A new approach to a legacy concern: Evaluating machine-learned Bayesian networks to predict childhood lead exposure risk from community water systems.

Lead in drinking water continues to put children at risk of irreversible neurological impairment. Understanding drinking water system characteristics that influence blood lead levels is needed to prevent ongoing exposures. This study sought to assess the relationship between children's blood lead levels and drinking water system characteristics using machine-learned Bayesian networks. Blood lead records from 2003 to 2017 for 40,742 children in Wake County, North Carolina were matched with the characteristics of 178 community water systems and sociodemographic characteristics of each child's neighborhood. Bayesian networks were machine-learned to evaluate the drinking water variables associated with blood lead levels ≥2 µg/dL and ≥5 µg/dL. The model was used to predict geographic areas and water utilities with increased lead exposure risk. Drinking water characteristics were not significantly associated with children's blood lead levels ≥5 µg/dL but were important predictors of blood lead levels ≥2 µg/dL. Whether 10% of water samples exceeded 2 ppb of lead in the most recent year prior to the blood test was the most important water system predictor and increased the risk of blood lead levels ≥2 µg/dL by 42%. The model achieved an area under the receiver operating characteristic curve of 0.792 (±0.8%) during ten-fold cross validation, indicating good predictive performance. Water system characteristics may thus be used to predict areas that are at risk of higher blood lead levels. Current drinking water regulatory thresholds for lead may be insufficient to detect the levels in drinking water associated with children's blood lead levels.

Intraoperative Fluorescence Angiography in Implant-Based Breast Reconstruction: Identifying Risk Factors and Outcomes.

BACKGROUND: Intraoperative fluorescence angiography (FA) has been described as a useful adjunct to physical examination in predicting mastectomy skin flap viability for immediate breast reconstruction. Its use has been described as a screening tool for mastectomy skin flap viability as well as a test used only for patients at high risk for mastectomy skin flap loss. We performed a national database review of implant-based breast reconstruction surgeries to determine the practice patterns of FA in this patient cohort and to determine if this technology impacted clinical outcomes. METHODS: A national insurance claims database was reviewed to select patients having undergone direct-to-implant (DTI) and immediate tissue expander (TE) placement with and without intraoperative FA as well as patients who had FA at the time of mastectomy without reconstruction. Patient characteristics that prompted FA and postoperative outcomes with and without FA were evaluated to determine its clinical impact in the observed practice pattern. RESULTS: Of the 48,464 patients identified, 836 had FA. More than twice as many patients undergoing DTI had FA than patients undergoing immediate TE placement (10.4% vs 5%, P < 0.0001). Twelve percent of patients receiving FA at the time of mastectomy had reconstruction delayed. Fluorescence angiography was associated with a trend toward lower overall complication rates in DTI patients (8.0% vs 11.9% without FA) but a significantly higher overall complication rate with immediate TE placement (13.8% vs 10.5% without FA, P = 0.018) and was associated with higher reoperation (12.0% vs 8.3% without FA, P = 0.037) in the TE group. There was no difference in other individual complications, readmission, or explantation for either clinical group with and without FA. Regression analysis identified obesity (odds ratio, 1.32; P < 0.001) and younger age (odds ratio, 1.74; P < 0.001) to be associated with performing FA, whereas obesity, diabetes, and tobacco use were associated with higher complication rates. CONCLUSIONS: Younger and otherwise healthier obese patients were more likely to have FA. A greater proportion of DTI patients had FA than TE patients with improved outcomes in the former group and worse outcomes in the latter group. Obesity, tobacco use, and diabetes were associated with worse outcomes, whereas only obesity was associated with FA use.

The State of Breast Cancer Reconstruction in Virginia: An Evidence-Based Framework for Identifying Locoregional Health Disparities.

