RESUMO
Bile duct regeneration is hypothesised to prevent biliary strictures, a leading cause of morbidity after liver transplantation. Assessing the capacity for biliary regeneration may identify grafts as suitable for transplantation that are currently declined, but has been unfeasible until now. This study used Long-Term Ex-Situ Normothermic Machine Perfusion (LT-NMP) to assess biliary regeneration. Human livers that were declined for transplantation were perfused at 36°C for up to 13.5 days. Bile duct biopsies, bile and perfusate were collected throughout perfusion, which were examined for features of injury and regeneration. Biliary regeneration was defined as new Ki-67 positive biliary epithelium following severe injury. Ten livers were perfused for a median duration of 7.5 days. Severe bile duct injury occurred in all grafts, and biliary regeneration occurred in 70% of grafts. Traditional biomarkers of biliary viability such as bile glucose improved during perfusion but this was not associated with biliary regeneration (p>0.05). In contrast, the maintenance of IL-6 and VEGF-A levels in bile were associated with biliary regeneration (p=0.017 for both cytokines). This is the first study to demonstrate biliary regeneration during LT-NMP and identify a cytokine signature in bile as a novel biomarker for biliary regeneration during LT-NMP.
RESUMO
Infectious diarrhoea is common post-allogeneic haematopoietic stem-cell transplantation (alloHSCT). While the epidemiology of Clostridioides difficile infection (CDI) post-alloHSCT has been described, the impact of other diarrhoeal pathogens is uncertain. We reviewed all alloHSCT between 2017 and 2022 at a single large transplant centre; 374 patients were identified and included. The 1-year incidence of infectious diarrhoea was 23%, divided into viral (13/374, 3%), CDI (65/374, 17%) and other bacterial infections (16/374, 4%). There was a significant association between infectious diarrhoea within 1 year post-transplant and the occurrence of severe acute lower gastrointestinal graft-versus-host disease (GVHD, OR = 4.64, 95% CI 2.57-8.38, p < 0.001) and inferior GVHD-free, relapse-free survival on analysis adjusted for age, donor type, stem cell source and T-cell depletion (aHR = 1.64, 95% CI = 1.18-2.27, p = 0.003). When the classes of infectious diarrhoea were compared to no infection, bacterial (OR = 6.38, 95% CI 1.90-21.40, p = 0.003), CDI (OR = 3.80, 95% CI 1.91-7.53, p < 0.001) and multiple infections (OR = 11.16, 95% CI 2.84-43.92, p < 0.001) were all independently associated with a higher risk of severe GI GVHD. Conversely, viral infections were not (OR = 2.98, 95% CI 0.57-15.43, p = 0.20). Non-viral infectious diarrhoea is significantly associated with the development of GVHD. Research to examine whether the prevention of infectious diarrhoea via infection control measures or modulation of the microbiome reduces the incidence of GVHD is needed.
Assuntos
Infecções por Clostridium , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Infecções por Clostridium/etiologia , Diarreia/epidemiologia , Diarreia/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.
Assuntos
Povo Asiático , Comportamento Sedentário , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Transversais , Análise de Dados , PaisRESUMO
OBJECTIVE: To characterise lifestyle patterns (comprising dietary and movement behaviour aspects) of children in Singapore and examine the correlates of these patterns. DESIGN: An observational study approach was used. Children recorded their diet and activities over two weekdays and two weekend days on a validated web-based assessment, My E-Diary for Activities and Lifestyle (MEDAL). Lifestyle patterns were derived using principal component analysis, and the correlations of these with multiple known determinants organised by distal, intermediate, and proximal levels of influence were studied. SETTING: Children of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. PARTICIPANTS: Ten-year-old children (n = 397). RESULTS: Three lifestyle patterns, "high snacks and processed food", "balanced" and "mixed", were identified. We focused on the more health-promoting "balanced" pattern, characterised by lower screen-viewing and higher consumption of fruits, vegetables, wholegrains, and dairy. Among the distal factors, girls were more adherent to the "balanced" pattern compared to boys, and children of parents with lower education levels were less adherent to this pattern. Among intermediate factors, children of mothers with higher diet quality were more adherent to the "balanced" pattern. Among the proximal factors, engagement in active transport, leisure sports, and educational activities outside of school were positively associated with the "balanced" pattern, whereas screen-viewing while travelling was negatively associated with this pattern. Having siblings, pet ownership, mother's physical activity, parenting style, parental bonding, child's outdoor time, and breakfast consumption were not associated with children's lifestyle patterns. CONCLUSIONS: These findings provide direction for future interventions by identifying vulnerable groups and contexts that should be prioritised.
