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Background: The American Society of Plastic Surgeons commissioned the multidisciplinary Performance Measure Development Work Group on Reconstruction after Skin Cancer Resection to identify and draft quality measures for the care of patients undergoing skin cancer reconstruction. Included stakeholders were the American Academy of Otolaryngology-Head and Neck Surgery, the American Academy of Facial Plastic and Reconstructive Surgery, the American Academy of Dermatology, the American Society of Dermatologic Surgery, the American College of Mohs Surgery, the American Society for Mohs Surgery, and a patient representative., Methods: Two outcome measures and five process measures were identified. The outcome measures included the following: (1) patient satisfaction with information provided by their surgeon before their facial procedure, and (2) postprocedural urgent care or emergency room use. The process measures focus on antibiotic stewardship, anticoagulation continuation and/or coordination of care, opioid avoidance, and verification of clear margins., Results: All measures in this report were approved by the American Society of Plastic Surgeons Quality and Performance Measures Work Group and Executive Committee, and the stakeholder societies., Conclusion: The work group recommends the use of these measures for quality initiatives, Continuing Medical Education, Continuous Certification, Qualified Clinical Data Registry reporting, and national quality reporting programs., (Copyright © 2024 by the American Society of Plastic Surgeons.)

The population is aging, and the prevalence of chronic wounds is increasing. Because neovascularization is essential for tissue repair and both local and systemic factors affect new blood vessel formation, we hypothesize that altering either pathway would reciprocally enhance wound healing in the aged. To test this hypothesis, p53 was locally suppressed and endothelial progenitor cells (EPCs) were systemically mobilized in a murine model of senescent wound healing.Bilateral 6-mm full-thickness stented wounds were made on the dorsum of Zmpste24 mice. Animals received weekly topical p53 small interfering RNA (siRNA) (n = 25), weekly topical nonsense siRNA (n = 25), daily subcutaneous AMD3100 injections (n = 25), or daily subcutaneous saline injections (n = 25). Wounds were photographically assessed and harvested for reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunostaining over 40 days. Circulating EPC levels were measured using fluorescence-activated cell sorting analysis.Local p53 siRNA significantly improved Zmpste24 wound healing (18 ± 2 vs 40 ± 3 days; P ≤ 0.0001). p53 siRNA significantly increased local provasculogenic factors (hypoxia-inducible factor 1 α, stromal cell-derived factor 1 α, and vascular endothelial growth factor; P ≤ 0.05) and decreased local proapoptotic factors (p53, PUMA, and Bax; P ≤ 0.05). Local p53 siRNA also significantly increased the number of circulating EPCs (8 ± 0.2% vs 2.6 ± 0.1%; P ≤ 0.0001). AMD3100 treatment also significantly improved wound healing (20 ± 2 vs 40 ± 3 days; P ≤ 0.0001) and increased EPCs mobilization (7.8 ± 0.4% vs 2.6 ± 0.1%; P ≤ 0.0001). In addition, systemic AMD3100 increased local provasculogenic factors (hypoxia-inducible factor 1 α, stromal cell-derived factor 1 α, and vascular endothelial growth factor; P ≤ 0.05) and decreased local proapoptotic factors (p53, PUMA, and Bax; P ≤ 0.05). Both treatments significantly increased the number of blood vessels in the wound bed (P ≤ 0.0001).The marked delay in Zmpste24 wound healing is significantly improved by local (p53 siRNA) and systemic (AMD3100) treatments. The resulting decrease in proapoptotic factors and increase in provasculogenic factors in the wound bed as well as the increased level of circulating EPCs appear to reverse age-related wound healing impairment by enhancing wound neovascularization.

