Roland Assi

Vein graft adaptation and fistula maturation in the arterial environment

Veins are exposed to the arterial environment during two common surgical procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both cases, veins adapt to the arterial environment that is characterized by different hemodynamic conditions and increased oxygen tension compared with the venous environment. Successful venous adaptation to the arterial environment is critical for long-term success of the vein graft or AVF and, in both cases, is generally characterized by venous dilation and wall thickening. However, AVF are exposed to a high flow, high shear stress, low-pressure arterial environment and adapt mainly via outward dilation with less intimal thickening. Vein grafts are exposed to a moderate flow, moderate shear stress, high-pressure arterial environment and adapt mainly via increased wall thickening with less outward dilation. We review the data that describe these differences, as well as the underlying molecular mechanisms that mediate these processes. Despite extensive research, there are few differences in the molecular pathways that regulate cell proliferation and migration or matrix synthesis, secretion, or degradation currently identified between vein graft adaptation and AVF maturation that account for the different types of venous adaptation to arterial environments.

Hospital Readmission After Pulmonary Lobectomy Is Not Affected by Surgical Approach

BACKGROUND The aim of this study is to identify the predictors of hospital readmission or early unplanned return to clinic within 30 days of discharge after pulmonary lobectomy. METHODS The medical records of patients undergoing lobectomy by the thoracic surgery service between January 2009 and July 2012 were reviewed. All lobectomies were included irrespective of the etiology of disease. Multivariate logistic regression methods were used to identify predictors of readmission and or early unplanned return to clinic. RESULTS Two hundred thirteen patients underwent a pulmonary lobectomy during the study period (median age, 67 years). Pathologic diagnosis was malignant in 94% of the patients and benign in 6%. Minimally invasive approaches were used in 69% of the patients, whereas open thoracotomy was used in 31%. Median hospital length of stay was 4 days, and postoperative mortality occurred in 1 patient (0.5%). The Charlson comorbidity index was 1 ± 1. Predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lung for carbon monoxide were 68% ± 18% and 64% ± 17%, respectively. Postoperative complications occurred in 31% of patients; 13% required readmission to the hospital within 30 days of discharge or early unplanned return to clinic. Predictors of readmission or early unplanned return to clinic were unplanned transfer to the intensive care unit (odds ratio, 10.4; 95% confidence interval, 1.1 to 103.5; p = 0.04) and Charlson comorbidity index greater than 0 (odds ratio, 1.5; 95% confidence interval, 1.04 to 2.03; p = 0.03). Readmission or early unplanned return to clinic was independent of surgical approach (p = 0.32). CONCLUSIONS Patients who require a postoperative transfer to the intensive care unit or with higher Charlson comorbidity index are at higher risk for hospital readmission after pulmonary lobectomy. Readmission was not affected by the surgical approach. Whether a different strategy to follow-up for these high-risk patients can prevent readmission remains to be determined.

The mouse aortocaval fistula recapitulates human arteriovenous fistula maturation

Several models of arteriovenous fistula (AVF) have excellent patency and help in understanding the mechanisms of venous adaptation to the arterial environment. However, these models fail to exhibit either maturation failure or fail to develop stenoses, both of which are critical modes of AVF failure in human patients. We used high-resolution Doppler ultrasound to serially follow mice with AVFs created by direct 25-gauge needle puncture. By day 21, 75% of AVFs dilate, thicken, and increase flow, i.e., mature, and 25% fail due to immediate thrombosis or maturation failure. Mature AVF thicken due to increased amounts of smooth muscle cells. By day 42, 67% of mature AVFs remain patent, but 33% of AVFs fail due to perianastomotic thickening. These results show that the mouse aortocaval model has an easily detectable maturation phase in the first 21 days followed by a potential failure phase in the subsequent 21 days. This model is the first animal model of AVF to show a course that recapitulates aspects of human AVF maturation.

Delivery of mesenchymal stem cells in biomimetic engineered scaffolds promotes healing of diabetic ulcers.

AIM We hypothesized that delivery of mesenchymal stem cells (MSCs) in a biomimetic collagen scaffold improves wound healing in a diabetic mouse model. MATERIALS & METHODS Rolled collagen scaffolds containing MSCs were implanted or applied topically to diabetic C57BL/6 mice with excisional wounds. RESULTS Rolled scaffolds were hypoxic, inducing MSC synthesis and secretion of VEGF. Diabetic mice with wounds treated with rolled scaffolds containing MSCs showed increased healing compared with controls. Histologic examination showed increased cellular proliferation, increased VEGF expression and capillary density, and increased numbers of macrophages, fibroblasts and smooth muscle cells. Addition of laminin to the collagen scaffold enhanced these effects. CONCLUSION Activated MSCs delivered in a biomimetic-collagen scaffold enhanced wound healing in a translationally relevant diabetic mouse model.

