Hyperbaric Oxygen Therapy in Management of Diabetic Foot Ulcers: Indocyanine Green Angiography May Be Used as a Biomarker to Analyze Perfusion and Predict Response to Treatment.

SUMMARY: The authors present indocyanine green angiography to assess the effects of hyperbaric oxygen therapy and as a potential biomarker to predict healing of chronic wounds. They hypothesize that favorable initial response to hyperbaric oxygen therapy (improved perfusion) would be an early indicator of eventual response to the treatment (wound healing). Two groups were recruited: patients with chronic wounds and unwounded healthy controls. Inclusion criteria included adults with only one active wound of Wagner grade III diabetic foot ulcer or caused by soft-tissue radionecrosis. Patients with chronic wounds underwent 30 to 40 consecutive hyperbaric oxygen therapy sessions, once per day, 5 days per week; controls underwent two consecutive sessions. Indocyanine green angiography was performed before and after the sessions, and perfusion patterns were analyzed. Healing was determined clinically and defined as full skin epithelialization with no clinical evidence of wound drainage. Fourteen chronic-wound patients and 10 controls were enrolled. Unlike unwounded healthy volunteers, a significant increase in indocyanine green angiography perfusion was found in chronic-wound patients immediately after therapy (p < 0.03). Moreover, the authors found that 100 percent of the wounds that demonstrated improved perfusion from session 1 to session 2 went on to heal within 30 days of hyperbaric oxygen therapy completion, compared with none in the subgroup that did not demonstrate improved perfusion (p < 0.01). This study demonstrates a beneficial impact of hyperbaric oxygen therapy on perfusion in chronic wounds by ameliorating hypoxia and improving angiogenesis, and also proposes a potential role for indocyanine green angiography in early identification of those who would benefit the most from hyperbaric oxygen therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Er:YAG laser vs. sharp debridement in management of chronic wounds: Effects on pain and bacterial load.

Chronic wounds affect roughly 6.5 million patients in the US annually. Current standard of therapy entails weekly sharp debridement. However, the sharp technique is associated with significant pain, while having minimal impact on the bioburden. Our study proposes the Er:YAG laser as an alternative method of debridement that may decrease procedural pain, reduce bioburden, and potentially improve overall healing. This pilot study was performed as a prospective, randomized, controlled, crossover clinical trial, containing two groups: (1) one group underwent single laser debridement session first, followed by single sharp debridement session one week later; and (2) the other group underwent single sharp debridement session first, followed by single laser debridement session one week later. Variables analyzed included pain during debridement, pre- and post-debridement wound sizes, pre- and post-debridement bacterial loads and patient preference. Twenty-two patients were enrolled (12 patients in Group 1, plus 10 patients in Group 2). The mean pain score for patients undergoing laser debridement was 3.0 ± 1.7 vs. 4.8 ± 2.6 for those undergoing sharp debridement (p = 0.003). The mean percent change in wound size 1-week post-laser debridement was -20.8% ± 80.1%, as compared with -36.7% ± 54.3% 1-week post-sharp debridement (p = 0.6). The percentage of patients who had a bacterial load in the low/negative category increased from 27.3% to 59.1% immediately after laser debridement (p = 0.04), vs. 54.5% to 68.2% immediately after sharp debridement (p = 0.38). Moreover, there was a sustained decrease in bacterial load 1-week post-laser debridement, as compared with no sustained decrease 1-week post-sharp debridement (p < 0.02). Overall, 52.9% of patients preferred laser debridement vs. 35.3% for sharp debridement. We believe that Er:YAG laser serves as a promising technology in chronic wounds, functioning as a potentially superior alternative to sharp debridement, the current standard of therapy.

The Tissue-Engineered Tendon-Bone Interface: In Vitro and In Vivo Synergistic Effects of Adipose-Derived Stem Cells, Platelet-Rich Plasma, and Extracellular Matrix Hydrogel.