BACKGROUND: Age, race, socioeconomic status, and proximity to plastic surgeons have been shown to impact receipt of reconstruction after mastectomy in several national studies. Given that targeted outreach efforts and programs to address these discrepancies would occur locoregionally, investigation of these reconstructive trends on a state level is warranted. STUDY DESIGN: Patients diagnosed with breast cancer in Virginia between 2000 and 2018 were identified in the Virginia Department of Health Cancer Registry. Patients who underwent mastectomy breast conservation surgery, and/or breast reconstruction at the time of oncologic surgery were identified. Patient demographics were analyzed, and logistic regression analyses were used to determine the likelihood of receipt of mastectomy, receipt of mastectomy versus breast conservation surgery, receipt of mastectomy with reconstruction versus mastectomy alone, and receipt of mastectomy with reconstruction versus breast conservation surgery with respect to the demographic variables. Geographically weighted regression analyses were also performed to determine impact of geographic location on receipt of mastectomy and reconstruction after mastectomy. RESULTS: A total of 78,682 patients in Virginia underwent surgical treatment for breast cancer between 2000 and 2018. Living outside a metropolitan area, increased age, lower socioeconomic status, non-White race, and lower number of plastic surgeons within 50 miles were associated with decreased rates of postmastectomy reconstruction. Rural setting, lower socioeconomic status, and lower plastic surgeon supply were also associated with decreased rates of breast conservation surgery. Reconstruction after mastectomy was lowest in the northwest, central, and southwest regions of Virginia. CONCLUSIONS: Within the state of Virginia, programs to improve access to breast reconstruction for patients residing in rural regions, as well as non-White patients, older patients, and those in lower socioeconomic groups should be implemented. Future studies would implement and study the efficacy of such outreach programs, which could then be applied and tailored to other states or regions to address sociodemographic disparities in access to breast reconstruction.

Immunomodulation of Acellular Dermal Matrix Through Interleukin 4 Enhances Vascular Infiltration.

BACKGROUND: Acellular dermal matrix (ADM) supported implant-based reconstruction remains the most commonly performed mode of reconstruction after breast cancer. Acellular dermal matrix clinical usage has reported benefits but requires rapid and efficient vascular and cellular incorporation into the recipient to have the best outcomes. Orderly transition from M1 to M2 macrophage phenotypic profile, coordinated in part by interleukin 4 (IL-4), is an important component of vascular stabilization and remodeling. Using the ADM substrate as a delivery device for immunomodulation of macrophage phenotype holds the potential to improve integration. METHODS: Interleukin 4 was adsorbed onto ADM samples and drug elution curves were measured. Next, experimental groups of 8 C57BL/6 mice had 5-mm ADM discs surgically placed in a dorsal window chamber with a vascularized skin flap on one side and a plastic cover slip on the other in a model of implant-based breast reconstruction. Group 1 consisted of IL-4 (5 µg) adsorbed into the ADM preoperatively and group 2 consisted of an untreated ADM control. Serial gross examinations were performed with histology at day 21 for markers of vascularization, mesenchymal cell infiltration, and macrophage lineage. RESULTS: Drug elution curves showed sustained IL-4 release for 10 days after adsorption. Serial gross examination showed similar rates of superficial vascular investment of the ADM beginning at the periphery by day 14 and increasing through day 21. Interleukin-4 treatment led to significantly increased CD31 staining of vascular endothelial cells within the ADM over the control group (P < 0.05) at 21 days. Although vimentin staining did not indicate a significant increase in fibroblasts overall, IL-4 did result in a significant increase in expression of α-smooth muscle actin. The expression of macrophage phenotype markers Arginase1 and iNOS present within the ADM were not significantly affected by IL-4 treatment at the day 21 time point. CONCLUSIONS: Acellular dermal matrix has the potential to be used for immunomodulatory cytokine delivery during the timeframe of healing. Using implanted ADM as a delivery vehicle to drive IL-4 mediated angiogenesis and vascular remodeling significantly enhanced vascularity within the ADM substrate.

'Kindness and empathy beyond all else': Challenges to professional identities of Higher Education teachers during COVID-19 times.

COVID-19 has continued to effect higher education globally in significant ways. During 2020, many institutions shifted learning online overnight as the sector closed its doors and opened new sites for remote teaching. This article reports on an international study [Phillips et al., 2021] that sought to capture how cross-sectoral teachers experienced these emergency changes during the first months of restrictions. The data, analysed using narrative identity theory, revealed concerns that fall into two broad categories: technologies and relationships. Significantly, it was not a loss of content delivery or changes to assessment that prompted the greatest anxiety for our colleagues, but that they held significant concerns about their students' mental health; inequities of access to a range of services including technological; and challenges connecting emotionally with their students at a distance. The results provide actionable strategies for higher education institutions to apply in future emergencies where remote teaching is necessary.

