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OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.
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Intestinos , Listas de Espera , Humanos , Estudos Retrospectivos , Masculino , Feminino , Criança , Pré-Escolar , Lactente , Intestinos/transplante , Adolescente , Insuficiência Intestinal , Síndrome do Intestino Curto/cirurgia , Hepatopatias/cirurgiaRESUMO
INTRODUCTION: Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations. METHODS: Community-dwelling participants aged 65 and older (N = 3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Multivariate linear regression models adjusted for SDoH were used in the main analysis. This study used cross-sectional data from the 1066 population-based study. RESULTS: Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p < 0.001), lower socioeconomic status (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). After adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p = 0.31 [-0.19, 0.59] and Native predominant p = 0.74 [-0.24, 0.33]). DISCUSSION: The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia prevalence in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to effectively reduce dementia risk in these communities. HIGHLIGHTS: Countries in Latin America express a large variability in social determinants of health and levels of admixture. After adjustment for downstream societal factors linked to SDoH, genetic ancestry shows no link to dementia. Population ancestry profiles alone do not influence cognitive performance. SDoH are key drivers of racial disparities in dementia and cognitive performance.
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Demência , Determinantes Sociais da Saúde , Humanos , Demência/genética , Demência/epidemiologia , Masculino , Feminino , Prevalência , Idoso , América Latina , Estudos Transversais , Fatores de Risco , Idoso de 80 Anos ou mais , México/epidemiologia , México/etnologiaRESUMO
INTRODUCTION: Apolipoprotein E (APOE) is considered the major susceptibility gene for developing Alzheimer's disease. However, the strength of this risk factor is not well established across diverse Hispanic populations. METHODS: We investigated the associations among APOE genotype, dementia prevalence, and memory performance (immediate and delayed recall scores) in Caribbean Hispanics (CH), African Americans (AA), Hispanic Americans (HA) and non-Hispanic White Americans (NHW). Multivariable logistic regressions and negative binomial regressions were used to examine these associations by subsample. RESULTS: Our final dataset included 13,516 participants (5198 men, 8318 women) across all subsamples, with a mean age of 74.8 years. Prevalence of APOE ε4 allele was similar in CHs, HAs, and NHWs (21.8%-25.4%), but was substantially higher in AAs (33.6%; P < 0.001). APOE ε4 carriers had higher dementia prevalence across all groups. DISCUSSION: APOE ε4 was similarly associated with increased relative risk of dementia and lower memory performance in all subsamples.
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Doença de Alzheimer , Apolipoproteína E4 , Masculino , Humanos , Feminino , Idoso , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Genótipo , Hispânico ou Latino/genética , Região do Caribe , AlelosRESUMO
BACKGROUND: Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations. METHODS: Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic populations with dementia, parkinsonism, and parkinsonism-dementia (PDD) relative to healthy aging. The Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess NPSs. RESULTS: NPSs were highly prevalent in Hispanic populations with neurodegenerative disease; approximately 34.3%, 56.1%, and 61.2% of the participants with parkinsonism, dementia, and PDD exhibited three or more NPSs, respectively. NPSs were the major contributor to caregiver burden. DISCUSSION: Clinicians involved in the care of elderly populations should proactively screen for NPSs, especially in patients with parkinsonism, dementia, and PPD, and develop intervention plans to support families and caregivers. Highlights Neuropsychiatric symptoms (NPSs) are highly prevalent in Hispanic populations with neurodegenerative diseases. In healthy Hispanic populations, NPSs are predominantly mild and not clinically significant. The most common NPSs include depression, sleep disorders, irritability, and agitation. NPSs explain a substantial proportion of the variance in global caregiver burden.