Assuntos
Estilo de Vida , Humanos , Singapura , Masculino , Feminino , Criança , Dieta/estatística & dados numéricos , Exercício FísicoRESUMO
BACKGROUND & AIMS: Guidelines suggest endoscopic screening for esophageal adenocarcinoma (EAC) among individuals with symptoms of gastroesophageal reflux disease (GERD) and additional risk factors. We aimed to determine at what age to perform screening and whether sex and race should influence the decision. METHODS: We conducted comparative cost-effectiveness analyses using 3 independent simulation models. For each combination of sex and race (White/Black, 100,000 individuals each), we considered 41 screening strategies, including one-time or repeated screening. The optimal strategy was that with the highest effectiveness and an incremental cost-effectiveness ratio <$100,000 per quality-adjusted life-year gained. RESULTS: Among White men, 536 EAC deaths were projected without screening, and screening individuals with GERD twice at ages 45 and 60 years was optimal. Screening the entire White male population once at age 55 years was optimal in 26% of probabilistic sensitivity analysis runs. Black men had fewer EAC deaths without screening (n = 84), and screening those with GERD once at age 55 years was optimal. Although White women had slightly more EAC deaths (n = 103) than Black men, the optimal strategy was no screening, although screening those with GERD once at age 55 years was optimal in 29% of probabilistic sensitivity analysis runs. Black women had a very low burden of EAC deaths (n = 29), and no screening was optimal, as benefits were very small and some strategies caused net harm. CONCLUSIONS: The optimal strategy for screening differs by race and sex. White men with GERD symptoms can potentially be screened more intensely than is recommended currently. Screening women is not cost-effective and may cause net harm for Black women.
Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Refluxo Gastroesofágico , Adenocarcinoma/epidemiologia , Esôfago de Barrett/diagnóstico , Análise Custo-Benefício , Neoplasias Esofágicas/epidemiologia , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Guidelines suggest 1-time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at an increased risk of esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals after a normal index EGD. METHODS: We conducted a national retrospective analysis within the U S Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC, or esophagogastric junction adenocarcinoma (EGJAC) and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC. RESULTS: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years after an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of them, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC after the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. A longer duration between EGD was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years 1.31; 95% confidence interval [CI] 1.19-1.44), particularly among those who were younger during the index EGD (ages 19-29 years: aOR 3.92; 95% CI 1.24-12.4; ages 60-69 years: aOR 1.19; 95% CI 1.01-1.40). DISCUSSION: The yield of repeat EGD for BE/EAC/EGJAC seems to increase with time after a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings.
Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Humanos , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/patologia , Estudos Retrospectivos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma/complicações , Endoscopia Gastrointestinal/efeitos adversosRESUMO
A 74-year-old Pacific Island man with end-stage renal failure planning to start haemodialysis presented with persistent bleeding after tunnelled dialysis catheter insertion. The laboratory findings revealed a prolonged activated partial thromboplastin time of 118 s, prothrombin ratio of 4.2, factor V activity of <2% and a factor V inhibitor of 40 Bethesda Units. No clear underlying aetiology was identified. The bleeding settled with conservative measures and the factor V inhibitor was successfully treated with oral cyclophosphamide for 6 weeks.
