The Impact of Diabetes Mellitus on Wound Healing in Breast Reconstruction.

BACKGROUND: Although diabetes mellitus (DM) is a known risk factor for surgical complications in general, there is little published evidence to establish such an effect among patients undergoing breast reconstruction (BR). The purpose of this study was to assess the impact of DM on complications in patients undergoing postmastectomy BR. METHODS: Patients who underwent BR at our institution from November 2002 to November 2012 were identified. Clinical and demographic data of patients with type 1 or type 2 DM were reviewed. Complications occurring within 60 days of surgery were compared between diabetic and nondiabetic patients for both autologous and nonautologous reconstruction types. RESULTS: A total of 1371 BR were performed in 1035 patients. There were 877 (64.0%) autologous reconstructions and 494 (36.0%) implant-based reconstructions. Patients with DM (n = 64) had significantly higher preoperative blood glucose levels (137.5 vs 100.1, P < 0.05). Postoperatively, DM patients reconstructed with implants had a significantly higher incidence of delayed wound healing (22.2% vs 9.7%; P = 0.04). This was not observed in patients with DM reconstructed with autologous tissue (7.4% vs 6.6%; P = 0.70). Diabetic patients had a significantly higher incidence of hypertension and were older than nondiabetic patients. To control for these variables and other potential confounders, multiple logistic regression analysis was performed. Again, diabetic patients had a significantly higher incidence of delayed wound healing following implant-based reconstruction (odds ratio, 2.52, 95% confidence interval = 1.2-6.2) but not autologous reconstruction (odds ratio, 0.97; 95% confidence interval = 0.2-4.6). CONCLUSIONS: Diabetes heightens the risk of wound healing complications among patients undergoing implant-based reconstruction.

Perineal reconstruction following abdominoperineal resection: Comprehensive review of the literature.

Abdominoperineal resection (APR) in patients with anorectal carcinomas may involve flap-based perineal reconstruction techniques, such as rectus abdominis, myocutaneous, gracilis, and gluteal flaps. There is no consensus on the optimal approach. We evaluated the outcomes of perineal reconstruction following APR in the literature and identified a predominance of abdominal-based approaches, though overall outcomes were similar compared with thigh or perineal-based options. Statistical power to detect small differences in outcomes is limited, however, due to the retrospective design, relatively short-term follow-up, and potential selection bias based on morbidities associated with reconstructive techniques. Lacking randomized studies to define optimum approaches to perineal reconstruction, clinicians should individualize surgical strategy.

Does the timing of postoperative showering impact infection rates? A systematic review and meta-analysis.

INTRODUCTION: Optimum timing of postoperative showering varies. Earlier showering improves patient satisfaction, but the impact of the timing of showering on postoperative infection is unclear. We conducted a systematic literature review and meta-analysis to investigate the outcomes of various postoperative showering practices. METHODS: We searched PubMed to identify relevant human clinical studies in English, and searched these for additional references. Articles were reviewed for patient demographics, surgical specialty and procedure, wound closure method, placement of drains, showering protocol, and rates of infection and complications. Only randomized controlled trials were analyzed. A random-effects meta-analysis model was used to determine overall infection and complication rates between patients allowed to shower within the first 48 h postoperatively or later. RESULTS: Out of 357 studies, seven and five were included in the infection and complications rate meta-analyses, respectively. A total of 1,881 and 958 patients were included in each analysis; 605 and 477 patients in each analysis were allowed to shower on or before postoperative day 2 ("early"), while the remainder were prohibited from showering until postoperative day 3 to beyond one week ("delayed") postoperatively. There was no difference in infection (p = 0.45, [-0.0052, 2 × 0.007 95% CI]) or complication rate (p = 0.36, [-0.0046, 2 × 0.005 95% CI]) with earlier vs. delayed showering protocols. CONCLUSION: Published literature demonstrates no increase in the overall rate of wound infections or complications when patients showered earlier in the postoperative period. Additional randomized studies are needed to determine the ideal time for postoperative showering. These data should be considered by surgeons while determining when to permit patients to shower after surgery.

Proteomics analysis reveals novel components in the detergent-insoluble subproteome in Alzheimer's disease.