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Demência , Doenças Neurodegenerativas , Transtornos Parkinsonianos , Humanos , Idoso , Demência/diagnóstico , Doenças Neurodegenerativas/epidemiologia , Prevalência , América Latina/epidemiologia , Cuidadores/psicologia , Testes NeuropsicológicosRESUMO
Biliary strictures after liver transplantation are common and when refractive to endoscopic and percutaneous intervention require surgical revision. Robotic technology facilitates minimally invasive biliary reconstruction and has not previously been described after liver transplantation. Robotic biliary revisions were retrospectively compared to all the historical open cases over a time period from May 2013 to October 2020. During the study period there were 3 robotic and 4 open surgical biliary revisions with a follow-up of at least 6months. All cases were hepaticojejunostomies for late choledocho-choledochostomy anastomotic strictures presenting > 4âweeks after transplant and refractive to at least 3 endoscopic and/or percutaneous interventions. Median (range) case time was longer in the robotic group, 373 minutes (286-373) compared to open group, 280 minutes (163-321). The median length of stay was shorter in the robotic group, 4âdays (1--4) compared to open group 7âdays (4-10). Morbidity included 2 wound infections in the open group (grade II), 1 infected hematoma in the robotic group (grade Ilia), and 1 bile leak on the open group (grade Ilia). There was no biliary stricture recurrence or mortality in either group. Robotic biliary revision is a safe alternative to traditional open biliary revision for refractive biliary strictures after liver transplantation.
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Colestase , Transplante de Fígado , Procedimentos Cirúrgicos Robóticos , Colestase/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Humanos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Tumor boards constitute the main consensus and clinical decision-making body of multidisciplinary teams (MDTs) in cancer care. With the increasing clinical complexity of treatment options (eg, targeted therapies, multimodal treatments) and the progressive incorporation of new areas of intervention (eg, survivorship care), tumor boards are now required to play a central role in all cancer processes. However, although frameworks are in place to evaluate MDT quality, only few web-based tools are available for this purpose; indeed, no web-based MDT evaluation tools have been developed for or adapted to the Spanish National Health System. OBJECTIVE: The first aim of this study was to develop a web-based self-assessment model (Autoevaluación de Equipos Multidisciplinares de Atención al Cáncer [AEMAC]) for evaluating multidisciplinary cancer teams in Spain and the second aim was to validate this tool by testing its metric properties, acceptability, and usability. METHODS: We designed and validated the AEMAC program in 3 stages. In the first stage (research), we reviewed the available scientific evidence and performed a qualitative case study of good practice in multidisciplinary care within the Spanish National Health System (n=4 centers and 28 health care professionals). The results were used to define the thematic areas and quality criteria for the self-evaluation model, which were then discussed and validated by a group of experts. The second stage (development) involved the technological development of a web app that would be accessible from any mobile device. In the third stage (piloting and validation), we conducted 4 pilot tests (n=15 tumor boards, 243 professionals) and used the results to analyze the acceptability and usefulness of the tool. RESULTS: We designed a self-assessment model based on 5 thematic areas encompassing a total of 25 quality components, which users rated on a 3-option development scale. The evaluation process, which was managed entirely from the web app, consisted of individual self-assessment, group prioritization, and creation of an improvement plan. Cronbach alpha (.86), McDonald's omega (0.88), and various fit indices (comparative fit index between 0.95 and 1 and goodness-of-fit index between 0.97 and 0.99 for all 5 aspects) confirmed internal consistency. The mean rating for overall satisfaction with the tool and for consistency between the content of the tool and the reality of tumor boards was 7.6 out of 10. CONCLUSIONS: The results obtained during the period of research and piloting of the AEMAC program showed that it has an appropriate structure and metric properties and could therefore be implemented in a real context and generalized to other hospitals. As a virtual tool, it helps to measure the key aspects of MDT quality, such as effectiveness of collaboration and communication, leadership, and the organizational environment.
