Resident Wilderness Medicine Curriculum Consensus Guidelines: Summarization and Recommendations for Resident Rotations in Wilderness Medicine.

INTRODUCTION: Wilderness medicine education is one of the fastest growing facets of both graduate and undergraduate medical education. Currently, there are curriculum guidelines for both student electives and fellowships in wilderness medicine. However, there are no guidelines for resident elective curricula. The student/resident education committee of the Wilderness Medical Society (WMS) convened a task force to develop curriculum guidelines for these electives. METHODS: A survey of previously described core wilderness medicine topics was sent to a cohort of educators involved in wilderness medicine resident electives. They were asked to rank topics on the basis of their importance of being included on a Likert scale. Multivariate analysis of medians was used to distinguish among topics to determine which topics were voted most and least necessary for a curriculum. RESULTS: Of the database members contacted, 35 responded to the survey. The described current state of residency electives was that 16 institutions offered their own elective (46%). For subject preferences, multivariate analysis of scoring distribution medians demonstrated a significantly higher pattern of responses (P<0.01) for subjects with a median of 3 (must include) than for the lowest-scoring subjects that had a median of 1 (can include). Every topic was rated "must" by at least 1 respondent. Topics were further subdivided into an educational framework reflecting a common approach to education of wilderness medicine fellows focusing on education, leadership, knowledge, and skills. CONCLUSIONS: There was a wide variety in the ranking of topics; however, there were multiple topics on which a consensus for inclusion was reached. These topics are organized and presented here as a suggested curriculum by the student/resident education committee of the WMS.

No Change in the Use of Antivenom in Copperhead Snakebites in Ohio.

INTRODUCTION: Historically, copperhead snake (Agkistrodon contortrix) envenomations were not treated with antivenom owing to related adverse events and little benefit. However, recent studies have shown improved outcomes with antivenom use. We hypothesized that the frequency of antivenom use for copperhead envenomation in Ohio has increased as benefits of administration became more widely known. METHODS: All copperhead snakebites reported to the Ohio poison control centers from 2006 through 2016 were compiled. Antivenom use, bite severity, and disposition were abstracted. A nonparametric test for trend was used to evaluate changes over time for the number of patients treated with antivenom and patient disposition. Logistic regression was used to assess the odds of admission vs discharge with antivenom administration, bite severity, age, and sex as independent variables. RESULTS: Ninety-eight patients reported copperhead snakebites to the poison control centers. The test of trend showed no change in the proportion of patients treated with antivenom by year (P=0.42). There was no difference in the proportion of patients discharged home (P=0.38) per year. Logistic regression showed antivenom use was associated with an odds ratio for admission of 46.7 (95% CI: 7.3-296.4). CONCLUSIONS: The frequency of antivenom use for copperhead bites did not significantly increase between 2006 and 2016. Administration of antivenom was associated with a large increase in the odds of admission to the hospital, even when controlling for bite severity. Further education regarding the benefits and safety of antivenom may increase its use for copperhead snakebites, but may lead to an increase in hospital admissions.

Are viruses associated with disc herniation? A clinical case series.

BACKGROUND: There is some limited evidence for the presence of viruses in herniated disc material including a previous case series that claimed to provide "unequivocal evidence of the presence of herpes virus DNA in intervertebral disc specimens of patients with lumbar disc herniation suggesting the potential role of herpes viruses as a contributing factor to the pathogenesis of degenerative disc disease". This study has not been replicated. The objective of our study was to determine if viruses were present in herniated disc fragments in participants with a prior history of back pain. METHODS: We recruited fifteen participants with a history of prior low-back pain prior to undergoing disc herniation surgery in the lumbar spine. Harvested disc samples were subject to next generation sequencing for detection of both RNA and DNA viral pathogens. Additionally, samples were analysed by a broadly reactive PCR targeting herpesviral DNA. Ethics approval was granted by the Human Research Ethics Committees of both Murdoch University, and St John of God Hospital, Western Australia. RESULTS: Of the fifteen research participants, 8 were female. Mean age was 49.4 years (SD 14.5 yrs) with a range of 24-70 years. All participants had prior back pain with mean time since first ever attack being 8.8 years (SD 8.8 yrs). No samples contained significant DNA sequences relating to known human viral agents. Inconsequential retroviral sequences were commonly found and were a mixture of putative animal and human retroviral protein coding segments. All samples were negative for herpesvirus DNA when analysed by pan-herpesvirus PCR. CONCLUSIONS: This study found no viral pathogens in any intervertebral disc fragments of patients who had previous back pain and underwent discectomy for disc herniation and thus it is unlikely that viruses are associated with disc herniation, however given the contradiction between key studies enhanced replication of this experiment is recommended.

