine enhances mitochondrial turnover and bioenergetics by relaxing hyperfusion in a controlled fashion. Oral administration of N6-furfuryladenosine enhances mitochondrial turnover in the diabetic mouse retina (Ins2Akita males), improving clinical correlates and conferring neuroprotection regardless of glycaemic status. Our findings provide translational insights for neuroprotection in the diabetic retina through the holistic recovery of MQC.


Assuntos
Adenosina , Diabetes Mellitus Experimental , Cinetina , Dinâmica Mitocondrial , Masculino , Camundongos , Humanos , Animais , Neuroproteção , Diabetes Mellitus Experimental/metabolismo , Retina/metabolismo , Mitocôndrias/metabolismo
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