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1.
J Vasc Surg ; 79(6): 1457-1465, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38286153

RESUMEN

OBJECTIVE: Cryopreserved (CP) products are utilized during challenging cases when autogenous or prosthetic conduit use is not feasible. Despite decades of experience with cadaveric greater saphenous vein (GSV), there is limited available data regarding the outcomes and patency of other CP products, specifically arterial and deep venous grafts. This study was designed to evaluate outcomes of non-GSV CP conduits in patients undergoing urgent, emergent, and elective arterial reconstruction at our institution. We hypothesized that non-GSV CP allografts have adequate patency and outcomes and are therefore a feasible alternative to GSV in settings where autologous graft is unavailable or prosthetic grafts are contraindicated. METHODS: This study was approved by the Institutional Review Board at our institution. We retrospectively reviewed charts of patients undergoing arterial reconstructions using CP conduits from 2010 to 2022. Data collected included demographics, comorbidities, smoking status, indications for surgery, indication for CP conduit use, anatomic reconstruction, urgency of procedure, and blood loss. Time-to-event outcomes included primary and secondary graft patency rates, follow-up amputations, and mortality; other complications included follow-up infection/reinfection and 30-day complications, including return to the operating room and perioperative mortality. Time-to-event analyses were evaluated using product-limit survival estimates. RESULTS: Of 96 identified patients receiving CP conduits, 56 patients received non-GSV conduits for 66 arterial reconstructions. The most common type of non-GSV CP product used was femoral artery (31 patients), followed by aorto-iliac artery (22 patients), and femoral vein (19 patients), with some patients receiving more than one reconstruction or CP product. Patients were mostly male (75%), with a mean age of 63.1 years and a mean body mass index of 26.7 kg/m2. Indications for CP conduit use included infection in 53 patients, hostile environment in 36 patients, contaminated field in 30 patients, tissue coverage concerns in 30 patients, inadequate conduit in nine patients, and patient preference in one patient. Notably, multiple patients had more than one indication. Most surgeries (95%) were performed in urgent or emergent settings. Supra-inguinal reconstructions were most common (53%), followed by extra-anatomic bypasses (47%). Thirty-day mortality occurred in 10 patients (19%). Fifteen patients (27%) required return to the operating room for indications related to the vascular reconstructions, with 10 (18%) cases being unplanned and five (9%) cases planned/staged. Overall survival at 6, 12, and 24 months was 80%, 68%, and 59%, respectively. Primary patency at 6, 12, and 24 months was 86%, 70%, and 62%, respectively. Amputation freedom at 6 months, 12 months, and 24 months was 98%, 95%, and 86%, respectively for non-traumatic indications. CONCLUSIONS: Non-GSV CP products may be used in complex arterial reconstructions when autogenous or prosthetic options are not feasible or available.


Asunto(s)
Criopreservación , Grado de Desobstrucción Vascular , Humanos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Factores de Riesgo , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Arterias/cirugía , Arterias/trasplante , Amputación Quirúrgica , Enfermedad Arterial Periférica/cirugía , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico por imagen , Recuperación del Miembro , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Anciano de 80 o más Años , Prótesis Vascular , Complicaciones Posoperatorias/etiología
2.
J Vasc Surg Cases Innov Tech ; 9(1): 101080, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36747607

RESUMEN

Background: Thoracic outlet syndrome (TOS) is a rare condition caused by compression of the neurovascular structures within the thoracic outlet. Different classifications of TOS exist depending on the neurovascular structure being compressed: neurogenic, venous, or arterial. Any of these forms can present independently or coexist with one other. TOS symptoms are sometimes precipitated by the presence of boney abnormalities that often require surgical intervention for ultimate resolution. This retrospective review will examine the presentations and outcomes of patients with TOS whose cause was a boney abnormality. Methods: A total of 73 patients who underwent thoracic outlet surgery between 2016 and 2021 were retrospectively reviewed via electronic medical records. Twelve (16%) patients demonstrated boney abnormalities on presentation causing their symptoms. The patients with boney abnormalities were analyzed based on venous, arterial, or neurogenic TOS diagnosis. Results: Of the 12 patients with boney abnormalities, 5 were classified as venous TOS, 6 patients as neurogenic TOS, and 1 as arterial TOS. The boney abnormalities were as follows: venous TOS: three clavicular fractures, one nonfused congenital clavicle, and one residual rib; neurogenic TOS: three fractured first ribs, one fractured clavicle, and two cervical ribs; and arterial TOS: fused first and second rib with bilateral cervical ribs and arterial compression. Postoperatively, there were no artery, vein, or nerve injuries. Five patients had a pneumothorax treated over night with a chest tube, and one patient had a superficial wound infection. The median hospital stay was 1 day. All patients completed physical therapy after surgery. All patients have symptom resolution at follow-up. Conclusions: Patients with boney abnormalities constitute about one-fifth of patients who can present with all three forms of TOS: neurogenic, arterial, and venous, and some will have more than one of these presentations. Results in patients undergoing surgery with boney abnormalities causing thoracic outlet syndrome are excellent with symptom resolution and without substantial complications.

