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1.
Clin Transplant ; 38(1): e15159, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37792580

RESUMO

Ectopic variceal bleeding is a potentially under recognized source of gastrointestinal (GI) hemorrhage. While vascular complications following pancreatic transplant are relatively common, the development of symptomatic ectopic venous varices has rarely been reported. We report two patients with a remote history of simultaneous kidney pancreas transplant (SPK) presenting two decades after transplant with an occult GI bleed. In both cases, a lengthy diagnostic course was required. The varices were treated with coil embolization via transhepatic approach. Our findings add to the limited literature on this topic and aid in the recognition, diagnosis, and management of this unusual presentation.


Assuntos
Embolização Terapêutica , Varizes Esofágicas e Gástricas , Transplante de Pâncreas , Varizes , Humanos , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Varizes/complicações , Varizes/terapia , Transplante de Pâncreas/efeitos adversos
2.
Clin Transplant ; 37(11): e15099, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37589889

RESUMO

BACKGROUND: Living donor liver transplantation (LDLT) in the elderly population is currently not well studied. There are single-center studies indicating that patient age should not be a barrier to LDLT, with similar outcomes compared to younger recipients. METHODS: Using UNOS/STAR data from 2010 to 2022 we retrospectively analyzed patients ≥70 years old receiving a living donor graft (LDLT ≥70y group) versus a deceased donor graft (DDLT ≥70y group). In addition, we compared recipients ≥70 years old undergoing LDLT versus patients 18-69 years old also undergoing LDLT. Donor and recipient baseline characteristics, as well as postoperative outcomes including graft and patient survival were analyzed and compared between groups. RESULTS: Recipients in the LDLT ≥70y group showed less disease burden and spent significantly less time on the waitlist when compared to recipients in the DDLT ≥70y group (102 [49-201] days versus 170 [36-336] days) respectively; p = .004. With the exception of a longer length of stay (LOS) in the LDLT ≥70y group (p ≤ .001), postoperative outcomes were comparable with recipients in the DDLT ≥70y group, including similar graft and patient survival rates at 1-, 3-, and 5-years. When compared to younger recipients of a graft from a living donor, patients in the LDLT ≥70y group had similar post-transplant functional status, re-transplant rates and similar causes contributing to graft failure. However, significantly lower graft and patient survival rates were observed. CONCLUSION: LDLT for recipients aged 70 or greater represents a faster access to transplantation in a safe and feasible manner when compared to similar- aged recipients undergoing DDLT.


Assuntos
Transplante de Fígado , Humanos , Idoso , Estados Unidos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores Vivos , Tempo de Internação , Sobrevivência de Enxerto , Resultado do Tratamento
3.
Clin Transplant ; 36(12): e14801, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35997030

RESUMO

INTRODUCTION: Split liver transplantation (SLT) emerged due to its potential to contribute to the organ pool and reduce organ shortage. However, SLT is technically challenging and has been associated with higher rates of postoperative complications leading to concerns about graft and patient survival. Moreover, there are few studies on matched-pair adult recipients of SLT and whole-liver transplant (WLT), with conflicting results. METHODS: This retrospective study analyze outcomes among adults who underwent SLT at our institution from 2010 to 2019. A 1:1 propensity score matching analysis was performed based on important donor and recipient variables. Baseline characteristics and postoperative outcomes were analyzed and compared between groups. Actuarial graft and patient survival were analyzed by KM curves. RESULTS: Out of 592 adults receiving a LT in our institution, 21 SLT adult recipients were identified and matched with 21 adults undergoing WLT. As expected donor age was significantly lower in SLT recipients (16 (15-22) vs. 32 (17-47), P = .012). Additional donor characteristics, including anthropometrics, and ischemic times were similar between groups. Baseline recipient characteristics and postoperative outcomes, including length of stay, vascular complications, biliary complications, and re-transplantation were comparable between SLT and WLT recipients. Graft (95/95/95 vs. 100/94/94, P = .98) and patient (100/100/100 vs. 100/94/94, P = .30) survival at 1-, 3-, 5-years, were similar between the SLT- and WLT group, respectively. CONCLUSION: Split liver transplantation has the potential to increase the availability of organs for adult recipients without compromising individual outcomes.