Safety Profile and Predictors of Aesthetic Outcomes After Prepectoral Breast Reconstruction With Meshed Acellular Dermal Matrix.

INTRODUCTION: Prepectoral acellular dermal matrix (ADM)-assisted breast reconstruction has demonstrated improved pain scores, faster return to full range of motion, and an appropriate postoperative safety profile when compared with cohorts with submuscular implant placement; however, there are limited data on aesthetic outcomes. Basic science biointegration research has previously demonstrated faster ADM incorporation with fenestrated compared with confluent ADM. We report the safety profile of anterior support meshed ADM prepectoral breast reconstruction and analyze predictive factors for aesthetic outcomes after gel implant placement. METHODS: All consecutive immediate staged prepectoral expander-to-implant breast reconstructions with more than 6 months of follow-up were compared with a partially submuscular cohort for demographics, comorbidities, and postoperative complications. All patients 1 to 3.5 years after gel implant placement were evaluated for the impact of clinical characteristics on aesthetic outcomes. RESULTS: Two hundred twenty-four prepectoral tissue expander placements were compared with 535 partially submuscular tissue expanders with no significant differences in demographics. There was increased wound dehiscence repaired in clinic and insignificantly decreased seromas with prepectoral expander placement. One hundred sixty breasts were reconstructed with gel implants, and 12 underwent autologous reconstruction during the conduct of the study. The remaining 21 patients were continuing expansion, and 3 succumbed to disease progression. Regression analysis of 86 breast reconstructions showed that a body mass index of greater than 30, fat grafting, and highly cohesive anatomic implants decreased rippling, whereas radiation increased capsular contracture (P < 0.05). CONCLUSIONS: Prepectoral meshed ADM breast reconstruction has an equivalent safety profile to partially submuscular ADM-assisted reconstruction and early aesthetic ratings comparable with other published accounts of implant-based reconstruction. Radiated skin envelopes carry higher capsular contracture rates. Thin patients have a higher risk of visible rippling, whereas fat grafting and higher cohesivity implants are associated with less rippling.

Systemic Fibrocyte Levels and Keloid Expression of the Chemoattractant CXCL12 Are Upregulated Compared With Patients With Normal Scar.

BACKGROUND: Fibrocytes are bone marrow mesenchymal precursors with a surface phenotype compatible with leukocytes, fibroblasts, and hematopoietic progenitors that have been shown to traffic to wound healing sites in response to described chemokine pathways. Keloids are focal fibrotic responses to cutaneous trauma characterized by disordered collagen, which may be associated with elevated systemic fibrocyte levels and/or wound bed chemokine expression. METHODS: Blood specimens from patients with longstanding keloids and those who form grossly normal scars were assayed by fluorescence activated cell sorting analysis for fibrocytes (CD45+, Col I+). The expression of the fibrocyte chemotactic cell surface marker CXCR4, intracellular markers of fibroblast differentiation (pSMAD2/3), and plasma levels of the CXCR4 cognate CXCL12 were compared. Keloid specimens and grossly normal scars were excised, and local expression of CXCL12 was assayed. RESULTS: Keloid-forming patients demonstrated a significantly greater number of circulating fibrocytes (17.4 × 105 cells/mL) than control patients (1.01 × 105 cells/mL, P = 0.004). The absolute number of fibrocytes expressing CXCR4 was significantly greater (P = 0.012) in keloid-forming patients. Systemic CXCL12 levels were insignificantly greater in keloid-forming patients than controls. Keloid specimens had significantly greater CXCL12 expression (529.3 pg/mL) than normal scar (undetectable). CONCLUSIONS: Systemic fibrocyte levels and the CXCR4/CXCL12 biologic axis responsible for fibrocyte trafficking to areas of regional fibrosis were both upregulated in patients who form keloids compared with controls. Keloids persistently expressed CXLC12, which serves both as the main chemoattractant for fibrocytes and a downstream mediator for local inflammation, suggesting a role for this biologic axis in keloid formation and possibly recurrence.

The Biointegration of a Porcine Acellular Dermal Matrix in a Novel Radiated Breast Reconstruction Model.