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Neoplasias , Autoavaliação (Psicologia) , Humanos , Internet , Neoplasias/terapia , Projetos Piloto , EspanhaRESUMO
BACKGROUND: Infective endocarditis (IE) secondary to Staphylococcus aureus bacteremia (SAB) has high morbidity and mortality. The systematic use of echocardiography in SAB is controversial. We aimed to validate VIRSTA and Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT) scores for predicting the risk of IE in Colombian patients with SAB and, consequently, to determine the need for echocardiography. METHODS: Cohort of patients hospitalized with SAB in 2 high complexity institutions in Medellin, Colombia, between 2012 and 2018. The diagnosis of IE was established based on the modified Duke criteria. The VIRSTA and PREDICT scores were calculated from the clinical records, and their operational performance was calculated. RESULTS: The final analysis included 922 patients, 62 (6.7%) of whom were diagnosed with IE. The frequency of IE in patients with a negative VIRSTA scale was 0.44% (2/454). The frequency of IE in patients with a negative PREDICT scale on day 5 was 4.8% (30/622). The sensitivity and negative predictive value (NPV) of the VIRSTA scale was 96.7% and 99.5%, respectively. For the PREDICT scale on day 5, the sensitivity and NPV were 51.6% and 95.1%, respectively. The discrimination, given by the area under the receiver operating characteristic curve, was 0.86 for VIRSTA and 0.64 for PREDICT. CONCLUSIONS: In patients with negative VIRSTA, screening echocardiography may be unnecessary because of the low frequency of IE. In PREDICT-negative patients, despite the low frequency of IE, it is not safe to omit echocardiography.
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Bacteriemia , Endocardite Bacteriana , Endocardite , Infecções Estafilocócicas , Bacteriemia/diagnóstico , Ecocardiografia , Endocardite Bacteriana/diagnóstico por imagem , Humanos , Infecções Estafilocócicas/diagnóstico por imagem , Staphylococcus aureusRESUMO
BACKGROUND: The Chilean allocation system for liver transplantation (LT) uses the MELD/PELD score to prioritize candidates on the waiting list. AIM: To assess if the Chilean allocation system for LT is equitable for pediatric candidates compared to their adult counterparts. MATERIAL AND METHODS: We used the Public Health Institute's registry between October 2011 and December 2017. We analyzed candidates with chronic hepatic diseases listed for LT. The primary outcome was the cadaveric liver transplantation (CLT) rate. Secondary outcomes were death or disease progression in the waiting list and living donor liver transplant (LDLT) rate. RESULTS: We analyzed 122 pediatric and 735 adult candidates. Forty one percent of pediatric candidates obtained a CLT compared to 48% of adults (p = NS). Among patients aged under two years of age, the access to CLT on the waiting list there was 28% of CLT, compared to 48% in adults (p = 0.001). Fifty-seven percent of candidates aged under two years were listed for cholestatic diseases, obtaining a CLT in 18% and requiring a LDLT in 49%. The median time in the waiting list for CLT was 5.9 months in pediatric candidates and 5.1 in adults, while the median time to death in the waiting list was 2.8 and 5.6 months, respectively. The mortality rate at one year in candidates under two years old was 38.1% compared to 32.5% in adults. CONCLUSIONS: Pediatric candidates with chronic liver diseases, especially under two years of age, have greater access difficulties to CLT than adults. Half of the pediatric candidates die on the waiting list before three months. The mortality among candidates under two years of age in the waiting list is excessively high.
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Hepatopatias , Transplante de Fígado , Adulto , Criança , Pré-Escolar , Chile/epidemiologia , Humanos , Hepatopatias/cirurgia , Doadores Vivos , Índice de Gravidade de Doença , Listas de EsperaRESUMO
BACKGROUND: The combined use of a FGFR1 blocker and aromatase inhibitors is appealing for treating breast cancer patients with FGFR1 amplification. However, no pharmacodynamic studies have addressed the effects of this combined target modulation. We conducted a phase 0/I clinical trial in an adjuvant setting, with the goal of obtaining pharmacodynamic proof of the effects of combined aromatase and FGFR1 inhibition and to establish the RP2D for nintedanib combined with letrozole. PATIENTS AND METHODS: Women with early-stage luminal breast cancer were eligible for enrollment in the study. Dose level 1 was nintedanib (150 mg/bid) plus letrozole (2.5 mg/day) administered for a single 28-day cycle (DLT assessment period), followed by a classic 3 + 3 schedule. FGF23 and 17-B-estradiol levels were determined on days 0 and 15; pharmacokinetic parameters were assessed on days 1 and 28. Patients were allowed to continue treatment for 6 cycles. The primary study endpoint was a demonstration of FGFR1 modulation (defined as a 