Wound fluid under occlusive dressings from diabetic patients show an increased angiogenic response and fibroblast migration.

INTRODUCTION: Metabolic diseases like diabetes mellitus often show prolonged healing and chronic wounds. Occlusive wound dressings are known to support wound closure by creating a moist environment which supports collagen synthesis, epithelialization and angiogenesis. We aimed to assess the effect of occlusion on diabetic wound fluid on the cellular level regarding fibroblast activity and angiogenetic response. MATERIAL AND METHODS: 22 split skin donor sites from 22 patients (11 patients with diabetes mellitus) were treated with occlusive dressings intraoperatively. On day 3, fluid and blood serum samples were harvested while changing the dressings. The influence of wound fluid on fibroblasts was assessed by measuring metabolic activity (Alamar Blue assay, Casey Counter), cell stress/death (LDH assay) and migration (in vitro wound healing assay) of fibroblasts. Angiogenesis of endothelial cells (HUVEC) was analyzed with the tube formation assay. Furthermore, a Magnetic Luminex Assay for multi-cytokines detection was performed focusing on inflammatory and pro-angiogenetic cytokines. RESULTS: The influence of wound fluid under occlusive dressings from diabetic patients showed a significantly increased angiogenic response and fibroblast migration compared to the non-diabetic patient group. Additionally, cell stress was increased in the diabetic group. Cytokine analysis showed an increase in VEGF-A in the diabetic group. CONCLUSION: Occlusive dressings may stimulate regenerative effects in diabetic wounds. Our in-vitro study shows the influence of wound fluid under occlusive dressings from diabetic patients on angiogenesis, migration and proliferation of fibroblasts, which are essential modulators of wound healing and scar modulation.

Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.

OBJECTIVE: We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. BACKGROUND: The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. METHODS: From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. RESULTS: Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. CONCLUSIONS: Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

Cadaveric study of breast measurements during augmentation with implants.

BACKGROUND: The goal of this study was to compare immediate changes in breast shape and nipple position using different implant shapes and volumes, with variable release of the pectoralis major muscle in fresh cadavers. METHODS: Seventeen fresh cadaveric breasts were analyzed. Six different augmentation procedures were performed, including pocket dissection in the submuscular and subglandular planes, and partial and full release of the pectoralis major muscle insertion. Round and contoured implant volumes of 200, 300, 400, 500, and 600 ml were used, resulting in a total of 30 procedures per breast. RESULTS: Projection was greater when subjects received contoured implants versus round implants in all volumes both in submuscular and in subglandular pockets (p < 0.001). For implants larger than 200 ml, projection was greater when a subglandular pocket was chosen (p < 0.02), for both round and contoured implants. Nipple-to-inframammary fold distance was increased with contoured implants compared with round implants in both subglandular and submuscular pockets for all implant volumes (p < 0.05). CONCLUSIONS: Implant shape, volume, and pocket location influence projection, causing it to increase in a linear fashion. Partial pectoralis major release seems to affect projection only for small volumes, but does not influence nipple position in the immediate setting. As projection increases with augmentation volume, cephalad movement of the nipple is produced by a relative increase in nipple-to-inframammary fold distance compared with the midclavicular point-to-nipple distance in our cadaveric sample.

Increased hospital volume is associated with improved outcomes following abdominal-based breast reconstruction.

Previous studies of outcomes following abdominal-based breast reconstruction largely use data from single-centre/surgeon experience. Such studies are limited in evaluating the effect of operative volume on outcomes. Abdominal-based breast reconstructive procedures were identified in the 2009-2010 HCUP Nationwide Inpatient Sample. Outcomes included in-hospital microvascular complications in free flap cases (requiring exploration/anastomosis revision), procedure-related and total complications in all cases, and length of stay (LOS). High-volume hospitals were defined as 90th percentile of case volume or higher (>30 flaps/year). Univariate and multivariate analyses were performed to identify predictors of outcomes. Of the 4107 patients identified, mean age was 50.7 years; 71% were white, 68% underwent free flap reconstruction, and 25% underwent bilateral reconstruction. The total complication rate was 13.2%, and the microvascular complication rate was 7.0%. Mean LOS was 4.5 days. There were 436 hospitals; 59% of cases were performed at high-volume institutions. Patients at high-volume hospitals more often underwent free flap reconstruction compared to low-volume hospitals (82.4% vs 50.5%, p < 0.001). On unadjusted analysis, microvascular complication rates of 6.4% vs 8.2% were observed for high-volume compared to low-volume hospitals (p = 0.080). After adjusting for case-mix, high-volume hospitals were associated with a decreased likelihood of suffering a microvascular complication (OR = 0.71, p = 0.026), procedure-related complication (OR = 0.79, p = 0.033), or total complication (OR = 0.75, p = 0.004). The majority of cases nationwide are performed at a small number of high-volume hospitals. These hospitals appear to discharge patients earlier and have lower microvascular, procedure-related, and total complication rates when controlling for case-mix.

