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1.
Clin Infect Dis ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129438

RESUMO

BACKGROUND: For patients at risk for multidrug-resistant organisms, IDSA/ATS guidelines recommend empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Following negative cultures, the guidelines recommend antimicrobial de-escalation. We assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized pneumonia patients with negative cultures. METHODS: We included adults admitted with pneumonia in 2010-2015 to 164 US hospitals if they had negative blood and/or respiratory cultures and received both anti-MRSA and antipseudomonal agents other than quinolones. De-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Patients were propensity-adjusted for de-escalation and compared on in-hospital 14-day mortality, late deterioration (ICU transfer), length-of-stay (LOS) and costs. We also compared adjusted outcomes across hospital de-escalation rate quartiles. RESULTS: Of 14,170 patients, 1924 (13%) had both initial empiric drugs stopped by hospital day 4. Hospital de-escalation rates ranged from 2%-35% and hospital de-escalation rate quartile was not significantly associated with outcomes. At hospitals in the top quartile of de-escalation, even among patients at lowest risk for mortality, the de-escalation rates were < 50%. In propensity-adjusted analysis, patients with de-escalation had lower odds of subsequent transfer to ICU (adjusted odds ratio 0.38; 95%CI 0.18-0.79); LOS (adjusted ratio of means 0.76, 95% CI 0.75-0.78) and costs (0.74, 95%CI 0.72-0.76). CONCLUSIONS: A minority of eligible pneumonia patients had antibiotics de-escalated by hospital day 4 following negative cultures and de-escalation rates varied widely between hospitals. To adhere to recent guidelines will require substantial changes in practice.

2.
JAMA Netw Open ; 3(1): e1919325, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31922554
3.
Am J Sports Med ; 48(2): 432-443, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31851536

RESUMO

BACKGROUND: Shoulder pain and dysfunction are common indications for rotator cuff repair surgery, yet the factors that are associated with these symptoms are not fully understood. PURPOSE/HYPOTHESIS: This study aimed to investigate the associations of patient and disease-specific factors with baseline patient-reported outcome measures (PROMs) in patients undergoing rotator cuff repair. We hypothesized that tear size and mental health status, as assessed by the Veterans RAND 12-Item Health Survey mental component score (VR-12 MCS), would be associated with baseline total Penn Shoulder Score (PSS) and its pain, function, and satisfaction subscale scores. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We prospectively identified 12 patient factors and 12 disease-specific factors as possible statistical predictors for baseline PROMs in patients undergoing surgical repair of superior-posterior rotator cuff tears at a single institution over a 3-year period. Multivariable statistical modeling and Akaike information criterion comparisons were used to investigate the unique associations with, and relative importance of, these factors in accounting for variation in baseline PSS and its subscale scores. RESULTS: A total of 1442 patients who had undergone surgery by 23 surgeons met inclusion criteria, with a baseline median total PSS of 38.5 (pain, 12; function, 24.2; satisfaction, 2). Adjusted R2 in multivariable models demonstrated that the 24 general patient and disease-specific factors accounted for 22% to 24% of the variability in total PSS and its pain and function subscale scores. Large/massive tear size was significantly associated with worse PSS total score and function score but not pain or satisfaction scores. Lower VR-12 MCS was significantly associated with worse total PSS and all 3 subscale scores. Among other factors significantly associated with baseline PROMs were sex, race, preoperative opioid use, years of education, employment status, acromion status, and adhesive capsulitis. Lower VR-12 MCS, preoperative opioid use, female sex, and black race were the factors most strongly associated with baseline PROMs. CONCLUSION: Large/massive tear size, lower VR-12 MCS, and several additional patient and disease-specific factors are associated with baseline PROMs in patients undergoing rotator cuff repair. Further studies are needed to investigate whether these factors will also predict poor postoperative PROMs.