Neurodegenerative diseases are often defined pathologically by the presence of protein aggregates. These aggregates, including amyloid plaques in Alzheimer's disease (AD), result from the abnormal accumulation and processing of proteins, and may ultimately lead to neuronal dysfunction and cell death. To date, conventional biochemical studies have revealed abundant core components in protein aggregates. However, rapidly improving proteomics technologies offer opportunities to revisit pathologic aggregate composition, and to identify less abundant but potentially important functional molecules that participate in neurodegeneration. The purpose of this study was to establish a proteomic strategy for the profiling of neurodegenerative disease tissues for disease-specific changes in protein abundance. Using high resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we analyzed detergent-insoluble frontal cortex samples from AD and unaffected control cases. In addition, we analyzed samples from frontotemporal lobar degeneration (FTLD) cases to identify AD-specific changes not present in other neurodegenerative diseases. We used a labeling-free quantification technique to compare the abundance of identified peptides in the samples based on extracted ion current (XIC) of their corresponding ions. Of the 512 identified proteins, quantitation demonstrated significant changes in 81 AD-specific proteins. Following additional manual filtering, 11 proteins were accepted with high confidence as increased in AD compared to control and FTLD brains, including beta-amyloid, tau and apolipoprotein E, all well-established AD-linked proteins. In addition, we identified and validated the presence of serine protease 15, ankyrin B, and 14-3-3 eta in the detergent-insoluble fraction. Our results provide further evidence for the capacity of proteomics applications to identify conserved sets of disease-specific proteins in AD, to enhance our understanding of disease pathogenesis, and to deliver new candidates for the development of effective therapies for this, and other, devastating neurodegenerative disorders.

Correction of the tuberous breast deformity in a prepubescent male patient: A surgical approach to an unusual problem.

PURPOSE: The management of the tuberous breast deformity in the female patient is well described. However, the presence of this variant in male patients is particularly rare, and few reports on the management of this condition are available. CASE PRESENTATION: A 12-year-old prepubescent male with bilateral gynecomastia and tuberous breast deformities was referred to our department for treatment. Our surgical management, including free nipple areolar complex harvest, mastectomy, removal of excess skin and subsequent nipple grafting, is presented in detail. We observed a cosmetically acceptable result with restoration of a masculine-appearing nipple-areolar complex and good patient satisfaction at 6-month follow-up. CONCLUSIONS: Tuberous breast deformities in male patients are rare. Our treatment of a prepubertal male patient with this deformity using mastectomies and free nipple areolar complex grafting provided a cosmetically acceptable result. Here, we review the current literature on tuberous breast deformities in males and describe our approach to treatment.

Innovations in the Plastic Surgery Care Pathway: Using Telemedicine for Clinical Efficiency and Patient Satisfaction.

BACKGROUND: Telemedicine delivers clinical information and permits discussion between providers and patients at a distance. Postoperative visits may be a burden to patients-many of whom travel long distances and miss work opportunities. By implementing a telehealth opportunity, the authors sought to develop a process that optimizes efficiency and provides optimal patient satisfaction. METHODS: Using quality improvement methods that have been highly effective in the business sector, we developed a testable workflow for patients in the postoperative telehealth setting. Seventy-two patients were enrolled and surveyed. A preoperative survey sought to determine travel distance, comfort with technology, access to the Internet and video-enabled devices, and the patient's interest in telehealth. A postoperative survey focused on patient satisfaction with the experience. RESULTS: Using the Lean Six Sigma methodology, the authors developed a telehealth workflow to optimize clinical efficiency. Preoperative surveys revealed that the majority (73 percent) of patients preferred in-person follow-up visits in the clinic. However, the postoperative survey distributed after the telehealth encounter found that nearly 100 percent of patients were satisfied with the telehealth experience. Ninety-six percent of patients said that their questions were answered, and 97 percent of patients stated that they would use telehealth again in the future. CONCLUSIONS: Telehealth encounters enable real-time clinical decision-making by providing patients and visiting nurses access to providers and decreasing patient transportation needs and wait times. Although initially hesitant to opt for a telehealth encounter in lieu of a traditional visit, the great majority of patients voiced satisfaction with the telehealth experience. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Interaction of genetic and environmental factors in a Drosophila parkinsonism model.

