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1.
J Radiol Prot ; 44(3)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39168137

RESUMO

Radiopharmacy staff members are subject to extremity radiation doses, particularly to the fingertips. Dosemeters, such as, thermoluminescent detectors (TLDs) are currently used for monitoring fingertip doses. This study aimed to use real-time dosemeters to monitor radiopharmacy extremity doses to identify specific procedural steps associated with higher fingertip doses and, subsequently, reduce dose through promotion of optimised radiation protection practises. Five radiopharmacy operators were monitored using an ED3 active extremity dosemeter with a detector attached to each tip of the index fingers. Dose rate and accumulated dose data were matched to the handled radioactivity data, of99mTc-labelled radiopharmaceuticals only, with the dose per activity (µSv MBq-1) calculated for each step. Once baseline dose data was established, an educational session identified technique adjustments toward improved radiation protection. A subsequent monitored session was undertaken with the dose data compared to quantify changes in operator doses. Radiopharmacy steps which significantly contributed to extremity doses were identified. The average accumulated dose per activity across all procedural steps for the99mTc-labelled radiopharmaceuticals for all operators before the educational session was 0.042 ± 0.045µSv MBq-1and 0.042 ± 0.041µSv MBq-1(n= 89) for non-dominant and dominant index fingertips, respectively, and 0.030 ± 0.044µSv MBq-1and 0.031 ± 0.032µSv MBq-1(n= 97), respectively, afterwards. Overall, there was an average 40.7% reduction in the total extremity dose received after the educational session. Real-time electronic extremity dosemeters for monitoring radiopharmacy extremity dose presented as a useful tool for incorporation into radiation protection education and training, towards optimised radiopharmacy technique.


Assuntos
Exposição Ocupacional , Doses de Radiação , Dosímetros de Radiação , Monitoramento de Radiação , Proteção Radiológica , Compostos Radiofarmacêuticos , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Humanos , Monitoramento de Radiação/métodos , Monitoramento de Radiação/instrumentação , Compostos Radiofarmacêuticos/análise , Dedos/efeitos da radiação , Dosimetria Termoluminescente
2.
J Intellect Disabil Res ; 68(4): 293-316, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38379511

RESUMO

BACKGROUND: Lifestyle modification interventions for adults with intellectual disabilities have had, to date, mixed effectiveness. This study aimed to understand how lifestyle modification interventions for adults with intellectual disabilities work, for whom they work and in what circumstances. METHODS: A realist evidence synthesis was conducted that incorporated input from adults with intellectual disabilities and expert researchers. Following the development of an initial programme theory based on key literature and input from people with lived experience and academics working in this field, five major databases (MEDLINE, EMBASE, CINAHL, PsycINFO and ASSIA) and clinical trial repositories were systematically searched. Data from 79 studies were synthesised to develop context, mechanism and outcome configurations (CMOCs). RESULTS: The contexts and mechanisms identified related to the ability of adults with intellectual disabilities to actively take part in the intervention, which in turn contributes to what works, for whom and in what circumstances. The included CMOCs related to support involvement, negotiating the balance between autonomy and behaviour change, fostering social connectedness and fun, accessibility and suitability of intervention strategies and delivery and broader behavioural pathways to lifestyle change. It is also essential to work with people with lived experiences when developing and evaluating interventions. CONCLUSIONS: Future lifestyle interventions research should be participatory in nature, and accessible data collection methods should also be explored as a way of including people with severe and profound intellectual disabilities in research. More emphasis should be given to the broader benefits of lifestyle change, such as opportunities for social interaction and connectedness.


Assuntos
Deficiência Intelectual , Humanos , Deficiência Intelectual/reabilitação , Adulto , Participação do Paciente
3.
J Intellect Disabil Res ; 68(5): 387-445, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38414293

