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AIM: To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC). METHOD: The Tuberous Sclerosis 2000 study is a prospective, longitudinal UK study of TSC. In phase 1, mutation type, TSC family history, tuber characteristics, presence of cardiac rhabdomyomas, seizure characteristics, and intellectual ability were assessed in 125 children affected with TSC (64 females, 61 males; median age 39mo, range 4-254). In phase 2, 88 participants (49 females, 39 males; median age 148mo, range 93-323) were assessed for neurodevelopmental outcomes including intellectual ability, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Perinatal histories of 88 participants with TSC and 80 unaffected siblings were collected retrospectively using the Obstetric Enquiry Schedule and coded with a modified Gillberg Optimality Scale to measure levels of perinatal adversity. Data were analysed using Mann-Whitney U tests, Spearman's rank correlation, and linear regression with robust standard errors. RESULTS: Children with familial TSC experienced significantly greater perinatal adversity than unaffected siblings. Perinatal adversity was higher in children with TSC-affected mothers than those with unaffected mothers. There was no significant association between perinatal adversities and neurodevelopmental outcomes after controlling for confounders. INTERPRETATION: Maternal TSC is a significant marker of elevated perinatal risk in addition to risks incurred by fetal genotype. Pregnancies complicated by maternal or fetal TSC require higher vigilance, and mechanisms underlying increased perinatal adversity require further research. WHAT THIS PAPER ADDS: Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC). Maternal TSC was associated with higher frequencies of several perinatal risk markers. Paternal TSC was not associated with higher levels of perinatal adversity. Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly. Perinatal adversities were not associated with neurodevelopmental outcomes.
Assuntos
Transtorno do Espectro Autista , Esclerose Tuberosa , Adulto , Idoso de 80 Anos ou mais , Transtorno do Espectro Autista/complicações , Criança , Feminino , Humanos , Masculino , Mutação , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/epidemiologia , Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genéticaRESUMO
OBJECTIVES: Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is typically considered to have minimal yield in gastric cancer, and so is not consistently recommended by international guidelines. However, its yield is considerable in esophageal and junctional cancer, identifying unsuspected metastases and risk-stratifying patients using metabolic nodal stage (mN). We aimed to determine the contemporary utility of routine 18F-FDG PET-CT in gastric cancer. METHODS: We routinely stage patients with non-junctional gastric cancer with PET-CT, provided initial CT does not demonstrate unequivocal metastases. We performed a retrospective study of all such patients staged in our institution from January 2007 to July 2016. Our primary endpoint was detection of incurable disease. Our secondary endpoint was disease-free survival following gastrectomy. Decision theory, economic, and predictive models were generated. RESULTS: The primary tumor was FDG-avid in 225/279 patients (80.6%). Seventy-two (25.8%) had FDG-avid nodes (resectable by D2 lymphadenectomy). This was not influenced by the Lauren classification. Unsuspected metastases were identified in 20 patients (7.2%). In 13 (4.7%), these would not have been otherwise identified. Decision theory and economic modeling supported routine PET-CT. Patients with FDG-avid nodes were more likely to have incurable disease (51.4% versus 15.5%; p < 0.001), and a worse prognosis if not: multivariate hazard ratio 2.19 (1.23-3.91; p = 0.008). Prognosis worsened with mN stage. CONCLUSIONS: PET-CT appears useful when used routinely for non-junctional gastric cancer, and should be considered in international recommendations. Any extra costs appear small and offset by avoiding futile investigations and radical treatment. mN stage identifies patients at risk of early recurrence and death. KEY POINTS: ⢠PET-CT is typically not considered useful when staging gastric cancer. We describe a retrospective study of 279 patients routinely staged with PET-CT in the absence of metastases on CT. ⢠The primary tumor was avid in 80% of patients. Twenty-five percent had resectable avid nodes. PET-CT identified previously unsuspected metastases in 7% of patients, which would likely not have been identified by conventional staging without PET-CT in 5%. These patients were much more likely to have avid nodes. ⢠Beyond avoiding futile investigations and radical treatment in this 5%, we found patients with FDG-avid nodes (metabolic nodal stage, mN) to have a worse disease-free survival after gastrectomy.
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Adenocarcinoma/secundário , Fluordesoxiglucose F18/farmacologia , Gastrectomia , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Gástricas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos/farmacologia , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida/tendências , Reino Unido/epidemiologiaRESUMO
[This corrects the article DOI: 10.1016/j.eclinm.2022.101762.].
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Background: The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population. Methods: A systematic literature search was conducted using multiple electronic databases (MEDLINE and The Cochrane Library, Scopus, CINAHL, and medRxiv) until January 2022. Studies with at least 100 people with confirmed or self-reported COVID-19 symptoms at ≥28 days following infection onset were included. Patient-reported outcome measures and clinical investigations were both assessed. Results were analysed descriptively, and meta-analyses were conducted to derive prevalence estimates. This study was pre-registered (PROSPERO-ID: CRD42021238247). Findings: 194 studies totalling 735,006 participants were included, with five studies conducted in those <18 years of age. Most studies were conducted in Europe (n = 106) or Asia (n = 49), and the time to follow-up ranged from ≥28 days to 387 days. 122 studies reported data on hospitalised patients, 18 on non-hospitalised, and 54 on hospitalised and non-hospitalised combined (mixed). On average, at least 45% of COVID-19 survivors, regardless of hospitalisation status, went on to experience at least one unresolved symptom (mean follow-up 126 days). Fatigue was frequently reported across hospitalised (28.4%; 95% CI 24.7%-32.5%), non-hospitalised (34.8%; 95% CI 17.6%-57.2%), and mixed (25.2%; 95% CI 17.7%-34.6%) cohorts. Amongst the hospitalised cohort, abnormal CT patterns/x-rays were frequently reported (45.3%; 95% CI 35.3%-55.7%), alongside ground glass opacification (41.1%; 95% CI 25.7%-58.5%), and impaired diffusion capacity for carbon monoxide (31.7%; 95% CI 25.8%-3.2%). Interpretation: Our work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at â¼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies. Funding: No funding.