4.
Clin Infect Dis ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665249

RESUMO

BACKGROUND: Choice of empiric therapy for pneumonia depends on risk for antimicrobial resistance. Models to predict resistance are derived from blood and respiratory culture results. We compared these results to understand if organisms and resistance patterns differed by site. We also compared characteristics and outcomes of patients with positive cultures by site. METHODS: We studied adult patients discharged from 177 US hospitals from July 2010-June 2015, with principal diagnoses of pneumonia, or principal diagnoses of respiratory failure, ARDS, respiratory arrest, or sepsis with a secondary diagnosis of pneumonia, and who had blood or respiratory cultures performed. Demographics, treatment, microbiologic results and outcomes were examined. RESULTS: Among 138,561 hospitalizations of patients with pneumonia who had blood or respiratory cultures obtained at admission, 12,888 (9.3%) yielded positive cultures-6,438 respiratory cultures, 5,992 blood cultures and 458 both. Forty-two percent had isolates resistant to first-line therapy for community-acquired pneumonia. Isolates from respiratory samples were more often resistant than were isolates from blood (54.2 vs. 26.6, p=0.001). Patients with both culture sites positive had higher mortality, longer lengths of stay and higher costs than patients who had only blood or respiratory cultures positive. Among respiratory cultures, the most common pathogens were S. aureus (34%) and P. aeruginosa (17%), while blood cultures most commonly grew S. Pneumoniae (33%), followed by S. aureus (22%). CONCLUSIONS: Patients with positive respiratory tract cultures are clinically different from those with positive blood cultures and resistance patterns differ by source. Models of antibiotic resistance should account for culture source.

5.
J Am Soc Nephrol ; 30(7): 1147-1150, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31208985
6.
JAMA Netw Open ; 2(6): e195172, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31173120

RESUMO

Importance: Patients with alcohol use disorder (AUD) are at elevated risk of developing pneumonia, but few studies have assessed the outcomes of pneumonia in patients with AUD. Objectives: To compare the causes, treatment, and outcomes of pneumonia in patients with and without AUD and to understand the associations of comorbid illnesses, alcohol withdrawal, and any residual effects due to alcohol itself with patient outcomes. Design, Setting, and Participants: A retrospective cohort study was conducted of 137 496 patients 18 years or older with pneumonia who were admitted to 177 US hospitals participating in the Premier Healthcare Database from July 1, 2010, to June 30, 2015. Statistical analysis was conducted from October 27, 2017, to August 20, 2018. Exposure: Alcohol use disorders identified from International Classification of Diseases, Ninth Revision, Clinical Modification codes. Main Outcomes and Measures: Pneumonia cause, antibiotic treatment, inpatient mortality, clinical deterioration, length of stay, and cost. Associations of AUD with these variables were studied using generalized linear mixed models. Results: Of 137 496 patients with community-acquired pneumonia (70 358 women and 67 138 men; mean [SD] age, 69.5 [16.2] years), 3.5% had an AUD. Patients with an AUD were younger than those without an AUD (median age, 58.0 vs 73.0 years; P < .001), more often male (77.3% vs 47.8%; P < .001), and more often had principal diagnoses of aspiration pneumonia (10.9% vs 9.8%; P < .001), sepsis (38.6% vs 30.7%; P < .001), or respiratory failure (9.3% vs 5.5%; P < .001). Their cultures more often grew Streptococcus pneumoniae (43.7% vs 25.5%; P < .001) and less frequently grew organisms resistant to guideline-recommended antibiotics (25.0% vs 43.7%; P < .001). Patients with an AUD were treated more often with piperacillin-tazobactam (26.2% vs 22.5%; P < .001) but equally as often with anti-methicillin-resistant Staphylococcus aureus agents (32.9% vs 31.8%; P = .11) compared with patients without AUDs. When adjusted for demographic characteristics and insurance, AUD was associated with higher mortality (odds ratio, 1.40; 95% CI, 1.25-1.56), length of stay (risk-adjusted geometric mean ratio, 1.24; 95% CI, 1.20-1.27), and costs (risk-adjusted geometric mean ratio, 1.33; 95% CI, 1.28-1.38). After additional adjustment for differences in comorbidities and risk factors for resistant organisms, AUD was no longer associated with mortality but remained associated with late mechanical ventilation (odds ratio, 1.28; 95% CI, 1.12-1.46), length of stay (risk-adjusted geometric mean ratio, 1.04; 95% CI, 1.01-1.06), and costs (risk-adjusted geometric mean ratio, 1.06; 95% CI, 1.03-1.09). Models segregating patients undergoing alcohol withdrawal showed that poorer outcomes among patients with AUD were confined to the subgroup undergoing alcohol withdrawal. Conclusions and Relevance: This study suggests that, compared with hospitalized patients with community-acquired pneumonia but without AUD, those with AUD less often harbor resistant organisms. The higher age-adjusted risk of death among patients with AUD appears to be largely attributable to differences in comorbidities, whereas greater use of health care resources may be attributable to alcohol withdrawal.