3.
J Vasc Surg Venous Lymphat Disord ; 11(1): 156-160, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36273741

RESUMEN

BACKGROUND: Venous thoracic outlet syndrome (VTOS) is a debilitating condition with several well-documented treatment paradigms. We reviewed the outcomes from a large academic institution of patients who had undergone transaxillary first rib resection with delayed venography (TA) or infraclavicular first rib and subclavius muscle resection with concomitant venography (ICV) for VTOS with subclavian vein thrombosis. METHODS: We performed a retrospective review of the medical records of all patients who had undergone first rib resection and scalenectomy for VTOS with subclavian vein thrombosis at a single academic institution. The demographics, presentation, operative records, and outcomes were collected. Descriptive statistics were used to compare the two groups. RESULTS: A total of 73 patients had undergone first rib resection for VTOS during the study period. Of the 73 patients, 36 (49%) had presented with thrombosis of the subclavian vein and were included in the present review. Of the 36 patients, 26 (72%) had undergone TA and 10 (28%) had undergone ICV. No significant differences were seen between the two groups in female gender (54% vs 50%; P = 1.00) or age (28.7 years vs 29.5 years; P = .88). A higher percentage of the ICV group had undergone preoperative thrombolysis (70% vs 27%; P = .02). All the patients in the ICV group had undergone intraoperative balloon venoplasty at resection. The mean time from thrombosis to resection was 2.3 months. All of the TA group had undergone venography at 2 weeks postoperatively. Venography had revealed 15 stenotic veins requiring venoplasty, 8 widely patent veins, 1 acutely thrombosed vein, and 3 chronically occluded veins. The time from initial thrombosis to surgical intervention was 10 months for the patent group, 6 months for the stenotic group, and 4 months for the occluded group. In the TA group, 19% of the patients had required chest tube placement intraoperatively for pneumothorax. In the ICV group, complications included postoperative hematoma (n = 1), wound infection (n = 1), and hemothorax (n = 1). The mean length of stay was 1.04 days for the TA group and 2.00 days for the ICV group (P < .0001). The mean follow-up was 10.4 months and 15.8 months for the TA and ICV groups, respectively. No mortalities were reported. No differences in the vein patency rates were seen between the two groups at follow-up (TA, 93%; vs ICV, 100%; P = 1.00). All the patients were asymptomatic at follow-up. CONCLUSIONS: The outcomes for the patients who had undergone TA or ICV for subclavian vein thrombosis were excellent with no mortality and few complications. The subclavian vein patency rates were high, and all the patients were asymptomatic at follow-up.


Asunto(s)
Síndrome del Desfiladero Torácico , Trombosis de la Vena , Humanos , Femenino , Adulto , Vena Subclavia/diagnóstico por imagen , Vena Subclavia/cirugía , Resultado del Tratamiento , Síndrome del Desfiladero Torácico/diagnóstico por imagen , Síndrome del Desfiladero Torácico/cirugía , Costillas/diagnóstico por imagen , Costillas/cirugía , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/cirugía , Estudios Retrospectivos , Constricción Patológica
4.
Am Surg ; 89(11): 4501-4507, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35971786

RESUMEN

BACKGROUND: Frailty is associated with adverse surgical outcomes including post-operative complications, needs for post-acute care, and mortality. While multiple frailty screening tools exist, most are time and resource intensive. Here we examine the association of an automated electronic frailty index (eFI), derived from routine data in the Electronic Health Record (EHR), with outcomes in vascular surgery patients undergoing open, lower extremity revascularization. METHODS: A retrospective analysis at a single academic medical center from 2015 to 2019 was completed. Information extracted from the EHR included demographics, eFI, comorbidity, and procedure type. Frailty status was defined as fit (eFI≤0.10), pre-frail (0.100.21). Outcomes included length of stay (LOS), 30-day readmission, and non-home discharge. RESULTS: We included 295 patients (mean age 65.9 years; 31% female), with the majority classified as pre-frail (57%) or frail (32%). Frail patients exhibited a higher degree of comorbidity and were more likely to be classified as American Society of Anesthesiologist class IV (frail: 46%, pre-frail: 27%, and fit: 18%, P = 0.0012). There were no statistically significant differences in procedure type, LOS, or 30-day readmissions based on eFI. Frail patients were more likely to expire in the hospital or be discharged to an acute care facility (31%) compared to pre-frail (14%) and fit patients (15%, P = 0.002). Adjusting for comorbidity, risk of non-home discharge was higher comparing frail to pre-frail patients (OR 3.01, 95% CI 1.40-6.48). DISCUSSION: Frail patients, based on eFI, undergoing elective, open, lower extremity revascularization were twice as likely to not be discharged home.


Asunto(s)
Fragilidad , Enfermedades Vasculares Periféricas , Procedimientos Quirúrgicos Vasculares , Anciano , Femenino , Humanos , Masculino , Anciano Frágil , Fragilidad/diagnóstico , Alta del Paciente , Enfermedades Vasculares Periféricas/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Procedimientos Quirúrgicos Vasculares/efectos adversos
5.
Ann Vasc Surg ; 87: 286-294, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35817384

RESUMEN

BACKGROUND: Autogenous arteriovenous fistula (AVF) remains the standard of hemodialysis (HD) access; however, it cannot be reasonably obtained in all patients. For patients with contraindications to AVFs, prosthetic arteriovenous graft (AVG) remains an alternative. AVGs are plagued by high failure rates; however, there is a paucity of literature examining this. This study aims to examine a single-center review of outcomes of forearm loop AVGs in patients requiring HD access. METHODS: A single institution, retrospective chart review was completed from 2012 to 2019, including demographics, end-stage renal disease etiology, brachial vessel diameters, and comorbidities. Logistic regression and Cox proportional hazard models were evaluated. Outcomes were defined as primary patency (time elapsed from graft creation until it was utilized as the patient's primary access), primary-assisted patency (time from primary access to intervention to maintain patency), and functional patency (time from graft placement until graft failure). Additionally, multinomial regression models were used to evaluate associations with categorical number of required interventions. RESULTS: Ninety-eight patients [mean age 61.8 (13.9) years, 42.9% female] were identified as having brachial artery to brachial vein AVG creation during the study period, of which 75% achieved primary patency. Primary-assisted patency was 0.36 [standard error (SE) 0.07] at 6 months and 0.12 (SE 0.05) at 1 year. Functional patency was 0.75 (SE 0.07) at 6 months and 0.43 (SE 0.09) at 1 year. No association between preoperative vessel diameters and primary-assisted or functional patency was observed. Interestingly, there was a significant negative association between previous ipsilateral access and achievement of primary patency with a 60% decrease in odds of achieving primary patency in patients with previous ipsilateral access [odds ratio 0.4, 95% confidence interval (CI) 0.1-0.9, P = 0.03]. There was also noted to be a significant association between the presence of an ipsilateral catheter and increased risk of subsequent abandonment of the AVG (hazard ratio 2.6, 95% CI 1.1-5.8, P = 0.02). CONCLUSIONS: Prosthetic forearm loop AVGs remain hindered in their utility as they show high rates of graft failure within a year of creation. A significant patient-specific factor leading to this was not clearly demonstrated. As guidelines change regarding the nature of dialysis access for patients on HD, these results draw into question the utility of prosthetic forearm loop grafts in patients requiring long-term HD access.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Implantación de Prótesis Vascular , Humanos , Femenino , Persona de Mediana Edad , Masculino , Derivación Arteriovenosa Quirúrgica/efectos adversos , Derivación Arteriovenosa Quirúrgica/métodos , Antebrazo/irrigación sanguínea , Grado de Desobstrucción Vascular , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/terapia , Estudios Retrospectivos , Implantación de Prótesis Vascular/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Factores de Tiempo , Diálisis Renal/efectos adversos
6.
J Vasc Surg ; 75(1): 186-194, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34478808

