Engineering the Electronic Structure of Single-Atom Iron Sites with Boosted Oxygen Bifunctional Activity for Zinc-Air Batteries.

Rechargeable zinc-air batteries typically require efficient, durable, and inexpensive bifunctional electrocatalysts to support oxygen reduction/evolution reactions (ORR/OER). However, sluggish kinetics and mass transportation challenges must be addressed if the performance of these catalysts is to be enhanced. Herein, a strategy to fabricate a catalyst comprising atomically dispersed iron atoms supported on a mesoporous nitrogen-doped carbon support (Fe SAs/NC) with accessible metal sites and optimized electronic metal-support interactions is developed. Both the experimental results and theoretical calculations reveal that the engineered electronic structures of the metal active sites can regulate the charge distribution of Fe centers to optimize the adsorption/desorption of oxygenated intermediates. The Fe SAs/NC containing Fe1 N4 O1 sites achieves remarkable ORR activity over the entire pH range, with half-wave potentials of 0.93, 0.83, and 0.75 V (vs reversible hydrogen electrode) in alkaline, acidic, and neutral electrolytes, respectively. In addition, it demonstrates a promising low overpotential of 320 mV at 10 mA cm-2 for OER in alkaline conditions. The zinc-air battery assembled with Fe SAs/NC exhibits superior performance than that of Pt/C+RuO2 counterpart in terms of peak power density, specific capacity, and cycling stability. These findings demonstrate the importance of the electronic structure engineering of metal sites in directing catalytic activity.

Facile Synthesis of Single Iron Atoms over MoS2 Nanosheets via Spontaneous Reduction for Highly Efficient Selective Oxidation of Alcohols.

The facile creation of high-performance single-atom catalysts (SACs) is intriguing in heterogeneous catalysis, especially on 2D transition-metal dichalcogenides. An efficient spontaneous reduction approach to access atomically dispersed iron atoms supported over defect-containing MoS2 nanosheets is herein reported. Advanced characterization methods demonstrate that the isolated iron atoms situate atop of molybdenum atoms and coordinate with three neighboring sulfur atoms. This Fe SAC delivers exceptional catalytic efficiency (1 atm O2 @ 120 °C) in the selective oxidation of benzyl alcohol to benzaldehyde, with 99% selectivity under almost 100% conversion. The turnover frequency is calculated to be as high as 2105 h-1 . Moreover, it shows admirable recyclability, storage stability, and substrate tolerance. Density functional theory calculations reveal that the high catalytic activity stems from the optimized electronic structure of single iron atoms over the MoS2 support.

Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor.

BACKGROUND: PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). METHODS: We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0-2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted. RESULTS: Objective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab. CONCLUSIONS: Belapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.

Single dose partial breast irradiation using an MRI linear accelerator in the supine and prone treatment position.

BACKGROUND: In selected patients with early-stage and low-risk breast cancer, an MRI-linac based treatment might enable a radiosurgical, non-invasive alternative for current standard breast conserving therapy. AIM: To investigate whether single dose accelerated partial breast (APBI) to the intact tumor in both the prone and supine radiotherapy positions on the MRI-linac is dosimetrically feasible with respect to predefined coverage and organs at risk (OAR) constraints. MATERIAL & METHODS: For 20 patients with cTis or low-risk cT1N0M0 non-lobular breast carcinoma, previously treated with single dose preoperative APBI in the supine (n = 10) or prone (n = 10) position, additional intensity modulated radiotherapy plans with 7 coplanar beams in the presence of a 1.5T magnetic field were generated. A 20 Gy and 15 Gy dose was prescribed to the gross tumor and clinical target volume, respectively. The percentage of plans achieving predefined organ at risk (OAR) constraints, currently used in clinical practice, was assessed. Dosimetry differences between the prone versus supine approach and the MRI-linac versus clinically delivered plans were evaluated. RESULTS: All MRI-linac plans met the coverage and predefined OAR constraints. The prone approach appeared to be more favorable with respect to the chest wall, and ipsilateral lung dose compared to the supine position. No dosimetric differences were observed for the ipsilateral breast. No treatment position was clearly more beneficial for the skin or heart, since dosimetry varied among parameters. Overall, the MRI-linac and clinical plans were comparable, with minor absolute dosimetric differences. CONCLUSION: MRI-linac based single dose APBI to the intact tumor is a promising and a dosimetrically feasible strategy in patients with low-risk breast cancer. Preliminary OAR dosimetry favored the prone radiotherapy position.