25% increase in the plasma FGF23 level). RESULTS: A total of 19 patients were enrolled in the study (10 in the expansion cohort following dose escalation). At the RP2D (nintedanib 200 mg/bid plus letrozole 2.5 mg/day), we observed a 55% mean increase in the plasma FGF23 level, and 81.2% of the patients had no detectable level of 17-B-estradiol in their plasma (87.5% of the patients treated with letrozole alone). Nintedanib and letrozole displayed a pharmacokinetic interaction that led to three- and twofold increases in their respective plasma concentrations. Most G3 toxic events (5 out of 6: 2 diarrhea and 3 hypertransaminasemia) occurred subsequent to the DLT assessment period. CONCLUSION: Combined treatment with nintedanib (200 mg/bid) plus letrozole (2.5 mg/day) effectively suppressed FGFR1 and aromatase activity, and these respective doses can be used as starting doses in any subsequent trials. However, drug-drug interactions may produce tolerability issues when these drugs are co-administered for an extended time period (e.g., 6 months). Patients enrolled in future trials with these drugs should be carefully monitored for their FGF23 levels and signs of toxicity, and those findings should guide individualized treatment decisions. TRIAL REGISTRATION: This trial was registered at www.clinicaltrials.gov under reg. # NCT02619162, on December 2, 2015.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/farmacocinética , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Monitoramento de Medicamentos , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Indóis/administração & dosagem , Indóis/farmacocinética , Letrozol/administração & dosagem , Letrozol/farmacocinética , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to characterize the neurotoxicity of three different regimens of nab-paclitaxel compared with a standard regimen of solvent-based (sb) paclitaxel for the first-line treatment of HER2-negative metastatic breast cancer based on the Total Neurotoxicity Score (TNS), a tool specifically developed to assess chemotherapy-induced neurotoxicity. MATERIALS AND METHODS: This was a randomized, open-label study testing 4-week cycles of 80 mg/m2 sb-paclitaxel (PACL80/w) on days 1, 8, and 15; 100 mg/m2 nab-paclitaxel on days 1, 8, and 15 (NAB100/w); 150 mg/m2 nab-paclitaxel on days 1, 8, and 15 (NAB150/w); and 150 mg/m2 nab-paclitaxel on days 1 and 15 (NAB150/2w). In addition to the TNS, neuropathy was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Tumor response and quality of life were also evaluated. RESULTS: Neurotoxicity, as evaluated by the TNS, did not significantly differ between the sb-paclitaxel group and any of the nab-paclitaxel groups. The frequency of (any grade) polyneuropathy, as measured by the NCI-CTCAE, was lower in the PACL80/w (n = 7, 50%) and NAB150/2w (n = 10, 62.5%) groups than in the NAB100/w (n = 13, 81.3%) or NAB150/w (n = 11, 78.6%) group. Although the differences were not statistically significant, compared with the other groups, in the NAB150/w group, the time to occurrence of grade ≥2 polyneuropathy was shorter, and the median time to recovery from grade ≥2 polyneuropathy was longer. Dose delays and reductions due to neurotoxicity and impact of neurotoxicity on the patients' experience of symptoms and functional limitations was greater with NAB150/w. Among the seven polymorphisms selected for genotyping, the variant alleles of EPHA5-rs7349683, EPHA6-rs301927, and EPHA8-rs209709 were associated with an increased risk of paclitaxel-induced neuropathy. CONCLUSION: The results of this exploratory study showed that, regardless of the dose, nab-paclitaxel did not differ from sb-paclitaxel in terms of neurotoxicity as evaluated with the TNS. However, results from NCI-CTCAE, dose delays and reductions, and functional tools consistently indicate that NAB150/w regimen is associated with a greater risk of chemotherapy-induced neuropathy. Thus, our results question the superiority of the TNS over NCI-CTCAE for evaluating chemotherapy-induced neuropathy and guiding treatment decisions in this context. The selection of the nab-paclitaxel regimen should be individualized based on the clinical context and potentially supported by pharmacogenetic analysis. Registry: EudraCT, 2012-002361-36; NCT01763710 IMPLICATIONS FOR PRACTICE: The results of this study call into question the superiority of the Total Neurotoxicity Score over the National Cancer Institute Common Terminology Criteria for Adverse Events for evaluating chemotherapy-induced neuropathy and guiding treatment decisions in this context and suggest that a regimen of 150 mg/m2 nab-paclitaxel administered on days 1, 8, and 15 is associated with a greater risk of chemotherapy-induced neuropathy and hematological toxicity compared with other lower-dose nab-paclitaxel regimens or a standard regimen of solvent-based paclitaxel. The selection of the nab-paclitaxel regimen should be individualized based on the clinical context and could benefit from pharmacogenetics analysis.