Assuntos
Transplante de Fígado , Adulto , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Resultado do Tratamento , Doadores de Tecidos , Sobrevivência de Enxerto
4.
Mol Ecol ; 29(16): 3022-3037, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32621768

RESUMO

Sympatric tree species are subject to similar climatic drivers, posing a question as to whether they display comparable adaptive responses. However, no study has explicitly examined local adaptation of co-occurring parasitic and autotrophic plant species to the abiotic environment. Here we test the hypotheses that a generalist parasitic tree would display a weaker signal of selection and that genomic variation would associate with fewer climatic variables (particularly precipitation) but have similar spatial patterns to a sympatric autotrophic tree species. To test these hypotheses, we collected samples from 17 sites across the range of two tree species, the hemiparasite Nuytsia floribunda (n = 264) and sympatric autotroph Melaleuca rhaphiophylla (n = 272). We obtained 5,531 high-quality genome-wide single nucleotide polymorphisms (SNPs) for M. rhaphiophylla and 6,727 SNPs for N. floribunda using DArTseq genome scan technology. Population differentiation and environmental association approaches were used to identify signals of selection. Generalized dissimilarly modelling was used to detect climatic and spatial patterns of local adaptation across climatic gradients. Overall, 322 SNPs were identified as putatively adaptive for the autotroph, while only 57 SNPs were identified for the parasitic species. We found genomic variation to associate with different sets of bioclimatic variables for each species, with precipitation relatively less important for the parasite. Spatial patterns of predicted adaptive variability were different and indicate that co-occurring species with disparate life history traits may not respond equally to selective pressures (i.e., temperature and precipitation). Together, these findings provide insight into local adaptation of sympatric parasitic and autotrophic tree species to abiotic environments.


Assuntos
Parasitos , Árvores , Adaptação Fisiológica/genética , Animais , Genética Populacional , Genômica , Polimorfismo de Nucleotídeo Único/genética , Árvores/genética
5.
Kidney Int ; 91(2): 276-278, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28087008

RESUMO

Several landmark trials have assessed the effects of aggressive hypertension control on the progression of nondiabetic chronic kidney disease. Results generally have been disappointing. With the realization that lowering blood pressure, including with renin-angiotensin system blockade, failed to reliably prevent end-stage kidney disease, studies now are analyzing longer-term effects of hypertension control on survival in chronic kidney disease. This commentary reviews the current findings and extends the discussion to apolipoprotein L1 gene by blood pressure (or gene by environment) interactions.


Assuntos
Apolipoproteínas/genética , Pressão Sanguínea , Negro ou Afro-Americano , Apolipoproteína L1 , Genótipo , Humanos , Lipoproteínas HDL/genética , Fatores de Risco , Estados Unidos
6.
Am J Kidney Dis ; 70(2): 281-289, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28143671

RESUMO

Apolipoprotein L1 gene (APOL1) renal risk variants exhibit strong genetic associations with a spectrum of nondiabetic kidney diseases in individuals with recent African ancestry. Relationships between APOL1 kidney risk variants and cardiovascular disease (CVD) susceptibility and CVD-related death remain controversial. Some studies detected an increased risk for CVD, whereas others support protection from death and subclinical CVD and cerebrovascular disease. Because treatments for nondiabetic kidney disease may target this gene and its protein products, it remains critical to clarify the potential extrarenal effects of APOL1 kidney risk variants. This review addresses the current literature on APOL1 associations with CVD, cerebrovascular disease, and death. Potential causes of disparate results between studies are discussed.


Assuntos
Apolipoproteínas/genética , Doenças Cardiovasculares/genética , Lipoproteínas HDL/genética , Negro ou Afro-Americano/genética , Apolipoproteína L1 , Doenças Cardiovasculares/epidemiologia , Humanos , Fatores de Risco
7.
Am J Nephrol ; 46(4): 268-275, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28930719