Disturbed shear stress reduces Klf2 expression in arterial-venous fistulae in vivo

Laminar shear stress (SS) induces an antiproliferative and anti‐inflammatory endothelial phenotype and increases Klf2 expression. We altered the diameter of an arteriovenous fistula (AVF) in the mouse model to determine whether increased fistula diameter produces disturbed SS in vivo and if acutely increased disturbed SS results in decreased Klf2 expression. The mouse aortocaval fistula model was performed with 22, 25, or 28 gauge needles to puncture the aorta and the inferior vena cava. Duplex ultrasound was used to examine the AVF and its arterial inflow and venous outflow, and SS was calculated. Arterial samples were examined with western blot, immunohistochemistry, and immunofluorescence analysis for proteins and qPCR for RNA. Mice with larger diameter fistulae had diminished survival but increased AVF patency. Increased SS magnitudes and range of frequencies were directly proportional to the needle diameter in the arterial limb proximal to the fistula but not in the venous limb distal to the fistula, with 22‐gauge needles producing the most disturbed SS in vivo. Klf2 mRNA and protein expression was diminished in the artery proximal to the fistula in proportion to increasing SS. Increased fistula diameter produces increased SS magnitude and frequency, consistent with disturbed SS in vivo. Disturbed SS is associated with decreased mRNA and protein expression of Klf2. Disturbed SS and reduced Klf2 expression near the fistula are potential therapeutic targets to improve AVF maturation.

Metabolic Syndrome Predicts Restenosis after Carotid Endarterectomy

BACKGROUND Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis for most patients. Restenosis after CEA can lead to additional interventions and adverse outcomes, but the factors that predict restenosis are poorly understood. This study examined which risk factors, such as metabolic syndrome (MetS), are associated with restenosis after CEA. STUDY DESIGN This retrospective study examined the records of all patients who underwent CEA at the Veterans Affairs Connecticut Healthcare System during a 4-year period. Metabolic syndrome was defined as the presence of 3 or more of the following: hypertension (blood pressure ≥130 mmHg/≥85 mmHg); serum triglycerides ≥150 mg/dL; high-density lipoprotein ≤40 mg/dL; BMI ≥25 kg/m(2); and fasting blood glucose ≥110 mg/dL. Major adverse events were defined as death, stroke, or MI. Restenosis was defined as >50% stenosis on follow-up imaging. RESULTS Seventy-eight patients underwent 79 CEAs during the study period. All patients were male and 76% were white. Mean patient age was 72.6 years. The mean duration of follow-up was 5.2 years. Sixty-seven percent of patients had MetS. Patients with MetS were comparable with those without MetS in demographics and preoperative comorbidities, except for increased hypertension and diabetes, as expected, and chronic renal insufficiency (p = 0.05). There was no significant difference in long-term survival or freedom from MAE between patients with and without MetS. Restenosis was significantly higher in patients with MetS (p = 0.02) and occurred 2 years after CEA in patients with MetS only, with a large increase in restenosis after 5 years (p = 0.018). MetS was an independent predictor of restenosis in multivariable analysis (p = 0.01). CONCLUSIONS Metabolic syndrome is an independent predictor for restenosis after CEA in a high-risk population. More frequent and/or long-term surveillance might be warranted in patients with MetS after CEA.

Sexually transmitted infections of the anus and rectum

Sexually transmitted infections (STIs) represent a significant public health concern. Several STIs, once thought to be on the verge of extinction, have recently reemerged. This change is thought to be partially related to an increase in STIs of the anus and rectum. Importantly, the global human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) epidemic has contributed to the emergence of particular anorectal lesions that require specialized approaches. In this report, we review common anorectal STIs that are frequently referred to colorectal surgeons in the United States. Epidemiology, clinical presentation, and management are summarized, including the latest treatment recommendations. The particularity of anorectal diseases in HIV/AIDS is addressed, along with recent trends in anal cytology and human papillomavirus vaccination.