Assuntos
Alcoolismo/complicações , Infecções Comunitárias Adquiridas/complicações , Pneumonia Bacteriana/complicações , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/mortalidade , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/mortalidade , Farmacorresistência Bacteriana , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Pneumonia Aspirativa/complicações , Pneumonia Aspirativa/mortalidade , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Prognóstico , Insuficiência Respiratória/complicações , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Sepse/complicações , Sepse/mortalidade , Estados Unidos/epidemiologia
7.
Eur J Vasc Endovasc Surg ; 57(5): 719-728, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31000459

RESUMO

BACKGROUND: The arteriovenous fistula (AVF) is central to haemodialysis treatment, but up to half of surgically created AVF fail to mature. Chronic kidney disease often leads to mineral metabolism disturbances that may interfere with AVF maturation through adverse vascular effects. This study tested associations between mineral metabolism markers and vein histology at AVF creation and unassisted and overall clinical AVF maturation. METHODS: Concentrations of fibroblast growth factor 23, parathyroid hormone, calcium, phosphate, and vitamin D metabolites: 1,25(OH)2D, 24,25(OH)2D, 25(OH)D, and bioavailable 25(OH)D were measured in pre-operative serum samples from 562 of 602 participants in the Haemodialysis Fistula Maturation Study, a multicentre, prospective cohort study of patients undergoing surgical creation of an autologous upper extremity AVF. Unassisted and overall AVF maturation were ascertained for 540 and 527 participants, respectively, within nine months of surgery or four weeks of dialysis initiation. Study personnel obtained vein segments adjacent to the portion of the vein used for anastomosis, which were processed, embedded, and stained for measurement of neointimal hyperplasia, calcification, and collagen deposition in the medial wall. RESULTS: Participants in this substudy were 71% male, 43% black, and had a mean age of 55 years. Failure to achieve AVF maturation without assistance occurred in 288 (53%) participants for whom this outcome was determined. In demographic and further adjusted models, mineral metabolism markers were not significantly associated with vein histology characteristics, unassisted AVF maturation failure, or overall maturation failure, other than a biologically unexplained association of higher 24,25(OH)2D with overall failure. This exception aside, associations were non-significant for continuous and categorical analyses and relevant subgroups. CONCLUSIONS: Serum concentrations of measured mineral metabolites were not substantially associated with major histological characteristics of veins in patients undergoing AVF creation surgery, or with AVF maturation failure, suggesting that efforts to improve AVF maturation rates should increase attention to other processes such as vein mechanics, anatomy, and cellular metabolism among end stage renal disease patients.


Assuntos
Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Minerais/sangue , Diálise Renal/métodos , Remodelação Vascular , Adulto , Idoso , Biomarcadores/sangue , Calcificação Fisiológica , Cálcio/sangue , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Veias/metabolismo , Veias/patologia , Vitamina D/sangue
8.
J Am Soc Nephrol ; 29(11): 2735-2744, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309898

