Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen.

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy.

Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150µM or 400µM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.

Double negative pressure for seroma treatment in trocanteric area.

We report the use of topic negative pressure for seromas resulting from mobilization of tensor fascia lata miocutaneous flap in the trochanteric areas for pressure sores. In 5 consecutive patients we successfully treated seroma with the use of external and internal topic subatmospheric pressure.

Implications of transaxillary breast augmentation: lifetime probability of breast cancer development and sentinel node mapping interference.

After the "fifth-generation" breast implants with ultracohesive silicone gel technology are introduced, the Food and Drug Administration (FDA) will sooner or later retire the ban on the use of these devices in the United States. When this happens, the plastic surgery community must be prepared to face a massive demand for reoperations to change saline-filled breast implants because cohesive gel devices have the potential to provide a more natural breast shape, to minimize the risk of postoperative rippling, and to provide a greater degree of safety if the implant loses its integrity. Despite these advantages and extensive use throughout the rest of the world during the ban in the United States, silicone implants also have disadvantages. One drawback is that transaxillary breast augmentation with more "rigid" gel-filled implants may produce trauma to the armpit, may interfere with sentinel node mapping for breast cancer treatment, and may have future medicolegal implications.

A prospective, randomized, double-blind, controlled clinical trial comparing laser-assisted lipoplasty with suction-assisted lipoplasty.

BACKGROUND: The authors randomized and prospectively analyzed their clinical experience with the use of internal neodymium:yttrium-aluminum-garnet low-level laser-assisted lipoplasty compared with suction-assisted lipoplasty. METHODS: Suction-assisted lipoplasty was generated through a SmartLipo machine and delivered into the subcutaneous tissues through 2-mm solid optical probes. Ipsilateral suction-assisted lipoplasty and contralateral laser-assisted lipoplasty were performed on one or more comparable topographic areas of the body in the same patient. Laser-assisted lipoplasty and suction-assisted lipoplasty sides of 25 patients were compared with preoperative and postoperative photographs at 3 to 5 days, 12 to 15 days, and 6 to 11 months. Statistical analysis considered surgeon and patient satisfaction, time used in the procedures, learning curves, lipocrits, operative technique, postoperative pain, edema, ecchymosis, time of recovery, body mass index, DNA proteins, free fatty acids, and cytologic patterns of post-laser-assisted lipoplasty and suction-assisted lipoplasty adipocyte architecture. Photographs were sent to the patients (blinded to the operated sides) and two plastic surgeons unfamiliar with the cases for evaluation of results. RESULTS: All patients completed the preestablished follow-ups. No complications were observed. Less pain, lower lipocrits, higher triglycerides, and DNA cellular membrane traces were detected in the laser-assisted lipoplasty sides. All other considerations studied showed no differences with either technique in the three periods of the follow-up controls. Cytologic studies showed more damage of the adipocytes in the laser-assisted lipoplasty sides. CONCLUSIONS: No major clinical differences for suction-assisted lipoplasty versus laser-assisted lipoplasty were found. Higher concentrations of free-fatty acids after laser-assisted lipoplasty must alert us to possible hepatic and renal toxicity.

A clinical retrospective study comparing two short-scar face lifts: minimal access cranial suspension versus lateral SMASectomy.

BACKGROUND: The purpose of this study was to retrospectively compare the short- and long-term cosmetic outcomes of two minimal incision rhytidectomies and analyze their advantages and disadvantages. METHODS: The results of minimal access cranial suspension face lift versus minimal incision rhytidectomy with lateral SMASectomy were evaluated after 1 and 24 months. Statistical analysis considered surgeon/patient satisfaction, time used in the procedures, pain, and learning curves. Photographs were sent to the patients and two plastic surgeons, unfamiliar with the cases, for evaluation of results that were assessed by an objective grading system described by Strasser. RESULTS: Eighty-two patients completed 1 and 24 months' follow-up. Complications were two hematomas, two retroauricular-lobule dog-ears, and one hypertrophic preauricular scar. Surgical time was longer for the SMASectomy. Postoperative pain was worse for minimal access cranial suspension face lift. There were no differences in cosmetic results between the two techniques at 1-month and 2-year follow-up. Incorporating age, sex, postoperative pain, and duration of surgery as confounding factors did not modify the model. Surgeon/patient satisfaction showed no difference with either technique, but the photographic evaluation of all cases at 24 months revealed that more than 50 percent of the sample needed a tuck procedure to correct jowling and redundant skin. CONCLUSIONS: Advantages of short-scar face lifts are the avoidance of the postauricular and occipital incisions, and the disadvantages are the moderate results in the neck and nasolabial folds and their potential short duration. For 24 months in this study, the duration of results was similar for both minimal access cranial suspension and lateral SMASectomy.