Metabolic syndrome is associated with type II endoleak after endovascular abdominal aortic aneurysm repair

OBJECTIVE Type II endoleak is usually a benign finding after endovascular abdominal aortic aneurysm repair (EVAR). In some patients, however, type II endoleak leads to aneurysm sac expansion and the need for further intervention. We examined which factors, in particular the components of metabolic syndrome (MetS), would lead to an increase risk of endoleak after EVAR. METHODS The medical records of all patients who underwent EVAR between 2002 and 2011 at the Veterans Affairs Connecticut Healthcare System were reviewed. MetS was defined as the presence of three or more of the following: hypertension (blood pressure ≥130 mm Hg/≥90 mm Hg), serum triglycerides ≥150 mg/dL, serum high-density lipoproteins ≤50 mg/dL for women and ≤40 mg/dL for men, body mass index ≥30 kg/m(2), and fasting blood glucose ≥110 mg/dL. Development of endoleak, including specific endoleak type, was determined by review of standard radiologic surveillance. RESULTS During a 9-year period, 79 male patients (mean age, 73.5 years), underwent EVAR for infrarenal abdominal aortic aneurysm (mean 6.2 cm maximal transverse diameter). MetS was present in 52 patients (66%). The distribution of MetS factors among all patients was hypertension in 86%, hypertriglyceridemia in 72%, decreased high-density lipoprotein in 68%, diabetes in 37%, and a body mass index of ≥30 kg/m(2) in 30%. No survival difference was found between the MetS and non-MetS groups (P = .66). There was no difference in perioperative myocardial infarction or visceral ischemia immediately postoperatively between the two groups. Patients with MetS had a significant increase in acute kidney injury (n = 7, P = .0128). Endoleaks of all types were detected in 26% (n = 20) of all patients; patients with MetS had more endoleaks than patients without MetS (35% vs 7.4%, P = .0039). Of the 19 type II endoleaks, 79% were present at the time of EVAR and only 21% developed during surveillance; 95% had MetS (P = .0007). CONCLUSIONS Type II endoleak after EVAR for abdominal aortic aneurysm is associated with MetS. Whether these patients are subject to more subsequent intervention due to sac expansion is unclear. MetS may be a factor to consider in the treatment of type II endoleak.

Blastomycosis in Indiana: Clinical and Epidemiologic Patterns of Disease Gleaned from a Multicenter Retrospective Study

BACKGROUND To better understand clinical and epidemiologic patterns of blastomycosis, we report on a large series of blastomycosis in Indiana. METHODS All microbiologically and histopathologically confirmed cases of blastomycosis from four hospitals serving Central Indiana from 1985 to 2014 were identified. Available data were collected. Data on population estimates, annual precipitation, and construction in Indiana were evaluated for correlations with incidence rates of blastomycosis. RESULTS A total of 114 patients were identified. The mean age was 44.4 years; 27% had diabetes mellitus, and 16% were immunosuppressed. Most presented with pneumonia (90%); 48% had extrapulmonary disease (CNS involvement in 9%), and 15% developed ARDS. Cultures, cytopathology, and histopathology were positive in 86%, 27%, and 85% of the sample, respectively, and fungal antigen was positive in 76%. Amphotericin B was administered in 49%, and 87% received an azole. Total mortality was 12%. Immunosuppression (OR = 3.0), diabetes mellitus (OR = 2.9), and multilobar pneumonia (OR = 2.9) were associated with increased likelihood of ICU admission. There was a significant increase in incidence over time in Marion County. There was no correlation with amount of precipitation, but the rise in incidence coincided with a 2005 state initiative to expand Indianas highway infrastructure. CONCLUSIONS The incidence of blastomycosis in Central Indiana may be on the rise. Physicians in endemic areas should be aware of the potentially fulminant consequences of the disease.

Characteristics of patients with injury secondary to smoking on home oxygen therapy transferred intubated to a burn center.

BACKGROUND The aim of this study was to compare outcomes of patients who sustained burn and ostensible inhalation injuries while on home oxygen therapy with those suffering equivalent injuries via other mechanisms. STUDY DESIGN Between December 2002 and January 2006, 109 burn patients were transferred to our center intubated. Their charts were retrospectively reviewed. Patients who sustained injuries while on home oxygen therapy were age and total body surface area matched to patients with inhalation and burn injuries secondary to other mechanisms. RESULTS Fourteen of 109 patients were injured while smoking on home oxygen therapy (15.26%). All 14 had COPD. Mean age was 63 years (range 53 to 77 years) and average total body surface area burned was 4% (range 0% to 10%). Charges for the 14 hospitalizations totaled