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Albuminas/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/efeitos adversos , Polineuropatias/induzido quimicamente , Polineuropatias/patologia , Idoso , Albuminas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/secundário , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Polimorfismo Genético , Polineuropatias/genética , Qualidade de Vida , Receptor ErbB-2/metabolismo , Receptores da Família Eph/genéticaRESUMO
In women, age-related bone loss is associated with increased risk of bone fracture. Existing therapies are associated with severe side effects; thus, there is a need to find alternative medicines with less or optimal side effects. Cissus quadrangularis (CQ), an Ayurvedic medicine used to enhance fracture healing, was tested for its bone protective properties and studied to discern the mechanism by which it is beneficial to bone. Female Sprague Dawley rats were either sham operated or ovariectomized and were fed CQ for 3 months. Several biochemical markers, cytokines and hormones were assayed. Femur, tibia and lumbar vertebrae were subjected to pQCT and µCT densitometry. MC3T3 cells were cultured, treated with CQ and used to analyze miRNA content and subjected to qPCR for gene expression analysis related to bone metabolism. CQO rats showed protected bone mass and microarchitecture of trabecular bone in the distal femoral metaphysis and the proximal tibial metaphysis. The lumbar vertebrae, however, showed no significant changes. Serum protein expression levels of P1NP increased and Trap5b and CTX levels decreased with in vivo CQ treatment. Some influence on the anti- and pro-inflammatory markers was also observed. Significantly high level of estradiol in the CQO rats was observed. In vitro expression of a few genes related to bone metabolism showed that osteocalcin increased significantly. The other genes-collagen I expression, SPP1, BMP2, DCAT1-decreased significantly. Certain miRNA that regulate bone turnover using the BMP pathway and Wnt signaling pathways were upregulated by CQ. qPCR after acute treatment with CQ showed significantly increased levels of osteocalcin and decreased levels of Wnt/ß catenin antagonist DCAT1. Overall, CQ protected the microarchitecture of the long bones from ovariectomy-induced bone loss. This may be because of decreased inflammation and modulation through the BMP and Wnt signaling pathways. We conclude that CQ is a potential therapeutic agent to treat postmenopausal osteoporosis with no side effects.
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Remodelação Óssea , Cissus/química , Ovariectomia , Extratos Vegetais/farmacologia , Animais , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Linhagem Celular , Citocinas/sangue , Comportamento Alimentar , Feminino , Hormônios/sangue , Humanos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Vértebras Lombares/efeitos dos fármacos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia/efeitos adversos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/patologiaRESUMO
BACKGROUND/AIMS: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. METHODS: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. RESULTS: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-ß, PDGFsRα, PDGF-AB and BB, CD163, TGF-ß VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, -pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.