A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.

BACKGROUND: Despite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single-center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression ≥50%. METHODS: We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation-positive, advanced NSCLC and PD-L1-positive (≥1%, 22C3 antibody) tumors. Pembrolizumab was administered 200 mg every 3 weeks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab. RESULTS: Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. Eighty-two percent of trial patients were treatment naïve, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression ≥50%. Only 1 patient had an objective response (9%), but repeat analysis of this patient's tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment-related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern. CONCLUSIONS: Pembrolizumab's lack of efficacy in TKI naïve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression ≥50%, suggests that it is not an appropriate therapeutic choice in this setting.

Guidelines for the management of postoperative obstructive symptoms in children with Hirschsprung disease.

Although most children with Hirschsprung disease ultimately do well, many experience a variety of ongoing problems after pull-through surgery. The most common include obstructive symptoms, soiling, enterocolitis and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative obstructive symptoms in children with Hirschsprung disease. The American Pediatric Surgical Association Board of Governors established a Hirschsprung Disease Interest Group. Group discussions, literature review and expert consensus were then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with obstructive symptoms following pull-through for Hirschsprung disease. Causes of obstructive symptoms post-pull-through include mechanical obstruction; persistent or acquired aganglionosis, hypoganglionosis, or transition zone pull-through; internal sphincter achalasia; disordered motility in the proximal intestine that contains ganglion cells; or functional megacolon caused by stool-holding behavior. An algorithm for the diagnosis and management of obstructive symptoms after a pull-through for Hirschsprung disease is presented. A stepwise, logical approach to the diagnosis and management of patients experiencing obstructive symptoms following pull-through for Hirschsprung disease can facilitate treatment. Level of evidence V.

A central role for Ras1 in morphogenesis of the basidiomycete Schizophyllum commune.

Fungi have been used as model systems to define general processes in eukaryotes, for example, the one gene-one enzyme hypothesis, as well as to study polar growth or pathogenesis. Here, we show a central role for the regulator protein Ras in a mushroom-forming, filamentous basidiomycete linking growth, pheromone signaling, sexual development, and meiosis to different signal transduction pathways. ras1 and Ras-specific gap1 mutants were generated and used to modify the intracellular activation state of the Ras module. Transformants containing constitutive ras1 alleles (ras1(G12V) and ras1(Q61L)), as well as their compatible mating interactions, did show strong phenotypes for growth (associated with Cdc42 signaling) and mating (associated with mitogen-activated protein kinase signaling). Normal fruiting bodies with abnormal spores exhibiting a reduced germination rate were produced by outcrossing of these mutant strains. Homozygous Δgap1 primordia, expected to experience increased Ras signaling, showed overlapping phenotypes with a block in basidium development and meiosis. Investigation of cyclic AMP (cAMP)-dependent protein kinase A indicated that constitutively active ras1, as well as Δgap1 mutant strains, exhibit a strong increase in Tpk activity. Ras1-dependent, cAMP-mediated signal transduction is, in addition to the known signaling pathways, involved in fruiting body formation in Schizophyllum commune. To integrate these analyses of Ras signaling, microarray studies were performed. Mutant strains containing constitutively active Ras1, deletion of RasGap1, or constitutively active Cdc42 were characterized and compared. At the transcriptome level, specific regulation highlighting the phenotypic differences of the mutants is clearly visible.

Relaxin augments the inflammatory IL6 response in the choriodecidua.