RESUMO

BACKGROUND: The utility of early postoperative ultrasound measurements in predicting arteriovenous fistula (AVF) clinical maturation is uncertain. METHODS: We investigated the relationships of ultrasound parameters with AVF clinical maturation in newly created AVF, measured at 1 day and 2 and 6 weeks, in 602 participants of a multicenter, observational cohort study. A backward elimination algorithm identified ultrasound measurements that independently predicted unassisted and overall AVF maturation. Candidate variables included AVF blood flow, diameter, and depth, upper arm arterial diameter, presence of stenosis, presence of accessory veins, seven case-mix factors (age, sex, black race, AVF location, diabetes, dialysis status, and body mass index), and clinical center. We evaluated the accuracy of the resulting models for clinical prediction. RESULTS: At each ultrasound measurement time, AVF blood flow, diameter, and depth each predicted in a statistically significant manner both unassisted and overall clinical maturation. Moreover, neither the remaining ultrasound parameters nor case-mix factors were associated with clinical AVF maturation after accounting for blood flow, diameter, and depth, although maturation probabilities differed among clinical centers before and after accounting for these parameters. The crossvalidated area under the receiver operating characteristic curve for models constructed using these three ultrasound parameters was 0.69, 0.74, and 0.79 at 1 day and 2 and 6 weeks, respectively, for unassisted AVF clinical maturation and 0.69, 0.71, and 0.76, respectively, for overall AVF maturation. CONCLUSIONS: AVF blood flow, diameter, and depth moderately predicted unassisted and overall AVF clinical maturation. The other factors considered did not further improve AVF maturation prediction.


Assuntos
Derivação Arteriovenosa Cirúrgica , Diálise Renal/métodos , Grau de Desobstrução Vascular , Adulto , Idoso , Algoritmos , Velocidade do Fluxo Sanguíneo , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiologia , Artéria Braquial/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Ultrassonografia
9.
Am J Nephrol ; 48(1): 56-64, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30071516

RESUMO

BACKGROUND: The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, approximately half of AVFs fail to mature. The use of angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) exerts favorable endothelial effects and may promote AVF maturation. We tested associations of ACE-I and ARBs, CCBs, beta-blockers, and diuretics with the maturation of newly created AVFs. METHODS: We evaluated 602 participants from the Hemodialysis Fistula Maturation Study, a multi-center, prospective cohort study of AVF maturation. We ascertained the use of each medication class within 45 days of AVF creation surgery. We defined maturation outcomes by clinical use within 9 months of surgery or 4 weeks of initiating hemodialysis. RESULTS: Unassisted AVF maturation failure without intervention occurred in 54.0% of participants, and overall AVF maturation failure (with or without intervention) occurred in 30.1%. After covariate adjustment, CCB use was associated with a 25% lower risk of overall AVF maturation failure (95% CI 3%-41% lower) but a non-significant 10% lower risk of unassisted maturation failure (95% CI 23% lower to 5% higher). ACE-I/ARB, beta-blocker, and diuretic use was not significantly associated with AVF maturation outcomes. None of the antihypertensive medication classes were associated with changes in AVF diameter or blood flow over 6 weeks following surgery. CONCLUSIONS: CCB use may be associated with a lower risk of overall AVF maturation failure. Further studies are needed to determine whether CCBs might play a causal role in improving AVF maturation outcomes.


Assuntos
Anti-Hipertensivos/administração & dosagem , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Falência Renal Crônica/terapia , Grau de Desobstrução Vascular/efeitos dos fármacos , Adulto , Idoso , Derivação Arteriovenosa Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/métodos , Falha de Tratamento
10.
Clin J Am Soc Nephrol ; 13(8): 1225-1233, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30045914