RESUMO

BACKGROUND: Arteriovenous accesses (AVA) in patients performing hemodialysis (HD) are labeled "permanent" for AV fistulas (AVF) or grafts (AVG) and "temporary" for tunneled central venous catheters (TCVC). Durability and outcomes of permanent vascular accesses based on the sequence in which they were placed or used receives little attention. This study analyzed longitudinal transitions between TCVC-based and AVA-based HD outcomes according to the order of placement. METHODS: All 391 patients initiating chronic HD via a TCVC between 2012 and 2013 at 12 outpatient academic dialysis units were included in this study. Chronological distributions of HD vascular accesses were recorded over a mean (SD) of 2.8 (0.9) years and sequentially grouped into periods for TCVC-delivered and AVA-delivered (AVF or AVG) HD. Primary AVA failure and cumulative access survival were evaluated based on access placement sequence and type, adjusting for age. RESULTS: In total, 92.3% (361/391) of patients underwent 497 AVA placement surgeries. Analyzing the initial 3 surgeries, primary AVF failure rates increased with each successive fistula placement (p = 0.008). Among the 82.9% (324/391) of TCVC patients successfully converted to an AVA, 30.9% returned to a TCVC, followed by a 58.0% conversion rate to another AVA. Annual per-patient vascular access transition rates were 2.02 (0.09) HD periods using a TCVC and 0.54 (0.03) HD periods using an AVA. Comparing the first AVA used with the second, cumulative access survivals were 701.0 (370.0) vs. 426.5 (275.0) days, respectively. Excluding those never converting to an AVF or AVG, 169 (52.2%) subsequently converted from a TCVC to a permanent access and received HD via AVA for ≥80% of treatments. CONCLUSIONS: HD vascular access outcomes differ based on the sequence of placement. In spite of frequent AVA placements, only half of patients effectively achieved a "permanent" vascular access and used an AVA for the majority of HD treatments.


Assuntos
Derivação Arteriovenosa Cirúrgica/estatística & dados numéricos , Cateterismo Venoso Central/estatística & dados numéricos , Cateteres Venosos Centrais/efeitos adversos , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/métodos , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Nutr Cancer ; 69(3): 481-489, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28129008

RESUMO

Free or loosely chelated iron has tumor-promoting properties in vitro. Curcumin, a polyphenol derived from the food spice turmeric (Curcuma longa), is a potent antioxidant that binds iron. The primary aim of this study was to investigate whether curcuminoids prevent tumor-promoting effects of iron in T51B cells, a non-neoplastic rat liver epithelial cell line. Purified curcuminoids (curcumin) or a standardized turmeric extract similarly reduced oxidative stress and cytotoxicity associated with iron overload (IC50 values near 10 µM, P < 0.05). Inhibition of iron-induced tumor promotion (seen upon treatment with 200 µM ferric ammonium citrate ± curcumin/turmeric for 16 wk in culture; subsequently assayed by soft agar colony formation) was nearly complete at 20 µM of total curcuminoids (P < 0.05), a concentration predicted to only partially chelate the added iron. Surprisingly, lower curcumin concentrations (10 µM) increased tumor promotion (P < 0.01). Curcuminoids delivered as a standardized turmeric extract were taken up better by cells, had a longer half-life, and appeared more effective in blocking tumor promotion (P < 0.01), suggesting enhanced curcuminoid delivery to cells in culture. The primary finding that curcuminoids can inhibit tumor promotion caused by iron in T51B cells is tempered by evidence for an underlying increase in neoplastic transformation at lower concentrations.


Assuntos
Carcinógenos/toxicidade , Curcuma/química , Curcumina/farmacologia , Ferro/toxicidade , Animais , Antioxidantes/farmacologia , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Compostos Férricos/farmacologia , Ferro/sangue , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Compostos de Amônio Quaternário/farmacologia , Ratos
9.
Ann Bot ; 119(2): 289-300, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27634576

RESUMO

BACKGROUND AND AIMS: Low-altitude mountains constitute important centres of diversity in landscapes with little topographic variation, such as the Southwest Australian Floristic Region (SWAFR). They also provide unique climatic and edaphic conditions that may allow them to function as refugia. We investigate whether the Porongurups (altitude 655 m) in the SWAFR will provide a refugium for the endemic Ornduffia calthifolia and O. marchantii under forecast climate change. METHODS: We used species distribution modelling based on WorldClim climatic data, 30-m elevation data and a 2-m-resolution LiDAR-derived digital elevation model (DEM) to predict current and future distributions of the Ornduffia species at local and regional scales based on 605 field-based abundance estimates. Future distributions were forecast using RCP2.6 and RCP4.5 projections. To determine whether local edaphic and biotic factors impact these forecasts, we tested whether soil depth and vegetation height were significant predictors of abundance using generalized additive models (GAMs). KEY RESULTS: Species distribution modelling revealed the importance of elevation and topographic variables at the local scale for determining distributions of both species, which also preferred shadier locations and higher slopes. However, O. calthifolia occurred at higher (cooler) elevations with rugged, concave topography, while O. marchantii occurred in disturbed sites at lower locations with less rugged, convex topography. Under future climates both species are likely to severely contract under the milder RCP2.6 projection (approx. 2 °C of global warming), but are unlikely to persist if warming is more severe (RCP4.5). GAMs showed that soil depth and vegetation height are important predictors of O. calthifolia and O. marchantii distributions, respectively. CONCLUSIONS: The Porongurups constitute an important refugium for O. calthifolia and O. marchantii, but limits to this capacity may be reached if global warming exceeds 2 °C. This capacity is moderated at local scales by biotic and edaphic factors.