BACKGROUND: Suboptimal healing of the tendon-bone interface remains an unsolved problem. The authors hypothesized that (1) platelet-rich plasma and prolonged in vitro incubation will produce interface scaffolds with greater reseeding of viable adipose-derived stem cells; and (2) when implanted with extracellular matrix hydrogel, constructs will display superior in vivo strength repair and biocompatibility. METHODS: Achilles-calcaneal composite tendon-bone interface scaffold grafts were harvested from 30 Wistar rats. After physicochemical decellularization and lyophilization, scaffolds were revitalized in rat plasma or 100% activated rat platelet-rich plasma and reseeded with viable adipose-derived stem cells. For part 2 of the study, 90 Sprague-Dawley rats underwent reconstruction with one of five decellularized, lyophilized scaffold revitalization/reseeding conditions: (1) phosphate-buffered saline; (2) lyophilized, 100% activated platelet-rich plasma; (3) platelet-rich plasma and extracellular matrix hydrogel; (4) platelet-rich plasma and 14-day reseeding with ASC-luc2-eGFP cells; and (5) plasma, reseeding, and hydrogel. RESULTS: In part 1, platelet-rich plasma-revitalized grafts demonstrated greater live viable adipose-derived stem cell loads at 3, 7, and 14 days and total adipose-derived stem cell loads at 7 and 14 days with visibly greater live surface cellularity, layering, migration, and penetration. In part 2, bioluminescence imaging confirmed cell viability to day 22 after implantation. Biomechanical strength testing demonstrated a significant increase in ultimate failure load for reseeded groups compared with all other groups at week 2, whereas only reseeded grafts with hydrogel remained significantly stronger at weeks 4 and 8. Histologic examination demonstrated most increased tendinous cellular invasion and fibrocartilage repopulation at 8 weeks in the reseeded group with hydrogel. Masson trichrome staining demonstrated persistence of the scaffold structure at week 8 and blinded ImageJ analysis demonstrated significantly more type III collagen in the reseeded/hydrogel group at 2, 4, and 8 weeks. CONCLUSIONS: Decellularized lyophilized allogeneic tendon-bone interface scaffolds can be optimized by revitalization in platelet-rich plasma, reseeding with viable adipose-derived stem cells, and supplemented by an extracellular matrix tendon hydrogel at the time of implantation. When this is done, they display greater repair strength and biocompatibility.

Comparing Muscle and Fasciocutaneous Free Flaps in Lower Extremity Reconstruction--Does It Matter?

INTRODUCTION: Plastic surgeons are often asked to assist with the reconstruction of lower extremity wounds. These patients many times require free tissue transfer for coverage given paucity of soft tissue. Anecdotally, many orthopedic surgeons prefer muscle coverage--particularly in the setting of potentially infected bone. Today's surgeons now easily harvest and transfer fasciocutaneous flaps--a versatile option with less donor-site morbidity. We hypothesized that there would be no difference in outcomes between these 2 types of reconstruction. METHODS: We performed a single-institution retrospective review of lower extremity free flap reconstructions in the last 10 years. Demographics, preoperative and postoperative course, and the documented time to weight-bearing and bony union were collected. Major cohorts compared were muscle free flaps and fasciocutaneous free flaps, further divided into subgroups including acute trauma, tumor resection, osteomyelitis, and nonunion. Data comparisons were made using paired t test and Fischer exact tests. RESULTS: There were 121 patients who met inclusion criteria--86 in the muscle flap group, and 35 in the fasciocutaneous group and demographics were equal. Total complication rates were higher in smokers than nonsmokers (P < 0.03). There was no significant difference in major or minor complication rates between muscle and fasciocutaneous flaps in any subgroup. In both the acute fracture group and the infected nonunion group, there was a significantly faster return to weight bearing in the fasciocutaneous group (P < 0.03) although there was no difference in documented time to bony union. Patients who underwent fasciocutaneous reconstruction were more likely to require revisionary surgery for improved aesthetics (P < 0.001). CONCLUSIONS: Our data suggest that in essentially all clinical parameters, there is no difference between free flap type used for soft tissue coverage of the lower extremity. Patients undergoing reconstruction with a fasciocutaneous flap may return to weight bearing earlier--although they are more likely to require elective flap revisions. These results imply essentially equivalent outcomes regardless of flap type or operative indication, in contrast with some of the biases in the orthopedic community. The particular flap chosen for any reconstruction should remain solely at the discretion of the plastic surgeon.