UNLABELLED: Intrauterine infection frequently leads to preterm birth (PTB), with the pathophysiology involving activation of the innate immune system and its associated inflammatory response. The choriodecidua produces relaxin (RLN) and elevated levels are associated with preterm premature rupture of the fetal membranes. However, it is not increased in bacterially-mediated PTB, but may act as an endogenous sterile inflammatory mediator. Elevated systemic RLN levels from the corpus luteum are also associated with PTB, but the mechanism is unknown. In clinical obstetrics, intrauterine inflammation or infection can coexist with elevated RLN. Therefore, in this study, we further characterized the effects of RLN alone or together with an inflammatory mediator on the production of IL1B, CSF2 (GM-CSF), IL6, IL8 and TNF, from chorionic cytotrophoblasts (CyT), decidual fibroblasts (DF) and stromal cells (DSC), using interleukin-1 beta (IL1B) to mimic sterile inflammation or lipopolysaccharide (LPS) for bacterial infection. Endogenous differences between the cells showed that the CyT expressed more RLN, its receptor RXFP1 and the RXFP1 splice variant D. CyT also showed the most robust cAMP response to RLN with increased IL6 secreted after 4 h, preceded by increased transcription at 1 h, likely due to activation of RXFP1 and cAMP. When all cell types were treated with IL1B and RLN, RLN augmented secretion of IL6 and IL8 from CyT and DF, but not DSC. Similarly, RLN augmented LPS-induced IL6 secretion from CyT and DF. Despite the structural similarity between TLR4 and RXFP1, blocking TLR4 in CyT had no effect on RLN-induced IL6 secretion, suggesting specific activation of RXFP1. Thus, we have shown that in the presence of a low level of intrauterine inflammation/infection, elevated RLN could act on the CyT and DF to augment the inflammatory response, contributing to the pathophysiology of PTB. SUMMARY: RLN augments the inflammatory responses induced by IL1B or LPS in chorionic cytotrophoblasts and decidual fibroblasts.

The current state of health care reform: the physicians' burden.

Congress has passed expansive legislation to "fix" health care. US health care, however, is not "broken"; rather, it functions according to purpose. The legal standard sets health care's purpose as high-quality care, not care at a pervasive quantity or low cost. Juries focus on quality irrespective of cost, and the court's concern is not cost but whether the defendant physician has met the standard of care. As the US health system does deliver high-quality (albeit high-cost) care, it is not broken; instead, the system that defines it is broken. The legal system defines the standard of care as the care that an average physician would deliver under similar circumstances. As 91% of physicians admit to practicing defensively excessive care, the legal care standard is therefore excessive care. However, the new health care legislation passed by Congress does not address tort reform. Instead, it reduces physician remuneration and increases penalty-driven cost care control regulations. Caught between a care standard that demands high quality regardless of cost and penalty-driven federal mandates demanding low-cost care regardless of the legal care standard, physicians bear the new law's ultimate burden. US health care should not continue to focus on quality over cost and quantity; more important, the law should not continue to dictate that it do so. Rather, the system must import cost-effective care, and the law must so direct. To reduce health care costs, the legal system must first recognize a standard of care that respects cost-or tort reform that protects those physicians who do.

Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification.

BACKGROUND: In early-stage breast cancer, adjuvant chemotherapy is associated with significant systemic toxicity with only a modest survival benefit. Therefore, there is considerable interest in identifying predictive markers of response to therapy. Doxorubicin, one of the most common drugs used to treat breast cancer, is an anthracycline chemotherapeutic agent, a class of drugs known to be affected by hypoxia. Accordingly, we examined whether expression of the endogenous hypoxia marker carbonic anhydrase IX (CA IX) is predictive of outcome in early-stage breast cancer patients treated with doxorubicin. METHODS: We obtained 209 early-stage pre-treatment surgically-resected breast tumours from patients, who received doxorubicin in their chemotherapeutic regimen and had >10 years of follow-up. Immunohistochemistry was used to detect CA IX, and we used fluorescence in situ hybridisation to detect both human epidermal growth factor receptor (HER2) and DNA topoisomerase II-alpha (TOP2A) gene amplification. RESULTS: Carbonic anhydrase IX intensity was significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients receiving 300 mg m(-2) of doxorubicin (HR=1.82 and 3.77; P=0.0014 and 0.010, respectively). There was a significant, inverse correlation between CA IX score and oestrogen receptor expression, but no significant correlations were seen with either HER2 or TOP2A ratio. CONCLUSION: We demonstrate that CA IX expression is correlated with worse PFS and OS for breast cancer patients treated with doxorubicin, independent of HER2 or TOP2A gene amplification. This study provides evidence that using CA IX to detect hypoxia in surgically-resected breast tumours may be of clinical use in choosing an appropriate chemotherapy regimen.