RESUMO

BACKGROUND AND OBJECTIVES: HDL particles obtained from patients on chronic hemodialysis exhibit lower cholesterol efflux capacity and are enriched in inflammatory proteins compared with those in healthy individuals. Observed alterations in HDL proteins could be due to effects of CKD, but also may be influenced by the hemodialysis procedure, which stimulates proinflammatory and prothrombotic pathways. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared HDL-associated proteins in 143 participants who initiated hemodialysis within the previous year with those of 110 participants with advanced CKD from the Hemodialysis Fistula Maturation Study. We quantified concentrations of 38 HDL-associated proteins relative to total HDL protein using targeted mass spectrometry assays that included a stable isotope-labeled internal standard. We used linear regression to compare the relative abundances of HDL-associated proteins after adjustment and required a false discovery rate q value ≤10% to control for multiple testing. We further assessed the association between hemodialysis initiation and cholesterol efflux capacity in a subset of 80 participants. RESULTS: After adjustment for demographics, comorbidities, and other clinical characteristics, eight HDL-associated proteins met the prespecified false discovery threshold for association. Recent hemodialysis initiation was associated with higher HDL-associated concentrations of serum amyloid A1, A2, and A4; hemoglobin-ß; haptoglobin-related protein; cholesterylester transfer protein; phospholipid transfer protein; and apo E. The trend for participants recently initiating hemodialysis for lower cholesterol efflux capacity compared with individuals with advanced CKD did not reach statistical significance. CONCLUSIONS: Compared with advanced CKD, hemodialysis initiation within the previous year is associated with higher concentrations of eight HDL proteins related to inflammation and lipid metabolism. Identified associations differ from those recently observed for nondialysis-requiring CKD. Hemodialysis initiation may further impair cholesterol efflux capacity. Further work is needed to clarify the clinical significance of the identified proteins with respect to cardiovascular risk. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_07_25_CJASNPodcast_18_8_W.mp3.


Assuntos
Lipoproteínas HDL/química , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/metabolismo
11.
Mult Scler J Exp Transl Clin ; 4(1): 2055217318765288, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29623216

RESUMO

Background: Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. Objective: To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. Methods: In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 106 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. Results: One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Conclusion: Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

12.
Am J Kidney Dis ; 71(5): 677-689, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29398178

RESUMO

BACKGROUND: Half of surgically created arteriovenous fistulas (AVFs) require additional intervention to effectively support hemodialysis. Postoperative care and complications may affect clinical maturation. STUDY DESIGN: Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study. SETTING & PARTICIPANTS: 491 patients with single-stage AVFs who had neither thrombosis nor AVF intervention before a 6-week postoperative ultrasonographic examination and who required maintenance hemodialysis. PREDICTORS: Postoperative care processes and complications. OUTCOMES: Attempted cannulation, successful cannulation, and unassisted and overall clinical maturation as defined by the HFM Study criteria. RESULTS: AVF cannulation was attempted in 443 of 491 (90.2%) participants and was eventually successful in 430 of these 443 (97.1%) participants. 263 of these 430 (61.2%) reached unassisted and 118 (27.4%) reached assisted AVF maturation (overall maturation, 381/430 [88.6%]). Attempted cannulation was less likely in patients of surgeons with policies for routine 2-week versus later-than-2-week first postoperative visits (OR, 0.21; 95% CI, 0.06-0.70), routine second postoperative follow-up visits (OR, 0.39; 95% CI, 0.15-0.97), and a routine clinical postoperative ultrasound (OR, 0.28; 95% CI, 0.14-0.55). Attempted cannulation was also less likely among patients undergoing procedures to assist maturation (OR, 0.51; 95% CI, 0.27-0.98). Unassisted maturation was more likely for patients treated in facilities with access coordinators (OR, 1.91; 95% CI, 1.17-3.12), but less likely after precannulation nonstudy ultrasounds (OR per ultrasound, 0.42 [95% CI, 0.26-0.68]) and initial unsuccessful cannulation attempts (OR per each additional attempt, 0.90 [95% CI, 0.83-0.98]). Overall maturation was less likely with infiltration before successful cannulation (OR, 0.44; 95% CI, 0.22-0.89). Among participants receiving maintenance hemodialysis before AVF surgery, unassisted and overall maturation were less likely with longer intervals from surgery to initial cannulation (ORs for each additional month of 0.81 [95% CI, 0.76-0.88] and 0.93 [95% CI, 0.89-0.98], respectively) and from initial to successful cannulation (ORs for each additional week of 0.87 [95% CI, 0.81-0.94] and 0.88 [95% CI, 0.83-0.94], respectively). LIMITATIONS: Surgeons' management policies were assessed only by questionnaire at study onset. Most participants received upper-arm AVFs, planned 2-stage AVFs were excluded, and maturation time windows were imposed. Some care processes may have been missed and the observational design limits causal attribution. CONCLUSIONS: Multiple processes of care and complications are associated with AVF maturation outcomes.


