Supercharged deep inferior epigastric perforator flap for reconstruction of soft tissue defect after excision of giant invasive squamous cell carcinoma of the thigh in a refractory diabetic with Pseudomonas aeruginosa infection.

Patients with large defects after oncologic surgery often require enhanced surgical planning to optimize reconstructive outcomes. As such, medically complex patients require innovative solutions when utilizing abdominal flaps due to concern for ischemia of the distal tissue. Vascular augmentations, such as supercharging or turbocharging, serve to increase perfusion in these medical complex patients to ensure flap survival. In this report, we highlight the use of a supercharged bilateral pedicled deep inferior epigastric perforator (DIEP) flap in a patient with a 231 cm2 thigh defect in the setting of uncontrolled diabetes. A 57-year-old male with poorly-controlled diabetes (blood sugar prior to surgery 510 mg/dL) and iron deficiency anemia presented with a two-year history of a large nonmetastatic squamous cell carcinoma (SCC) measuring 19 × 9 cm2 on the right thigh. Positron emission tomography/computed tomography and biopsies of the right retroperitoneal and inguinal lymph nodes diagnosed the mass as Stage 3 localized SCC. After excision, we performed immediate reconstruction of the resultant defect with a supercharged bilateral pedicled DIEP flap. The flap was pedicled on the ipsilateral DIEP and the contralateral perforator was anastomosed to the descending branch of the lateral circumflex femoral artery (DLCFA) at the inferior aspect of the defect. A venous coupler was used for the veins and the arteries were hand-sewn in end-to-end fashion. The supercharged bilateral pedicled DIEP flap was utilized for enhanced augmented perfusion to the distal edge of the pedicled flap in a high-risk patient. The patient's clinical course was complicated by a Pseudomonas infection of a small hematoma requiring operative washout and debridement of necrotic fat. However, the flap survived and covered the defect completely. The patient required outpatient antibiotics for the Pseudomonas infection which resolved completely without further need for operative intervention. At 6-month follow up, the reconstruction was stable with no tumor recurrence on clinical exam. Our results suggest that a supercharged pedicled DIEP flap may be a viable option for large defects of the thigh and can may be utilized in medically complex patients with poor capacity for wound healing.

Novel use and utilization of robotic Hoyer-Hook system for suspension of panniculus morbidus.

Panniculus morbidus is a complication of morbid obesity characterized by massive abdominal folds that hang below the beltline. Ulceration, dermatitis, and sinus tract formation of the pannus can cause significant morbidity to the patient and impair activities of daily living. If patients fail medical management, the next step is surgical excision. Challenging aspects of the procedure include adequate suspension of the pannus, cost, and prevention of intra-abdominal injuries. We present a case of a 70-year-old female with panniculus morbidus with endometrial carcinoma. We successfully performed a panniculectomy using a novel combination of towel hooks and the Hoyer lift to suspend the abdomen. In the same anesthesia event, she underwent robotic-assisted hysterectomy. No intra-operative or post-operative complications were encountered, and the patient was satisfied with her results. In this case, we demonstrated an effective and cost-efficient approach to panniculectomy in the severely obese patient.

A Non-Invasive Method for Monitoring Osteogenesis and Osseointegration Using Near-Infrared Fluorescent Imaging: A Model of Maxilla Implantation in Rats.