Background: Enthusiasm for the deep inferior epigastric artery perforator (DIEP) flap for autologous breast reconstruction has grown in recent years. However, this flap is not performed at all centers or by all plastic surgeons for breast reconstruction, and it is unclear whether practice patterns have measurably changed. This study aimed to (1) evaluate changing trends in breast flap use in the United States in recent years and (2) identify how these trends have affected charges and costs associated with autologous breast reconstruction., Methods: Patients undergoing autologous breast reconstruction [latissimus dorsi (LD), pedicled transverse rectus abdominus myocutaneous (pTRAM), free TRAM (fTRAM), and DIEP] were identified using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database (2009-2011). A total of 19,182 hospital discharges were reviewed. Patient demographics, hospital teaching center status, payer status, length of stay, total charges, and total costs per discharge were reviewed. Statistical analysis was performed using linear regression, t test, and analysis of variance models., Results: Between 2009 and 2011, the total number of discharges did not change significantly. Patient age distribution was similar for all flap groups. For individual flaps, there was a significant increase in DIEP flaps (P = 0.03), with a decreasing trend for other abdominal-based flaps. The patients receiving DIEP flap breast reconstruction were covered by private insurance at a higher rate than all other flap procedures (P = 0.03), whereas other potential cost determinants did not differ significantly between the groups. The mean charge per flap was $40,704 for LD, $51,933 for pTRAM, $69,909 for fTRAM, and $82,320 for DIEP. The mean cost per flap was $12,017 for LD, $15,538 for pTRAM, $20,756 for fTRAM, and $23,616 for DIEP., Conclusions: Between 2009 and 2011, the total amount of autologous breast reconstruction discharges was relatively stable, but the number of DIEP flaps increased significantly. Review of the Healthcare Cost and Utilization Project Nationwide Inpatient Sample data shows that, compared with LD, pTRAM, and fTRAM flaps, the DIEP flap is associated with higher charges and costs.

Background: The transfer of patients with hand injuries involves a commitment of substantial resources, emphasizing the importance of understanding factors that may influence referral patterns. Anecdotal experience suggests that the likelihood of transfer increases during nights and weekends. This study aimed to analyze patterns of hand trauma transfers to Duke University Medical Center with respect to timing and patient insurance status., Methods: The authors performed a retrospective chart review and analysis of 1147 consecutive patient transfers from 2005 to 2010 at a single level 1 university trauma center. Data categories included timing of transfer, patient demographics, insurance status, diagnosis, and procedures performed. Statistical analysis was performed using SAS software (SAS Institute Inc., Cary, N.C.)., Results: Of the patient sample, 39.8 percent was female, 30 percent were African American, and 57.3 percent were white. Contrary to our expectations, transfers were more likely during the day (p = 0.0001). Likewise, patients were more likely to present on weekdays than on weekends (p = .001). Although uninsured patients were not disproportionately represented overall, they were more frequently transferred at night (p = 0.0001), despite having the same complexity of injuries as privately insured patients. Conversely, patients with private insurance were less likely to be transferred at night (p = 0.0001)., Conclusions: Similar to studies in other surgical specialties, this analysis demonstrates significant associations between insurance status and hand injury transfer patterns. The current climate, including declining numbers of surgeons willing to provide emergency hand care, diminishing reimbursements, and an expanding uninsured patient population, threatens to exacerbate these concerning trends in trauma patient management.

Background: Pulmonary aspergilloma is resected to control life-threatening complications such as massive hemoptysis. The role of prophylactic resection in asymptomatic patients is unclear., Methods: A retrospective review was conducted of 60 patients treated at a tertiary center from 1980 to 2010., Results: The mean age in 34 (56.7%) men and 26 (43.3%) women was 51 years. Immunosuppression, most commonly from chronic steroid use, was present in 17 (28.3%) patients, and preexisting lung disease was present in 47 (78.3%) patients. Hemoptysis occurred in 33 (55%) patients, whereas 9 (15.0%) patients were asymptomatic. Aspergilloma was simple in 13 (21.7%) patients and complex in 47 (78.3%) patients. Surgical approach was by thoracotomy (n=51 [85.0%]), video-assisted thoracoscopic surgery (n=7 [11.7%]), or a cavernostomy (n=2 [3.3%]). Sublobar resections (n=28 [46.7%]) were most common, followed by lobectomy (n=27 [45%]) and pneumonectomy (n=3 [5%]). Postoperative morbidity occurred in 18 (30%) patients, with prolonged air leak the most frequent complication (n=9 [15%]). Two (3.3%) patients experienced empyema, and 4 (6.7%) patients had bronchopleural fistulas (BPFs). Two patients died within 30 days (3.3%). During a mean follow-up of 54.1±62.2 months, 3 patients had recurrent aspergillomas (5.0%). Actuarial 10-year survival was 62.5% for simple and 68.5% for complex aspergillomas (p=0.858). Comorbid conditions (human immunodeficiency virus [HIV] positivity, malignancy) and male sex were associated with lower survival., Conclusions: Selective surgical treatment favoring lesser pulmonary resection results in fungal eradication and control in most patients. Overall survival is similar after surgical management of simple and complex aspergillomas., (Copyright © 2014. Published by Elsevier Inc.)