Concordance between qualitative and quantitative cultures in burned patients. Analysis of 2886 cultures.

OBJECTIVE: To determine the concordance between superficial cultures (SC) and quantitative cultures (QC) in the diagnosis of wound infection in burn patients. SAMPLE: All SC and QC taken from the same patient, site and during the same surgery were analysed. VARIABLES: On the SC, the microorganism (MO) and its amount defined subjectively by the microbiologist was recorded (negative, very low, low, regular and abundant). On the QC, the MO and its amount were expressed as colony forming units per gram of tissue (CFUs/g). STATISTICS: Kappa index of agreement beyond chance; Wilcoxon and Kruskall-Wallis for continuous variables and chi(2) for categorical variables were used with a p<0.05 indicating statistical significance. RESULTS: One thousand four hundred and forty three pairs of cultures were analyzed. The concordance between SC and QC (Kappa index) was 52%. On the SC, only when the microbiologist subjectively informed "abundant" MOs there was a significant difference (p<0.0001). There were 6.1% of QCs with more than 10(5) CFUs/g and the most frequent MOs isolated were: S. aureus (27.9%), E. coli (11.6%), P. aeruginosa (11.6%), E. faecalis (11.6%) and S. epidermidis (7.0%). CONCLUSIONS: SC has a moderate concordance with the QC showing a low reliability between the two methods. The subjective information given by the microbiology technician in the SC is not precise. A study in which the two methods be compared blindly against the reference standard, in a prospective cohort of patients, it is needed to discriminate which of two methods it is the most accurate one determining sensitivity and specificity.

Geometric analysis of the V-Y advancement flap and its clinical applications.

BACKGROUND: Geometry is fundamental in the comprehension of local flap design. The purpose of this study was to discuss the differences between the V-Y advancement flap and other local flaps, understand its geometry, and analyze its clinical applications. METHODS: The analysis was based on qualitative measurements of an injury, taking into consideration the following dimensions: largest diameter, shortest diameter, and depth. Standardization of the flap design consisted of directing its advancement over the shortest diameter and making the V base match the size of the largest diameter. The flap was analyzed in two planes: the horizontal plane includes the V-Y design and the vertical plane includes the flap pedicle. The height of the flap can be obtained by simple trigonometry, taking into consideration the largest diameter and alpha angle in the horizontal plane. In the vertical plane, where the pedicle and pivot plane are positioned, for known shortest diameter and depth, the final depth of the pivot plane can be calculated using Pythagoras' principles. RESULTS: This analysis was applied to 25 patients with adequate skin coverage at follow-up. A correction factor was added to reduce the overdeepening of the vertical plane calculations. The final concepts for clinical application in the classic deep pedicle V-Y flap design are to calculate the length of the V by modifying the alpha angle and to move the pivot plane deeper to accomplish optimal flap movement. CONCLUSIONS: Using these principles, tension-free closure of the Y and appropriate advancement of the flap are obtained.

SMAS graft of the nasolabial area during deep plane rhytidectomy.

The extensive list of treatments for the nasolabial area illustrates that the problem is not solved yet. Although a better understanding of the anatomy and physiology of the nasolabial area has been developed, the ideal treatment has not been found. It seems that a combined approach based on summation of partially effective modalities is the best option. The authors present their experience with combined deep plane rhytidectomy, malar fat lift, and superficial musculoaponeurotic system graft in the treatment of the aging nasolabial area. Results in 70 consecutive patients are presented with this simple, nonscarring, inexpensive technique.