RESUMEN

OBJECTIVE: Opiate use, dependence, and the associated morbidity and mortality are major current public health problems in the United States. Little is known about patterns of opioid use in patients with peripheral arterial disease (PAD). The purpose of this study was to identify the prevalence of chronic preoperative and postoperative prescription opioid use in patients with PAD. A secondary aim was to determine the demographic, comorbid conditions, and operative characteristics associated with chronic opioid use. METHODS: Using a single-institution database of patients with PAD undergoing open or endovascular lower extremity intervention from 2013 to 2014, data regarding opiate use and associated conditions were abstracted for analysis. Patients were excluded if they did not live in North Carolina or surgery was not for PAD. Preoperative (PreCOU) and postoperative chronic opioid use (PostCOU) were defined as consistent opioid prescription filling in the 3 months before and after the index procedure, respectively. Opioid prescription filling was assessed using the North Carolina Controlled Substance Reporting System. Demographics, comorbid conditions, other adjunct pain medication data, and operative characteristics were abstracted from our institutional electronic medical record. Associations with PreCOU were evaluated using the t test, Wilcoxon test, or two-sample median test (continuous), or the χ2 or Fisher exact tests (categorical). RESULTS: A total of 202 patients undergoing open (108; 53.5%) or endovascular (94; 46.5%) revascularization for claudication or critical limb ischemia were identified for analysis. The mean age was 64.6 years, and 36% were female. Claudication was the indication for revascularization in 26.7% of patients, and critical limb ischemia was the indication in 73.3% of patients. The median preoperative ankle-brachial index (ABI) was 0.50. Sixty-eight patients (34%) met the definition for PreCOU. PreCOU was associated with female gender, history of chronic musculoskeletal pain, benzodiazepine use, and self-reported illicit drug use. Less than 50% of patients reported use of non-opiate adjunct pain medications. No association was observed between PreCOU and pre- or postoperative ABI, or number of prior lower extremity interventions. Following revascularization, the median ABI was 0.88. PreCOU was not associated with significant differences in postoperative complications, length of stay, or mortality. Overall, 71 patients (35%) met the definition for PostCOU, 14 of whom had no history of preoperative chronic opiate use. Ten patients with PreCOU did not demonstrate PostCOU. CONCLUSIONS: Chronic opiate use was common in patients with PAD with a prevalence of approximately 35%, both prior to and following revascularization. Revascularization was associated with a termination of chronic opiate use in less than 15% of patients with PreCOU. Additionally, 10% of patients who did not use opiates chronically before their revascularization did so afterwards. Patients with PAD requiring intervention represent a high-risk group with regards to chronic opiate use. Increased diligence in identifying opioid use among patients with PAD and optimizing the use of non-narcotic adjunct pain medications may result in a lower prevalence of chronic opiate use and its attendant adverse effects.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Angioplastia/efectos adversos , Isquemia Crónica que Amenaza las Extremidades/cirugía , Claudicación Intermitente/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Anciano , Angioplastia/estadística & datos numéricos , Isquemia Crónica que Amenaza las Extremidades/complicaciones , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Claudicación Intermitente/complicaciones , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Periodo Posoperatorio , Periodo Preoperatorio , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
7.
J Vasc Surg ; 73(1): 250-257, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32360376