Relaxin modulates proinflammatory cytokine secretion from human decidual macrophages.

Relaxin (RLN) is a systemic hormone from the corpus luteum, and its levels remain low during normal human gestation. Indeed, elevation of circulating RLN has long been associated with preterm birth, for which there has been no physiological explanation. Recent studies have shown that RLN suppresses endotoxin-induced cytokine secretion from THP-1 monocytic cells by acting on the glucocorticoid receptor (GR), but its effects on primary macrophages are unknown. Therefore, in the present study, we examined the effects of RLN on cytokine secretion from primary decidual macrophages (DMs) obtained at term before labor. Unlike THP-1 cells, RLN had no effects on the cytokine responses induced by either lipopolysaccharide (LPS) or interleukin (IL) 1B, mimicking infection-induced or sterile inflammation, respectively. However, RLN alone for 4 h significantly decreased (P < 0.05) colony-stimulating factor 2 (CSF2; also known as granulocyte-macrophage colony-stimulating factor) and IL8 but for 24 h significantly increased IL6 (P < 0.01). We show that DMs express both the RLN receptor (RXFP1) and the GR. RLN suppression of CSF2 and IL8 was sensitive to the GR-antagonist mifepristone (RU-486). However, RLN activation of RXFP1 induced a dose-dependent cAMP response, which when mimicked by forskolin also caused significantly increased (P < 0.05) secretion of IL6. Thus, RLN may be anti-inflammatory in DMs via activation of the GR but proinflammatory via activation of RXFP1 and cAMP. In summary, we have shown that RLN targeting DMs may modulate proinflammatory cytokine secretion at the maternal-fetal interface and contribute to the localized inflammatory response associated with parturition in women.

Bochdalek hernia in the adult: demographics, presentation, and surgical management.

BACKGROUND: Bochdalek hernias are a very rare form of diaphragmatic hernias. There are no robust studies that reveal the true natural history of this disease process. The aim of this study was to summarize clinically relevant data for the purpose of assisting surgeons with the work-up, diagnosis, and treatment of adult patients with Bochdalek hernia. METHODS: A literature search was performed using PubMed, Google scholar, EMBASE and the following keywords: Bochdalek hernia, congenital diaphragmatic hernia, and posterolateral hernia. All case reports and series after 1955 that pertained to adults were included in the review. The following data points were queried: age, sex, presentation, studies utilized during work-up, laterality, surgical approach, hernia sac management, specific minimally invasive surgical techniques, and follow-up. RESULTS: A total of 124 articles comprising 173 patients met the inclusion criteria. Based on the data provided, several conclusions regarding this disease process can be made. Most patients present with symptoms related to their hernia (86%). Pain is the most common complaint (69%). While laparotomy is the most widely used surgical approach (38%), minimally invasive surgical techniques have gained popularity since their first report in 1995. Laparoscopic repair can be performed with a low complication rate (7%) and short hospital stay (4 days). CONCLUSIONS: Using modern surgical techniques to include laparoscopy, repair can be performed safely, with a short hospital stay, and with minimal morbidity or mortality.

Characterization of covalently bonded proteins on poly(methyl methacrylate) by X-ray photoelectron spectroscopy.

X-ray photoelectron spectroscopy (XPS) has been used to characterize a poly(methyl methacrylate) (PMMA) surface with covalently attached proteins. The PMMA surfaces were first aminated using hexamethyldiamine; the resulting -NH(2) sites were reacted with the hetero-bifunctional cross-linker Sulfo-EMCS to form a maleimide-terminated surface. The N-hydroxysuccinimide ester terminal and maleimide terminal groups of Sulfo-EMCS reacts with amine and sulfhydryl groups, respectively, exposed on the surface of the proteins. This study characterizes Thermotoga maritima beta-glucosidase 1 (TmGH1), which belongs to a family of proteins that facilitate hydrolysis of glucose-related monomers with retention of conformation. The surfaces were characterized by XPS to monitor surface composition, and to elucidate protein orientation on the surface. Results suggest that a covalently bonded surface of TmGH1 on PMMA has been obtained. These results demonstrate the feasibility of using XPS to study protein surface chemistry and demonstrate a useful method to anchor cysteine-terminated proteins for the purposes of creating biosensors or platforms for mechanical force experiments to investigate protein structure.