RESUMO

BACKGROUND: Adults with intellectual disabilities (IDs) are susceptible to multiple health risk behaviours such as alcohol consumption, smoking, low physical activity, sedentary behaviour and poor diet. Lifestyle modification interventions can prevent or reduce negative health consequences caused by these behaviours. We aim to determine the effectiveness of lifestyle modification interventions and their components in targeting health risk behaviours in adults with IDs. METHODS: A systematic review and meta-analysis were conducted. Electronic databases, clinical trial registries, grey literature and citations of systematic reviews and included studies were searched in January 2021 (updated February 2022). Randomised controlled trials and non-randomised controlled trials targeting alcohol consumption, smoking, low physical activity, sedentary behaviours and poor diet in adults (aged ≥ 18 years) with ID were included. Meta-analysis was conducted at the intervention level (pairwise and network meta-analysis) and the component-level (component network meta-analysis). Studies were coded using Michie's 19-item theory coding scheme and 94-item behaviour change taxonomies. Risk of bias was assessed using the Cochrane Risk of Bias (ROB) Version 2 and Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I). The study involved a patient and public involvement (PPI) group, including people with lived experience, who contributed extensively by shaping the methodology, providing valuable insights in interpreting results and organising of dissemination events. RESULTS: Our literature search identified 12 180 articles, of which 80 studies with 4805 participants were included in the review. The complexity of lifestyle modification intervention was dismantled by identifying six core components that influenced outcomes. Interventions targeting single or multiple health risk behaviours could have a single or combination of multiple core-components. Interventions (2 RCTS; 4 non-RCTs; 228 participants) targeting alcohol consumption and smoking behaviour were effective but based on limited evidence. Similarly, interventions targeting low physical activity only (16 RCTs; 17 non-RCTs; 1413 participants) or multiple behaviours (low physical activity only, sedentary behaviours and poor diet) (17 RCTs; 24 non-RCTs; 3164 participants) yielded mixed effectiveness in outcomes. Most interventions targeting low physical activity only or multiple behaviours generated positive effects on various outcomes while some interventions led to no change or worsened outcomes, which could be attributed to the presence of a single core-component or a combination of similar core components in interventions. The intervention-level meta-analysis for weight management outcomes showed that none of the interventions were associated with a statistically significant change in outcomes when compared with treatment-as-usual and each other. Interventions with core-components combination of energy deficit diet, aerobic exercise and behaviour change techniques showed the highest weight loss [mean difference (MD) = -3.61, 95% credible interval (CrI) -9.68 to 1.95] and those with core-components combination dietary advice and aerobic exercise showed a weight gain (MD 0.94, 95% CrI -3.93 to 4.91). Similar findings were found with the component network meta-analysis for which additional components were identified. Most studies had a high and moderate risk of bias. Various theories and behaviour change techniques were used in intervention development and adaptation. CONCLUSION: Our systematic review is the first to comprehensively explore lifestyle modification interventions targeting a range of single and multiple health risk behaviours in adults with ID, co-produced with people with lived experience. It has practical implications for future research as it highlights the importance of mixed-methods research in understanding lifestyle modification interventions and the need for population-specific improvements in the field (e.g., tailored interventions, development of evaluation instruments or tools, use of rigorous research methodologies and comprehensive reporting frameworks). Wide dissemination of related knowledge and the involvement of PPI groups, including people with lived experience, will help future researchers design interventions that consider the unique needs, desires and abilities of people with ID.


Assuntos
Deficiência Intelectual , Humanos , Deficiência Intelectual/reabilitação , Adulto , Comportamentos de Risco à Saúde , Exercício Físico , Consumo de Bebidas Alcoólicas/terapia , Consumo de Bebidas Alcoólicas/prevenção & controle
4.
Pediatr Radiol ; 52(10): 1921-1934, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36002772

RESUMO

Congenital lung lesions are a rare group of developmental pulmonary abnormalities that are often first identified prenatally on routine second-trimester US. Congenital pulmonary airway malformation (CPAM) is the most common anomaly while others include bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and bronchial atresia. Clinical presentation is highly variable, ranging from apparent in utero resolution to severe mass effect with resultant hydrops fetalis and fetal demise. Differentiation among these lesions can be challenging because overlapping imaging features are often present. The roles of the radiologist are to identify key imaging findings that help in diagnosing congenital lung lesions and to recognize any ominous features that might require prenatal or perinatal intervention. High-resolution US and complementary rapid-acquisition fetal MRI provide valuable information necessary for lesion characterization. Postnatal US and CT angiography are helpful for lesion evaluation and for possible surgical planning. This article reviews the embryology of the lungs, the normal prenatal imaging appearance of the thorax and its contents, and the prenatal and neonatal imaging characteristics, prognosis and management of various congenital lung lesions.


Assuntos
Sequestro Broncopulmonar , Malformação Adenomatoide Cística Congênita do Pulmão , Pneumonia , Anormalidades do Sistema Respiratório , Sequestro Broncopulmonar/diagnóstico por imagem , Sequestro Broncopulmonar/patologia , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico , Malformação Adenomatoide Cística Congênita do Pulmão/patologia , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Feminino , Humanos , Recém-Nascido , Pulmão/diagnóstico por imagem , Pulmão/patologia , Gravidez , Anormalidades do Sistema Respiratório/diagnóstico por imagem , Anormalidades do Sistema Respiratório/patologia , Ultrassonografia Pré-Natal/métodos
5.
NPJ Precis Oncol ; 6(1): 13, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35233056

RESUMO

The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting.