RESUMEN

OBJECTIVES: Frailty is associated with adverse outcomes among patients with vascular disease. Grip strength measurement is a comparatively simple, quick, and inexpensive screening test for weakness (a component of frailty) that is potentially applicable to clinical practice. We hypothesized that grip strength and categorical weakness are associated with clinical outcomes among patients with vascular disease. To test this hypothesis, we conducted a longitudinal cohort study evaluating associations between grip strength measured during outpatient clinic visits for vascular disease and clinical outcomes, including survival and perioperative outcomes. METHODS: Adult patients recruited from outpatient vascular surgery and/or vascular medicine clinics underwent dominant hand grip strength measurement using a hand dynamometer. Participants were categorized as weak based on grip strength, sex, and body mass index. Multivariable logistic models were used to evaluate perioperative outcomes. Mortality was evaluated using Cox proportional hazards models adjusted for sex, age, and operative intervention during follow-up. RESULTS: We enrolled 321 participants. The mean patients age was 69.0 ± 9.4 years, and 33% were women. Mean grip strength was 32.0 ± 12.1 kg, and 92 participants (29%) were categorized as weak. The median follow-up was 24.0 months. Adverse perioperative events occurred in 32 of 84 patients undergoing procedures. Grip strength was associated with decreased risk of perioperative adverse events (hazard ratio [HR], 0.41 per 12.7 kg increase; 95% confidence interval [CI], 0.20-0.85; P = .0171) in a model adjusted for open versus endovascular procedure (HR, 12.75 for open; 95% CI, 2.54-63.90; P = .0020) and sex (HR, 3.05 for male; 95% CI, 0.75-12.4; P = .120). Grip strength was also associated with a lower risk of nonhome discharge (HR, 0.34 per 12.7 kg increase; 95% CI, 0.14-0.82; P = .016) adjusted for sex (HR, 2.14 for male; 95% CI, 0.48-9.50; P = .31) and open versus endovascular procedure (HR, 10.36 for open; 95% CI, 1.20-89.47; P = .034). No associations between grip strength and length of stay were observed. Mortality occurred in 48 participants (14.9%) during follow-up. Grip strength was inversely associated with mortality (HR, 0.46 per 12.5 kg increase; 95% CI, 0.29-0.73; P = .0009) in a model adjusted for sex (HR, 5.08 for male; 95% CI, 2.1-12.3; P = .0003), age (HR, 1.04 per year; 95% CI, 1.01-1.08), and operative intervention during follow-up (HR, 1.23; 95% CI, 0.71-2.52). Categorical weakness was also associated with mortality (HR, 1.81 vs nonfrail; P = .048) in a model adjusted for age (HR, 1.06 per year; P = .002) and surgical intervention (HR, 1.36; 95% CI, 1.02-0.09; P = .331). CONCLUSIONS: Grip strength is associated with all-cause mortality, perioperative adverse events, and nonhome discharge among patients with vascular disease. These observations support the usefulness of grip strength as a simple and inexpensive risk screening tool for patients with vascular disease.


Asunto(s)
Procedimientos Endovasculares/efectos adversos , Fuerza de la Mano/fisiología , Alta del Paciente/tendencias , Complicaciones Posoperatorias/mortalidad , Enfermedades Vasculares/diagnóstico , Factores de Edad , Anciano , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Humanos , Masculino , Complicaciones Posoperatorias/diagnóstico , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología , Enfermedades Vasculares/fisiopatología , Enfermedades Vasculares/cirugía
8.
Ann Vasc Surg ; 73: 254-263, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33248240

RESUMEN

BACKGROUND: Diabetes mellitus is a major risk factor for progression to lower extremity amputation (LEA) due to progressive neuropathy and glycemia-induced vasculopathy. In this study, we evaluated risk factors for incident LEA type 2 diabetics during a randomized controlled trial and extended post-trial follow-up. METHODS: The Action to Control Cardiovascular Risk in Diabetes trial randomized 10,251 type 2 diabetics to intensive glycemic control (Hemoglobin A1c (HbA1c) target <6.0%) versus standard glycemic control (HbA1c target 7.0-7.9%). Using backward elimination logistic regression models, we examined relationships between neuropathy using the Michigan Neuropathy Screening Instrument (MNSI) and glycemic control and incident LEA during the clinical trial and subsequent follow-up. RESULTS: 9,746 patients were followed for a mean of 7.9 +/-3.1 (median 8.9) years after randomization. Ninety-eight (1%) participants underwent an incident LEA during the trial or post-trial follow-up period. Baseline demographics and traditional risk factors were examined by incident amputation status. Multivariable models revealed that abnormal 10 gm filament test (HR 4.50, 95% CI 2.92-6.95, P < 0.0001), presence of ulceration (HR 4.22, 95% CI 1.65-10.8, P = 0.0004), abnormal appearance on foot examination (HR 4.75, 95% CI 2.30-9.83, P < 0.0001), and mean postrandomization HbA1c (HR 1.65, 95% CI 1.35-2.00, P < 0.0001) were strongly predictive of LEA when accounting for other common risk factors for amputation. CONCLUSIONS: In this post hoc analysis of a large randomized controlled population of diabetic patients, we found that components of the MNSI score including presence of ulceration, abnormal appearance of the foot, and 10 gm filament monofilament scoring were strongly predictive of LEA. This adds a valuable clinical tool in the risk stratification of diabetic patients for LEA.


Asunto(s)
Amputación Quirúrgica , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Angiopatías Diabéticas/terapia , Neuropatías Diabéticas/terapia , Control Glucémico , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/inervación , Anciano , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/etiología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/etiología , Progresión de la Enfermedad , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
9.
Contemp Clin Trials Commun ; 14: 100357, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31016270

RESUMEN

Timely placement of an arteriovenous (AV) vascular access (native AV fistula [AVF] or prosthetic AV graft [AVG]) is necessary to limit the use of tunneled central venous catheters (TCVC) in patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD). National guidelines recommend placement of AVF as the AV access of first choice in all patients to improve patient survival. The benefits of AVF over AVG are less certain in the older adults, as age-related biological changes independently modulate patient outcomes. This manuscript describes the rationale, study design and protocol for a randomized controlled pilot study of the feasibility and effects of AVG-first access placement in older adults with no prior AV access surgery. Fifty patients age ≥65 years, with incident ESKD on HD via TCVC or advanced kidney disease facing imminent HD initiation, and suitable upper extremity vasculature for initial placement of an AVF or AVG, will be randomly assigned to receive either an upper extremity AVG-first (intervention) or AVF-first (comparator) access. The study will establish feasibility of randomizing older adults to the two types of AV access surgery, evaluate relationships between measurements of preoperative physical function and vascular access development, compare vascular access outcomes between groups, and gather longitudinal assessments of upper extremity muscle strength, gait speed, performance of activities of daily living, and patient satisfaction with their vascular access and quality of life. Results will assist with the planning of a larger, multicenter trial assessing patient-centered outcomes.