MOC-PS(SM) CME article: patient safety in the office-based setting.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Discern the importance of the physician's office administrative structure. 2. Recognize the necessity of a system for quality assessment. 3. Assess which procedures are safe in the office-based setting. 4. Know the basic steps for properly evaluating patients for office-based plastic surgery. SUMMARY: This article reviews the literature on office-based patient safety issues. It places special emphasis on the statements and advisories published by the American Society of Plastic Surgeons' Convened Task Force on Patient Safety in the Office-Based Setting. The article divides patient safety in the health care delivery system into four broad categories. First, patient safety starts with emphasis at the administrative level. The physician or independent governing body must develop a system of quality assessment that functions to minimize preventable errors and report outcomes and errors. Second, the clinical aspects of patient safety require that the physician evaluate whether the procedure(s) and the patient are proper for the office setting. Third, this article gives special attention to liposuction, the most frequently performed office-based plastic surgery procedure. Finally, the article reviews the management of postoperative pain, nausea, and vomiting. Patient safety must be every physician's highest priority, as reflected in the Hippocratic Oath: primum non nocere ("first, do no harm").

Perioperative medical comorbidities in the orthopaedic patient.

Evaluation and management of medical comorbidities in the perioperative period can help improve surgical morbidity and mortality. Perioperative evaluation essentially is risk assessment and minimization. Patients undergoing orthopaedic treatment may benefit from temporizing measures to reduce systemic complications associated with some procedures. Patients at increased risk of cardiac ischemia should undergo risk stratification to determine possible perioperative interventions. Use of perioperative medications and/or consultation with specialists can help to address heart murmurs, bacterial endocarditis, prior stenting, heart failure, and hypertension. Patients with severe or unstable chronic obstructive pulmonary disease require the involvement of pulmonary care specialists. Renal failure can require nephrology consultation, particularly in cases of worsening renal function or urinary outflow obstruction. Hematologic considerations include bleeding and clotting. Prophylaxis should be used in patients with risk factors for peptic ulcer, as well as respiratory failure and hypotension. Nutritional status and liver disease also must be monitored and treated preoperatively. Orthopaedic diabetic patients should be placed on modified oral hypoglycemic or insulin regimens; recalcitrant cases merit consultation. Effective communication among all members of the patient's caregiving team is paramount.

Immediate shrinkage of optociliary shunt vessels after fractionated external beam radiation for meningioma of the optic nerve sheath.

Fractionated stereotactic radiation has become the standard treatment of meningioma of the optic nerve sheath. The mechanism responsible for improvement in visual function is unclear, because neuroimaging after treatment usually shows no discernable change in tumor appearance. We report immediate regression of optociliary shunt vessels in a patient after radiation treatment of an optic nerve sheath meningioma. This observation indicates that radiation treatment can cause rapid reduction of optic nerve compression, even without appreciable reduction in the size of the meningioma.

Surface modification of poly(dimethylsiloxane) with a perfluorinated alkoxysilane for selectivity toward fluorous tagged peptides.

Poly(dimethylsiloxane) (PDMS) and similar polymers have proved to be of widespread interest for use in microfluidic and similar microanalytical devices. Surface modification of PDMS is required to extend the range of applications for devices made of this polymer, however. Here we report on the grafting of perfluorooctyltriethoxysilane via hydrolysis onto an oxidized PDMS substrate in order to form a fluorinated microchannel. Such a fluorinated device could be used for separating fluorous tagged proteins or peptides, similar to that which has been recently demonstrated in a capillary electrophoresis system or in an open tubular capillary column. The modified polymer is characterized using chemical force titrations, contact angle measurements, and X-ray photoelectron spectroscopy (XPS). We also report on a novel means of performing electroosmotic measurements on this material to determine the surface zeta potential. As might be expected, contact angle and chemical force titration measurements indicate the fluorinated surface to be highly hydrophobic. XPS indicates that fluorocarbon groups segregate to the surface of the polymer over a period of days following the initial surface modification, presumably driven by a lower surface free energy. One of the most interesting results is the zeta potential measurements, which show that significant surface charge can be maintained across a wide range of pH on this modified polymer, sufficient to promote electroosmotic flow in a microfluidic chip. Matrix-assisted time-of-flight mass spectrometry (MALDI-TOF MS) measurements show that a fluorous-tagged peptide will selectively adsorb on the fluorinated PDMS in aqueous solution, demonstrating that the fluorinated polymer could be used in devices designed for the enrichment or enhanced detection of fluorous-labeled proteins and peptides.