Assuntos
Fístula Arteriovenosa/cirurgia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Cateterismo/métodos , Falência Renal Crônica/reabilitação , Diálise Renal/efeitos adversos , Dispositivos de Acesso Vascular/efeitos adversos , Adulto , Idoso , Fístula Arteriovenosa/diagnóstico por imagem , Estudos de Coortes , Remoção de Dispositivo/métodos , Feminino , Seguimentos , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Diálise Renal/métodos , Reoperação/métodos , Medição de Risco , Resultado do Tratamento , Ultrassonografia Doppler/métodos
13.
Urology ; 112: 119-120, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29290417
14.
Mult Scler ; 24(4): 501-511, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28381130

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest. OBJECTIVE: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. METHODS: Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 106 MSCs/kg were thawed and administered IV. RESULTS: In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 106 MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation. CONCLUSION: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Adolescente , Adulto , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Transplante Autólogo/métodos , Adulto Jovem
15.
Trends Cogn Sci ; 22(2): 111-123, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29183655

RESUMO

The ability to accurately predict violence and other forms of serious antisocial behavior would provide important societal benefits, and there is substantial enthusiasm for the potential predictive accuracy of neuroimaging techniques. Here, we review the current status of violence prediction using actuarial and clinical methods, and assess the current state of neuroprediction. We then outline several questions that need to be addressed by future studies of neuroprediction if neuroimaging and other neuroscientific markers are to be successfully translated into public policy.


Assuntos
Transtorno da Personalidade Antissocial/diagnóstico , Neurociências , Violência , Humanos
16.
J Am Soc Nephrol ; 28(10): 3005-3013, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28710091

RESUMO

Intimal hyperplasia and stenosis are often cited as causes of arteriovenous fistula maturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segment of the vein used to create the fistula was collected intraoperatively for histomorphometric examination. On ultrasounds performed 1 day and 2 and 6 weeks after fistula creation, we assessed fistula venous stenosis using pre-specified criteria on the basis of ratios of luminal diameters and peak blood flow velocities at certain locations along the vessel. We determined fistula clinical maturation using criteria for usability during dialysis. Preexisting venous intimal hyperplasia, expressed per 10% increase in a hyperplasia index (range of 0%-100%), modestly associated with lower fistula blood flow rate (relative change, -2.5%; 95% confidence interval [95% CI], -4.6% to -0.4%; P=0.02) at 6 weeks but did not significantly associate with stenosis (odds ratio [OR], 1.07; 95% CI, 1.00 to 1.16; P=0.07) at 6 weeks or failure to mature clinically without procedural assistance (OR, 1.07; 95% CI, 0.99 to 1.15; P=0.07). Fistula venous stenosis at 6 weeks associated with maturation failure (OR, 1.98; 95% CI, 1.25 to 3.12; P=0.004) after controlling for case mix factors, dialysis status, and fistula location. These findings suggest that postoperative fistula venous stenosis associates with fistula maturation failure. Preoperative venous hyperplasia may associate with maturation failure but if so, only modestly.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Constrição Patológica/etiologia , Doenças Vasculares Periféricas/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Constrição Patológica/diagnóstico por imagem , Feminino , Humanos , Hiperplasia/complicações , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Prospectivos , Fluxo Sanguíneo Regional , Diálise Renal , Túnica Íntima/patologia , Ultrassonografia
17.
J Am Soc Nephrol ; 28(10): 3076-3088, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28724774

RESUMO

Stenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain. We also studied a representative subset of veins for markers of monocyte/macrophage content, cell proliferation, apoptosis, and neoangiogenesis. Neointima occupied >20% of the lumen in 57% of fully circumferential vein samples, and neointimal hyperplasia associated positively with age and inversely with black race. The neointima was usually irregularly thickened, sometimes concentric, and contained α-smooth muscle actin-expressing cells of smooth muscle or myofibroblast origin. Proteoglycans admixed with lesser amounts of collagen constituted the predominant matrix in the neointima. In 82% of vein samples, the media of vessel walls contained large aggregates of collagen. A minority of veins expressed markers of inflammation, cell proliferation, cell death, calcification, or neoangiogenesis. In conclusion, we observed preexisting abnormalities, including neointimal hyperplasia and prominent accumulation of extracellular matrix, in veins used for AVF creation from a substantial proportion of this cohort.