[Anaplastic large cell lymphoma associated with breast implants, diagnosed by fine needle aspiration. Report of one case]. / Linfoma anaplásico de células grandes asociado a implantes mamarios diagnosticado mediante punción por aguja fina. Caso clínico.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin T-cell lymphoma, recently defined in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms. It occurs more commonly when textured implants are used and appears clinically as a late seroma. Cytologically, these lesions are composed of large atypical cells with pleomorphic nucleus and an immunophenotype positive for T cell markers and CD30, and negative for ALK1. We report a 56-years-old woman with breast implants who developed a periprosthetic seroma three years after surgery. A fine needle aspiration of the lesion was carried out. Cytology and the immunocytochemical study revealed cells compatible with BIA-ALCL. The flow cytometric study was negative. Excisional biopsy of the capsule was performed, observing that the neoplastic cells were confined to the inner surface of the capsule. Imaging studies did not find evidence of disseminated disease. The present case demonstrates the importance of the study of any late periprosthetic effusion, which can be performed using fine needle aspiration.

Field and Laboratory Studies Linking Hydrologic, Geochemical, and Microbiological Processes and Enhanced Denitrification during Infiltration for Managed Recharge.

We present linked field and laboratory studies investigating controls on enhanced nitrate processing during infiltration for managed aquifer recharge. We examine how carbon-rich permeable reactive barriers (PRBs) made of woodchips or biochar, placed in the path of infiltrating water, stimulate microbial denitrification. In field studies with infiltration of 0.2-0.3 m/day and initial nitrate concentrations of [NO3-N] = 20-28 mg/L, we observed that woodchips promoted 37 ± 6.6% nitrate removal (primarily via denitrification), and biochar promoted 33 ± 12% nitrate removal (likely via denitrification and physical absorption effects). In contrast, unamended soil at the same site generated <5% denitrification. We find that the presence of a carbon-rich PRB has a modest effect on the underlying soil microbial community structure in these experiments, indicating that existing consortia have the capability to carry out denitrification given favorable conditions. In laboratory studies using intact cores from the same site, we extend the results to quantify how infiltration rate influences denitrification, with and without a carbon-rich PRB. We find that the influence of both PRB materials is diminished at higher infiltration rates (>0.7 m/day) but can still result in denitrification. These results demonstrate a quantitative relationship between infiltration rate and denitrification that depends on the presence and nature of a PRB. Combined results from these field and laboratory experiments, with complementary studies of denitrification during infiltration through other soils, suggest a framework for understanding linked hydrologic and chemical controls on microbial denitrification (and potentially other redox-sensitive processes) that could improve water quality during managed recharge.

Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study.

OBJECTIVE: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. METHODS: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. RESULTS: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. CONCLUSIONS: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.

Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice.

Background: Targeted capture sequencing can potentially facilitate precision medicine, but the feasibility of this approach in gastrointestinal (GI) malignancies is unknown. Patients and methods: The FOrMAT (Feasibility of a Molecular Characterisation Approach to Treatment) study was a feasibility study enrolling patients with advanced GI malignancies from February 2014 to November 2015. Targeted capture sequencing (mainly using archival formalin-fixed paraffin-embedded diagnostic/resection samples) was carried out to detect mutations, copy number variations and translocations in up to 46 genes which had prognostic/predictive significance or were targets in current/upcoming clinical trials. Results: Of the 222 patients recruited, 215 patients (96.8%) had available tissue samples, 125 patients (56.3%) had ≥16 genes successfully sequenced and 136 patients (61.2%) had ≥1 genes successfully sequenced. Sample characteristics influenced the proportion of successfully sequenced samples, e.g. tumour type (colorectal 70.9%, biliary 52.6%, oesophagogastric 50.7%, pancreas 27.3%, P = 0.002), tumour cellularity (high versus low: 78.3% versus 13.3%, P ≤ 0.001), tumour content (high versus low: 78.6% versus 27.3%, P = 0.001) and type of sample (resection versus biopsy: 82.4% versus 47.6%, P ≤ 0.001). Currently, actionable alterations were detected in 90 (40.5%) of the 222 patients recruited (66% of the 136 patients sequenced) and 2 patients subsequently received a targeted therapy. The most frequently detected currently actionable alterations were mutations in KRAS, BRAF, TP53 and PIK3CA. For the 205 patients with archival samples, the median time to obtain sequencing results was 18.9 weeks, including a median of 4.9 weeks for sample retrieval and 5.1 weeks for sequencing. Conclusions: Targeted sequencing detected actionable alterations in formalin-fixed paraffin-embedded samples, but tissue characteristics are of critical importance in determining sequencing success. Routine molecular profiling of GI tumours outside of clinical trials is not an effective use of healthcare resources unless more targeted drugs become available. ClinicalTrials.gov identifier: NCT02112357.