BACKGROUND: Ideal acellular dermal matrices (ADM) for breast reconstruction exhibit native extracellular matrix (ECM) structure to allow rapid biointegration and appropriate mechanical properties for desired clinical outcomes. In a novel in vivo model of irradiated breast reconstruction, we describe the cellular and vascular ingrowth of Artia, a porcine product chemically prepared to mimic the biomechanics of human ADM, with retained natural ECM structure to encourage cellular ingrowth. METHODS: Utilizing the murine dorsal skinfold model, Artia was implanted into 16 C57bl/6 mice. Eight of the mice received a single dose 35 Gy radiation to the skin, followed by 12 weeks to produce radiation fibrosis and 8 mice served as nonradiated controls. Real-time photoacoustic microscopy of vascular integration and oxygen saturation within the ADM were made over 14 days. At 21 days, vascular ingrowth (CD31), fibroblast scar tissue formation (alpha smooth-muscle actin α-SMA, vimentin), and macrophage function (M2/M1 ratio) were evaluated. Scanning electron microscopy images of Artia were produced to help interpret the potential orientation of cellular and vascular ingrowth. RESULTS: Repeated photoacoustic microscopy imaging demonstrated vascular ingrowth increasing over 14 days, with a commensurate increase in oxygen saturation within both radiated and nonradiated ADM-albeit at an insignificantly lower rate in the radiated group. By day 21, robust CD31 staining was seen that was insignificantly greater in the nonradiated group. Of the fibroblast markers, vimentin expression was significantly greater in the radiated group (P < 0.05). Macrophage lineage phenotype was consistent with remodeling physiology in both radiated and nonradiated groups. Scanning electron microscopy demonstrated transversely organized collagen fibrils with natural porous ECM structure to allow cellular ingrowth. CONCLUSIONS: Artia demonstrates appropriate biointegration, with increased oxygen saturation by 14 days, consistent with the performance of other collagen substrates in this model. Radiation fibrosis resulted in higher vimentin expression yet did not impact macrophage phenotype while only modestly decreasing Artia biointegration suggesting that ADM may have a role in reconstructive efforts in a radiated setting. Taken together with its enhanced biomechanics, this porcine ADM product is well poised to be clinically applicable to breast reconstruction.

Exposure-based assessment and economic valuation of adverse birth outcomes and cancer risk due to nitrate in United States drinking water.

BACKGROUND: Nitrate ingestion from drinking water has been associated with an increased risk of adverse birth outcomes as well as elevated risk of colorectal cancer and several other cancers. Yet, to date, no studies have attempted to quantify the health and economic impacts due to nitrate in drinking water in the United States. METHODS: This study presents a first-of-its-kind comprehensive assessment of nitrate exposure from drinking water for the entire United States population. This exposure assessment serves as the basis for our analysis of the annual nitrate-attributable disease cases in the United States and the associated economic losses due to medical costs and lost productivity. Additionally, through a meta-analysis of studies on drinking water nitrate and colorectal cancer, we examine the exposure-response relationship for nitrate and cancer risk. RESULTS: On the basis of national nitrate occurrence data and relative risk ratios reported in the epidemiology literature, we calculated that annually, 2939 cases of very low birth weight, 1725 cases of very preterm birth, and 41 cases of neural tube defects could be related to nitrate exposure from drinking water. For cancer risk, combining nitrate-specific risk estimates for colorectal, ovarian, thyroid, kidney, and bladder cancers results in a range of 2300 to 12,594 annual nitrate-attributable cancer cases (mean: 6537 estimated cases). For medical expenditures alone, this burden of cancer corresponds to an annual economic cost of 250 million to 1.5 billion U.S. dollars, together with a potential 1.3 to 6.5 billion dollar impact due to lost productivity. With the meta-analysis of eight studies of drinking water nitrate and colorectal cancer, we observed a statistically significant positive association for nitrate exposure and colorectal cancer risk and calculated a one-in-one million cancer risk level of 0.14 mg/L nitrate in drinking water. CONCLUSION: Health and economic analyses presented here suggest that lowering exposure to nitrate in drinking water could bring economic benefits by alleviating the impacts of nitrate-associated diseases.

Applying a cumulative risk framework to drinking water assessment: a commentary.