Assuntos
Fator V , Falência Renal Crônica , Masculino , Humanos , Idoso , Diálise Renal/efeitos adversos , Hemorragia/etiologia , Falência Renal Crônica/terapia , Ilhas do PacíficoRESUMO
OBJECTIVES: Risk factors and causes of acute ischemic stroke (AIS) are more diverse in young adults, and traditional stroke classifications may be inadequate. Precise characterisation of AIS is important for guiding management and prognostication. We describe stroke subtypes, risk factors and etiologies for AIS in a young Asian adult population. MATERIALS AND METHODS: Young AIS patients aged 18-50 years admitted to two comprehensive stroke centres from 2020-2022 were included. Stroke etiologies and risk factors were adjudicated using Trial of Org 10172 in Acute Stroke Treatment (TOAST) and International Pediatric Stroke Study (IPSS) risk factors. Potential embolic sources (PES) were identified in a subgroup with embolic stroke of undetermined source (ESUS). These were compared across sex, ethnicities and age groups (18-39 years versus 40-50 years). RESULTS: A total of 276 AIS patients were included, with mean age 43±5.7 years and 70.3% male. Median duration of follow-up was 5 months (IQR: 3-10). The most common TOAST subtypes were small-vessel disease (32.6%) and undetermined etiology (24.6%). IPSS risk factors were identified in 95% of all patients and 90% with undetermined etiology. IPSS risk factors included atherosclerosis (59.5%), cardiac disorders (18.7%), prothrombotic states (12.4%) and arteriopathy (7.7%). In this cohort, 20.3% had ESUS, of which 73.2% had at least one PES, which increased to 84.2% in those <40 years old. CONCLUSIONS: Young adults have diverse risk factors and causes of AIS. IPSS risk factors and ESUS-PES construct are comprehensive classification systems that may better reflect heterogeneous risk factors and etiologies in young stroke patients.
RESUMO
OBJECTIVE: Living with a child with a life-limiting condition (LLC), for which there is no hope of cure and premature death is expected, places much stress on a family unit. Familial communication has the potential to serve as a buffer when children are faced with stressful situations. The overall aim of the study was to learn more about illness-related communication between parents and well-siblings, giving particular consideration to the amount of illness-related communication, and sibling satisfaction with familial communication. METHODS: Participants included 48 well-siblings (aged 6-21 years) of children with LLCs and their parents. Parents and well-siblings independently completed validated measures of familial communication and sibling functioning. Parents also provided demographic information and completed a questionnaire assessing amount of illness-related information provided to well-siblings. RESULTS: Parents reported that 47.8% of well-siblings never or rarely initiated conversations about their sibling's illness. Moreover, 52.2% of well-siblings never or rarely spoke about death. Amount of illness-related communication between parents and well-siblings was most strongly predicted by parental resilience and well-sibling age. Parents engaged in significantly more illness-related communication with girls than boys (t(44)=-2.28, p = .028). Well-siblings (p < .01) and parents (p < .05) rated satisfaction with familial communication significantly higher than published norms. The only significant predictor of well-sibling satisfaction with familial communication was greater familial cohesion. Family communication variables were not significantly correlated with measures of sibling functioning (all p's>.05). CONCLUSIONS: This study provides new information regarding parent and well-sibling communication in families who have a child with a LLC.
Assuntos
Pais , Irmãos , Criança , Comunicação , Família , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: Guidelines cite extensive gastric intestinal metaplasia (GIM) as a bigger risk factor for gastric cancer (GC) than limited GIM and an indication for endoscopic surveillance. Data on progression of extensive GIM to GC in the USA are limited. This study aimed to estimate the prevalence and progression rates of extensive GIM in a US cohort. METHODS: This retrospective study assessed the prevalence of extensive GIM between 1/1/1990 and 8/1/2019 at a large academic medical center. Multivariable regression was used to identify predictors of extensive GIM. Incidence of GC on follow-up was calculated as number of new diagnoses divided by person-years of follow-up. Presence of GIM on subsequent follow-up endoscopy was assessed. RESULTS: Of 1256 individuals with GIM, 352 (28%) had extensive GIM and 904 (72%) had limited GIM. On multivariable analysis, older age (OR 1.01, 95% CI 1.00-1.02) and Hispanic ethnicity (OR 1.55, 95% CI 1.11-2.16) were predictive of extensive GIM. The annual incidence of GC for GIM overall was 0.09%. There was no difference in progression to GC between extensive or limited GIM (IRR 0, 95% CI 0-2.6), or to advanced lesions overall (IRR 0.37, 95% CI 0.04-1.62). 70% of individuals had persistent GIM on follow-up biopsy, and 22% with limited GIM had extensive GIM on follow-up biopsy. CONCLUSIONS: 28% of individuals with GIM have the extensive subtype, and are more likely to be older and of Hispanic ethnicity. There was no difference in progression to GC between extensive and limited GIM. Further research is needed to better assess risk of GIM in the US context.