6.
Semin Ultrasound CT MR ; 43(1): 115-129, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35164905

RESUMO

Ultrasonography (US) is the primary imaging modality for the evaluation of pediatric scrotal disease. The ability to obtain exceptional anatomical detail and testicular perfusion information without ionizing radiation makes it the essential tool for evaluating scrotal pain and palpable masses. Challenges arise in both the performance and interpretation of scrotal US in the child. Optimizing imaging parameters and recognizing key differentiating US features help minimize misinterpretations that can lead to poor patient outcomes. Key pearls and pitfalls in pediatric scrotal ultrasound methods and diagnoses are reviewed. Knowledge of what is normal for the various ages of childhood from neonate through adolescence is necessary for accurate US analysis. Imaging evaluation of key causes of the acute painful scrotum including testicular appendage torsion, epididymitis, and testicular torsion are discussed. Sonographic features for the diagnosis of benign and malignant scrotal masses, microlithiasis, and cryptorchidism are reviewed.


Assuntos
Epididimite , Doenças dos Genitais Masculinos , Torção do Cordão Espermático , Adolescente , Criança , Humanos , Recém-Nascido , Masculino , Escroto/diagnóstico por imagem , Torção do Cordão Espermático/diagnóstico por imagem , Ultrassonografia
8.
Pediatr Radiol ; 51(12): 2198-2213, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33978799

RESUMO

Pediatric applications of contrast-enhanced ultrasound (CEUS) are growing. Evaluation of the kidneys and adrenal glands in children using intravenous administration of US contrast agents, however, is still an off-label indication. Pediatric CEUS applications for kidneys are similar to those in adults, including ischemic disorders, pseudo- versus real tumors, indeterminate lesions, complex cystic lesions, complicated pyelonephritis, and abscesses. CEUS applications for evaluation of adrenal glands in children are limited, mainly focusing on the assessment and follow-up of adrenal trauma and the differentiation between an adrenal hemorrhage and a mass. This review addresses the current experience in pediatric CEUS of the kidneys and adrenal glands. By extrapolating the established knowledge for US contrast evaluations in the adult kidney to the pediatric context we can note opportunities for CEUS clinical use in children.


Assuntos
Meios de Contraste , Rim , Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Criança , Diagnóstico Diferencial , Humanos , Rim/diagnóstico por imagem , Ultrassonografia
9.
J Pediatr Surg ; 56(11): 2010-2015, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33573804

RESUMO

BACKGROUND: Ultrasonography (US) is the preferred imaging for suspected pediatric appendicitis. We hypothesize that children with elevated Body-Mass-Index-for-age percentile (BMIP) may be more likely to have an inaccurate or equivocal (IE) US. METHODS: After IRB approval, a four-year review was performed on pediatric patients evaluated for appendicitis by US. The CDC BMIP Calculator was used. IE subgroups were analyzed together for comparison against the accurate group. RESULTS: 1059 patients were included: median age 11.3 years (IQR: 8.2, 14.6), 506 (47.8%) males. Median BMIP was 65.9 (IQR: 33.9, 89.6). US accurately diagnosed 857 (80.9%), incorrectly diagnosed 76 (7.2%), 126 (11.9%) were equivocal. Overall sensitivity was 0.85, specificity 0.96, PPV 0.93 and NPV 0.91. Obese children (BMIP ≥95%), had higher odds of IE US (OR: 1.86, 95% CI: 1.28, 2.70; p = 0.001). When analyzed by sex, risk increased in obese males (OR: 2.55, 95% CI:1.53, 4.24; p = 0.0003) but normalized in obese females (OR: 1.30, 95% CI:0.74, 2.28; p = 0.35). CONCLUSIONS: An elevated BMIP may increase difficulty in visualizing the appendix, resulting in inaccurate or equivocal findings. This risk is seen specifically in obese males. If US findings do not correlate with clinical assessment in obese children with abdominal pain, further evaluation may be warranted.