The health risks of drinking water contaminants and the economic benefits of drinking water standards are typically assessed one chemical at a time, an approach that misses the health impacts of co-occurring contaminants in drinking water. In contrast, a cumulative risk framework has become common in air quality evaluations such as the U.S. Environmental Protection Agency's National Air Toxics Assessment. We posit that the drinking water field would benefit from making the transition to a unified assessment framework for multiple contaminants that can overcome the long-standing challenge of treating cancer and non-cancer contaminants separately. Here we present a cumulative risk methodology that combines a risk-based cancer metric with a weighted health indicator index for non-cancer contaminants and incorporates disability weights from the Global Burden of Disease study. Our methodology generates a numeric toxicity score reflecting the potential health impacts for the sum of contaminants present in each sample of drinking water. Further research is needed to refine the risk and toxicity parameters for specific contaminants and to address the mode of interaction between co-occurring chemicals. As this cumulative risk model goes through future refinements, we anticipate that it would provide information that can help communities and policy makers evaluate different options for drinking water treatment.

Prepectoral Wise-Pattern Staged Implant-Based Breast Reconstruction for Obese or Ptotic Patients.

INTRODUCTION: The obese or ptotic breast demonstrates significant difficulty in breast reconstruction after mastectomy with increased rates of perioperative complications compared with the general population, regardless of reconstruction type. Implant-based reconstruction in this patient population with the traditional horizontal elliptical skin-sparing mastectomy tends to have aesthetically displeasing qualities secondary to skin flap redundancy and blunting of the breast contour. Wise-pattern closures have been described with submuscular direct-to-implant and 2-stage reconstructions, with more favorable complication profile when staged. Our study aims to report outcomes and safety of a prepectoral 2-stage wise-pattern closure technique in the obese and/or ptotic population. METHODS: A retrospective chart review was performed to identify all overweight, obese, and/or grade III ptotic patients who have undergone a 2-stage, wise-pattern skin closure with prepectoral placement of tissue expander by a single surgeon. Patient demographics, comorbidities, and perioperative descriptors were reported. Delayed wound healing, infection, seroma formation, and explantation or reoperation were recorded for each patient involved in the study. RESULTS: Thirty-seven obese and/or ptotic breasts among 21 patients underwent immediate prepectoral tissue expander placement with wise-pattern skin reduction closure with mean body mass index of 35.3 kg/m, and 25% of patients were diabetic The most common complication rates by breast were seroma formation (50%) and wound/dehiscence at T-point (28.6%), which all ultimately healed with intervention as described. One major (2.7%) and 1 minor (2.7%) infection were successfully treated with antibiotics. There were no cases of implant exposure. Two operative complex repairs and 1 elective explantation were performed. Diabetes and increasing body mass index were statistically associated with an increased overall perioperative complication rate. CONCLUSIONS: Prepectoral, 2-stage breast reconstruction with wise-pattern skin reduction performs well in obese and/or ptotic patients with favorable rates of perioperative complications. Wound dehiscence was prevalent but managed with wound care when complex repair was not required to expedite adjuvant chemotherapy. Infection rates and reoperation rates were low, and all patients reported positive aesthetic results at the completion of reconstruction.

Early Functional Outcomes After Prepectoral Breast Reconstruction: A Case-Matched Cohort Study.

INTRODUCTION: Staged, tissue expander-based implant reconstruction continues to be the most common mode of breast reconstruction after mastectomy and has evolved significantly for the past 60 years. Prepectoral acellular dermal matrix (ADM)-assisted breast reconstruction is gaining popularity with complication rates similar to total submuscular and ADM-assisted partially submuscular reconstruction. Ours is among the first reports comparing postoperative pain and early functional outcomes between 2-stage ADM-assisted prepectoral and partial submuscular breast reconstruction. METHODS: Patients reconstructed with a 2-stage, ADM-assisted prepectoral approach were case matched with patients who had undergone ADM-assisted, partial submuscular reconstruction. Demographics and complication rates were compared. Primary outcomes included postoperative pain, number of days until full active shoulder range of motion was achieved, and postoperative days until drain removal. RESULTS: Forty-five breasts among 24 patients were reconstructed with ADM-assisted prepectoral tissue expanders after mastectomy and 90 breasts among 48 patients were reconstructed with ADM-assisted partial submuscular placement. There was a similarly acceptable complication profile between the 2 groups. The prepectoral group had significantly lower inpatient pain scores, required significantly less intravenous opioids and less oral opioids as outpatients. The prepectoral group saw a return to full active range of shoulder motion in half the number days of the partial submuscular group. Drain duration was similar between groups. CONCLUSIONS: Prepectoral ADM-assisted breast reconstruction can be performed safely and with significantly less pain and earlier return to function than partial submuscular expander placement. Expander placement exclusively in the prepectoral pocket did not result in increased drain duration while affording patients the benefits of avoiding surgical elevation of the pectoralis muscle.