Currently, computed tomography and conventional X-ray radiography usually generate a micro-artifact around metal implants. This metal artifact frequently causes false positive or negative diagnoses of bone maturation or pathological peri-implantitis around implants. In an attempt to repair the artifacts, a highly specific nanoprobe, an osteogenic biomarker, and nano-Au-Pamidronate were designed to monitor the osteogenesis. In total, 12 Sprague Dawley rats were included in the study and could be chategorized in 3 groups: 4 rats in the X-ray and CT group, 4 rats in the NIRF group, and 4 rats in the sham group. A titanium alloy screw was implanted in the anterior hard palate. The X-ray, CT, and NIRF images were taken 28 days after implantation. The X-ray showed that the tissue surrounded the implant tightly; however, a gap of metal artifacts was noted around the interface between dental implants and palatal bone. Compared to the CT image, a fluorescence image was noted around the implant site in the NIRF group. Furthermore, the histological implant-bone tissue also exhibited a significant NIRF signal. In conclusion, this novel NIRF molecular imaging system precisely identifies the image loss caused by metal artifacts and can be applied to monitoring bone maturation around orthopedic implants. In addition, by observing the new bone formation, a new principle and timetable for an implant osseointegrated with bone can be established and a new type of implant fixture or surface treatment can be evaluated using this system.

Non-surgical Management of Locally Advanced Basal Cell Carcinoma of the Upper Extremity With Vismodegib.

Basal cell carcinoma (BCC) is a common skin malignancy that can present reconstructive challenges in patients with locally advanced diseases of the extremities. This article highlights three cases of locally advanced BCC of the extremities managed with vismodegib (Erivedge, Genentech). Vismodegib is a sonic hedgehog pathway (Shh) inhibitor approved by the FDA for use in metastatic or recurrent BCC. All three patients in our case series demonstrated significant clinical responses with reductions in tumor size which obviated the need for complex reconstructive surgery or amputation.

From mono-PEGylation towards anti-nonspecific protein interaction: comparison of dihydrolipoic acid versus glutathione-capped fluorescent gold nanoclusters using gel electrophoresis.

Ultrafine fluorescent gold nanoclusters (AuNCs) have emerged as biocompatible nanoprobes for biomedical imaging in vivo, and the precision surface chemistry of AuNCs is the key for attaining their clinical application. Comparison of two promising candidates for future nanomedicine, i.e. dihydrolipoic acid- versus glutathione-capped AuNCs (AuNC@DHLA vs. AuNC@GSH), was conducted for the first time to clarify their polyethylene glycol-related bioconjugate chemistry (PEGylation) and protein interactions. Gel electrophoresis was performed to separate the number of AuNCs PEGylation, and the molecular weight of the PEG spacer dominated the resolution of the separation in the gel. We have engineered and isolated the mono-PEGylated AuNCs either from the indirect carbodiimide bioconjugate chemistry or the direct Au-S binding. One-pot synthesis showed great efficiency for isolating mono-PEGylated AuNC@GSH from the tailored controlled aggregation of Au(i)-thiolate complexes on in situ generated Au(0) cores. Post-PEGylation of AuNC@GSH was also feasible using monodendate thiol-terminated PEG, but bidendate ligands of AuNC@DHLA exhibited low PEGylated efficiency by Au-S binding. In addition, mono-PEGylated AuNC@GSH significantly enhanced the ability of anti-nonspecific protein adsorption, but mono-PEGylated AuNC@DHLA cannot avoid the nonspecific binding with serum albumin. In addition, specific nano-assembly involving mono-biotinylated AuNCs with streptavidin were also compared using gel electrophoresis. These results provide key insights into the selection, preparation and design of functional AuNCs as nanoprobes for versatile biomedical applications.

Two new, near-infrared, fluorescent probes as potential tools for imaging bone repair.

A precise imaging technique to evaluate osteogenesis, osteodifferentiation, and osseointegration following peri-implant surgery is in high clinical demand. Herein, we report the generation of two new, near-infrared (NIR) fluorescent probes for use in the molecular imaging of bone repair. The first probe aims to monitor the in vitro differentiation of human mesenchymal stem cells (MSCs) into osteoblasts. A NIR fluorochrome was conjugated to a cyclic peptide that binds to integrin α5ß1, a factor that promotes osteogenesis in MSCs and therefore functioned as an osteoblast-specific marker. The second probe aims to monitor osteogenesis, and was generated by conjugating the drug pamidronate to a NIR fluorescent gold nanocluster. Pamidronate specifically binds to hydroxyapatite (HA), a mineral present in bone that is produced by osteoblasts, and therefore provides a functional marker for new bone formation. Our results show that both probes bind to their specific targets in vitro-differentiated osteoblasts, and not to undifferentiated MSCs, and emit NIR fluorescence for functional detection. This in vitro work demonstrates the ability of these probes to bind to active osteoblasts and their mineral deposits and highlight their potential utility as clinical tools for the imaging of the osseointegration process at the molecular level.