Assuntos
Biodiversidade , Fenômenos Fisiológicos Vegetais , Altitude , Austrália , Mudança Climática , Plantas/classificação , Refúgio de Vida Selvagem
10.
Curr Oncol ; 31(2): 1079-1090, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38392074

RESUMO

The treatment of unresectable colorectal liver metastasis (CRLM) has previously been limited to palliative chemotherapy. Traditionally, the role of liver transplant has not been associated with sufficient survival to justify a patient undergoing a major operation with the associated requirement for postoperative immunosuppression. With improvements in chemotherapy options, a certain subset of patients can experience stable disease for years, which has prompted investigation into the role of liver transplant in these patients. Several recent studies have shown promising results in well-selected patients, with posttransplant survival approaching that of liver transplant recipients for other diseases. Here, we present a review of the data and current protocols for liver transplant for unresectable CRLM.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Neoplasias Colorretais/patologia , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hepatectomia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico
11.
Ecology ; 94(1): 62-71, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23600241

RESUMO

Ecological stoichiometry can explain major trends in how interactions among species change across fertility gradients, but important questions remain. For example, stoichiometry predicts that fertilization should cause plants to reduce carbon allocation to arbuscular mycorrhizal fungi and, consequently, reduce fungal abundance, but responses in the field are highly variable. In a field experiment, we tested three hypotheses that could drive this variation: (1) fungi are nitrogen limited in very nitrogen-poor soils, so fertilization increases their abundance; (2) the N:P ratio of fertilization affects plant carbon allocation to fungi; (3) plant species differences affect fungal response. Our results support all three hypotheses: stoichiometry and species idiosyncrasies jointly determined fungal response to fertilization. We provide field evidence in support of the hypothesis that nitrogen can limit fungal abundance in temperate grasslands. We also show that fungal abundance in soil (hyphal length) differed beneath two dominant plant species: big bluestem (Andropogon gerardii) and smooth brome (Bromus inermis). These grass species also differed in the degree to which they reduced root colonization with fertilization, but these differences in allocation did not lead to differential responses to fertilization in terms of fungal abundance in the soil. This study shows that, while ecological stoichiometry is a useful framework for understanding the effects of eutrophication on this important and widespread species interaction, including these subtleties can increase the predictive power of the theory.


Assuntos
Andropogon/microbiologia , Bromus/microbiologia , Ecossistema , Micorrizas/fisiologia , Carbono/química , Carbono/metabolismo , Concentração de Íons de Hidrogênio , Nitrogênio/química , Nitrogênio/metabolismo , Fósforo/química , Fósforo/metabolismo , Solo/química , Especificidade da Espécie
13.
J Ren Nutr ; 23(3): 199-202, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23510670

RESUMO

Diabetes mellitus is the leading cause of chronic kidney disease and end-stage renal failure in westernized societies, including the United States. In addition to renal manifestations, complications of poorly controlled diabetes include accelerated atherosclerosis, congestive heart failure, neuropathy, and retinopathy. The estimated total cost of diabetes care in the United States was $174 billion in 2007-a number expected to increase markedly in the coming decades. Clinicians must be able to accurately recognize patients with poor glycemic control to have opportunities to intensify treatment and potentially reduce hyperglycemia-related complications. Detecting hyperglycemia is uniquely difficult in patients with severe kidney disease. This paper reviews the literature on the accuracy of glucose monitoring assays in diabetic patients with advanced nephropathy. Interpretation of commonly used tests is affected to a great extent by the uremic milieu and frequently complicates disease management.


Assuntos
Glicemia/análise , Nefropatias Diabéticas/terapia , Índice Glicêmico , Falência Renal Crônica/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Produtos Finais de Glicação Avançada , Humanos , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Hiperglicemia/fisiopatologia , Rim/fisiopatologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/fisiopatologia , Albumina Sérica/análise , Albumina Sérica/metabolismo , Estados Unidos , Albumina Sérica Glicada
14.
Am Nat ; 179(5): 567-81, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22504540