The mechanotransduction mechanisms linking distraction device activation to new bone formation remain unknown. We hypothesize that the tension stress of activation during distraction osteogenesis is transmitted through lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and application of an external distraction device. After a 3-day latency period, half the animals (n = 12) underwent device activation at 0.25 mm twice daily for 6 days (total activation, 3 mm), and the other half (n = 12) had no activation. On day 10, the animals were injected with fluorescent reactive red lacunocanalicular tracer before killing. Mandibles were harvested, embedded, and sectioned, and reactive red epifluorescence lacunocanalicular flow was measured. Protein was harvested for focal adhesion kinase 1 (FAK1), NESPRIN1, SUN1, LAMIN A/C, and SMAD1 Western blotting as well as for bone morphogenetic protein (BMP)-2 enzyme-linked immunosorbent assay and alkaline phosphatase assay. Lacunocanalicular fluid flow was significantly greater in the distracted samples (60.5 ± 14 vs 10.3 ± 4 molecules of equivalent soluble fluorochrome per megapixel, P = 0.01). Flow distribution demonstrated the highest lacunocanalicular flow near the center of the distraction gap. Increased lacunocanalicular flow resulted in increased FAK1 (P = 0.009), NESPRIN1 (P = 0.01), SUN1 (P = 0.01), and LAMIN A/C (P = 0.008) expression. Focal adhesion kinase 1 activation in the presence of BMP-2 protein expression (P = 0.001) resulted in increased intranuclear SMAD1 phosphorylation (P = 0.04) and alkaline phosphatase activity (P < 0.0001). These findings suggest that activation of the distraction osteogenesis device affects cellular response through changes in lacunocanalicular fluid flow.

Background: The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24(-/-)) mouse could serve as a model of senescent wound healing., Methods: Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24(-/-) mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry., Results: Zmpste24(-/-) mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24(-/-) wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial., Conclusions: The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24(-/-) progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.

Background: Lipoaspirate centrifugation creates graded density of adipose tissue. High-density fat contains more vasculogenic cytokines and progenitor cells and has greater graft survival than low-density fat. The authors hypothesize that accelerating the bone marrow-derived progenitor cell response to injected low-density fat will improve its graft survival., Methods: Male 8-week-old FVB mice (n=60) were grafted with either high-density (n=20) or low-density (n=40) human lipoaspirate. Half of the mice receiving low-density fat (n=20) were treated with a stem cell mobilizer for 14 days. Grafted fat was harvested at 2 and 10 weeks for analysis., Results: Low-density fat, low-density fat plus daily AMD3100, and high-density fat had 26±3.0, 61.2±7.5, and 49.6±3.5 percent graft survival, respectively, at 2 weeks (low-density fat versus low-density fat plus daily AMD3100 and low-density fat versus high-density fat, both p<0.01). Similar results were observed 10 weeks after grafting. Mice receiving low-density fat plus daily AMD3100 had significantly more vasculogenic progenitor cells per cubic centimeter of peripheral blood (p<0.01) and more new blood vessels (p<0.01). Both low-density fat plus daily AMD3100 and high-density fat contained more stromal-derived factor-1α and vascular endothelial growth factor mRNA/protein., Conclusion: Endogenous progenitor cell mobilization enhances low-density fat neovascularization, increases vasculogenic cytokine expression, and improves graft survival to a level equal to that of high-density fat grafts.