Assuntos
Apendicite , Obesidade Infantil , Apendicite/diagnóstico por imagem , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Obesidade Infantil/complicações , Obesidade Infantil/diagnóstico por imagem , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia
10.
Brain Behav Immun Health ; 4: 100058, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34589844

RESUMO

Offspring adrenal function may be negatively affected in utero by maternal stressors such as microbial infection. Maternal supplementation with immunomodulatory compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) may help minimize the adverse effects of maternal stress on fetal hypothalamic-pituitary-adrenal development and improve offspring health. Presently, n-3 PUFA sources are primarily fish-based, but n-3 PUFA microalgae (AL) may be an alternative. Previously, it was determined that maternal AL or fish oil (FO) supplementation to sows, in addition to maternal stress induced by Escherichia coli lipopolysaccharide (LPS) challenge appeared to have a greater influence on the stress response of male offspring compared to females. To further elaborate on these findings, this study assessed the effects of maternal AL or FO supplementation combined with a maternal LPS challenge on adrenal gene expression in male offspring fed a nursery diet containing low-quality protein sources. Forty-eight sows were fed gestation diets starting on gestation day (gd) 75 containing either 3.12% AL, 3.1% FO, or a control diet containing 1.89% corn oil. On gd 112, half the sows in each treatment were administered 10 â€‹µg/kg LPS i.m. Piglets were weaned at 21 days of age onto a common low-quality plant-based protein diet, and one week after weaning, four piglets per sow were administered 40 â€‹µg/kg LPS i.m. Two hours later, the piglets were euthanized to obtain adrenal tissue, and total RNA was extracted to carry out transcriptome analysis using the Affymetrix GeneChip WT Plus assay and subsequent validation by real-time PCR. Analysis revealed that adrenal steroidogenesis, fatty acid metabolism and immune function were significantly influenced by maternal diet and stress. Increased expression of immune-related genes including lymphocyte antigen 96, TLR-2 and NF-κB suggests that maternal AL supplementation may increase offspring sensitivity to inflammation after weaning. Decreased expression of lymphocyte antigen 96 in male offspring from sows receiving maternal LPS challenge also suggests a possible role of maternal stress in diminishing the offspring immune response to immune stress challenge. Increased expression of the genes encoding the 11BHSD2 enzyme in offspring from sows fed FO may also reduce the magnitude of the stress response. These data provide insight to the immune and metabolic mechanisms that may be influenced by maternal diet and stress.

11.
Ann Oncol ; 30(11): 1821-1830, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504139

RESUMO

BACKGROUND: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors. METHODS: Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed. RESULTS: Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0-9; unknown in one patient). Median HER2 CN was 17 (range 7-139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% [90% confidence interval 14.2% to 39.2%]. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay. CONCLUSION: T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.


Assuntos
Ado-Trastuzumab Emtansina/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias/tratamento farmacológico , Receptor ErbB-2/genética , Ado-Trastuzumab Emtansina/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Amplificação de Genes , Humanos , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Medicina de Precisão/métodos , Intervalo Livre de Progressão , Receptor ErbB-2/antagonistas & inibidores , Estados Unidos/epidemiologia
12.
Ann Pharmacother ; 53(8): 794-800, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30803243

RESUMO

Background: Literature indicating clinically relevant benefits of an adjunctive somatostatin analog to standard therapies in nonvariceal upper-gastrointestinal bleeding (NVUGIB) is lacking. Objective: The primary objective of this study was to find the association between outcomes in patients with NVUGIB treated with octreotide and a proton pump inhibitor (PPI; combination group) compared with those treated with a PPI alone. Methods: We conducted a retrospective cohort study of adults admitted within a 5-hospital health care system with a NVUGIB treated with a PPI continuous infusion with or without an octreotide infusion. Notable exclusion criteria included varices, history of cirrhosis without endoscopy, or active gastrointestinal cancer. The primary outcome was association of combination treatment versus PPI alone with hospital length of stay (LOS). Results: A total of 180 patients were included (combination group: n = 90; PPI: n = 90). In univariate analyses, the median hospital and intensive care unit (ICU) LOS in the combination group versus PPI was 6.1 versus 4.9 days (P = 0.25) and 2.3 versus 1.9 days (P = 0.24), and rebleeding and mortality occurred in 9% versus 12% (P = 0.63) and 6.7% versus 5.6% (P = 1.00) of patients. Median units of packed red blood cells in the combination therapy versus PPI group was 3 vs 2 units (P = 0.43). After propensity score adjustment in multivariable analyses, hospital and ICU LOS, rebleeding, and mortality all remained nonsignificant. Conclusion and Relevance: Our study observed no difference in clinical end points. This suggests that octreotide provides no additional major clinical benefit in NVUGIB, and PPI therapy alone may be sufficient.