Publisher Correction: Non-Toxic Gold Nanoclusters for Solution-Processed White Light-Emitting Diodes.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Non-Toxic Gold Nanoclusters for Solution-Processed White Light-Emitting Diodes.

Solution-processed optoelectronic devices are attractive because of the potential low-cost fabrication and the compatibility with flexible substrate. However, the utilization of toxic elements such as lead and cadmium in current optoelectronic devices on the basis of colloidal quantum dots raises environmental concerns. Here we demonstrate that white-light-emitting diodes can be achieved by utilizing non-toxic and environment-friendly gold nanoclusters. Yellow-light-emitting gold nanoclusters were synthesized and capped with trioctylphosphine. These gold nanoclusters were then blended with the blue-light-emitting organic host materials to form the emissive layer. A current efficiency of 0.13 cd/A was achieved. The Commission Internationale de l'Eclairage chromaticity coordinates of (0.27, 0.33) were obtained from our experimental analysis, which is quite close to the ideal pure white emission coordinates (0.33, 0.33). Potential applications include innovative lighting devices and monitor backlight.

Preparing Cancer Patients and Family Caregivers for Lung Surgery: Development of a Multimedia Self-Management Intervention.

The surgical treatment of lung malignancies often results in persistent symptoms, psychosocial distress, and decrements in quality of life (QOL) for cancer patients and their family caregivers (FCGs). The potential benefits of providing patients and FCGs with preparatory education that begins in the preoperative setting have been explored in multiple medical conditions, with positive impact observed on postoperative recovery, psychological distress, and QOL. However, few studies have explored the benefits of preparatory educational interventions to promote self-management in cancer surgery, including lung surgery. This paper describes the systematic approach used in the development of a multimedia self-management intervention to prepare cancer patients and their FCGs for lung surgery. Intervention development was informed by (1) contemporary published evidence on the impact of lung surgery on patients and FCG, (2) our previous research that explored QOL, symptoms, and caregiver burden after lung surgery, (3) the use of the chronic care self-management model (CCM) to guide intervention design, and (4) written comments and feedback from patients and FCGs that informed intervention development and refinement. Pilot-testing of the intervention is in process, and a future randomized trial will determine the efficacy of the intervention to improve patient, FCG, and system outcomes.

A Multimedia Self-management Intervention to Prepare Cancer Patients and Family Caregivers for Lung Surgery and Postoperative Recovery.

BACKGROUND: The purpose of this study was to evaluate the feasibility and acceptability of a multimedia self-management (MSM) intervention to prepare patients and family caregivers for lung surgery. PATIENTS AND METHODS: This is a quasi-experimental, 2-group, sequential enrollment pilot study of a 4-session multimedia intervention (audio/visual + print) to enhance self-management and quality of life (QOL) for patients and family caregivers. The intervention, Preparing for Lung Surgery, begins before surgery, and continues through hospitalization and discharge, with 2 telephone support sessions after discharge. Outcomes were assessed before surgery (preintervention), at discharge, and 2 to 4 weeks postdischarge (postintervention). Patient outcomes were assessed using the Functional Assessment of Cancer Therapy-General (QOL), MD Anderson Symptom Inventory and Functional Assessment of Cancer Therapy-Pulmonary Symptom Index (symptoms), self-efficacy, surgery-related knowledge, and patient activation. Family caregiver outcomes included City of Hope-QOL-Family (QOL), Caregiver Burden Scale, and knowledge. Paired t tests were used for exploratory evaluations of score changes from pre- to postintervention. RESULTS: Sixty participants (38 patients, 22 family caregivers) enrolled in the study (70% accrual). Postintervention scores were significantly improved for patients' emotional QOL (P = .001). Trends for improvements were observed for patient self-efficacy, surgery-related knowledge, and activation. Family caregivers' surgery-related knowledge was significantly improved (P = .02). Overall, participants were highly satisfied with the acceptability/usability of the intervention (3.6-3.7 of 4.0). CONCLUSION: A standardized MSM intervention was feasible and acceptable in supporting readiness and preparedness for lung surgery and postoperative recovery. A larger randomized trial is needed to verify the impact of the MSM intervention on patient/family caregiver outcomes and health care resource use.