The Role of Triple-Antibiotic Saline Irrigation in Breast Implant Surgery.

Implant-based breast reconstruction accounts for more than 70% of all breast reconstructions, and breast augmentation is the most commonly performed cosmetic operation annually. The clinically significant impact of infection and capsular contracture after breast implant surgery has brought clinicians to create infection reduction protocols for both oncologic and cosmetic operations alike. The use of triple-antibiotic saline irrigation has become a recommended intraoperative maneuver within these protocols to minimize surgical site infections, but the constituents of the irrigation, its individual efficacy, and the acceptability of including povidone-iodine within irrigation recipes have been debated. This review will investigate the microbiological data behind the selection of the constituents of triple-antibiotic saline. In vitro testing of the effectiveness of topical antibiotics used in saline irrigation against microorganisms responsible for breast implant infection is reviewed. Clinical data are presented describing the impact of triple-antibiotic saline on implant infection and capsular contracture after cosmetic and reconstructive surgery.

Arteriogenesis in murine adipose tissue is contingent on CD68+ /CD206+ macrophages.

OBJECTIVE: The surgical transfer of skin, fat, and/or muscle from a donor site to a recipient site within the same patient is a widely performed procedure in reconstructive surgeries. A surgical pretreatment strategy that is intended to increase perfusion in the flap, termed "flap delay," is a commonly employed technique by plastic surgeons prior to flap transplantation. Here, we explored whether CD68+ /CD206+ macrophages are required for arteriogenesis within the flap by performing gain-of-function and loss-of-function studies in a previously published flap delay murine model. METHODS AND RESULTS: Local injection of M2-polarized macrophages into the flap resulted in an increase in collateral vessel diameter. Application of a thin biomaterial film loaded with a pharmacological agent (FTY720), which has been previously shown to recruit CD68+ /CD206+ macrophages to remodeling tissue, increased CD68+ /CD206+ cell recruitment and collateral vessel enlargement. Conversely, when local macrophage populations were depleted within the inguinal fat pad via clodronate liposome delivery, we observed fewer CD68+ cells accompanied by diminished collateral vessel enlargement. CONCLUSIONS: Our study underscores the importance of macrophages during microvascular adaptations that are induced by flap delay. These studies suggest a mechanism for a translatable therapeutic target that may be used to enhance the clinical flap delay procedure.

Proposed best practice for projects that involve modelling and simulation.

Modelling and simulation has been used in many ways when developing new treatments. To be useful and credible, it is generally agreed that modelling and simulation should be undertaken according to some kind of best practice. A number of authors have suggested elements required for best practice in modelling and simulation. Elements that have been suggested include the pre-specification of goals, assumptions, methods, and outputs. However, a project that involves modelling and simulation could be simple or complex and could be of relatively low or high importance to the project. It has been argued that the level of detail and the strictness of pre-specification should be allowed to vary, depending on the complexity and importance of the project. This best practice document does not prescribe how to develop a statistical model. Rather, it describes the elements required for the specification of a project and requires that the practitioner justify in the specification the omission of any of the elements and, in addition, justify the level of detail provided about each element. This document is an initiative of the Special Interest Group for modelling and simulation. The Special Interest Group for modelling and simulation is a body open to members of Statisticians in the Pharmaceutical Industry and the European Federation of Statisticians in the Pharmaceutical Industry. Examples of a very detailed specification and a less detailed specification are included as appendices.

Macrophage Recruitment and Polarization During Collateral Vessel Remodeling in Murine Adipose Tissue.