Leptin signaling and hyperparathyroidism: clinical and genetic associations.

BACKGROUND: The role of leptin in mediating calcium-related metabolic processes is not well understood. STUDY DESIGN: We enrolled patients with hyperparathyroidism undergoing parathyroidectomy in a prospective study to assess postoperative changes to serum leptin and parathyroid hormone levels and to determine the presence of LEPR (leptin receptor) polymorphisms. Patients undergoing hemithyroidectomy under identical surgical conditions were enrolled as controls. Wilcoxon signed-rank test was used to analyze changes in leptin. Pearson correlations and Bland-Altman methods were used to examine the between-subject and within-subject correlations in changes in leptin and parathyroid hormone levels. Five single-nucleotide polymorphisms in the LEPR gene were genotyped, and linear regression analysis was performed for each polymorphism. RESULTS: Among the 71 patients included in the clinical study, after-surgery leptin levels decreased significantly in the parathyroid adenoma (p < 0.001) and parathyroid hyperplasia subgroups (p = 0.002) and increased in the control group (p = 0.007). On multivariate analysis, parathyroid disease subtype, baseline leptin levels, age, body mass index, and calcium at diagnosis was associated with changes in leptin. Among the 132 patients included in the genotyping analysis, under a recessive model of inheritance, single-nucleotide polymorphism rs1137101 had a significant association with the largest parathyroid gland and total mass of parathyroid tissue removed (p = 0.045 and p = 0.040, respectively). When analyzing obese patients only, rs1137100 and rs1137101 were significantly associated with total parathyroid size (p = 0.0343 and p = 0.0259, respectively). CONCLUSIONS: Our results suggest a role for the parathyroid gland in regulating leptin production. Genetic contributions from the leptin pathway might predispose to hyperparathyroidism.

Deepithelialized flap closure: an adjunct to complex ventral hernia repairs.

Ventral hernias are a major surgical challenge with complications such as wound separations, infections, and recurrences contributing to patient morbidity. We describe a new adjunctive technique that may be helpful in repairing difficult ventral hernias: it involves using an appropriately chosen, redundant abdominal skin edge that is deepithelialized and used to reinforce the hernia repair. A series of 7 patients aged 23 to 84 years in whom the technique was used is presented. All patients had complete repair of their incisional ventral hernia defects without complications of infection, wound dehiscence, seroma formation, reoperation, or hernia recurrence. Furthermore, patients reported a subjective improvement in performing daily activities. Mean follow-up in this series was 19.2 months, with a range from 15.0 to 26.8 months. Advantages include the redistribution of mechanical tension, reinforcement of the midline site of greatest pressure, elimination of dead space, and staggering of suture lines to prevent direct external contamination of prosthetic material should wound dehiscence occur.

A proposal for the timing of management of patients with melanoma presenting during pregnancy.

The treatment of melanoma during and immediately after pregnancy poses a significant challenge to surgeons, oncologists, and patients alike. With the overall increase in incidence of melanoma in the United States and worldwide, it is likely that more surgeons will be faced with management decisions regarding pregnant patients with melanoma. We report on five patients who presented to the Yale Melanoma Unit with melanoma during their pregnancy. We propose the management option of resection of the primary tumor under local anesthesia, and postponing of the sentinel lymph node biopsy until after the birth of the child. The completion lymphadenectomy can be performed if these nodes are found to be harboring metastases. We further discuss treatment options and propose an algorithm for management of patients diagnosed with melanoma while pregnant.