Characteristics of Reconstituted Lyophilized Tendon Hydrogel: An Injectable Scaffold for Tendon Regeneration.

BACKGROUND: The authors have developed a tendon hydrogel that may be injected into the site of tendon injury to improve speed and strength of repair. The aim of this study was to compare the biological and physical properties of fresh, hydrated tendon hydrogel with its reconstituted lyophilized counterpart with the goal of increasing clinical feasibility. MATERIALS: Hydrogel was prepared from fresh human cadaveric flexor tendon. Fresh gel was compared to gel aliquots that were lyophilized and reconstituted with sterile deionized water. Scanning electron microscopy was used to examine the microarchitecture of gelated samples. Rat adipose-derived stem cells were seeded in hydrogel, and cell viability was assessed after 7 days. MTS colorimetric assay was used to evaluate both the effect of prolonged storage on gel and the ability of reconstituted lyophilized hydrogel to activate platelet-rich plasma. The viability and proliferation of luciferase-transfected adipose-derived stem cells embedded within hydrogel in vivo was assessed by a bioluminescence in vivo imaging system. RESULTS: Reconstituted lyophilized hydrogel demonstrated similar handling properties compared to fresh gel. Adipose-derived stem cells remained viable 7 days after reseeding in both conditions. Lyophilized hydrogel retained its ability to activate platelet-rich plasma and retained 95 percent of its maximal proliferative capacity at 30 days. The in vivo imaging system demonstrated similar cell proliferation, with signal persisting through day 13. CONCLUSIONS: Reconstitution of lyophilized hydrogel stimulated cell proliferation and platelet-rich plasma activation to a greater degree than did fresh hydrogel. Efficacy after prolonged storage was also shown to be superior. Therefore, this lyophilized formulation of tendon hydrogel may have wider clinical applicability.

In Vitro Characteristics of Porcine Tendon Hydrogel for Tendon Regeneration.

PURPOSE: Previous work has characterized the development of a human tendon hydrogel capable of improving mechanical strength after tendon injury. Animal tendon hydrogel has not yet been described, but would prove beneficial due to the cost and ethical concerns associated with the use of human cadaveric tendon. This study details the manufacture and assesses the biocompatibility of porcine tendon hydrogel seeded with human adipoderived stem cells (ASCs). MATERIALS AND METHODS: Porcine tendon was dissected from surrounding connective and muscle tissue and decellularized via 0.2% sodium dodecyl sulfate and 0.2% sodium dodecyl sulfate/ethylenediaminetetraacetic acid wash solutions before lyophilization. Tendon was milled and reconstituted by previously described methods. Decellularization was confirmed by hematoxylin-eosin staining, SYTO Green 11 nucleic acid dye, and DNeasy assay. The protein composition of milled tendon matrix before and after digestion was identified by mass spectrometry. Rheological properties were determined using an ARG2 rheometer. Biocompatibility was assessed by live/dead assay. The proliferation of human ASCs seeded in porcine and human hydrogel was measured by MTS assay. All experimental conditions were performed in triplicate. RESULTS: Decellularization of porcine tendon was successful. Mass spectrometry showed that collagen composes one third of milled porcine tendon before and after pepsin digestion. Rheology demonstrated that porcine hydrogel maintains a fluid consistency over a range of temperatures, unlike human hydrogel, which tends to solidify. Live/dead staining revealed that human ASCs survive in hydrogel 7 days after seeding and retain spindle-like morphology. MTS assay at day 3 and day 5 showed that human ASC proliferation was marginally greater in human hydrogel. CONCLUSIONS: After reconstitution and digestion, porcine hydrogel was capable of supporting growth of human ASCs. The minimal difference in proliferative capacity suggests that porcine tendon hydrogel may be an effective and viable alternative to human hydrogel for the enhancement of tendon healing.

Digital Sympathectomy in Patients With Scleroderma: An Overview of the Practice and Referral Patterns and Perceptions of Rheumatologists.