OBJECTIVE: During autologous flap transplantation for reconstructive surgeries, plastic surgeons use a surgical pre-treatment strategy called "flap delay," which entails ligating a feeding artery into an adipose tissue flap 10-14 days prior to transfer. It is believed that this blood flow alteration leads to vascular remodeling in the flap, resulting in better flap survival following transfer; however, the structural changes in the microvascular network are poorly understood. Here, we evaluate microvascular adaptations within adipose tissue in a murine model of flap delay. METHODS AND RESULTS: We used a murine flap delay model in which we ligated an artery supplying the inguinal fat pad. Although the extent of angiogenesis appeared minimal, significant diameter expansion of pre-existing collateral arterioles was observed. There was a 5-fold increase in recruitment of CX3CR1(+) monocytes to ligated tissue, a threefold increase in CD68(+) /CD206(+) macrophages in ligated tissue, a 40% increase in collateral vessel diameters supplying ligated tissue, and a 6-fold increase in the number of proliferating cells in ligated tissue. CONCLUSIONS: Our study describes microvascular adaptations in adipose in response to altered blood flow and underscores the importance of macrophages. Our data supports the development of therapies that target macrophages in order to enhance vascular remodeling in flaps.

Reducing Infectious Complications in Implant Based Breast Reconstruction: Impact of Early Expansion and Prolonged Drain Use.

INTRODUCTION: The most common modality of breast reconstruction continues to be implant based, with infection being the most significant complication. Risk factors including radiation, obesity, and smoking have been associated with infection and other surgical complications. We hypothesized that prolonged drain use may likewise be associated with postoperative complications, particularly infection, and that early postoperative expansion may allow for earlier drain removal and improved outcomes. METHODS: A retrospective chart review was performed to identify all immediate, tissue expander-based breast reconstruction patients using acellular dermal matrix. Time to first expansion, postoperative day (POD) of drain removal, and complication data including infection, seroma, wound separation, and skin necrosis were collected. Early expansion was defined as occurring before POD14, and prolonged drain duration as removal after POD21. Logistic regression was used to identify risk factors for complications. Fisher's exact test was used to compare complications between early and late drain removal and early and late expansion. Spearman correlation was used to define the relationship of early expansion and drain duration. RESULTS: Three hundred twenty-three breast reconstructions met inclusion criteria. Our overall infection rate was 11.8%, seroma was 2.2%, skin necrosis 1.9%, and wound separation 4.3%. Logistic regression revealed prolonged drain use as an independent risk factor for infection (odds ratio, 3.3; P = 0.002). Earlier expansion was correlated with earlier post operative drain removal (r = 0.3, P = 0.001) with fewer early expansion patients (7.4%) requiring prolonged drain use than those undergoing late expansion (24.7%). Smoking was also associated with skin flap necrosis (odds ratio, 8.0; P = 0.002). CONCLUSIONS: Prolonged drain use was associated with postoperative infection and may represent an independent source of infection or may be an indicator of delayed healing. Early tissue expansion was associated with earlier drain removal and so may help avoid infectious complications and improve outcomes. Early expansion was not associated with an increase in complications. Results from this study have informed our current drain management practice. Whether this has led to a reduction in our infection rate is a future topic of study.

Tissue Monitoring with Three-Wavelength Light Emitting Diode-Based Near-Infrared Spectroscopy.

Background Flap monitoring with near-infrared spectroscopy (NIRS) facilitates early detection of vascular compromise. However, standard NIRS devices that employ two wavelengths of light to assess tissue oxygenation (StO2) are susceptible to artifact from background noise and demonstrate significant variability in the clinical setting. As the number of wavelengths detected by a NIRS device is increased, the precision of StO2 measurements can be improved and additional chromophores other than oxyhemoglobin and deoxyhemoglobin can be measured. A three-wavelength light emitting diode NIRS device (Artinis, Zetten, the Netherlands) that also detects cytochrome aa3 , a measure of intracellular oxygen demand, was compared with the standard two-wavelength device commonly used for flap monitoring (ViOptix device, ViOptix Inc., Freemont, CA) to determine if there is an improvement in the precision of tissue oxygen measurements. Methods ViOptix and Artinis were applied to the forearms of human volunteers (n = 15) and a blood pressure cuff was placed around the upper arm to occlude arterial and venous flow. StO2 measurements were obtained from both devices. Artinis also yielded cytochrome aa3 oxidation state measurements. Results StO2 measurements from both devices were proportionate during ischemia (R2 = 0.79, p < 0.01). Monte Carlo stimulation showed Artinis outperformed ViOptix (p < 0.01) as a measure of change in StO2 during ischemia. Artinis did not detect a reduction in cytochrome aa3 associated with the decrease in StO2 during ischemia. Conclusion The addition of a third wavelength to NIRS monitoring may improve the precision of StO2 trend monitoring. However, the three-wavelength device lacked the sensitivity to reliably measure changes in cytochrome aa3 .