10.
Ann Vasc Surg ; 58: 309-316, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30742889

RESUMEN

BACKGROUND: Free digital platforms are smartphone-compatible and permit self-directed curriculum development based on learners' interests and educational needs. We developed a free mobile vascular surgery handbook initiated, authored, and edited by surgical house officers and surveyed on the content and users. METHODS: Using a free digital platform, house officers developed a vascular surgery handbook. Initiated by a single user for conference preparation and clinical care, the use expanded through sharing among residents. The handbook was then deployed at a second medical center, with free access granted to users after completing a survey. Handbook and content use were evaluated based on user ratings ≥4 on a Likert scale from 1 to 5, where 1 = "strongly disagree" and 5 = "completely agree." Domains assessed included handbook ease of use, content, and relevance to a variety of learning environments and goals (e.g., preparation for the operating room, rounds, clinic, teaching conferences, and examinations). Analytic methods included qualitative analysis, graphical evaluation, and categorical tests. RESULTS: The handbook is organized into sections, with each consisting of multiple pages and/or posts related to the section topic. Sections with the most content included lower extremity arterial disease, endovascular aneurysm repair/thoracic endovascular aortic repair, venous disease, anticoagulation, and anatomy/exposures. Fifty-four users participated in the evaluation phase, including different types of surgical residents (35%), medical students (30%), and anesthesia residents (22%). Sixty-nine percent of participants were in their position for <2 years. The average age was 29.1 years, and 57% were women. Preferred learning styles among users at the time of enrollment primarily included question banks (52%), followed by slide-based lectures (15%) and "chalk talk" lectures (13%). Of the users who participated in the presurvey, 43 users participated in the postsurvey with a general agreement on the handbook being an easy-to-use resource that was useful for gaining overall knowledge and contained accurate information. Users generally agreed they would recommend the handbook to a colleague. CONCLUSIONS: References customized to user needs can be developed through crowdsourcing and published with free digital resources. These approaches allow mobile access to useful information during conferences and clinical care. House officers' self-perceived educational needs can be targeted for tailored educational initiatives.


Asunto(s)
Teléfono Celular , Instrucción por Computador/instrumentación , Colaboración de las Masas , Educación de Postgrado en Medicina/métodos , Educación de Pregrado en Medicina/métodos , Internado y Residencia , Aplicaciones Móviles , Estudiantes de Medicina , Cirujanos/educación , Procedimientos Quirúrgicos Vasculares/educación , Adulto , Actitud del Personal de Salud , Curriculum , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Difusión de la Información , Masculino , Estudiantes de Medicina/psicología , Cirujanos/psicología , Escritura , Adulto Joven
11.
J Am Coll Surg ; 227(6): 596-604, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30336205

RESUMEN

BACKGROUND: Diabetes mellitus is a major risk factor for peripheral arterial disease and lower extremity amputation (LEA). We evaluated the effects of intensive glucose control (IGC) on risk of LEA in patients with type 2 diabetes during a randomized-controlled multicenter trial. STUDY DESIGN: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial randomized patients with type 2 diabetes to IGC (HbA1c target < 6.0%) or standard glycemic control (SGC; HbA1c target 7.0% to 7.9%). Using analysis of mean HbA1c, we examined relationships between glycemic control and incident/recurrent LEA during the clinical trial/follow-up. RESULTS: Mean post-randomization HbA1c over the course of the trial and post-trial follow-up was 7.3% ± 0.9% (6.8% ± 0.8% in the IGC arm, 7.7% ± 0.7% in the SGC arm). There were 124 participants who had at least 1 LEA during the study period; 73 were randomized to the SGC arm and 51 to the IGC arm (p = 0.049). Randomization to IGC was associated with decreased LEA rate (HR 0.69, 95% CI 0.483 to 0.987, p = 0.042). In multivariable models, mean HbA1c was a powerful predictor of LEA (HR 2.07 per 1% increase in HbA1c, 95% CI 1.67 to 2.57, p < 0.0001). Post-randomization mean HbA1c remained a strong predictor of LEA after controlling for other important covariates and competing risk of death (HR 1.94 per 1% increase in HbA1c, 95% CI 1.52 to 2.46, p < 0.0001). CONCLUSIONS: In patients with type 2 diabetes, IGC was associated with a reduction in the risk for LEA. After 3.7 years of IGC, there was an enduring protective effect against LEA. Improved glycemic control was a strong predictor of decreased risk for subsequent LEA. This study suggests that tight glycemic control, even over a short time period, has potential to reduce risk of limb loss.


Asunto(s)
Amputación Quirúrgica , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Extremidad Inferior , Anciano , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/terapia , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/etiología , Enfermedad Arterial Periférica/terapia
12.
J Vasc Surg ; 67(5): 1512-1520, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29276105