Assuntos
Derivação Arteriovenosa Cirúrgica , Neointima/patologia , Calcificação Vascular/patologia , Veias/patologia , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/patologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Renal
18.
Am J Kidney Dis ; 69(6): 805-814, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28359657

RESUMO

BACKGROUND: Disturbances in vitamin D metabolism are common in patients with end-stage renal disease and may contribute to vascular dysfunction. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: We evaluated 558 of 602 participants at baseline of the Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study of a cohort of patients with chronic kidney disease awaiting arteriovenous fistula (AVF) creation surgery. FACTOR: 4 vitamin D metabolites measured with liquid chromatography-tandem mass spectroscopy from samples obtained within 4 weeks prior to AVF surgery. OUTCOMES: Vasodilator functions and measurements of arterial stiffness. MEASUREMENTS: Trained HFM Study personnel measured brachial artery flow-mediated dilation, nitroglycerin-mediated dilation, and carotid-femoral and carotid-radial pulse wave velocities (PWVs) prior to AVF creation. We evaluated associations after basic adjustment for sex, age, and clinical site and more fully adjusted additionally for baseline education, smoking, body mass index, diabetes, dialysis status, and medication use. RESULTS: Mean participant age was 55±13 (SD) years and 65% were receiving maintenance dialysis. None of the vitamin D metabolites were significantly associated with flow-mediated dilation, carotid-femoral PWV, or carotid-radial PWV in basic or fully adjusted analyses. Higher serum concentrations of bioavailable vitamin D and 1,25-dihydroxyvitamin D were associated with 0.62% and 0.58% greater nitroglycerin-mediated dilation values, respectively, in basic models; however, these associations were no longer statistically significant with full adjustment. There were no significant associations of vitamin D metabolites with carotid-femoral or carotid-radial PWV in fully adjusted analyses. LIMITATIONS: Cross-sectional ascertainment of vitamin D metabolites and vascular functions late during the course of kidney disease. CONCLUSIONS: Serum concentrations of vitamin D metabolites are not associated with vasodilator functions or vascular stiffness at baseline in a cohort study of patients with chronic kidney disease awaiting AVF creation surgery. Laboratory measurements of vitamin D metabolites are unlikely to provide useful information regarding vascular functions in this setting.


Assuntos
25-Hidroxivitamina D 2/sangue , Anastomose Cirúrgica , Calcifediol/sangue , Ergocalciferóis/sangue , Falência Renal Crônica/terapia , Diálise Renal , Rigidez Vascular/fisiologia , Vasodilatação/fisiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Artérias/cirurgia , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiopatologia , Artérias Carótidas/fisiopatologia , Cromatografia Líquida , Estudos de Coortes , Estudos Transversais , Feminino , Artéria Femoral/fisiopatologia , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Nitroglicerina/farmacologia , Estudos Prospectivos , Análise de Onda de Pulso , Artéria Radial/fisiopatologia , Espectrometria de Massas em Tandem , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Veias/cirurgia , Vitamina D/sangue
19.
J Vasc Surg ; 64(4): 1050-1058.e1, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27478007