Assuntos
Lesões Pré-Cancerosas , Neoplasias Gástricas , Endoscopia Gastrointestinal , Humanos , Hiperplasia , Metaplasia/epidemiologia , Lesões Pré-Cancerosas/patologia , Prevalência , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Living with a child who has a life-limiting condition (LLC) is likely to have a major impact on all family members. There is a need to have a clearer understanding of the nature and extent of this impact on parents and well-siblings. The current study aimed to investigate the psychosocial functioning of well-siblings and parents living with a child with an LLC. Further, the study aimed to assess the resilience resources of both well-siblings and parents, giving consideration to how these relate to psychosocial functioning. METHODS: Participants included 48 well-siblings (6-21 years) and 42 parents of children with LLCs. Parents and well-siblings independently completed validated measures of child and adult functioning and personal resilience. Parents provided demographic information about the patient and family. RESULTS: The emotional, social and school functioning of well-siblings in the current study was found to be significantly poorer than published norms (all p's < .01). Parental self-reported depression, anxiety and stress scores were also all significantly poorer than published norms (all p's < .01). There was negligible agreement between well-sibling self-reported functioning and parental proxy-report of the well-siblings functioning (all r's < .126, all p's > .464). Sibling self-reported resilience was positively correlated with each of the measures of psychosocial functioning (all r's > .318, p's < .05). Parental resilience was significantly negatively correlated with depressive symptoms (r = -.369, p < .05) and anxiety symptoms (r = -.473, p < .01) but not stress scores (r = -.074, p = .644). CONCLUSION: Family members living with a child who has an LLC were found to have significantly poorer psychosocial functioning than published norms. Although one cannot infer a causal direction from the current study, greater self-reported well-sibling and parental resilience were associated with aspects of better self-reported psychosocial functioning. Future studies should assess the impact of psychosocial interventions aimed at enhancing the resilience and functioning of both well-siblings and parents.
Assuntos
Pais , Irmãos , Adulto , Criança , Família , Humanos , Pais/psicologia , Funcionamento Psicossocial , Autorrelato , Irmãos/psicologiaRESUMO
PURPOSE: To evaluate the application value of two-dimensional shear wave elastography (2D-SWE) for non-invasive diagnosis of liver cirrhosis (LC) in patients with biliary atresia (BA) before Kasai portoenterostomy (KP), and the cutoff value of liver stiffness measurement (LSM) for diagnosing LC. METHODS: The clinical data of 51 patients with BA who were diagnosed via surgery and pathological results from May 2017 to December 2018 in the department of general surgery, Beijing Children's Hospital, Capital Medical University, were retrospectively analyzed. The liver tissue specimens obtained during KP were evaluated according to the METAVIR criteria. The LSM was obtained using the 2D-SWE technique before KP. RESULTS: There was a grade positive correlation between LSM and METAVIR staging, and the Spearman correlation coefficient was 0.432 (P = 0.002). The AUC for 2D-SWE diagnosing LC (METAVIR score S = 4) in patients with BA before KP was 0.843 (95% confidence interval 0.736 ~ 0.950). The best cutoff value was 16.05 kPa, and the corresponding sensitivity was 75.0%, specificity was 83.7%, positive predictive value (PPV) was 46.1%, negative predictive value (NPV) was 94.7%, and the accuracy was 82.4%. CONCLUSION: 2D-SWE can be used to noninvasively diagnose LC in patients with BA before KP, and the cutoff value is 16.05 kPa.