Rates and Correlates of Syphilis Reinfection in Men Who Have Sex with Men.

PURPOSE: This study examined rates and correlates of syphilis reinfection in men who have sex with men (MSM). METHODS: From 2012 to 2015, time to reinfection was assessed in 323 MSM receiving initial treatment for syphilis in San Francisco. RESULTS: One in five men was reinfected (71/323; 22%). The rate of syphilis reinfection was greater among HIV-infected men (adjusted hazard ratio [aHR] = 1.96; 95% confidence interval [95% CI] = 1.16-3.31) and ketamine users (aHR = 2.76; 95% CI = 1.09-7.00). CONCLUSION: Expanded prevention efforts are needed with HIV-infected and substance-using MSM to reduce the burden of reinfection in this population.

Impact of dihydrolipoic acid on mouse embryonic stem cells and related regulatory mechanisms.

α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). Recently, DHLA has been used as the hydrophilic nanomaterial preparations, and therefore, determination of its bio-safety profile is essential. In this article, we show that DHLA (50-100 µM) induces apoptotic processes in mouse embryonic stem cells (ESC-B5), but exerts no injury effects at treatment dosages below 50 µM. Higher concentrations of DHLA (50-100 µM) directly increased the reactive oxygen species (ROS) content in ESC-B5 cells, along with a significant increase in cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and -3, and cell death. Pretreatment with NO scavengers suppressed the apoptotic biochemical changes induced by 100 µM DHLA and promoted the gene expression levels of p53 and p21 involved in apoptotic signaling. Our results collectively indicate that DHLA at concentrations of 50-100 µM triggers apoptosis of ESC-B5 cells, which involves both ROS and NO. Importantly, at doses of less than 50 µM (0-25 µM), DHLA does not exert hazardous effects on ESC-B5 cell properties, including viability, development and differentiation. These results provide important information in terms of dosage safety and biocompatibility of DHLA to facilitate its further use as a precursor for biomaterial preparation.

Rapid transformation of protein-caged nanomaterials into microbubbles as bimodal imaging agents.

We present a general method for converting colloidal nanomaterials into microbubbles as ultrasound contrast agents. Protein-caged nanomaterials, made either by self-assembled nanoparticles' protein corona or by fluorescent gold nanoclusters, can be rapidly transformed into microbubbles via a sonochemical route, which promote disulfide cross-linking of cysteine residues between protein-caged nanomaterials and free albumin during acoustic cavitation. The proposed methods yielded microbubbles with multiple functions by adjusting the original nanoparticle/protein mixture. We also showed a new dual-modal imaging agent of fluorescent gold microbubbles in vitro and in vivo, which can hold many potential applications in medical diagnostics and therapy.

Dihydrolipoic acid induces cytotoxicity in mouse blastocysts through apoptosis processes.

