Pulsed electromagnetic fields dosing impacts postoperative pain in breast reduction patients.

BACKGROUND: Pulsed electromagnetic fields (PEMF) reduce postoperative pain and narcotic requirements in breast augmentation, reduction, and reconstruction patients. PEMF enhances both calmodulin-dependent nitric oxide and/or cyclic guanosine monophosphate signaling and phosphodiesterase activity, which blocks cyclic guanosine monophosphate. The clinical effect of these competing responses on PEMF dosing is not known. METHODS: Two prospective, nonrandomized, active cohorts of breast reduction patients, with 15 min PEMF per 2 h; "Q2 (active)", and 5 min PEMF per 20 min; "5/20 (active)", dosing regimens were added to a previously reported double-blind clinical study wherein 20 min PEMF per 4 h, "Q4 (active)", dosing significantly accelerated postoperative pain reduction compared with Q4 shams. Postoperative visual analog scale pain scores and narcotic use were compared with results from the previous study. RESULTS: Visual analog scale scores at 24 h were 43% and 35% of pain at 1 h in the Q4 (active) and Q2 (active) cohorts, respectively (P < 0.01). Pain at 24 h in the 5/20 (active) cohort was 87% of pain at 1 h, compared with 74% in the Q4 (sham) cohort (P = 0.451). Concomitantly, narcotic usage in the 5/20 (active) and Q4 (sham) cohorts was not different (P = 0.478), and 2-fold higher than the Q4 (active) and Q2 (active) cohorts (P < 0.02). CONCLUSIONS: This prospective study shows Q4/Q2, but not 5/20 PEMF dosing, accelerated postoperative pain reduction compared with historical shams. The 5/20 (active) regimen increases NO 4-fold faster than the Q4 (active) regimen, possibly accelerating phosphodiesterase inhibition of cyclic guanosine monophosphate sufficiently to block the PEMF effect. This study helps define the dosing limits of clinically useful PEMF signals.

Propranolol promotes accelerated and dysregulated adipogenesis in hemangioma stem cells.

BACKGROUND: Infantile hemangiomas (IHs) are the most common tumor of infancy, yet there are no Food and Drug Administration-approved therapeutics to date. Recently, the nonselective ß-adrenergic-blocker propranolol has been shown to be a safe and effective means of treating IHs, although its mechanism has yet to be elucidated. We have previously demonstrated that propranolol induces early and incomplete adipogenesis in stem cells derived from hemangiomas. We hypothesize that propranolol promotes dysregulated adipogenesis via the improper regulation of adipogenic genes. METHODS: Hemangioma stem cells (HemSCs) isolated from resected IH specimens were treated with adipogenic medium for 1 or 4 days in either propranolol or vehicle. Cell death was measured by the incorporation of annexin V and propidium iodide by flow cytometry. Adipogenesis was assessed by visualizing lipid droplet formation by Oil Red O staining. Proadipogenic genes C/EBPα, C/EBPß, C/EBPδ, PPARδ, PPARγ, RXRα, and RXRγ were analyzed by quantitative reverse transcription and polymerase chain reaction. RESULTS: Hemangioma stem cells treated with propranolol increased lipid droplet formation compared to vehicle-treated cells indicating increased adipogenesis. Cell death as measured by FACS analysis indicated that the propranolol-treated cells died due to necrosis and not apoptosis. During adipogenesis, transcript levels of PPARδ, PPARγ, C/EBPß, and C/EBPδ were significantly increased (P<0.01) in propranolol-treated cells relative to control cells. In contrast, RXRα and RXRγ levels were significantly decreased (P<0.05), and C/EBPα, a gene required for terminal adipocyte differentiation, was strongly suppressed by propranolol when compared to vehicle-treated cells (P<0.01). CONCLUSIONS: In HemSCs, propranolol accelerated dysregulated adipogenic differentiation characterized by improper adipogenic gene expression. Consistent with accelerated adipogenesis, propranolol significantly increased the expression of the proadipogenic genes, PPARγ, C/EBPß, and C/EBPγ compared to control. However, propranolol treatment also led to improper induction of PPARδ and suppression of C/EBPα, RXRα, and RXRγ. Taken together these data indicate that propranolol promoted dysregulated adipogenesis and inhibited the HemSCs from becoming functional adipocytes, ultimately resulting in cell death. Understanding this mechanism behind propranolol's effectiveness will be a vital factor in producing more effective therapies in the future.

The impact of operative time on complications after plastic surgery: a multivariate regression analysis of 1753 cases.