Assuntos
Atresia Biliar , Técnicas de Imagem por Elasticidade , Atresia Biliar/diagnóstico por imagem , Atresia Biliar/patologia , Atresia Biliar/cirurgia , Criança , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Estudos RetrospectivosRESUMO
Polysorbates (PS 20 and PS 80) are the most widely used surfactants in biopharmaceutical formulations to protect proteins from denaturation, aggregation, and surface adsorption. To date, around 70% of marketed therapeutic antibodies contain either PS 20 or PS 80 in their formulations. However, polysorbates are chemically diverse mixtures, which are prone to degradation by oxidation and hydrolysis to produce peroxides and fatty acids, which, in turn, induce protein oxidation, aggregation, and insoluble particle formation. These will negatively impact protein quality and stability. Thus, polysorbate degradation has emerged as one of the major challenges in the development and commercialization of therapeutic protein products. KLEPTOSE® HPßCD (hydroxypropyl beta-cyclodextrin), a new multifunctional excipient, has been shown to provide protein stabilization functions in biopharmaceutical downstream processes and in their final formulations. This study aims to evaluate HPßCD, a new molecule of its class, against polysorbates as a stabilizer in biologics formulations. In this study, the chemical stability of KLEPTOSE® HPßCDs is compared with polysorbates (20 and 80) under various stress conditions. When subjected to heat stress, HPßCDs show little change in product recovery (90.7-100.7% recovery for different HPßCDs), while polysorbates 20 and 80 show significant degradation, with only 11.5% and 7.3% undegraded product remaining, respectively. When subjected to other chemical stressors, namely, autoclave, light, and oxidative stresses, HPßCD remains almost stable, while polysorbates show more severe degradation, with 95.5% to 98.8% remaining for polysorbate 20 and 85.5% to 97.4% remaining for polysorbate 80. Further, profiling characterization and degradation analysis reveal that chemical structures of HPßCDs remain intact, while polysorbates undergo significant hydrolytic degradation and oxidation. Lastly, the physicochemical stability of monoclonal antibodies in formulations is investigated. When subjected to light stress, adalimumab, as a model mAb, formulated in the presence of HPßCD, shows a significant decrease in protein aggregation, and superior monomer and total protein recovery compared to PS 80-containing formulations. HPßCD also reduces both agitation and thermal stress-induced protein aggregation and prevents subvisible particle formation compared to PS 80.
Assuntos
Antineoplásicos Imunológicos , Produtos Biológicos , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Adalimumab , Anticorpos Monoclonais/química , Excipientes/química , Ácidos Graxos/química , Peróxidos , Polissorbatos/química , Agregados Proteicos , Tensoativos/química , beta-Ciclodextrinas/químicaRESUMO
Cardiac arrhythmias are common and often benign in pregnancy. However, haemodynamic instability can occur when tachyarrhythmias are accompanied by aortocaval compression, which can lead to loss of cardiac output. We present an atypical case of a pregnant woman with a supraventricular tachyarrhythmia, which degenerated into ventricular fibrillation arrest while supine due to aortocaval compression. Inducible atypical atrioventricular nodal re-entry tachycardia was subsequently detected on electrophysiological study and presumed to be the most likely initial supraventricular tachyarrhythmia.
RESUMO
INTRODUCTION: Regular endoscopic surveillance is the gold standard Barrett's esophagus (BE) surveillance, yet harms of surveillance for some patients may outweigh the benefits. We sought to characterize physicians' BE surveillance cessation recommendations. METHODS: We surveyed gastroenterologists about their BE surveillance recommendations varying patient age, comorbidity, and BE length. RESULTS: Clinicians varied in recommendations for repeat surveillance. Patient age showed the largest variation among decisions, whereas BE length varied the least. DISCUSSION: Age and comorbidities seem to influence BE surveillance cessation decisions, but with variation. Clear cessation guidelines balancing the risks and benefits for BE surveillance are warranted.