α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). In view of the recent application of DHLA as a hydrophilic nanomaterial preparation, determination of its biosafety profile is essential. In the current study, we examined the cytotoxic effects of DHLA on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, in vivo implantation by embryo transfer, and early embryonic development in an animal model. Blastocysts treated with 50 µM DHLA exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with DHLA were lower than that of their control counterparts. Moreover, in vitro treatment with 50 µM DHLA was associated with increased resorption of post-implantation embryos and decreased fetal weight. Data obtained using an in vivo mouse model further disclosed that consumption of drinking water containing 100 µM DHLA led to decreased early embryo development, specifically, inhibition of development to the blastocyst stage. However, it appears that concentrations of DHLA lower than 50 µM do not exert a hazardous effect on embryonic development. Our results collectively indicate that in vitro and in vivo exposure to concentrations of DHLA higher than 50 µM DHLA induces apoptosis and retards early pre- and post-implantation development, and support the potential of DHLA to induce embryonic cytotoxicity.

Synthesis and characterization of colloidal fluorescent silver nanoclusters.

Ultrasmall water-soluble silver nanoclusters are synthesized, and their properties are investigated. The silver nanoclusters have high colloidal stability and show fluorescence in the red. This demonstrates that like gold nanoclusters also silver nanoclusters can be fluorescent.

Osteogenic differentiation is synergistically influenced by osteoinductive treatment and direct cell-cell contact between murine osteoblasts and mesenchymal stem cells.

PURPOSE: The present study was designed to address whether osteoblasts play a synergistic role in promoting mesenchymal stem cell (MSC) osteogenesis in a direct cell-cell contact co-culture model. METHODS: Murine C3H10T1/2 and MC3T3-E1 cell lines were mixed and plated onto 12-well culture plates and co-cultured at various ratios of initial cell densities. To compare the possible improvement on osteogenic differentiation, co-culture cells were served with or without osteogenic supplements in culture medium. RESULTS: Weak osteogenesis was induced in MSCs co-cultured in an untreated medium with different ratios of osteoblasts. An osteoblast-dependent increase in osteogenic gene expression of Runx2, type I collagen, and osteocalcin was observed over time. Moreover, both alkaline phosphatase (ALP) activity and calcium deposition were distinctly enhanced at levels that were proportional to the quantity of osteoblasts in the culture. The increases in mRNA expression and ALP activity were greater in co-cultures treated with osteogenic supplements than in untreated cultures. However, the production of ALP activity followed by a distinct matrix mineralization was lower in osteogenic-treated cultures containing greater numbers of osteoblasts. This suggests that a higher density of osteoblasts may lead to weak osteogenesis of MSCs by direct cell-cell contact co-culture in an untreated environment. Furthermore, additional osteogenic supplements may act synergistically with osteoblasts to accelerate matrix mineralization by reducing the process of osteogenic differentiation in osteogenic treated co-cultures. CONCLUSIONS: The present work may improve the understanding of MSC osteogenesis and may provide benefits for regenerative medicine.

Effects of ultrasound on osteotomy healing in a rabbit fracture model.

This study investigated the effects of ultrasound (US) at different frequencies on fracture healing over a three-week period in a rabbit fibular fracture model. Forty-five adult New Zealand White rabbits were divided into five groups: a control group and four groups treated with US frequencies of 0.5, 1.0, 1.5 and 2.0 MHz (0.5 W/cm(2), 200-µs burst, pulsed 1:4). After anesthesia, transverse osteotomy was performed on the fibula bone. This was followed by intravital staining and fluorescence microscopic examination of new bone formation and biomechanical tests of torsional stiffness at the osteotomy site. Results showed that total new bone formation and torsional stiffness of the fibula were greater in all US-treated groups than in the control group. No significant difference was found between any of the four US-treated groups. The US treatment also enhanced bone growth of the sham-treated contralateral fracture site. These results suggest that US treatment at 0.5, 1.0, 1.5 or 2.0 MHz can enhance fracture healing in a rabbit model. Furthermore, the effects of US on fracture healing at present parameters might not be confined locally.

Clinical quality measures for intraoperative and perioperative management in carpal tunnel surgery.