Expert witness reform.

The legal system depends on the medical expert for evidence. Doctors readily complain about frivolous cases that go to trial, yet a lawyer cannot bring a frivolous claim to trial without a physician expert witness stating that the claim is not frivolous. An insurance company cannot raise premiums without medical expert witnesses servicing the increasing litigation against the insured. Physicians must look to themselves as a major contributor to rising malpractice insurance costs. For without the physician expert witness, no medical malpractice lawsuit can take place. It is the expert physician, not the attorneys or insurance companies, who defines "meritless" and "frivolous" and who ultimately controls the courts' medical malpractice caseload.

Increasing incidence of methicillin-resistant Staphylococcus aureus in hand infections: a 3-year county hospital experience.

BACKGROUND: Staphylococcus aureus is the most common cause of skin and soft-tissue infections. Methicillin-resistant S. aureus and community-acquired methicillin-resistant S. aureus have shown an increase in prevalence among soft-tissue infections over the past several years, with overall rates approaching 50 percent at the authors' institution in 2002. The object of this study was to determine the incidence of methicillin-resistant S. aureus with respect to hand infections, the antibiotic resistance pattern of methicillin-resistant S. aureus isolates, and implications for a change in antibiotic treatment algorithms for hand infections. METHODS: A retrospective chart review of 761 patients with hand infections tracked by International Classification of Diseases, 9th Revision codes for finger or hand abscesses from 2001 to 2003 was performed at Parkland Memorial Hospital, Dallas, Texas. Culture results were obtained from 436 patients and analyzed for type of organism, and sensitivity profiles were obtained for all methicillin-resistant S. aureus isolates. RESULTS: The median age of 761 patients was 40 years (range, 16 to 77 years); 71 percent were male and 28 percent were female. Of the 436 cultures reviewed, 371 (85 percent) had organisms identified. Methicillin-resistant S. aureus was the dominant single organism in hand infections cultured in all 3 years. The overall methicillin-resistant S. aureus rate was 61 percent of all hand infections in 2003. The percentage of S. aureus isolates identified as methicillin-resistant S. aureus increased from 55 percent to 78 percent over 3 years, up from 34 percent in 2001. Fortunately, 86 percent of these methicillin-resistant S. aureus isolates demonstrated sensitivity to conventional antibiotics, but a trend of resistance is developing. CONCLUSIONS: The incidence of community-acquired methicillin-resistant S. aureus increased from 34 percent to 61 percent over a 3-year period at the authors' county institution. An increasing trend of resistance patterns among conventional antibiotics was also demonstrated. As a result of this study, the treatment algorithm at Parkland Memorial Hospital has been modified to include abscess drainage accompanied by an antibiotic regimen targeted specifically at methicillin-resistant S. aureus. These data also have implications for broader application regarding simple skin infections and current antibiotic treatment algorithms.

Detecting genetic predisposition for complicated clinical outcomes after burn injury.

Sepsis, septic shock and organ failure are common among patients with moderate to severe burns. The inability of demographic and clinical factors to identify patients at high risk for such complications suggests that genetic variation may influence clinical outcome. Moreover, the genetic predisposition to death from infection has been estimated to be greater than for cardiovascular disease or cancer . While it is widely accepted that genetic factors influence many complex disease processes, controversy has emerged regarding the most appropriate methods for detection and even the validity of many published allelic associations . This article will review the few studies of genetic predisposition that have been conducted in the setting of burn injury, then discuss some of the obstacles and potential approaches for the discovery of additional allelic associations.