Assuntos
Esôfago de Barrett/patologia , Gastroenterologistas , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Idoso , Comorbidade , Esofagoscopia , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
CONTEXT: Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery. OBJECTIVE: To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA. DESIGN: Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019. PATIENTS: 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy. MEASUREMENTS: Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control. RESULTS: Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32-2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0-2.0) versus 2.6 (IQR 0.8-4.3), p < .001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery. CONCLUSION: In patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA.
Assuntos
Hiperaldosteronismo , Modelos Estatísticos , Glândulas Suprarrenais , Adrenalectomia , Humanos , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Little is known about the role of inflammation in the process of small vessel vascular dementia (VaD). Recently, the notion that small vessel VaD is caused solely by vascular pathology has been challenged by new evidence of concomitant breakdown of the blood-brain barrier and dysregulation of neuroinflammation in the white matter. METHODS: We examined selected inflammatory cytokines and chemokines in the plasma from patients with small vessel VaD (n = 41) and from age-matched controls (n = 131) using multiplex bead-based assays. Participants were recruited from a memory disorder clinic and from a hospital or community. RESULTS: When compared to controls, patients with small vessel VaD had a highly significant increase in the plasma interferon-γ-inducible protein 10 (IP-10) level (p < 0.0001) and a highly significant decrease in plasma macrophage inflammatory protein 1-beta (MIP-1ß) level (p < 0.0001). We also observed a significant increase in patients' levels of interleukin-10 (IL-10) (p = 0.022) as well as decreases in interleukin-8 (IL-8) (p = 0.004) and interleukin-7 (IL-7) (p = 0.011) when compared to age-matched controls. CONCLUSION: Both IP-10 and MIP-1ß are macrophage-related chemokines. The significant differences between cases and controls suggest a potential role for macrophages in small vessel VaD neuroinflammation. Although it remains unclear whether there is a causal effect of their alteration for small vessel VaD, a better understanding of these molecules in the pathogenesis of small vessel VaD may lead to improved diagnosis and future treatment outcomes against this disease.
Assuntos
Demência Vascular , Substância Branca , Estudos de Casos e Controles , Demência Vascular/patologia , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Microglia/metabolismo , Substância Branca/patologiaRESUMO
BACKGROUND: Vascular malformation of the colorectum is a rare disease that presents most commonly in early childhood. Some pull-through procedures have been performed for its treatment. However, laparotomy was routinely required. The aim of this study was to present features of this disease, as well as the outcomes of transanal endorectal pull-through (TEPT) with or without laparotomy. METHODS: A retrospective analysis was performed on consecutive patients with vascular malformation of the colorectum who underwent TEPT with or without laparotomy in our hospital between January 2010 and December 2019. Follow-up information included hematochezia, other bleeding and bowel function. Bowel function was assessed using the Rintala score. RESULTS: Twenty-seven patients were included (14 boys and 13 girls). Hematochezia and anemia were the main chief complaints. Perianal vasodilatation and prolapse of rectal mucosa with spurting blood were detected in 13 (48.1%) and 9 (33.3%), respectively. Eighteen patients (66.7%) underwent TEPT with laparotomy, and 9 patients underwent TEPT without laparotomy (including 5 TEPT under laparoscopic supervision) for lesions located beyond the distal sigmoid colon. Compared to TEPT with laparotomy, the length of resected bowel and operative time was significantly shorter in TEPT without laparotomy (p = 0.001 and p = 0.004). There was no statistical difference for intraoperative blood loss. Other vascular malformations were detected in 9 patients (33.3%); 3 were detected by laparoscopy. Three patients (11.1%) experienced postoperative complications. Follow-up was held with 24 patients (3 were lost to follow-up). The mean follow-up time was 51.9 ± 32.8 months. Four patients occasionally had bloody stools, without anemia. None had hematuria or vaginal bleeding. Median bowel function score was 20 (range 17-20). CONCLUSION: Hematochezia, anemia and hemorrhoid-like manifestations might be an indication for vascular malformation of the colorectum in children. TEPT was effective for vascular malformation of the colorectum, and TEPT without laparotomy was more suitable for the short lesions.