BACKGROUND: Little evidence within plastic surgery literature supports the precept that longer operative times lead to greater morbidity. OBJECTIVE: The authors investigate surgery duration as a determinant of morbidity, with the goal of defining a clinically relevant time for increased risk. METHODS: A retrospective chart review was conducted of patients who underwent a broad range of complex plastic surgical procedures (n = 1801 procedures) at UT Southwestern Medical Center in Dallas, Texas, from January 1, 2008 to January 31, 2012. Adjusting for possible confounders, multivariate logistic regression assessed surgery duration as an independent predictor of morbidity. To define a cutoff for increased risk, incidence of complications was compared among quintiles of surgery duration. Stratification by type of surgery controlled for procedural complexity. RESULTS: A total of 1753 cases were included in multivariate analyses with an overall complication rate of 27.8%. Most operations were combined (75.8%), averaging 4.9 concurrent procedures. Each hour increase in surgery duration was associated with a 21% rise in odds of morbidity (P < .0001). Compared with the first quintile of operative time (<2.0 hours), there was no change in complications until after 3.1 hours of surgery (odds ratio, 1.6; P = .017), with progressively greater odds increases of 3.1 times after 4.5 hours (P < .0001) and 4.7 times after 6.8 hours (P < .0001). When stratified by type of surgery, longer operations continued to be associated with greater morbidity. CONCLUSIONS: Surgery duration is an independent predictor of complications, with a significantly increased risk above 3 hours. Although procedural complexity undoubtedly affects morbidity, operative time should factor into surgical decision making.

Treatment of hyperhidrosis with botulinum toxin.

Botulinum toxin type A is a safe and effective method for treating focal hyperhidrosis, providing longer-lasting results than topical treatments without the necessity of invasive surgical procedures. Although more useful for axillary hyperhidrosis, botulinum toxin injections can also be effective in treating palmar and plantar disease. The effects of botulinum toxin last for six to nine months on average, and treatment is associated with a high satisfaction rate among patients. In this article, the authors discuss their preferred methods for treating axillary, palmar, and plantar hyperhidrosis. This article serves as guide for pretreatment evaluation, injection techniques, and posttreatment care.

An Alternative Treatment of Pseudogynecomastia in Male Patients After Massive Weight Loss.

BACKGROUND: There has been an increase in body contouring procedures following massive weight loss (MWL), including male breast reduction procedures. Treating male chest deformity after MWL using standard mastopexy techniques often leads to suboptimal results. OBJECTIVES: The authors describe a technique to treat pseudogynecomastia using a modified elliptical excision and nipple-areola complex (NAC) transposition on a thinned inferior dermal pedicle as an alternative to conventional techniques. METHODS: A retrospective chart review from January 2011 to January 2019 identified a total of 14 male patients who underwent excision of pseudogynecomastia using the described technique. RESULTS: Patients were characterized by age, method of weight loss, pre-weight loss body mass index (BMI), post-weight loss BMI, total weight loss, grade of pseudogynecomastia, and concurrent procedures performed. Patients were followed for a period ranging from 3 months to 1.5 years (average, 8.1 months). Pre-weight loss BMI and post-weight loss BMI averaged 52.0 kg/m2 and 29.6 kg/m2, respectively. The average weight lost was 79.72 kg and the average total amount of tissue removed was 2615 g. All patients had concurrent procedures with an average operative time of 274 minutes. Four out of 14 patients (28.6%) experienced minor complications, which included asymmetry, delayed wound healing, seroma, and hyperpigmentation. There were no wound infections, hematomas, flap necrosis, or dysesthesia. CONCLUSIONS: Due to several cosmetic advantages and low complication profile, our technique using a modified elliptical excision and NAC transfer on an inferior dermal pedicle is an attractive option for treating male chest deformity after MWL.

Pulsed Electromagnetic Fields Reduce Postoperative Interleukin-1ß, Pain, and Inflammation: A Double-Blind, Placebo-Controlled Study in TRAM Flap Breast Reconstruction Patients.