The effect of local rho-kinase inhibition on murine wound healing.

INTRODUCTION: The process of cutaneous wound healing and contraction is a complex orchestra of temporally and spatially controlled signaling moieties and pathways. Rho-kinase (ROCK) has been implicated as a key downstream effector of transforming growth factor ß1 (TGF-ß1) signal transduction, which ultimately coordinates α-smooth muscle actin (α-SMA)-mediated wound contraction. Previous in vitro studies of ROCK inhibition have demonstrated decreased fibroblast contraction and epithelial advancement after wounding. In vivo systemic ROCK inhibition revealed modest late wound healing attenuation in contrast to α-SMA knock-out rodents. The goal of this investigation was to explore the effect of local delivery of a ROCK inhibitor on an in vivo murine model of wound healing. METHODS: Full-thickness cutaneous wounds were created in 24 white mice and were treated daily with local topical delivery of 100 µL of 10(-4) M ROCK inhibitor (Y27632) or saline control. Percent wound surface area over time and compensatory epithelial advancement was quantified. After 12 days, tissue was harvested for assessment of inflammatory cellular density, immunohistochemistry for α-SMA, and TGF-ß protein expression. RESULTS: Wounds subjected to local ROCK inhibition were significantly larger than controls at early time points, and this effect of delayed wound contraction in ROCK-inhibited wounds persisted for 7 days after wounding (P < 0.05). The effect of ROCK inhibition on delay of wound contraction was normalized at day 12. There was no significant difference between control and ROCK-inhibited groups in the area of the nascent epithelium beyond the wound margin, wound inflammatory cellular density, and TGF-ß1 expression. However, ROCK inhibition led to as statistically significant decrease in α-SMA stress fiber formation compared to controls [32.5% (3.5%) vs 17.4% (2.6%); P < 0.05]. CONCLUSIONS: Local delivery of a ROCK inhibitor delayed the time course of murine wound contraction in a manner similar to that previously reported in α-SMA knock-out rodents, thus demonstrating an effective method for in vivo ROCK inhibition. Accordingly, α-SMA stress fiber formation was inhibited in treated wound beds without altering local inflammation, TGF-ß1 expression, or epithelial wound edge advancement.

Oncoplastic breast reduction surgery decreases rates of reoperation with no increased medical risk.

The purpose of this study is to compare the oncologic, medical, and surgical outcomes of lumpectomy versus oncoplastic breast reduction surgery (OBRS) on a national scale. A national insurance-based database was queried for patients who had a lumpectomy with or without a same-day breast reduction by Current Procedural Terminology (CPT) codes. Patients were then matched by obesity, body mass index range, age, region, neoadjuvant chemotherapy, and outcomes were compared. There were 421,455 patients in the lumpectomy group and 15,909 patients in the OBRS group. After matching, 15,134 patients were identified in each group. Repeat lumpectomy or subsequent mastectomy was more common in the lumpectomy group (15.2% vs. 12.2%, p < 0.001). OBRS patients had higher rates of 90-day surgical complications including dehiscence, infection, fat necrosis, breast abscesses, and antibiotic prescription (p < 0.001). Meanwhile, any medical complication was less common in the OBRS group (3.7% vs. 4.5%, p = 0.001). Logistic regression revealed that OBRS was associated with decreased odds of repeat lumpectomy (OR = 0.71, 95% CI 0.66-0.77, p < 0.001) with no significant increased odds of subsequent mastectomy (OR = 1.01, 95% CI 0.91-1.11, p = 0.914). OBRS was found to be associated with decreased risk for reoperation in the form of lumpectomy without increased likelihood of subsequent mastectomy. Although OBRS was associated with increased wound complications, medical complications were found to occur less frequently. This study endorses increased consideration of OBRS when lumpectomy or OBRS is appropriate.