PURPOSE: Periarterial sympathectomy is a treatment option for patients with systemic sclerosis (SSc) suffering from digital vasculopathy. Despite potential benefits of ulcer healing, pain improvement, and amputation prevention, this operation appears to be infrequently performed. The aims of our study are as follows: (1) to assess national digital sympathectomy rates in patients with SSc and (2) to improve our understanding of referring physicians' perceptions of operative management and access to hand surgeons. Our hypothesis is that rheumatologists' practices largely influence their referral patterns for digital sympathectomy. METHODS: To determine the rates and demographics of hospitalized patients with SSc who had undergone digital sympathectomy, we queried the Nationwide Inpatient Sample from 2006 to 2010. Additionally, we mailed a self-administered survey to a national sample of 500 board-certified rheumatologists to elicit their practice patterns and perceptions of digital sympathectomy. Using logistic regression, we analyzed potential predictor variables associated with rheumatologists performing the following: (1) routinely counseling patients about digital sympathectomy and (2) expressing the desire to refer these patients for operative evaluation. RESULTS: Of 348,539 hospitalizations associated with a diagnosis of SSc, only 0.2% were for digital sympathectomy. Our questionnaire revealed that only 50% of rheumatologists routinely counseled, whereas 67% expressed the desire to refer. Factors associated with increased rheumatologists' interest in surgical management for patients with SSc included positive perception of the operation's efficacy, comfort with postoperative management, and interdisciplinary relationship with a hand surgeon. DISCUSSION: Critical components to increasing appropriate utilization of digital sympathectomy include enhancing rheumatologists' understanding of the operation, comfort with postoperative management, and promoting strong, interdisciplinary relationships with hand surgeons. Increasing education and awareness, as well as establishing a solid referral network of hand surgeons may thereby improve patient access to digital sympathectomy.

Tendon regeneration with a novel tendon hydrogel: in vitro effects of platelet-rich plasma on rat adipose-derived stem cells.

BACKGROUND: Tendon hydrogel is a promising new injectable substance that has been shown to improve repair strength after tendon injury. This study assesses the capacity of platelet-rich plasma to stimulate proliferation and migration of rat adipose-derived stem cells in tendon hydrogel in vitro. METHODS: To assess proliferation, adipose-derived stem cells were exposed to plasma, plasma supplemented with growth factors, or platelet-rich plasma in culture medium and tendon hydrogel. To assess migration, adipose-derived stem cells were plated onto tendon hydrogel -coated wells and covered with medium containing plasma, plasma supplemented with growth factors, platelet-rich plasma, or bovine serum albumin. Migration from cell-seeded to cell-free zones was assessed at 12-hour intervals. RESULTS: Platelet-rich plasma augmented proliferation to a greater extent compared with plasma and plasma supplemented with growth factors (10%: optical density, 1.18 versus 0.75 versus 0.98, respectively). Platelet-rich plasma was superior to plasma in tendon hydrogel (10%: optical density, 1.19 versus 0.85) but did not augment proliferation to the extent that plasma supplemented with growth factors did (10%: optical density, 1.19 versus 1.56). Platelet-rich plasma enhanced the migration of adipose-derived stem cells compared with serum-free medium (bovine serum albumin) (36 hours: platelet-rich plasma, 1.88; plasma, 1.51; plasma plus growth factor, 1.80; bovine serum albumin, 1.43). CONCLUSIONS: Tendon healing is mediated by migration of cells to the injured area and cellular proliferation at that site. Tendon hydrogel supplemented with platelet-rich plasma stimulates these processes. Future studies will evaluate this combination's ability to stimulate healing in chronic tendon injuries in vivo.

Elucidation of the concise biosynthetic pathway of the communesin indole alkaloids.

The communesins are a prominent class of indole alkaloids isolated from Penicillium species. Owing to their daunting structural framework and potential as pharmaceuticals, communesins have inspired numerous synthetic studies. However, the genetic and biochemical basis of communesin biosynthesis has remained unexplored. Herein, we report the identification and characterization of the communesin (cns) biosynthetic gene cluster from Penicillium expansum. We confirmed that communesin is biosynthesized by the coupling of tryptamine and aurantioclavine, two building blocks derived from L-tryptophan. The postmodification steps were mapped by targeted-gene-deletion experiments and the structural elucidation of intermediates and new analogues. Our studies set the stage for the biochemical characterization of communesin biosynthesis. This knowledge will aid our understanding of how nature generates remarkable structural complexity from simple precursors.