BACKGROUND: Previous research documents suboptimal preoperative or postoperative care for patients undergoing surgery. However, few existing quality measures directly address the fundamental element of surgical care: intra-operative care processes. This study sought to develop quality measures for intraoperative, preoperative, and postoperative care for carpal tunnel surgery, a common operation in the USA. METHODS: We applied a variation of the well-established RAND/UCLA Appropriateness Method. Adherence to measures developed using this method has been associated with improved patient outcomes in several studies. Hand surgeons and quality measurement experts developed draft measures using guidelines and literature. Subsequently, in a two-round modified-Delphi process, a multidisciplinary panel of 11 national experts in carpal tunnel syndrome (including six surgeons) reviewed structured summaries of the evidence and rated the measures for validity (association with improved patient outcomes) and feasibility (ability to be assessed using medical records). RESULTS: Of 25 draft measures, panelists judged 22 (88%) to be valid and feasible. Nine intraoperative measures addressed the location and extent of surgical dissection, release after wrist trauma, endoscopic release, and four procedures sometimes performed during carpal tunnel surgery. Eleven measures covered preoperative and postoperative evaluation and management. CONCLUSIONS: We have developed several measures that experts, including surgeons, believe to reflect the quality of care processes occurring during carpal tunnel surgery and be assessable using medical records. Although quality measures like these cannot assess a surgeon's skill in handling the instruments, they can assess many important aspects of intraoperative care. Intraoperative measures should be developed for other procedures.

Nanoscale hepatoprotective herbal decoction attenuates hepatic stellate cell activity and chloroform-induced liver damage in mice.

BACKGROUND: San-Huang-Xie-Xin-Tang (SHXXT) decoction, a traditional Chinese medicine containing Rhei rhizome, Coptidis rhizome, and Scutellariae radix, is widely used in hepatoprotective therapy. However, preparation of the decoction requires addition of boiling water that causes loss of numerous effective components. METHODS: To improve the bioavailability of the decoction, nanoscale SHXXT was developed. Chloroform-induced liver injury and hepatic stellate cell activity in mice were used to demonstrate the hepatoprotective characteristics of nanoscale SHXXT decoction. RESULTS: Liver/body weight ratio and serum aspartate and alanine aminotranferase levels were recovered by the nanoscale SHXXT. TIMP-1 gene expression was inhibited and MMP-2 gene expression was accelerated in activated hepatic stellate cells. CONCLUSION: Nanoscale SHXXT decoction prepared in room temperature water could have preserved hepatoprotective ability. The results of this study indicate that nanoscale SHXXT could be extracted easily. The simple preparation of this herbal decoction is more convenient and energy-efficient.

Fluorescent gold nanoclusters as a biocompatible marker for in vitro and in vivo tracking of endothelial cells.

We have been investigating the fluorescent property and biocompatibility of novel fluorescent gold nanoclusters (FANC) in human aortic endothelial cells (HAEC) and endothelial progenitor cells (EPC). FANC (50-1000 nmol/L) was delivered into cells via the liposome complex. The fluorescence lasted for at least 28 days with a half-life of 9 days in vitro. Examination of 12 transcripts regulating the essential function of endothelial cells after a 72 h delivery showed that only the vascular cell adhesion molecule 1 and the vascular endothelial cadherin were down-regulated at high concentration (500 nmol/L). In addition, no activation of caspase 3 or proliferating cell nuclear antigens was detected. 3-[4,5-Dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) assay demonstrated that, unlike the markedly suppressed viability in cells treated with quantum dots, FANC had minimal effect on the viability, unless above 500 nmol/L, at which level a minor reduction of viability mainly caused by liposome was found. Tube formation assay showed no impaired angiogenesis in the EPC treated with FANC. In vivo study using hindlimb ischemic mice with an intramuscular injection of FANC-labeled human EPC showed that the cells preserved an angiogenic potential and exhibited traceable signals after 21 days. These findings demonstrated that FANC is a promising biocompatible fluorescent probe.