Assuntos
Hemorragia Gastrointestinal/tratamento farmacológico , Octreotida/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Quimioterapia Combinada , Feminino , Hemorragia Gastrointestinal/diagnóstico , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
13.
Vet Comp Oncol ; 16(1): 131-139, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28752538

RESUMO

Canine T-zone lymphoma (TZL) is a subtype of T-cell lymphoma characterized by unique histologic pattern and cytomorphology, immunophenotypic loss of CD45 expression, and an indolent clinical behaviour. Dogs with TZL typically present with 1 or more enlarged lymph nodes and/or lymphocytosis. We describe a novel extranodal presentation of TZL involving the tongue. Twelve dogs with tongue masses were diagnosed with lingual TZL based on a variable combination of immunophenotyping via flow cytometry, cytology, histopathology, immunohistochemistry and/or PCR for antigen receptor rearrangement (PARR) assay. Eleven dogs exhibited concurrent lymphocytosis and/or lymph node enlargement. Three cases were initially diagnosed as plasma cell tumours based on histology alone, thereby revealing a potential diagnostic challenge. Seven dogs achieved clinical remission and 4 achieved stable disease following variable treatment, consistent with the indolent nature of typical TZL involving the lymph nodes and peripheral blood. In 1 case the TZL resulted in progressive disease and failure to respond to treatment. In this case, the TZL exhibited histologic features of a higher grade neoplasm. This case series highlights a unique presentation of TZL and identifies a new differential diagnosis for lingual neoplasia. In this study, we characterize the clinical presentation, diagnostic features and patient outcomes of 12 dogs with lingual TZL.


Assuntos
Doenças do Cão/patologia , Linfoma de Células T/veterinária , Neoplasias da Língua/veterinária , Animais , Doenças do Cão/diagnóstico , Cães , Feminino , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Masculino , Língua/patologia , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/patologia
14.
Pharmacogenomics J ; 18(3): 480-486, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28786423

RESUMO

HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatment optimisation). HLA-DRB1*07:01 carriage was associated with serum alanine aminotransferase (ALT) elevations in lapatinib-treated patients (odds ratio 6.5, P=3 × 10-26, n=4482) and the risk and severity of ALT elevation for lapatinib-treated patients was higher in homozygous than heterozygous HLA-DRB1*07:01 genotype carriers. A higher ALT case incidence plus weaker HLA association observed during concurrent administration of lapatinib and taxane suggested a subset of liver injury in this combination group that was HLA-DRB1*07:01 independent. Furthermore, the incidence of ALT elevation demonstrated an expected correlation with geographic HLA-DRB1*07:01 carriage frequency. Robust ALT elevation risk estimates for HLA-DRB1*07:01 may support causality discrimination and safety risk management during the use of lapatinib combination therapy for the treatment of metastatic breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Cadeias HLA-DRB1/genética , Lapatinib/efeitos adversos , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lapatinib/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/patologia , Estadiamento de Neoplasias , Fatores de Risco , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
15.
Br J Anaesth ; 119(4): 606-615, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29121282

RESUMO

BACKGROUND: Administration of saline in renal transplantation is associated with hyperchloraemic metabolic acidosis, but the effect of normal saline (NS) on the risk of hyperkalaemia or postoperative graft function is uncertain. METHODS: We compared NS with Plasma-Lyte 148® (PL) given during surgery and for 48 h after surgery in patients undergoing deceased donor renal transplantation. The primary outcome was hyperkalaemia within 48 h after surgery. Secondary outcomes were need for hyperkalaemia treatment, change in acid-base status, and graft function. RESULTS: Twenty-five subjects were randomized to NS and 24 to PL. The incidence of hyperkalaemia in the first 48 h after surgery was higher in the NS group; 20 patients (80%) vs 12 patients (50%) in the PL group (risk difference: 0.3; 95% confidence interval: 0.05, 0.55; P=0.037). The mean (sd) peak serum potassium was NS 6.1 (0.8) compared with PL 5.4 (0.9) mmol litre-1 (P=0.009). Sixteen participants (64%) in the NS group required treatment for hyperkalaemia compared with five (21%) in the PL group (P=0.004). Participants receiving NS were more acidaemic [pH 7.32 (0.06) vs 7.39 (0.05), P=0.001] and had higher serum chloride concentrations (107 vs 101 mmol litre-1, P<0.001) at the end of surgery. No differences in the rate of delayed graft function were observed. Subjects receiving PL who did not require dialysis had a greater reduction in creatinine on day 2 (P=0.04). CONCLUSIONS: Compared with PL, participants receiving NS had a greater incidence of hyperkalaemia and hyperchloraemia and were more acidaemic. These biochemical differences were not associated with adverse clinical outcomes. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000023853.