RESUMO

By definition, mutualisms involve the exchange of goods or services between partners. It has been shown that mutualism can grade into parasitism, but even when exchange is mutually beneficial, a conflict of interest remains because each partner benefits from reaping more benefits at a lower cost. Metaphorically, the partners negotiate the conditions of trade, the outcome of which will determine the net benefit to each partner. Each partner can adjust its allocation to self-provisioning while negotiating the ratio at which benefits are exchanged. To understand how these two features of trade affect mutualisms, we used the example of the plant-arbuscular mycorrhizal mutualism and modeled uptake and trade of two resources, phosphorus and carbon. In most contexts, the fungus specialized on phosphorus uptake while the plant took up both phosphorus and carbon. However, when phosphorus was abundant and light was scarce, the plant specialized, taking up only carbon and relying on trade for phosphorus. Resource availability was the most important factor determining specialization and the outcome of negotiation and trade, but other aspects of the context were also important. These results suggest experiments to link these two key features of trade with environmental conditions to determine the outcome of mutualism.


Assuntos
Carbono/metabolismo , Modelos Biológicos , Micorrizas/metabolismo , Fósforo/metabolismo , Simbiose , Ecossistema
15.
Nature ; 442(7105): 916-9, 2006 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-16862116

RESUMO

Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival.


Assuntos
Cromossomos Humanos Par 17/genética , Demência/genética , Lobo Frontal/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação/genética , Precursores de Proteínas/genética , Lobo Temporal/fisiopatologia , Sobrevivência Celular , Códon de Terminação/genética , Demência/fisiopatologia , Lobo Frontal/metabolismo , Ligação Genética/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Mapeamento Físico do Cromossomo , Progranulinas , Precursores de Proteínas/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Lobo Temporal/metabolismo , Proteínas tau/deficiência , Proteínas tau/genética
16.
World J Hepatol ; 14(1): 287-294, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35126855

RESUMO

BACKGROUND: The liver has traditionally been regarded as resistant to antibody-mediated rejection (AMR). AMR in liver transplants is a field in its infancy compared to kidney and lung transplants. In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure (ALF) with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies (DSA). This case highlights the need for further investigations and heightened awareness for timely diagnosis. CASE SUMMARY: A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor. The recipient MELD at the time of transplant was 28. The flow cytometric crossmatches were noted to be positive for T and B lymphocytes. The patient had an uneventful recovery postoperatively. Starting on postoperative day 5 the patient developed fevers, elevated liver function tests, distributive shock, renal failure, and hepatic encephalopathy. She went into ALF with evidence of antibody mediated rejection with portal inflammation, bile duct injury, endothelitis, and extensive centrizonal necrosis, and C4d staining on allograft biopsy and elevated DSA. Despite various interventions including plasmapheresis and immunomodulating therapy, she continued to deteriorate. She was relisted and successfully underwent liver retransplantation. CONCLUSION: This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.

17.
Evol Appl ; 14(7): 1732-1746, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34295360

RESUMO

Parasitism is a pervasive phenomenon in nature with the relationship between species driving evolution in both parasite and host. Due to their host-dependent lifestyle, parasites may adapt to the abiotic environment in ways that differ from their hosts or from free-living relatives; yet rarely has this been assessed. Here, we test two competing hypotheses related to whether putatively adaptive genetic variation in a specialist mistletoe associates with the same, or different, climatic variables as its host species. We sampled 11 populations of the specialist mistletoe Amyema gibberula var. tatei (n = 154) and 10 populations of its associated host Hakea recurva subsp. recurva (n = 160). Reduced-representation sequencing was used to obtain genome-wide markers and putatively adaptive variation detected using genome scan methods. Climate associations were identified using generalized dissimilarity modelling, and these were mapped geographically to visualize the spatial patterns of genetic composition. Our results supported the hypothesis of parasites and host species responding differently to climatic variables. Temperature was relatively more important in predicting allelic turnover in the specialist mistletoe while precipitation was more important for the host. This suggests that parasitic plants and host species may respond differently to selective pressures, potentially as a result of differing nutrient acquisition strategies. Specifically, mistletoes acquire water from hosts (rather than the abiotic environment), which may provide a buffer to precipitation as a selective pressure. This work deepens and complements the physiological and other ecological studies of adaptation and provides a window into the evolutionary processes that underlie previously observed phenomena. Applying these methods to a comparative study in a host-parasite system has also highlighted factors that affect the study of selection pressure on nonmodel organisms, such as differing adaptation rates and lack of reference genomes.