Optimization of an injectable tendon hydrogel: the effects of platelet-rich plasma and adipose-derived stem cells on tendon healing in vivo.

INTRODUCTION: Acute and chronic tendon injuries would benefit from stronger and more expeditious healing. We hypothesize that supplementation of a biocompatible tendon hydrogel with platelet-rich plasma (PRP) and adipose-derived stem cells (ASCs) would augment the tendon healing process. MATERIALS AND METHODS: Using 55 Wistar rats, a full-thickness defect was created within the midsubstance of each Achilles tendon with the addition of one of five experimental conditions: (i) saline control (50-µL), (ii) tendon hydrogel (50-µL), (iii) tendon hydrogel (45-µL)+PRP (5-µL), (iv) tendon hydrogel (45-µL)+2×10(6)-ASCs/mL in phosphate buffered saline (5-µL), and (v) tendon hydrogel (45-µL)+2×10(6)-ASCs/mL in PRP (5-µL). Hydrogel was developed from decellularized, human cadaveric tendons. Fresh rat PRP was obtained per Amable et al.'s technique, and green fluorescent protein/luciferase-positive rat ASCs were utilized. Rats were sacrificed at weeks 1, 2, 4, and 8 after injury. Real-time in vivo bioluminescence imaging of groups with ASCs was performed. Upon sacrifice, Achilles tendons underwent biomechanical and histological evaluation. Comparisons across groups were analyzed using the two-sample Z-test for proportions and the Student's t-test for independent samples. Significance was set at p<0.05. RESULTS: (i) Bioluminescence imaging demonstrated that total photon flux was significantly increased for hydrogel+PRP+ASCs, versus hydrogel+ASCs for each postoperative day imaged (p<0.03). (ii) Mean ultimate failure load (UFL) was increased for hydrogel augmented with PRP and/or ASCs versus hydrogel alone at week 2 (p<0.03). By week 4, hydrogel alone reached a similar mean UFL to hydrogel augmented with PRP and/or ASCs (p>0.3). However, at week 8, hydrogel with PRP and ASCs demonstrated increased strength over other groups (p<0.05), except for hydrogel with PRP (p=0.25). (iii) Upon histological analysis, Hematoxylin and Eosin staining showed increased extracellular matrix formation in groups containing PRP and increased cellularity in groups containing ASCs. Groups containing both PRP and ASCs demonstrated both of these characteristics. CONCLUSION: PRP and ASCs are easily accessible bioactive products that have potentiating effects on tendon hydrogel. Augmentation with these two factors encourages earlier mechanical strength and functional restoration. Thus, biochemically, tendon hydrogel augmented with PRP and/or ASCs, serves as a promising therapeutic modality for augmenting the tendon healing process after injury.

A contemporary series of patients undergoing open debridement for necrotizing pancreatitis.

BACKGROUND: For patients with acute pancreatitis complicated by infected necrosis, minimally invasive techniques have taken hold without substantial comparison with open surgery. We present a contemporary series of open necrosectomies as a benchmark for newer techniques. METHODS: Using a prospective database, we retrospectively identified consecutive patients undergoing debridement for necrotizing pancreatitis (2006 to 2009). The primary endpoint was in-hospital mortality. RESULTS: Sixty-eight patients underwent debridement for pancreatic/peripancreatic necrosis. In-hospital mortality was 8.8% (n = 6). Infection (n = 43, 63%) and failure-to-thrive (n = 13, 19%) comprised the most common indications for necrosectomy. The false negative rate (FNR) for infection of percutaneous aspirate was 20.0%. Older age (P = .02), Acute Physiology and Chronic Health Evaluation II score upon admission (P = .03) or preoperatively (P < .01), preoperative intensive care unit admission (P = .01), and postoperative organ failure (P = .03) were associated with mortality. CONCLUSIONS: Open debridement for necrotizing pancreatitis results in a low mortality, providing a useful comparator for other interventions. Given the high FNR of percutaneous aspirate, debridement should not be predicated on proven infection.

Refinements and secondary surgery after flap reconstruction of the traumatized hand.