Assuntos
Hiperpotassemia/epidemiologia , Cuidados Intraoperatórios/métodos , Transplante de Rim , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/epidemiologia , Solução Salina/farmacologia , Adulto , Idoso , Austrália/epidemiologia , Método Duplo-Cego , Feminino , Hidratação/métodos , Gluconatos/farmacologia , Humanos , Hiperpotassemia/prevenção & controle , Cloreto de Magnésio/farmacologia , Masculino , Pessoa de Meia-Idade , Cloreto de Potássio/farmacologia , Estudos Prospectivos , Acetato de Sódio/farmacologia , Cloreto de Sódio/farmacologia , Resultado do Tratamento , Adulto Jovem
16.
Radiographics ; 37(6): 1892-1908, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29019757

RESUMO

The accurate diagnosis of ovarian torsion is imperative, as loss of the ovary can have long-term consequences in terms of fertility. However, a nonspecific clinical presentation in conjunction with a highly variable imaging appearance makes the diagnosis of ovarian torsion challenging. This is complicated even further in the pediatric population, as these patients cannot always articulate their symptoms or provide an adequate medical history. Therefore, imaging has a critical role in the diagnosis of ovarian torsion in pediatric patients. Common imaging findings of ovarian torsion in the prepubescent and adolescent populations include asymmetric enlargement of the ovary, peripheral location of ovarian follicles, and midline location of the ovary. A coexistent mass within the ovary may or may not be present. Antenatal torsion also can occur and may be discovered at routine or specific imaging of the fetus or postnatal imaging of the neonate. Imaging findings in the perinatal population that may suggest torsion include a cystic mass with a fluid-debris level and a complex, multiseptated mass. This article reviews ovarian torsion throughout the pediatric years-from the fetal period through adolescence. It reviews the clinical presentation and imaging findings of this abnormality while describing the relevant anatomy, embryologic features, and pathophysiology. Ovarian torsion may be variable in appearance owing to the age and degree of torsion, which is seen early as a large ovary with peripheral follicles and later, once necrosis has ensued, as a complex cystic mass. ©RSNA, 2017.


Assuntos
Doenças Ovarianas/diagnóstico por imagem , Anormalidade Torcional/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Fatores de Risco
17.
Pediatr Radiol ; 47(9): 1031-1045, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28779189

RESUMO

Neurosonography has proven to be helpful in neonatal brain diagnosis. Premature infants are at great risk for intraventricular hemorrhage and periventricular leukomalacia, key abnormalities affecting developmental outcome. Here we discuss technique, anatomy, variants and key points for diagnosis.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Ecoencefalografia/métodos , Recém-Nascido Prematuro , Leucomalácia Periventricular/diagnóstico por imagem , Humanos , Recém-Nascido , Prognóstico
20.
J Ultrasound Med ; 36(5): 1059-1063, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28295432

RESUMO

We describe a new finding, the "excessive bright echoes" sign, for the diagnosis of hypertrophic pyloric stenosis (HPS). Portal venous gas and gastric wall pneumatosis were noted in 4 vomiting infants proven to have HPS. Portal venous gas can be concerning for ischemic bowel. Gastric wall pneumatosis can be seen in association with necrotizing enterocolitis and has been associated with increased gastric pressure from severe, usually proximal, bowel obstruction. Our HPS cases had prominent bright punctate echoes on sonography of the liver, portal vein lumen, and gastric wall. Knowledge of this excessive bright echoes sign suggests the need for sonography of the antropyloric area. One should consider HPS as a differential diagnostic possibility when the combination of bright echoes within the liver parenchyma, consistent with portal venous gas, and bright echoes in the gastric wall, consistent with gastric pneumatosis, are seen.


Assuntos
Veia Porta/diagnóstico por imagem , Estenose Pilórica Hipertrófica/diagnóstico por imagem , Ultrassonografia/métodos , Diagnóstico Diferencial , Humanos , Lactente , Recém-Nascido , Masculino , Veia Porta/fisiopatologia , Estenose Pilórica Hipertrófica/fisiopatologia , Estenose Pilórica Hipertrófica/cirurgia , Piloro/diagnóstico por imagem , Piloro/fisiopatologia , Piloro/cirurgia , Estômago/diagnóstico por imagem , Estômago/fisiopatologia
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