Aesthetically pleasing and symmetrical breasts are the goal of reconstructive breast surgery. Sometimes, however, multiple procedures are needed to improve a reconstructed breast's symmetry and appearance. In order to avoid additional corrective procedures, we have developed a new method that uses a reverse engineering technique to produce what we call a new breast replica cast (NBRC). The NBRC is a mould of the contralateral healthy breast, designed according to preoperative laser 3D images. During surgery, the mould is used to help shape the new breast. With this method, we are able to achieve breast symmetry in terms of volume, projection, contour, and position on the chest wall more accurately, more quickly, and more safely than before., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Fat grafting has been shown clinically to improve the quality of burn scars. To date, no study has explored the mechanism of this effect. We aimed to do so by combining our murine model of fat grafting with a previously described murine model of thermal injury., Methods: Wild-type FVB mice (n=20) were anaesthetised, shaved and depilitated. Brass rods were heated to 100°C in a hot water bath before being applied to the dorsum of the mice for 10s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5cc of human fat/saline. Half were sacrificed 4 weeks following grafting, and half were sacrificed 8 weeks following grafting. Both groups underwent repeat Doppler scanning immediately prior to sacrifice. Burn scar samples were taken following sacrifice at both time points for protein quantification, CD31 staining and Picrosirius red staining., Results: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat=305±15.77mV, saline=242±15.83mV; p=0.026). Enzyme-linked immunosorbent assay (ELISA) analysis in fat-grafted animals demonstrated significant increase in vasculogenic proteins at 4 weeks (vascular endothelial growth factor (VEGF): fat=74.3±4.39ngml(-1), saline=34.3±5.23ngml(-1); p=0.004) (stromal cell-derived factor-1 (SDF-1): fat=51.8±1.23ngml(-1), saline grafted=10.2±3.22ngml(-1); p<0.001) and significant decreases in fibrotic markers at 8 weeks (transforming growth factor-ß1(TGF-ß): saline=9.30±0.93, fat=4.63±0.38ngml(-1); p=0.002) (matrix metallopeptidase 9 (MMP9): saline=13.05±1.21ngml(-1), fat=6.83±1.39ngml(-1); p=0.010). CD31 staining demonstrated significantly up-regulated vascularity at 4 weeks in fat-grafted animals (fat=30.8±3.39 vessels per high power field (hpf), saline=20.0±0.91 vessels per high power field (hpf); p=0.029). Sirius red staining demonstrated significantly reduced scar index in fat-grafted animals at 8 weeks (fat=0.69±0.10, saline=2.03±0.53; p=0.046)., Conclusions: Fat grafting resulted in more rapid revascularisation at the burn site as measured by laser Doppler flow, CD31 staining and chemical markers of angiogenesis. In turn, this resulted in decreased fibrosis as measured by Sirius red staining and chemical markers., (Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Maxillofacial skeletal injuries account for a large proportion of emergency department visits and often result in surgical consultation. Although many of the principles of detection and repair are basic, the evolution of technology and therapeutic strategies has led to improved patient outcomes. This article aims to provide a review of the imaging aspects involved in maxillofacial trauma and to delineate its relevance to management., (2012 Elsevier Inc. All rights reserved.)

Background: Distraction osteogenesis has revolutionized the treatment of craniofacial deformities, but it is limited by lengthy consolidation periods and tenuous healing in certain clinical settings, such as irradiated tissue. In this study, the authors aim to investigate whether increasing neovascularization by progenitor cell mobilization accelerates bone formation during distraction., Methods: Sprague-Dawley rats aged 8 weeks (n = 36) were subjected to unilateral mandibular distraction with 3-day latency, 7-day activation (0.25 mm twice daily), and 21-day consolidation periods. From the beginning of the consolidation period, animals received daily injections of either AMD3100 (bone marrow progenitor cell mobilizing agent) or sterile saline. Animals were euthanized on postoperative day 31; mandibles were harvested; and bone regeneration was assessed using micro-computed tomography, immunohistochemistry, bone morphogenetic protein-2 enzyme-linked immunosorbent assay, and mechanical testing., Results: Immunohistochemistry demonstrated that AMD3100 treatment increased vascular density and bone formation. Micro-computed tomography and dual-emission x-ray absorptiometry demonstrated that AMD3100-treated animals had improved bone generation compared with sham-treated controls. Greater force was required on three-point testing to break AMD3100-treated bone. Bone morphogenetic protein-2 expression was up-regulated with AMD3100. Interestingly, the nondistracted contralateral hemimandibles treated with AMD3100 were also stronger than sham-treated counterparts., Conclusions: Progenitor cell mobilization improves bone regeneration in a rat distraction model. Furthermore, because this effect is seen in healthy bone and in ischemic bone healing during distraction, the mechanism is not merely related to oxygenation, but could be a phenomenon of fluid flow.