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Circulação Colateral , Hepatopatias/fisiopatologia , Neovascularização Patológica/patologia , Pressão na Veia Porta , Adulto , Idoso , Animais , Doença Crônica , Feminino , Humanos , Fígado/patologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/fisiopatologia , Doadores de TecidosRESUMO
Nitrous oxide (N2O), a main greenhouse gas that contributes to ozone layer depletion, is released from soils. Even when it has been argued that agriculture is the main cause of its increase in the atmosphere, natural ecosystems are also an important source of N2O. However, the impacts of human activities on N2O emissions through biodiversity loss or primary productivity changes in natural ecosystems have rarely been assessed. Here, we analyzed the effects of vegetation attributes such as plant diversity and production, as drivers of N2O emission rates, in addition to environmental factors. We measured N2O emissions monthly during 1 year in 12 sites covering a large portion of the Rio de la Plata grasslands, Argentina, and related these emissions with climate, soil and vegetation attributes. We performed spatial and temporal models of N2O emissions separately, to evaluate which drivers control N2O in space and over time independently. Our results showed that in the spatial model, N2O emissions decreased with increments in plant species richness, with concomitant reductions in soil [Formula: see text] whereas N2O emissions increased with primary productivity. By contrast, in the temporal model, monthly precipitation and monthly temperature were the main drivers of N2O emissions, with positive correlations, showing important differences with the spatial model. Overall, our results show that biological drivers may exert substantial control of N2O emissions at large spatial scales, together with climate and soil variables. Our results suggest that biodiversity conservation of natural grasslands may reduce regional greenhouse gas emissions, besides maintaining other important ecosystem services.
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Gases de Efeito Estufa , Óxido Nitroso , Argentina , Ecossistema , Pradaria , SoloRESUMO
INTRODUCTION AND AIM: The Balance of Risk (BAR) Score, a simple scoring system that combines six independent donor and recipient variables to predict outcome after liver transplantation (LT), was validated in a large U.S./European cohort of patients. This study aims to assess the performance of the BAR score to predict survival after liver transplantation and determine the factors associated with short and long-term survival in Latin-American patients. MATERIAL AND METHODS: A retrospective cohort study was performed in 194 patients [112 (55.4%) males; mean age 52±14 years] who underwent 202 LT during the period 2003-2015. Demographic, clinical, pathological and surgical variables, as well as mortality and survival rates, were analyzed. The BAR score was investigated through a receiver operating characteristics (ROC) curve with the calculation of the area under the curve (AUC) to evaluate the predictive score power for 3-month, 1 and 5-year mortality in a matched donor-recipient cohort. Youden index was calculated to identify optimal cutoff points. RESULTS: The AUC of BAR score in predicting 3-month, 1-year and 5-year mortality were 0.755 (CI95% 0.689-0.812), 0.702 (CI95% 0.634-0.764) and 0.610 (CI95% 0.539-0.678) respectively. The best cut-off point was a BAR score ≥15 points. In the multivariate analysis BAR score <15 was associated with higher survival rates at 3 months and 1 and 5-years. CONCLUSIONS: BAR score <15 points is an independent predictor of better short and long-term survival in Latin-American patients undergoing LT. The BAR scoring system has an adequate diagnostic capacity allowing to predict 3 and 12-month mortality.
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Técnicas de Apoio para a Decisão , Transplante de Fígado , Adulto , Idoso , Chile , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Due to blood derivative requirements, many patients with hemophilia were exposed to Hepatitis C virus infection (HCV) before the availability of HCV testing. We report a 46-year-old male with Hemophilia A with a hepatitis virus C infection since 2004 causing a cirrhosis. Due to a hepatopulmonary syndrome, he received a liver allograph using a factor VIII replacement protocol, after eradicating the virus C. He had a good postoperative evolution, and no more factor VIII was required after transplantation until his last assessment.
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Hemofilia A/complicações , Hepatite C/complicações , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Fator IX/administração & dosagem , Fator VIII/administração & dosagem , Hemofilia A/terapia , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Liver transplantation (LT) is an option for people with liver failure who cannot be cured with other therapies and for some people with liver cancer. AIM: To describe, and analyze the first 300 LT clinical results, and to establish our learning curve. MATERIAL AND METHODS: Retrospective cohort study with data obtained from a prospectively collected LT Program database. We included all LT performed at a single center from March 1994 to September 2017. The database gathered demographics, diagnosis, indications for LT, surgical aspects and postoperative courses. We constructed a cumulative summation test for learning curve (LC-CUSUM) using 30-day post-LT mortality. Mortality at 30 days, and actuarial 1-, and 5-year survival rate were analyzed. RESULTS: A total of 281 patients aged 54 (0-71) years (129 women) underwent 300 LT. Ten percent of patients were younger than 18 years old. The first, second and third indications for LT were non-alcoholic steatohepatitis, chronic autoimmune hepatitis and alcoholic liver cirrhosis, respectively. Acute liver failure was the LT indication in 51 cases (17%). The overall complication rate was 71%. Infectious and biliary complications were the most common of them (47 and 31% respectively). The LC-CUSUM curve shows that the first 30 patients corresponded to the learning curve. The peri-operative mortality was 8%. Actuarial 1 and 5-year survival rates were 82 and 71.4%, respectively. CONCLUSIONS: Outcome improvement of a LT program depends on the accumulation of experience after the first 30 transplants and the peri-operative mortality directly impacted long-term survival.