Catastrophic loss of dopaminergic neurons is a hallmark of Parkinson's disease. Despite the recent identification of genes associated with familial parkinsonism, the etiology of most Parkinson's disease cases is not understood. Environmental toxins, such as the herbicide paraquat, appear to be risk factors, and it has been proposed that susceptibility is influenced by genetic background. The genetic model organism Drosophila is an advantageous system for the identification of genetic susceptibility factors. Genes that affect dopamine homeostasis are candidate susceptibility factors, because dopamine itself has been implicated in neuron damage. We find that paraquat can replicate a broad spectrum of parkinsonian behavioral symptoms in Drosophila that are associated with loss of specific subsets of dopaminergic neurons. In parallel with epidemiological studies that show an increased incidence of Parkinson's disease in males, male Drosophila exhibit paraquat symptoms earlier than females. We then tested the hypothesis that variation in dopamine-regulating genes, including those that regulate tetrahydrobiopterin, a requisite cofactor in dopamine synthesis, can alter susceptibility to paraquat-induced oxidative damage. Drosophila mutant strains that have increased or decreased dopamine and tetrahydrobiopterin production exhibit variation in susceptibility to paraquat. Surprisingly, protection against the neurotoxicity of paraquat is conferred by mutations that elevate dopamine pathway function, whereas mutations that diminish dopamine pools increase susceptibility. We also find that loss-of-function mutations in a negative regulator of dopamine production, Catecholamines-up, delay the onset of neurological symptoms, dopaminergic neuron death, and morbidity during paraquat exposure but confer sensitivity to hydrogen peroxide.

Direct binding of GTP cyclohydrolase and tyrosine hydroxylase: regulatory interactions between key enzymes in dopamine biosynthesis.

The signaling functions of dopamine require a finely tuned regulatory network for rapid induction and suppression of output. A key target of regulation is the enzyme tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, which is activated by phosphorylation and modulated by the availability of its cofactor, tetrahydrobiopterin. The first enzyme in the cofactor synthesis pathway, GTP cyclohydrolase I, is activated by phosphorylation and inhibited by tetrahydrobiopterin. We previously reported that deficits in GTP cyclohydrolase activity in Drosophila heterozygous for mutant alleles of the gene encoding this enzyme led to tightly corresponding diminution of in vivo tyrosine hydroxylase activity that could not be rescued by exogenous cofactor. We also found that the two enzymes could be coimmunoprecipitated from tissue extracts and proposed functional interactions between the enzymes that extended beyond provision of cofactor by one pathway for another. Here, we confirm the physical association of these enzymes, identifying interacting regions in both, and we demonstrate that their association can be regulated by phosphorylation. The functional consequences of the interaction include an increase in GTP cyclohydrolase activity, with concomitant protection from end-product feedback inhibition. In vivo, this effect would in turn provide sufficient cofactor when demand for catecholamine synthesis is greatest. The activity of tyrosine hydroxylase is also increased by this interaction, in excess of the stimulation resulting from phosphorylation alone. Vmax is elevated, with no change in Km. These results demonstrate that these enzymes engage in mutual positive regulation.

A typical N-terminal extensions confer novel regulatory properties on GTP cyclohydrolase isoforms in Drosophila melanogaster.

The cofactor tetrahydrobiopterin plays critical roles in the modulation of the signaling molecules dopamine, serotonin, and nitric oxide. Deficits in cofactor synthesis have been associated with several human hereditary diseases. Responsibility for the regulation of cofactor pools resides with the first enzyme in its biosynthetic pathway, GTP cyclohydrolase I. Because organisms must be able to rapidly respond to environmental and developmental cues to adjust output of these signaling molecules, complex regulatory mechanisms are vital for signal modulation. Mammalian GTP cyclohydrolase is subject to end-product inhibition via an associated regulatory protein and to positive regulation via phosphorylation, although target residues are unknown. GTP cyclohydrolase is composed of a highly conserved homodecameric catalytic core and non-conserved N-terminal domains proposed to be regulatory sites. We demonstrate for the first time in any organism that the N-terminal arms of the protein serve regulatory functions. We identify two different modes of regulation of the enzyme mediated through the N-terminal domains. The first is end-product feedback inhibition, catalytically similar to that of the mammalian enzyme, except that feedback inhibition by the cofactor requires sequences in the N-terminal arms rather than a separate regulatory protein. The second is a novel inhibitory interaction between the N-terminal arms and the active sites, which can be alleviated through the phosphorylation of serine residues within the N termini. Both mechanisms allow for acute and highly responsive regulation of cofactor production as required by downstream signaling pathways.