18.
Kidney Med ; 3(2): 248-256.e1, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851120

RESUMO

BACKGROUND: It is unclear whether surgical placement of an arteriovenous (AV) fistula (AVF) confers substantial clinical benefits over an AV graft (AVG) in older adults with end-stage kidney disease (ESKD). We report vascular access outcomes of a pilot clinical trial. STUDY DESIGN: Pilot randomized parallel-group open-label trial. SETTING & PARTICIPANTS: Patients 65 years and older with ESKD and no prior AV access receiving maintenance hemodialysis through a tunneled central venous catheter referred for AV access placement by their treating nephrologist. INTERVENTION: Participants were randomly assigned in a 1:1 ratio to surgical placement of an AVG or AVF. OUTCOMES: Index AV access primary failure, successful cannulation, adjuvant interventions and infections. RESULTS: Of 122 older adults receiving hemodialysis and no prior AV access surgery, 24% died before (n = 18) or were too sick for (n = 11) referral for a permanent AV access. Of 46 eligible patients, 36 (78%) consented and were randomly assigned to AVG (n = 18) and AVF (n = 18) placement, of whom 13 (72%) and 16 (89%) underwent index AV access surgical placement, respectively. At a median follow-up of 321.0 days, primary AV access failure was noted in 31% in each group. The proportion of patients with successful cannulation was 62% (8 of 13) in the AVG and 50% (8 of 16) in the AVF group; median times to successful cannulation were 75.0 and 113.5 days, respectively. Endovascular procedures were recorded in 38% and 44%, and surgical reinterventions, in 23% and 25%, respectively. AV access infection was seen in 3 (23%) and 2 (13%) patients, respectively. LIMITATIONS: Small sample size precludes statistical inference. CONCLUSIONS: Almost one-quarter of older adults with incident ESKD and a central venous catheter as primary access were not referred for AV access placement due to medical reasons. Based on these limited results, there is little reason to favor either an AVF or AVG in this population until results from a larger randomized clinical trial become available. FUNDING: Government funding to an author (Dr Murea is supported by National Institutes of Health∖National Institute on Aging grant 1R03 AG060178-01). TRIAL REGISTRATION: NCT03545113.

19.
Hum Mol Genet ; 17(23): 3631-42, 2008 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-18723524

RESUMO

Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting approximately 10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3'-untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared with homozygous C-allele carriers (95% CI: 1.50-6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Demência/genética , Variação Genética , Peptídeos e Proteínas de Sinalização Intercelular/química , Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/metabolismo , Idoso , Sequência de Bases , Sítios de Ligação , Encéfalo/metabolismo , Demência/metabolismo , Feminino , Regulação da Expressão Gênica , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , MicroRNAs/química , MicroRNAs/genética , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Progranulinas , Biossíntese de Proteínas
20.
Surg Obes Relat Dis ; 16(8): 1030-1034, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32540149

RESUMO

BACKGROUND: Complications related to laparoscopic adjustable gastric banding (LAGB) have led to an increased number of removals. An uncommon but potentially devastating complication is gastric band erosion into the gastric lumen, which can be managed by open surgical, laparoscopic, and endoscopic approaches. OBJECTIVE: A wide array of management techniques has been reported for removal of LAGB that have eroded into the stomach. We describe the preferred method for successful endoscopic band removal at our institution. SETTING: Community tertiary-care referral hospital accredited by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program. METHODS: A single-center, retrospective review of a prospectively maintained database was used to identify patients who underwent LAGB removal from 2009 to 2019. We identified the subset of patients with band erosion. We analyzed patient characteristics, presenting symptoms, diagnostic modalities, and method of band extraction. RESULTS: A total of 132 patients underwent LAGB removal, among whom 22 (16.7%) patients were diagnosed with erosion. Seven (32%) patients underwent laparoscopic removal, 14 (64%) patients underwent endoscopic removal, and 1 patient (4%) underwent combined laparoscopic and endoscopic approach. These latter patients had variable amounts of erosion and buckle visibility, but all underwent endoscopic retrieval. We found that using an endoscopic retrograde cholangiopancreatography guidewire with an endoscopic retrograde cholangiopancreatography mechanical lithotriptor for band transection and snare for retrieval have been effective. CONCLUSIONS: A standardized, multidisciplinary, and minimally invasive endoscopic approach for LAGB erosion has been found to be successful without the need for further surgical intervention and may be offered to patients upon discovery of erosion.


Assuntos
Cirurgia Bariátrica , Gastroplastia , Laparoscopia , Obesidade Mórbida , Cirurgia Bariátrica/efeitos adversos , Remoção de Dispositivo , Gastroplastia/efeitos adversos , Humanos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
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