Background: Although different cranioplasty storage methods are currently in use, no study has prospectively compared these methods. The authors compare freezing and subcutaneous storage methods in a rat model., Methods: Trephine defects (10 mm) were created in 45 Sprague-Dawley rats. The cranial bone grafts were stored in an autologous subcutaneous pocket (n = 15), frozen at -80°C (n = 15), immediately analyzed (n = 12), or immediately replanted into the defect (n = 3). After 10 days of storage, the subcutaneous or frozen grafts were either replanted (subcutaneous, n = 3; frozen, n = 3) or analyzed (subcutaneous, n = 12; frozen, n = 12). Grafts underwent histologic analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase assay, mechanical testing, and micro-computed tomographic imaging., Results: After 10 days of storage, physiologic assays demonstrated a significant decrease in cellular functionality (e.g., alkaline phosphatase assay concentration: fresh, 18.8 ± 0.77 mM/mg; subcutaneous, 12.2 ± 0.63 mM/mg; frozen, 8.07 ± 1.1 mM/mg; p < 0.012 for all comparisons). Mechanical integrity (maximal load) of fresh grafts was greatest (fresh, 9.26 ± 0.29 N; subcutaneous, 6.27 ± 0.64 N; frozen, 4.65 ± 0.29 N; fresh compared with frozen, p < 0.001; fresh compared with subcutaneous, p = 0.006). Replantation of subcutaneously stored and frozen grafts resulted in limited bony union and considerable resorption after 12 weeks; in contrast, replanted fresh grafts demonstrated bony union and little resorption., Conclusions: Current preservation methods for interval cranioplasty do not maintain bone graft viability. Subcutaneous storage appears to provide a small advantage compared with freezing.

Background: The etiology of right lower-quadrant pain in pregnant patients is a challenge in diagnosis. We discuss the surgical issues among pregnant patients with right lower-quadrant pain and demonstrate the method to diagnosis., Study Design: This was a prospective cohort study with enrollment during 2 years. Pregnant patients presenting with acute right lower-quadrant abdominal pain and requiring surgical consult were included. Demographics, gestational age, symptoms, workup, operative results, and pathology were recorded., Results: One-hundred patients were enrolled, 38 had nonspecific abdominal pain, 15 of whom were admitted. There were no differences in temperature, leukocyte count, and neutrophil shift among the admitted and nonadmitted patients. Forty-one patients underwent surgery and had a substantially higher gestational age, leukocyte count, and neutrophil shift than those who did not. Ultrasound was performed considerably more often on first-trimester patients (81.6%) compared with second- (58.1%) and third-trimester (57.9%) patients, and CT scan was used considerably less in the first trimester compared with the second and third trimesters, and considerably less than ultrasound for the first trimester. Sensitivity of ultrasound for appendicitis was inversely correlated to fetal gestational age, and CT scan retained high sensitivity and specificity throughout pregnancy., Conclusions: This is one of the first prospective studies assessing diagnoses and workup of pregnant patients with right lower-quadrant pain. We recommend abdominal ultrasound be the first imaging modality for patients for whom surgical consultation is necessary, thereby determining if the pathology is obstetric. If inconclusive, a CT scan is necessary to guide treatment., (Copyright © 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Clostridium difficile-associated disease (CDAD) is responsible for the majority of nosocomial diarrhea, and fulminant C difficile colitis can have mortality upwards of 80%. Early identification and treatment of fulminant C difficile colitis is critical to patient care, but timing of surgical intervention remains difficult. This review summarizes the epidemiology, predictors of development, and management of fulminant C difficile colitis., Methods: A literature search was conducted between January 1989 and May 2009 using the keywords "clostridium difficile colitis" or "fulminant clostridium difficile colitis" and "surgery." Articles not in English, those not involving human subjects, and case reports were excluded., Conclusion: Early diagnosis and treatment with subtotal colectomy and end ileostomy is critical in reducing the mortality associated with fulminant colitis. Patients who have a history of inflammatory bowel disease (IBD), recent surgery, prior treatment with intravenous immunoglobulin (IVIG), vasopressor requirements, leukocytosis, or increased lactate should have early surgical consultation and operative intervention., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate laparoscopic versus open surgery for suspected appendicitis during pregnancy., Methods: A hospital-based retrospective review of 65 consecutive pregnant patients who underwent surgery for suspected appendicitis from 1999 to 2008 was performed. Significance was determined by Pearson's chi(2) test, Fisher's exact test, Mann-Whitney test, and Kruskal-Wallis test., Results: Of the 65 patients, 48 cases were laparoscopic and 17 open. Use of the laparoscopic versus open approach was significantly increased in the first (100% vs. 0%, p < 0.001) and second trimesters (73% vs. 27%, p < 0.001). The open approach was used more frequently in third-trimester patients (71% vs. 29%, p = NS). Significance was demonstrated in mean length of hospital stay in the laparoscopic versus open group (3.4 vs. 4.2 days, p = 0.001). No maternal mortalities occurred. Follow-up of fetal outcome was achieved in 89% of patients. No difference was demonstrated in fetal loss (1 in laparoscopic group), APGAR score, birth weight, and preterm delivery rate by operative approach. Adverse outcome was associated with maternal temperature greater than 38 degrees C, leukocytosis greater than 16 x 10(9)/l, or more than 48 h between onset of symptoms and emergency room presentation., Conclusions: This article is the largest hospital-based series evaluating the laparoscopic versus open approach for pregnant patients with presumed acute appendicitis. While methodological limitations preclude a definitive recommendation, laparoscopy appears to be a safe, feasible, and efficacious approach for pregnant patients with presumed acute appendicitis. We conclude that it is likely not the surgical approach but the underlying diagnosis combined with maternal factors that determine the risk for pregnancy complications. A benefit of laparoscopy is the diagnostic ability to identify other intra-abdominal pathology which may mimic appendicitis and harbor pregnancy risks.