The traumatized hand often has soft tissue loss requiring flap reconstruction. Before proceeding with flap selection, the need for future refinement and secondary surgery should be taken into consideration. Although muscle flaps may offer better contour, fasciocutaneous flaps allow easier secondary flap elevation. After the initial flap reconstruction, indications for secondary procedures may be managed according to tissue type: bone, joint, tendon, nerve, and soft tissue.

Expanding the structural diversity of polyketides by exploring the cofactor tolerance of an inline methyltransferase domain.

A strategy for introducing structural diversity into polyketides by exploiting the promiscuity of an in-line methyltransferase domain in a multidomain polyketide synthase is reported. In vitro investigations using the highly-reducing fungal polyketide synthase CazF revealed that its methyltransferase domain accepts the nonnatural cofactor propargylic Se-adenosyl-l-methionine and can transfer the propargyl moiety onto its growing polyketide chain. This propargylated polyketide product can then be further chain-extended and cyclized to form propargyl-α pyrone or be processed fully into the alkyne-containing 4'-propargyl-chaetoviridin A.

Single-Institution Financial Analysis of Biologic Versus Synthetic Mesh Hernia Repair: A Retrospective Analysis of Patients Readmitted for Hernia Repair.

The advent and proliferation of commercially available biologic mesh material has expanded the repertoire of hernia repair materials available to the surgeon. Given the higher initial cost of these mesh materials relative to synthetic materials such as polypropylene, there has been debate regarding the purported benefit of the use of biologic mesh. This study is a single-institution review of complex hernia repairs using both biologic and synthetic mesh materials. The patients included in the analyses were admitted to the institution at least twice for management of hernia; this permitted specific evaluation of a given diagnosis, hernia, in the same patient, but at different points in time. In a subset of patients, hernia repair was performed upon the second admission with conversion from biologic or synthetic mesh, which had been placed at the initial repair. The objective of this study was to evaluate the financial implications of mesh choice. Specific parameters reviewed included type of mesh used, total costs of hospitalization, direct cost associated with the hernia repair, total collections, and percentage of collections relative to total charges. Through such analysis, our aim was to determine whether there were any variances in revenue and costs associated with the application of either mesh material or the associated clinical scenarios.

EcdGHK are three tailoring iron oxygenases for amino acid building blocks of the echinocandin scaffold.

The echinocandins are a small group of fungal N-acylated cyclic hexapeptides that are fungicidal for candida strains and fungistatic for aspergilli by targeting cell wall 1,3-ß-glucan synthases. The side chains of all six amino acid building blocks have hydroxyl groups, including the nonproteinogenic 4R,5R-dihydroxy-Orn1, 4R-OH-Pro3, 3S,4S-dihydroxy-homoTyr4, and 3S-OH-4S-Me-Pro6. The echinocandin (ecd) gene cluster contains two predicted nonheme mononuclear iron oxygenase genes (ecdG,K) and one encoding a P450 type heme protein (ecdH). Deletion of the ecdH gene in the producing strain Emericella rugulosa generates an echinocandin scaffold (echinocandin D) lacking both hydroxyl groups on Orn1. Correspondingly, the ΔecdG strain failed to hydroxylate C3 of the homoTyr residue, and purified EcdG hydroxylated free L-homoTyr at C3. The ΔecdK strain failed to generate mature echinocandin unless supplemented with either 4R-Me-Pro or 3S-OH-4S-Me-Pro, indicating blockage of a step upstream of Me-Pro formation. Purified EcdK is a Leu 5-hydroxylase, acting iteratively at C5 to yield γ-Me-Glu-γ-semialdehyde in equilibrium with the cyclic imine product. Evaluation of deshydroxyechinocandin scaffolds in the in vitro anticandidal assays revealed up to a 3-fold loss of potency for the ΔecdG scaffolds, but a 3-fold gain of potency for the ΔecdH scaffold, in line with prior results on deoxyechinocandin homologues.

Identification and characterization of the chaetoviridin and chaetomugilin gene cluster in Chaetomium globosum reveal dual functions of an iterative highly-reducing polyketide synthase.