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Doença de Hirschsprung , Laparoscopia , Malformações Vasculares , Criança , Pré-Escolar , Feminino , Doença de Hirschsprung/cirurgia , Humanos , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento , Malformações Vasculares/complicações , Malformações Vasculares/cirurgiaRESUMO
BACKGROUND: Web-based time-use diaries for schoolchildren are limited, and existing studies focus mostly on capturing physical activities and sedentary behaviors but less comprehensively on dietary behaviors. OBJECTIVE: This study aims to describe the development of My E-Diary for Activities and Lifestyle (MEDAL)-a self-administered, web-based time-use application to assess diet and movement behavior-and to evaluate its usability in schoolchildren in Singapore. METHODS: MEDAL was developed through formative research and an iterative user-centric design approach involving small groups of schoolchildren (ranging from n=5 to n=15, aged 7-13 years). To test the usability, children aged 10-11 years were recruited from 2 primary schools in Singapore to complete MEDAL for 2 weekdays and 2 weekend days and complete a 10-item usability questionnaire. RESULTS: The development process revealed that younger children (aged <9 years) were less able to complete MEDAL independently. Of the 204 participants (118/204, 57.8% boys, and 31/201, 15.4% overweight) in the usability study, 57.8% (118/204) completed 3 to 4 days of recording, whereas the rest recorded for 2 days or less. The median time taken to complete MEDAL was 14.2 minutes per day. The majority of participants agreed that instructions were clear (193/203, 95.1%), that MEDAL was easy to use (173/203, 85.2%), that they liked the application (172/202, 85.1%), and that they preferred recording their activities on the web than on paper (167/202, 82.7%). Among all the factors evaluated, recording for 4 days was the least satisfactory component reported. Compared with boys, girls reported better recall ability and agreed that the time spent on completing 1-day entry was appropriate. CONCLUSIONS: MEDAL appears to be a feasible application to capture diet and movement behaviors in children aged 10-12 years, particularly in the Asian context. Some gender differences in usability performance were observed, but the majority of the participants had a positive experience using MEDAL. The validation of the data collected through the application is in progress.
Assuntos
Distinções e Prêmios , Dieta , Criança , Feminino , Humanos , Internet , Estilo de Vida , Masculino , Comportamento SedentárioRESUMO
PURPOSE: Acute colon perforation is a pediatric surgical emergency. We aimed to analyze the different etiologies and clinical characteristics of acute non-traumatic colon perforation beyond the neonatal period and to identify surgical management and outcomes. METHODS: This retrospective study included 18 patients admitted with acute colon perforation and who received surgical treatment. RESULTS: Age of patients ranged between 1 month and 15 years. Five patients swallowed foreign objects (two swallowed magnets), two had colon perforation secondary to a malignant tumor (both colorectal adenocarcinoma) and two were iatrogenic (one prior colonoscopy, one air enema for intussusception). There was one perforation due to chemotherapy and Amyand's hernia respectively. The remaining seven patients had unknown etiologies; five of them were diagnosed with colitis. Fifteen (83.3 %) patients underwent open laparotomy, among which four attempted laparoscopy first. Three (16.7 %) patients underwent laparoscopic surgery. Fourteen (77.8 %) patients received simple suture repairs and four (22.2 %) received colonic resections and anastomosis. Four (22.2 %) patients received a protective diverting colostomy and three (16.7 %) received an ileostomy. CONCLUSIONS: There is a wide range of etiology besides necrotizing enterocolitis and trauma, but a significant portion of children present with unknown etiology. Type of surgery elected should be dependent on the patient's etiology, disease severity and experience of surgeons.