Background and Purpose: We examined the associations among the vascular beta-amyloid levels, smooth muscle actin, wall thickness, and lumen diameter to achieve greater understanding of the arteriolar changes that accompany Alzheimer disease (AD)., Methods: Post-mortem pathology brain specimens from 76 patients with AD and 19 non-AD age control subjects were studied. We analyzed arterioles of the frontal cortex (Brodmann area 10) by immunohistochemistry and morphometry, and derived measures of vascular beta-amyloid level, smooth muscle actin (SMA) volume, and arteriolar wall thickness and lumen diameter. APOE genotype was determined for each case., Results: Overall, there was a striking reciprocal relationship between arteriolar beta-amyloid volume and smooth muscle actin (P<0.0001). In addition, there was a strong positive association between progressively accumulating vascular beta-amyloid and augmentations in both wall thickness (P<0.0001) and lumen width (P<0.0001). In comparison with non-AD control subjects, smooth muscle actin was decreased in patients clinically diagnosed with AD and was reduced >10-fold in cases with AD pathology (Braak I to VI) compared with those lacking AD neuropathology. Significantly altered composition and structure of cortical vessels in pre-Braak stages corroborated our hypothesis that arterioles are devastated early in the AD pathological process. Smooth muscle actin, arteriolar wall thickness, and luminal diameter did not vary with Braak stage severity (P>0.05), indicating that substantial arteriolar damage may precede at least some of the interstitial plaques and neuronal tangles. Moreover, the structural and biochemical arteriolar abnormalities did not vary as a function of APOE genotype (P>0.05)., Conclusions: We postulate that in elderly patients, the continually progressing beta-amyloid-associated angiopathy, at the arteriolar level, harms the contractile apparatus and cerebral blood flow autoregulation, thereby making the downstream capillaries vulnerable to damage. Collectively, our observations lend further support to the idea that microvascular damage has a role, perhaps relatively early, in the onset of major AD pathology.

Hypotension occurs during cardiopulmonary bypass (CPB), in part because of induction of the inflammatory response, for which nitric oxide and guanylate cyclase play a central role. In this study we examined the hemodynamic effects of methylene blue (MB), an inhibitor of guanylate cyclase, administered during cardiopulmonary bypass (CPB) to patients taking angiotensin-converting enzyme inhibitors. Thirty patients undergoing cardiac surgery were randomized to receive either MB (3 mg/kg) or saline (S) after institution of CPB and cardioplegic arrest. CPB was managed similarly for all study patients. Hemodynamic data were assessed before, during, and after CPB. The use of vasopressors was recorded. All study patients experienced a similar reduction in mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) with the onset of CPB and cardioplegic arrest. MB increased MAP and SVR and this effect lasted for 40 minutes. The saline group demonstrated a persistently reduced MAP and SVR throughout CPB. The saline group received phenylephrine more frequently during CPB, and more norepinephrine after CPB to maintain a desirable MAP. The MB group recorded significantly lower serum lactate levels despite equal or greater MAP and SVR. In conclusion, administration of MB after institution of CPB for patients taking angiotensin-converting enzyme inhibitors increased MAP and SVR and reduced the need for vasopressors. Furthermore, serum lactate levels were lower in MB patients, suggesting more favorable tissue perfusion.