We report the identification and characterization of the caz biosynthetic cluster from Chaetomium globosum and the characterization of a highly reducing polyketide synthase (PKS) that acts in both a sequential and convergent manner with a nonreducing PKS to form the chaetomugilin and chaetoviridin azaphilones. Genetic inactivation studies verified the involvement of individual caz genes in the biosynthesis of the azaphilones. Through in vitro reconstitution, we demonstrated the in vitro synthesis of chaetoviridin A from the pyranoquinone intermediate cazisochromene using the highly reducing PKS and an acyltransferase.

Concurrent laparoscopic morgagni hernia repair and sleeve gastrectomy.

The Morgagni-type anterior diaphragmatic hernia is a congenital defect that is a very uncommon hernia presenting in an adult. Surgical repair is usually recommended upon diagnosis and often requires synthetic mesh for a durable, tension-free repair. The use of synthetic mesh concurrently with several of bariatric operations is controversial owing to the potential for mesh infection. In this report we describe a laparoscopic repair of a symptomatic Morgagni hernia with synthetic mesh, concurrently with sleeve gastrectomy, in a morbidly obese man. The patient was a 58-year-old man with a body mass index of 48 kg/m(2) and associated co-morbid conditions that included obstructive sleep apnea, hypertension, hyperlipidemia, impaired fasting glucose, and osteoarthritis. He was diagnosed with Morgagni hernia with exertional dyspnia. He underwent concurrent laparoscopic Morgagni hernia repair with mesh and sleeve gastrectomy. At 2 months after surgery the patient was doing well and tolerating solid foods, and his percentage excess weight loss was 35%. He was exercising regularly and had no exertional dyspnea. Laparoscopy is an attractive approach to performing multiple intra-abdominal procedures concurrently. The Morgagni hernia repair with mesh can be performed safely and effectively using a laparoscopic approach. This can be performed concurrently with bariatric surgery in the morbidly obese.

Interrupted Fischer indolization approach toward the communesin alkaloids and perophoramidine.

A concise approach toward the total synthesis of the communesin alkaloids and perophoramidine is reported. The strategy relies on the use of the interrupted Fischer indolization to build the tetracyclic indoline core of the natural products. Studies to probe the scope and limitations of this plan are presented. Although the methodology does not tolerate a C8-allyl substituent en route to the challenging vicinal quaternary stereocenters, variation at C7 and on the C ring is permitted.

Synthesis of (+)-phenserine using an interrupted Fischer indolization reaction.

A concise synthesis of the Alzheimer's therapeutic (+)-phenserine is described. The approach features an interrupted Fischer indolization to construct the pyrrolidinoindoline core, in addition to a classical resolution to arrive at phenserine in enantioenriched form.

Dirhodium-catalyzed phenol and aniline oxidations with T-HYDRO. Substrate scope and mechanism of oxidation.

Dirhodium caprolactamate, Rh(2)(cap)(4), is a very efficient catalyst for the generation of the tert-butylperoxy radical from tert-butyl hydroperoxide, and the tert-butylperoxy radical is a highly effective oxidant for phenols and anilines. These reactions are performed with 70% aqueous tert-butyl hydroperoxide using dirhodium caprolactamate in amounts as low as 0.01 mol % to oxidize para-substituted phenols to 4-(tert-butyldioxy)cyclohexadienones. Although these transformations have normally been performed in halocarbon solvents, there is a significant rate enhancement when Rh(2)(cap)(4)-catalyzed phenol oxidations are performed in toluene or chlorobenzene. Electron-rich and electron-poor phenolic substrates undergo selective oxidation in good to excellent yields, but steric influences from bulky para substituents force oxidation onto the ortho position resulting in ortho-quinones. Comparative results with RuCl(2)(PPh(3))(3) and CuI are provided, and mechanistic comparisons are made between these catalysts that are based on diastereoselectivity (reactions with estrone), regioselectivity (reactions with p-tert-butylphenol), and chemoselectivity in the formation of 4-(tert-butyldioxy)cyclohexadienones. The data obtained are consistent with hydrogen atom abstraction by the tert-butylperoxy radical followed by radical combination between the phenoxy radical and the tert-butylperoxy radical. Under similar reaction conditions, para-substituted anilines are oxidized to nitroarenes in good yield, presumably through the corresponding nitrosoarene, and primary amines are oxidized to carbonyl compounds by TBHP in the presence of catalytic amounts of Rh(2)(cap)(4).