Assuntos
Curva de Aprendizado , Transplante de Fígado/normas , Avaliação de Programas e Projetos de Saúde/normas , Adulto , Idoso , Chile , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
It is becoming increasingly common to hear life scientists say that high quality life science research relies upon high quality laboratory animal care. However, the idea that animal care is a crucial part of scientific knowledge production is at odds with previous social science and historical scholarship regarding laboratory animals. How are we to understand this discrepancy? To begin to address this question, this paper seeks to disentangle the values of scientists in identifying animal care as important to the production of high quality scientific research. To do this, we conducted a survey of scientists working in the United Kingdom who use animals in their research. The survey found that being British is associated with thinking that animal care is a crucial part of conducting high quality science. To understand this finding, we draw upon the concept of 'civic epistemologies' (Jasanoff 2005; Prainsack 2006) and argue that 'animals' and 'care' in Britain may converge in taken-for-granted assumptions about what constitutes good scientific knowledge. These ideas travel through things like state regulations or the editorial policies of science journals, but do not necessarily carry the embodied civic epistemology of 'animals' and 'science' from which such modes of regulating laboratory animal welfare comes.
Assuntos
Experimentação Animal , Bem-Estar do Animal , Animais de Laboratório , Cultura , Adulto , Experimentação Animal/normas , Bem-Estar do Animal/normas , Animais , Feminino , Humanos , Masculino , Cultura Organizacional , Pesquisadores/psicologia , Inquéritos e Questionários , Reino UnidoRESUMO
Abstrac: Before the advent of highly active antiretroviral therapy (HAART), patients infected with human immunodeficiency virus (HIV) were considered as having an absolute contraindication for liver transplantation (LT). Considering the increased life expectancy in HIV positive patients under HAART and the improvements in the management of graft recipients, these patients are now suitable for carrying out transplants in selected cases. We report a 26 years old HIV positive male who developed acute liver failure possibly caused by drug induced liver injury who underwent a successful liver transplantation.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/cirurgia , Transplante de Fígado/métodos , Adulto , Doença Hepática Induzida por Substâncias e Drogas/patologia , Humanos , Imunocompetência , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: In patients suffering intestinal failure due to short bowel, the goal of an Intestinal Rehabilitation Program is to optimize and tailor all aspects of clinical management, and eventually, wean patients off lifelong parenteral nutrition. AIM: To report the results of our program in patients suffering intestinal failure. PATIENTS AND METHODS: A registry of all patients referred to the Intestinal Failure unit between January 2009 and December 2015 was constructed. Initial work up included prior intestinal surgery, blood tests, endoscopic and imaging studies. Also demographic data, medical and surgical management as well as clinical follow-up, were registered. RESULTS: Data from 14 consecutive patients aged 26 to 84 years (13 women) was reviewed. Mean length of remnant small bowel was 100 cm and they were on parenteral nutrition for a median of eight months. Seven of 14 patients had short bowel secondary to mesenteric vascular events (embolism/thrombosis). Medical management and autologous reconstruction of the bowel included jejuno-colic anastomosis in six, enterorraphies in three, entero-rectal anastomosis in two, lengthening procedures in two, ileo-colic anastomosis in one and reversal Roux-Y gastric bypass in one. Thirteen of 14 patients were weaned off parenteral nutrition. CONCLUSIONS: Our Multidisciplinary Intestinal Rehabilitation Program, allowed weaning most of the studied patients off parenteral nutrition.