RESUMEN

OBJECTIVE: Frailty is associated with adverse events, length of stay, and nonhome discharge after vascular surgery. Frailty measures based on walking-based tests may be impractical or invalid for patients with walking impairment from symptoms or sequelae of vascular disease. We hypothesized that grip strength is associated with frailty, comorbidity, and cardiac risk among patients with vascular disease. METHODS: Dominant hand grip strength was measured during ambulatory clinic visits among patients with vascular disease (abdominal aortic aneurysm [AAA], carotid stenosis, and peripheral artery disease [PAD]). Frailty prevalence was defined on the basis of the 20th percentile of community-dwelling population estimates adjusted for age, gender, and body mass index. Associations between grip strength, Charlson Comorbidity Index (CCI), Revised Cardiac Risk Index (RCRI), and sarcopenia (based on total psoas area for patients with cross-sectional abdominal imaging) were evaluated using linear and logistic regression. RESULTS: Grip strength was measured in 311 participants; all had sufficient data for CCI calculation, 217 (69.8%) had sufficient data for RCRI, and 88 (28.3%) had cross-sectional imaging permitting psoas measurement. Eighty-six participants (27.7%) were categorized as frail on the basis of grip strength. Frailty was associated with CCI (odds ratio, 1.86; 95% confidence interval, 1.34-2.57; P = .0002) in the multivariable model. Frail participants also had a higher average number of RCRI components vs nonfrail patients (mean ± standard deviation, 1.8 ± 0.8 for frail vs 1.5 ± 0.7 for nonfrail; P = .018); frailty was also associated with RCRI in the adjusted multivariable model (odds ratio, 1.75; 95% confidence interval, 1.16-2.64; P = .008). Total psoas area was lower among patients categorized as frail vs nonfrail on the basis of grip strength (21.0 ± 6.6 vs 25.4 ± 7.4; P = .010). Each 10 cm2 increase in psoas area was associated with a 5.7 kg increase in grip strength in a multivariable model adjusting for age and gender (P < .0001). Adjusted least squares mean psoas diameter estimates were 25.5 ± 1.1 cm2 for participants with AAA, 26.7 ± 2.0 cm2 for participants with carotid stenosis, and 22.7 ± 0.8 cm2 for participants with PAD (P = .053 for PAD vs AAA; P = .057 for PAD vs carotid stenosis; and P = .564 for AAA vs carotid stenosis). CONCLUSIONS: Grip strength is useful for identifying frailty among patients with vascular disease. Frail status based on grip strength is associated with comorbidity, cardiac risk, and sarcopenia in this population. These findings suggest that grip strength may have utility as a simple and inexpensive risk screening tool that is easily implemented in ambulatory clinics, avoids the need for imaging, and overcomes possible limitations of walking-based measures. Lower mean psoas diameters among patients with PAD vs other diagnoses may warrant consideration of specific approaches to morphomic analysis.


Asunto(s)
Fragilidad/diagnóstico , Fuerza de la Mano , Cardiopatías/diagnóstico , Músculos Psoas/diagnóstico por imagen , Sarcopenia/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Comorbilidad , Estudios Transversales , Femenino , Anciano Frágil , Fragilidad/epidemiología , Fragilidad/fisiopatología , Evaluación Geriátrica , Estado de Salud , Cardiopatías/epidemiología , Cardiopatías/fisiopatología , Humanos , Análisis de los Mínimos Cuadrados , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Dinamómetro de Fuerza Muscular , North Carolina/epidemiología , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Sarcopenia/epidemiología , Sarcopenia/fisiopatología , Tomografía Computarizada por Rayos X , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/fisiopatología
13.
Ann Vasc Surg ; 44: 41-47, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28479452

RESUMEN

BACKGROUND: Health-related quality of life (QOL) is usually assessed after a defined interval following a single intervention, but critical limb ischemia (CLI) is a chronic condition where multiple interventions are often required over a patient's lifetime. We hypothesized that the impact of CLI treatment interventions on QOL is diminished in the setting of multiple previous interventions. To test this hypothesis, we performed a cross-sectional study evaluating associations between cumulative number of previous peripheral artery disease (PAD) treatment interventions and QOL adjusting for both comorbidity and disease severity. METHODS: Participants with CLI (abnormal ankle brachial index [ABI] plus rest pain and/or tissue loss) were enrolled in a cross-sectional study and completed a disease-specific QOL assessment, (the Vascular Quality of Life Questionnaire-6 [VascuQol-6]). Minimum ABI was used to assess disease severity, and comorbidity was evaluated based on Charlson Comorbidity Index. Cumulative number of PAD treatment interventions was defined based on the lifelong total for both legs. QOL associations were evaluated using a multivariable linear regression model adjusted for age and gender. RESULTS: Thirty-two patients with CLI participated. Mean age was 63 ± 10 years, 72% were men, and 63% were white; mean ABI was 0.6 ± 0.2. Mean VQ-6 score was 11.6 ± 4.2, and QOL was lower in patients with more previous interventions. Multivariable models demonstrated that an increasing number of previous treatment interventions negatively impacted QOL (P = 0.047), whereas positive associations were identified for female gender (P = 0.006) and ABI (P = 0.006). No association between comorbidity and QOL was identified. CONCLUSIONS: Vascular-specific factors appear to be key determinants of QOL among patients with CLI, whereas comorbidity appears less important. Strategies focused on definitive and durable revascularization may reduce cumulative interventions and potentially maximize QOL for patients with CLI.


Asunto(s)
Procedimientos Endovasculares , Isquemia/terapia , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/terapia , Calidad de Vida , Procedimientos Quirúrgicos Vasculares , Anciano , Amputación Quirúrgica , Índice Tobillo Braquial , Comorbilidad , Enfermedad Crítica , Estudios Transversales , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Isquemia/diagnóstico , Isquemia/fisiopatología , Isquemia/psicología , Recuperación del Miembro , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/psicología , Proyectos Piloto , Retratamiento , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos
14.
Ann Vasc Surg ; 38: 29-35, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27581131

RESUMEN

BACKGROUND: Endovascular intervention is considered the first-line treatment for chronic mesenteric ischemia (CMI) when feasible. Two-vessel revascularization is most definitive when celiac (CA) and superior mesenteric arteries (SMA) are diseased, but single-vessel intervention may be performed in patients with 2-vessel disease due to anatomic/technical factors. We evaluated anatomic predictors of clinical outcomes associated with endovascular treatment of CMI among patients with occlusive SMA lesions. METHODS: Patients with CMI treated with endovascular revascularization over 10 years were identified. Patients with SMA occlusions were selected for analysis. Between-group comparisons based on inclusion of an SMA revascularization were evaluated using t-test and chi-squared test. Freedom from symptomatic recurrence or repeat intervention was analyzed using proportional hazards regression. RESULTS: Fifty-four patients with CMI were analyzed. Sixteen (29.6%) patients had CA-only intervention, and 38 (70.4%) patients had SMA revascularization with or without CA intervention. No significant differences in demographics or comorbidity were identified between groups. In the CA-only intervention group, 8 of the 16 (50%) patients developed symptomatic recurrence compared with 8 of the 31 (21.1%) patients whose intervention included the SMA. Patients treated without SMA intervention also had decreased freedom from both symptomatic recurrence (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.2-8.6, P = 0.016) and repeat intervention (HR 5.5, 95% CI 1.8-16.3, P = 0.001). CONCLUSIONS: Among patients with CMI and occlusive SMA lesions, SMA revascularization appears to be the key determinant for symptomatic outcomes and repeat intervention. Patient counseling should include potential future need for surgical revascularization if endovascular SMA treatment cannot be accomplished.