BACKGROUND: Pulsed electromagnetic fields have been shown to reduce postoperative pain, inflammation, and narcotic requirements after breast reduction and augmentation surgical procedures. This study examined whether pulsed electromagnetic field therapy could produce similar results in patients undergoing unilateral transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction, a significantly more complex and painful surgical procedure. METHODS: In this double-blind, placebo-controlled, randomized study, 32 patients undergoing unilateral TRAM flap breast reconstruction received active or sham pulsed electromagnetic field therapy. Pain levels were measured by using a visual analogue scale; narcotic use and wound exudate volume were recorded starting 1 hour postoperatively. Wound exudates were analyzed for interleukin-1ß. RESULTS: Mean visual analogue scale pain scores were 2-fold higher in the sham cohort at 5 hours and 4-fold higher at 72 hours (p < 0.01), along with a concomitant 2-fold increase in narcotic use in sham patients (p < 0.01). Wound exudate volume was 2-fold higher in the sham cohort at 24 hours (p < 0.01), and mean interleukin-1ß concentration in wound exudates of sham patients was 5-fold higher at 24 hours (p < 0.001). CONCLUSIONS: Pulsed electromagnetic field therapy significantly reduced postoperative pain, inflammation, and narcotic use following TRAM flap breast reconstruction, paralleling its effect in breast reduction patients. Both studies also report a significant reduction of interleukin-1ß in the wound exudate, supporting a mechanism involving a pulsed electromagnetic field effect on nitric oxide/cyclic guanosine monophosphate signaling, which modulates the body's antiinflammatory pathways. Adjunctive pulsed electromagnetic field therapy could impact the speed and quality of wound repair in many surgical procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

A retrospective study to classify surgical indications for infantile hemangiomas.

Infantile hemangiomas (IHs) spontaneously involute, but some leave contour deformities necessitating surgical correction. There is a paucity of data reviewing predictive risk factors associated with a need for surgery to guide clinicians when counseling parents. Patients undergoing IH resection by a single surgeon from August 2004 to August 2011 were reviewed to determine patient (age, gender, birth history) and IH characteristics (size, location) associated with surgical intervention. Data were compared to published data from the Hemangioma Investigator Group (HIG). Statistical analysis was performed using Student's t-test, odds ratio, and logistic regression analysis. Out of 196 referred patients, 112 underwent surgery. There was a female preponderance (3.5:1). Two-thirds of patients (64.9%) first presented to the surgeon at ≤2 years of age, but most underwent surgery between 2 and 3 years (52.7%; average lag time, 11 months). 18 patients underwent surgery at ≤1 year of age. IH patients with preterm birth history had increased risk for needing surgical intervention (odds ratio 2.124, CI 1.31-3.44; p < 0.0012). A majority (84.7%) of resected IHs were located on the head or neck, significantly higher than the distribution from the HIG data (62.2%; p < 0.0001). Resected head and neck IHs were smaller than those below the neck (average, 8.85 cm(2) vs. 22.35 cm(2), p = 0.017). Preterm birth is associated with higher risk for requiring surgical intervention. IHs on the head and neck are more likely to be removed when compared to those below the neck, and at a smaller size threshold.

Propranolol accelerates adipogenesis in hemangioma stem cells and causes apoptosis of hemangioma endothelial cells.

BACKGROUND: Infantile hemangiomas can cause significant morbidity during proliferation, yet there is no U.S. Food and Drug Administration-approved treatment. They are believed to form from hemangioma stem cells, which differentiate toward a hemangioma endothelial cell phenotype. Recently, propranolol has demonstrated effectiveness in treating complicated infantile hemangiomas. The authors hypothesize that propranolol facilitates their involution by altering cellular behavior in both hemangioma endothelial and stem cells. METHODS: Hemangioma endothelial and stem cells were isolated from resected infantile hemangioma specimens. Cells were treated with 100 µM propranolol for 48 hours, and apoptosis was determined by the presence of annexin V antibody. Proliferation of stem and endothelial cells was assessed after treatment with 50 or 100 µM propranolol or vehicle, for 72 and 96 hours, respectively. Adipogenesis was induced in stem cells with and without propranolol. Pro-adipogenic genes PPARδ, PPARγ, C/EBPα, C/EBPß, C/EBPδ, RXRα, and RXRγ were analyzed by quantitative polymerase chain reaction. RESULTS: Annexin V levels were increased in propranolol-treated endothelial cells but not in stem cells. Proliferation of stem and endothelial cells was inhibited by propranolol in a dose-dependent manner. Propranolol-treated stem cells demonstrated accelerated adipogenesis when compared with untreated controls. Transcript levels of C/EBPß (p < 0.05), RXRγ (p < 0.05), and PPARγ (p < 0.02) were significantly increased when treated with 50 or 100 µM propranolol; and C/EBPδ (p < 0.05), RXRα (p < 0.05), and PPARδ (p < 0.01) transcripts were increased when treated with 100 µM propranolol. C/EBPα transcript levels remained unchanged at either dose. CONCLUSIONS: Propranolol increased apoptosis of hemangioma endothelial cells, but not stem cells, and accelerated adipogenesis of hemangioma stem cells. Thus, propranolol likely accelerates involution to fibrofatty residuum.