RESUMO

OBJECTIVE: Access-related hand ischemia (ARHI) is a major complication after hemodialysis access construction. This study was designed to prospectively describe its incidence, predictors, interventions, and associated access maturation. METHODS: The Hemodialysis Fistula Maturation Study is a multicenter prospective cohort study designed to identify predictors of autogenous arteriovenous access (arteriovenous fistula [AVF]) maturation. Symptoms and interventions for ARHI were documented, and participants who received interventions for ARHI were compared with other participants using a nested case-control design. Associations of ARHI with clinical, ultrasound, vascular function, and vein histologic variables were each individually evaluated using conditional logistic regression; the association with maturation was assessed by relative risk, Pearson χ(2) test, and multiple logistic regression. RESULTS: The study cohort included 602 participants with median follow-up of 2.1 years (10th-90th percentiles, 0.7-3.5 years). Mean age was 55.1 ± 13.4 (standard deviation) years; the majority were male (70%), white (47%), diabetic (59%), smokers (55%), and on dialysis (64%) and underwent an upper arm AVF (76%). Symptoms of ARHI occurred in 45 (7%) participants, and intervention was required in 26 (4%). Interventions included distal revascularization with interval ligation (13), ligation (7), banding (4), revision using distal inflow (1), and proximalization of arterial inflow (1). Interventions were performed ≤7 days after AVF creation in 4 participants (15%), between 8 and 30 days in 6 (23%), and >30 days in 16 (63%). Female gender (odds ratio, 3.17; 95% confidence interval, 1.27-7.91; P = .013), diabetes (13.62 [1.81-102.4]; P = .011), coronary artery disease (2.60 [1.03-6.58]; P = .044), higher preoperative venous capacitance (per %/10 mm Hg, 2.76 [1.07-6.52]; P = .021), and maximum venous outflow slope (per [mL/100 mL/min]/10 mm Hg, 1.13 [1.03-1.25]; P = .011) were significantly associated with interventions; a lower carotid-femoral pulse wave velocity and the outflow vein diameter in the early postoperative period (days 0-3) approached significance (P < .10). Intervention for ARHI was not associated with AVF maturation failure (unadjusted risk ratio, 1.18 [0.69-2.04], P = .56; adjusted odds ratio, 0.97 [0.41-2.31], P = .95). CONCLUSIONS: Remedial intervention for ARHI after AVF construction is uncommon. Diabetes, female gender, capacitant outflow veins, and coronary artery disease are all associated with an increased risk of intervention. These higher risk patients should be counseled preoperatively, their operative plans should be designed to reduce the risk of hand ischemia, and they should be observed closely.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Mãos/irrigação sanguínea , Isquemia/epidemiologia , Diálise Renal , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Isquemia/terapia , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Seleção de Pacientes , Estudos Prospectivos , Retratamento , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
20.
J Am Heart Assoc ; 5(7)2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27451463

RESUMO

BACKGROUND: End-stage renal disease is accompanied by functional and structural vascular abnormalities. The objective of this study was to characterize vascular function in a large cohort of patients with end-stage renal disease, using noninvasive physiological measurements, and to correlate function with demographic and clinical factors. METHODS AND RESULTS: We analyzed cross-sectional baseline data from the Hemodialysis Fistula Maturation Study, a multicenter prospective observational cohort study of 602 patients with end-stage renal disease from 7 centers. Brachial artery flow- and nitroglycerin-mediated dilation, carotid-femoral and -radial pulse wave velocity, and venous occlusion plethysmography were performed prior to arteriovenous fistula creation. Relationships of these vascular function measures with demographic, clinical, and laboratory factors were evaluated using linear mixed-effects models. Arterial function, as assessed by flow- and nitroglycerin-mediated dilation and carotid-femoral pulse wave velocity, worsened with increasing age and diabetes mellitus. Venous capacitance decreased with diabetes mellitus but not with age. Flow-mediated dilation was higher among patients undergoing maintenance dialysis than for those at predialysis, and a U-shaped relationship between serum phosphorus concentration and flow-mediated dilation was evident. Partial correlations among different measures of vascular function, adjusting for demographic factors, diabetes mellitus, and clinical center, were modest or essentially nonexistent. CONCLUSIONS: Multiple demographic and clinical factors were associated with the functions of vessels of different sizes and types in this large cohort of patients with end-stage renal disease. Low correlations between the different measures, controlling for demographic factors, diabetes mellitus, and center, indicated that these different types of vascular function otherwise vary heterogeneously across patients.


Assuntos
Anastomose Cirúrgica , Artéria Braquial/fisiopatologia , Falência Renal Crônica/terapia , Análise de Onda de Pulso , Diálise Renal , Procedimentos Cirúrgicos Vasculares , Vasodilatação/fisiologia , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Nitroglicerina , Pletismografia , Estudos Prospectivos , Vasodilatadores
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