Asunto(s)
Angioplastia de Balón , Arteria Celíaca , Arteria Mesentérica Superior , Isquemia Mesentérica/terapia , Oclusión Vascular Mesentérica/terapia , Anciano , Anciano de 80 o más Años , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/instrumentación , Arteria Celíaca/diagnóstico por imagen , Arteria Celíaca/fisiopatología , Distribución de Chi-Cuadrado , Enfermedad Crónica , Constricción Patológica , Femenino , Humanos , Masculino , Arteria Mesentérica Superior/diagnóstico por imagen , Arteria Mesentérica Superior/fisiopatología , Isquemia Mesentérica/diagnóstico por imagen , Isquemia Mesentérica/fisiopatología , Oclusión Vascular Mesentérica/diagnóstico por imagen , Oclusión Vascular Mesentérica/fisiopatología , Persona de Mediana Edad , Recurrencia , Retratamiento , Estudios Retrospectivos , Factores de Riesgo , Stents , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular
15.
Ann Vasc Surg ; 30: 118-22.e1-2, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26576843

RESUMEN

BACKGROUND: Vascular training includes both integrated residency ("0+5") and postresidency fellowship ("5+2") programs. The impact of training models on attitudes toward graduates as prospective hires is incompletely understood, and existing studies have primarily surveyed surgeons from academic centers. We surveyed surgeons who were in active clinical practice but not affiliated with a medical school or training program to compare perceptions of integrated versus postgraduate programs. METHODS: Vascular surgeons not affiliated with a university-based practice were identified from membership rosters of one regional and one national specialty society and e-mailed an anonymous survey. The survey evaluated respondents' training, practice distribution, general surgery responsibilities, hiring practices, and perception of the integrated and postgraduate trained vascular surgeons. Agreement among specific responses was evaluated using McNemar's test. RESULTS: The survey was sent to 406 surgeons with 71 (17.5%) responding. A total of 42% of respondents indicated that half or more of their cases consisted of open procedures and 10% reported general surgery coverage as part of their practice. More respondents indicated that they consider postgraduate trained surgeons very mature (41% vs. 7%, P < 0.0001) and better prepared for open cases (89% vs. 28%, P < 0.0001), as well as endovascular cases (96% vs. 87%, P = 0.0339). Overall 84% stated that they would interview an integrated program graduate, although only 72% indicated that they would hire one. Overall 16.9% identified ability to cover general surgery as either very important or somewhat important characteristic for a potential hire. CONCLUSIONS: Perceptions of 5+2 graduates as more mature and better prepared for opens surgical cases may influence hiring practices. This suggests that attitudes toward integrated versus 5+2 trained surgeons may differ between academic and community vascular surgeons. Further research is needed to assess whether these differences are related to actual differences in graduate skills, familiarity with integrated graduates, or other factors.


Asunto(s)
Actitud del Personal de Salud , Educación de Postgrado en Medicina , Becas , Internado y Residencia , Especialidades Quirúrgicas , Selección de Profesión , Servicios de Salud Comunitaria , Femenino , Humanos , Masculino , Percepción , Pautas de la Práctica en Medicina , Estados Unidos
16.
J Surg Educ ; 72(6): 1085-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26183786

RESUMEN

INTRODUCTION: In 2006 the Southern Association for Vascular Surgery (SAVS) implemented a mock oral examination program to prepare trainees for the Vascular Surgery Certifying Examination (VCE). METHODS: Participating examinees and examiners were identified from SAVS Recorder records and contacted via e-mail with a request to participate in an anonymous online survey. Examinees were asked about passage on American Board of Surgery examinations and perceptions of the mock oral program. Examiners were asked for their perceptions of the examination, applicant performance, and perceived areas for training improvement. Board passage rates for the group and national comparison data were provided in a de-identified fashion by American Board of Surgery. RESULTS: From 2006 to 2014, 158 examinees and 86 examiners participated in the SAVS mock orals program. In all, 33% of examinees and 35% of examiners completed the anonymous survey. Of the examinees, 27 (60%) reported passage of the mock oral examination on their first attempt and 7 of 9 (78%) reported passage on the second attempt. Second year in training was significantly associated with passage of the mock oral (p = 0.002). Of the examinees questioned, 100% "would recommend" the SAVS mock oral examinations to future trainees. Of the responding examiners, 90% felt that the SAVS mock oral examinations were "comparable" to the VCE and 87% "strongly agreed" that the exercise was a valuable preparatory tool. Examiners identified "ability to describe technical aspects of open vascular techniques" and "management of complications associated with vascular disease processes and operations" as commonly displayed deficits among examinees (80% and 77%, respectively). In all, 115 examinee participants from the SAVS mock orals had taken the VCE between 2006 and 2014. Of them, 90 (78%) passed the VCE on their first attempt. During the same time interval, the national first-time pass rate for the VCE was 86%. CONCLUSIONS: Although participation in the SAVS mock orals was overwhelmingly assessed as a positive preparatory experience by examinees and examiners, no incremental advantage in VCE passage was observed. Explanations for the worse-than-average performance on the VCE are not clear but likely involve numerous factors, including participation bias. Importantly, examiners in the SAVS mock oral process felt that the exercise closely simulated the VCE and uniformly reported pervasive deficits in the areas of demonstrated understanding of open surgical techniques and management of complications. This investigation guides further examination of VCE simulation exercises to assist in guiding the use of educational resources at both institutional and professional society levels.


Asunto(s)
Competencia Clínica , Entrenamiento Simulado , Procedimientos Quirúrgicos Vasculares/educación
18.
J Pharmacol Exp Ther ; 342(3): 808-15, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22700434

RESUMEN

Glucans are natural product carbohydrates that stimulate immunity. Glucans are internalized by the pattern recognition receptor, Dectin-1. Glucans were thought to be trafficked to phagolysosomes, but this is unproven. We examined the internalization and trafficking of soluble glucans in macrophages. Incubation of macrophages with glucan resulted in internalization of Dectin-1 and glucan. Inhibition of clathrin blocked internalization of the Dectin-1/glucan complex. Lipid raft depletion resulted in decreased Dectin levels and glucan uptake. Once internalized, glucans colocalized with early endosomes at 0 to 15 min, with the Golgi apparatus at 15 min to 24 h, and with Dectin-1 immediately (0 h) and again later (15 min-24 h). Glucans did not colocalize with lysosomes at any time interval examined. We conclude that the internalization of Dectin-1/glucan complexes in macrophages is mediated by clathrin and negatively regulated by lipid rafts and/or caveolin-1. Upon internalization, soluble glucans are trafficked via endosomes to the Golgi apparatus, not lysosomes.


Asunto(s)
Clatrina/metabolismo , Glucanos/metabolismo , Aparato de Golgi/metabolismo , Macrófagos/metabolismo , Animales , Clatrina/genética , Endosomas/genética , Endosomas/metabolismo , Glucanos/genética , Glucanos/farmacocinética , Aparato de Golgi/genética , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Lípidos/genética , Lisosomas/genética , Lisosomas/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Transporte de Proteínas
19.
J Pharmacol Exp Ther ; 318(2): 540-6, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16632639

RESUMEN

Dectin-1 is the primary pattern recognition receptor for fungal glucans. Dectin-1 mediates the internalization and biological response to glucans. We examined the effect of i.v. or i.p. glucan phosphate (GP) administration on Dectin-1 membrane expression in murine peripheral blood leukocytes, splenocytes, bone marrow, and peritoneal cells from 3 h to 10 days after injection. Circulating leukocytes were also examined for uptake and internalization of glucans from the blood. Fluorescent-labeled GP was taken up from the systemic circulation by circulating peripheral leukocytes, splenocytes, and peritoneal cells. Following internalization, glucan colocalized with Dectin-1 in an intracellular vesicle. A single parenteral injection of GP resulted in a significant reduction (approximately 33-85%) in peripheral leukocyte membrane-associated Dectin-1 positivity that lasted for up to 7 days. The loss of leukocyte membrane-associated Dectin-1 after GP administration was primarily due to decreased levels of Dectin-1 on neutrophil and monocyte membranes with no significant changes in the percentage of neutrophils or monocytes circulating in the blood. Administration of control carbohydrate polymers, i.e., mannan or pullulan, which are not ligands for Dectin-1, did not decrease Dectin-1 leukocyte positivity, indicating that the effect on Dectin-1 is specific to glucans. In fact, mannan administration increased leukocyte Dectin-1 positivity, thus demonstrating a differential effect on leukocyte Dectin-1, compared with GP. We conclude that systemic administration of GP has a specific and prolonged effect on loss of leukocyte membrane Dectin-1 positivity. These data may have important implications for developing dosing regimens for immunomodulatory carbohydrates.


Asunto(s)
Leucocitos/metabolismo , Proteínas de la Membrana/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , beta-Glucanos/farmacología , Animales , Células Cultivadas , Depresión Química , Citometría de Flujo , Colorantes Fluorescentes/síntesis química , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Lectinas Tipo C , Leucocitos/efectos de los fármacos , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Mananos/farmacología , Ratones , Ratones Endogámicos ICR , Microscopía Confocal , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , beta-Glucanos/química
20.
J Pharmacol Exp Ther ; 314(3): 1079-86, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15976018

RESUMEN

Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 +/- 3% of the glucan phosphate and 20 +/- 7% of the laminarin remained in the serum. Scleroglucan was rapidly absorbed and eliminated. The liver did not significantly contribute to the clearance of plasma glucan. Biological effects were further studied in mice. Following oral administration of 1 mg, glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue (GALT) cells. Internalization of glucan by intestinal epithelial cells was not Dectin-dependent. GALT expression of Dectin-1 and toll-like receptor (TLR) 2, but not TLR4, increased following oral administration of glucan. Oral glucan increased systemic levels of interleukin (IL)-12 (151 +/- 15%) in mice. Oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans. These data demonstrate that orally administered water-soluble glucans translocate from the gastrointestinal (GI) tract into the systemic circulation. The glucans are bound by GI epithelial and GALT cells, and they modulate the expression of pattern recognition receptors in the GALT, increase IL-12 expression, and induce protection against infectious challenge.


Asunto(s)
Glucanos/farmacología , Inmunidad Innata/efectos de los fármacos , Absorción Intestinal , Administración Oral , Animales , Disponibilidad Biológica , Candidiasis/inmunología , Citocinas/biosíntesis , Glucanos/administración & dosificación , Glucanos/farmacocinética , Lectinas Tipo C , Masculino , Proteínas de la Membrana/análisis , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos ICR , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/fisiología , Ganglios Linfáticos Agregados/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Inmunológicos/análisis , Infecciones Estafilocócicas/inmunología , Receptor Toll-Like 2
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