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study.

BACKGROUND: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this. OBJECTIVE: Describe clinical characteristics of children hospitalized for asthma exacerbation. METHODS: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist. RESULTS: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist. CONCLUSIONS: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children.

HLA-B*57 and IFNL4-related polymorphisms are associated with protection against HIV-1 disease progression in controllers.

Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers. Methods: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C. Conclusions: We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.

Limits of Strong Field Rescattering in the Relativistic Regime.

Recollision for a laser driven atomic system is investigated in the relativistic regime via a strong field quantum description and Monte Carlo semiclassical approach. We find the relativistic recollision energy cutoff is independent of the ponderomotive potential U_{p}, in contrast to the well-known 3.2U_{p} scaling. The relativistic recollision energy cutoff is determined by the ionization potential of the atomic system and achievable with non-negligible recollision flux before entering a "rescattering free" interaction. The ultimate energy cutoff is limited by the available intensities of short wavelength lasers and cannot exceed a few thousand Hartree, setting a boundary for recollision based attosecond physics.

Comparing hospital and telephone follow-up for patients treated for stage-I endometrial cancer (ENDCAT trial): a randomised, multicentre, non-inferiority trial.

OBJECTIVE: To evaluate the effectiveness of nurse-led telephone follow-up (TFU) for patients with stage-I endometrial cancer. DESIGN: Multicentre, randomised, non-inferiority trial. SETTING: Five centres in the North West of England. SAMPLE: A cohort of 259 women treated for stage-I endometrial cancer attending hospital outpatient clinics for routine follow-up. METHODS: Participants were randomly allocated to receive traditional hospital based follow-up (HFU) or nurse-led TFU. MAIN OUTCOME MEASURES: Primary outcomes were psychological morbidity (State Trait Anxiety Inventory, STAI-S) and patient satisfaction with the information provided. Secondary outcomes included patient satisfaction with service, quality of life, and time to detection of recurrence. RESULTS: The STAI-S scores post-randomisation were similar between groups [mean (SD): TFU 33.0 (11.0); HFU 35.5 (13.0)]. The estimated between-group difference in STAI-S was 0.7 (95% confidence interval, 95% CI -1.9 to 3.3); the confidence interval lies above the non-inferiority limit (-3.5), indicating the non-inferiority of TFU. There was no significant difference between groups in reported satisfaction with information (odds ratio, OR 0.9; 95% CI 0.4-2.1; P = 0.83). Women in the HFU group were more likely to report being kept waiting for their appointment (P = 0.001), that they did not need any information (P = 0.003), and were less likely to report that the nurse knew about their particular case and situation (P = 0.005). CONCLUSIONS: The TFU provides an effective alternative to HFU for patients with stage-I endometrial cancer, with no reported physical or psychological detriment. Patient satisfaction with information was high, with similar levels between groups. TWEETABLE ABSTRACT: ENDCAT trial shows effectiveness of nurse-led telephone follow-up for patients with stage-I endometrial cancer.

Estrogens protect male mice from obesity complications and influence glucocorticoid metabolism.

BACKGROUND: Although the prevalence of obesity is higher among women than men, they are somewhat protected from the associated cardiometabolic consequences. The increase in cardiovascular disease risk seen after the menopause suggests a role for estrogens. There is also growing evidence for the importance of estrogen on body fat and metabolism in males. We hypothesized that that estrogen administration would ameliorate the adverse effects of obesity on metabolic parameters in males. METHODS: Male and female C57Bl/6 mice were fed control or obesogenic (DIO) diets from 5 weeks of age until adulthood. Glucose tolerance testing was performed at 13 weeks of age. Mice were killed at 15 weeks of age and liver and adipose tissue were collected for analysis of gene expression. A second cohort of male mice underwent the same experimental design with the addition of estradiol pellet implantation or sham surgery at 6 weeks. RESULTS: DIO males had greater mesenteric adipose deposition and more severe increases in plasma glucose, insulin and lipids than females. Treatment of males with estradiol from 6 weeks of age prevented DIO-induced increases in adipose tissue mass and alterations in glucose-insulin homeostasis. We also identified sex differences in the transcript levels and activity of hepatic and adipose glucocorticoid metabolizing enzymes. Estrogen treatment feminized the pattern of DIO-induced changes in glucocorticoid metabolism, rendering males similar to females. CONCLUSIONS: Thus, DIO induces sex-specific changes in glucose-insulin homeostasis, which are ameliorated in males treated with estrogen, highlighting the importance of sex steroids in metabolism. Given that altered peripheral glucocorticoid metabolism has been observed in rodent and human obesity, our results also suggest that sexually dimorphic expression and activity of glucocorticoid metabolizing enzymes may have a role in the differential metabolic responses to obesity in males and females.

Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.

BACKGROUND/OBJECTIVES: Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women. SUBJECTS/METHODS: Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11ß hydroxysteroid dehydrogenase type 1 (11ßHSD1) in subcutaneous adipose tissue were studied. RESULTS: Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11ßHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11ßHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months. CONCLUSIONS: Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women.

BACKGROUND: Black women have lower visceral adipose tissue (VAT) but are less insulin sensitive than white women; the mechanisms responsible are unknown. OBJECTIVE: The study aimed to test the hypothesis that variation in subcutaneous adipose tissue (SAT) sensitivity to glucocorticoids might underlie these differences. METHODS: Body fatness (dual energy X-ray absorptiometry) and distribution (computerized tomography), insulin sensitivity (SI, intravenous and oral glucose tolerance tests), and expression of 11ß-hydroxysteroid dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid receptor-α (GRα), as well as genes involved in adipogenesis and inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT (GLUT) depots of 56 normal-weight or obese black and white premenopausal South African (SA) women. We used a combination of univariate and multivariate statistics to evaluate ethnic-specific patterns in adipose gene expression and related body composition and insulin sensitivity measures. RESULTS: Although 11HSD1 activity and mRNA did not differ by ethnicity, GRα mRNA levels were significantly lower in SAT of black compared with white women, particularly in the GLUT depot (0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). In black women, lower SAT GRα mRNA levels were associated with increased inflammatory gene transcript levels and abdominal SAT area, and reduced adipogenic gene transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated with increased VAT area and decreased SI in white, but not in black women. CONCLUSIONS: In black SA women, downregulation of GRα mRNA levels with obesity and reduced insulin sensitivity, possibly via increased SAT inflammation, is associated with reduced VAT accumulation.

Differential escape patterns within the dominant HLA-B*57:03-restricted HIV Gag epitope reflect distinct clade-specific functional constraints.

UNLABELLED: HLA-B*57:01 and HLA-B*57:03, the most prevalent HLA-B*57 subtypes in Caucasian and African populations, respectively, are the HLA alleles most protective against HIV disease progression. Understanding the mechanisms underlying this immune control is of critical importance, yet they remain unclear. Unexplained differences are observed in the impact of the dominant cytotoxic T lymphocyte (CTL) response restricted by HLA-B*57:01 and HLA-B*57:03 in chronic infection on the Gag epitope KAFSPEVIPMF (KF11; Gag 162 to 172). We previously showed that the HLA-B*57:03-KF11 response is associated with a >1-log-lower viral setpoint in C clade virus infection and that this response selects escape mutants within the epitope. We first examined the relationship of KF11 responses in B clade virus-infected subjects with HLA-B*57:01 to immune control and observed that a detectable KF11 response was associated with a >1-log-higher viral load (P = 0.02). No evidence of HLA-B*57:01-KF11-associated selection pressure was identified in previous comprehensive analyses of >1,800 B clade virus-infected subjects. We then studied a B clade virus-infected cohort in Barbados, where HLA-B*57:03 is highly prevalent. In contrast to findings for B clade virus-infected subjects expressing HLA-B*57:01, we observed strong selection pressure driven by the HLA-B*57:03-KF11 response for the escape mutation S173T. This mutation reduces recognition of virus-infected cells by HLA-B*57:03-KF11 CTLs and is associated with a >1-log increase in viral load in HLA-B*57:03-positive subjects (P = 0.009). We demonstrate functional constraints imposed by HIV clade relating to the residue at Gag 173 that explain the differential clade-specific escape patterns in HLA-B*57:03 subjects. Further studies are needed to evaluate the role of the KF11 response in HLA-B*57:01-associated HIV disease protection. IMPORTANCE: HLA-B*57 is the HLA class I molecule that affords the greatest protection against disease progression in HIV infection. Understanding the key mechanism(s) underlying immunosuppression of HIV is of importance in guiding therapeutic and vaccine-related approaches to improve the levels of HIV control occurring in nature. Numerous mechanisms have been proposed to explain the HLA associations with differential HIV disease outcome, but no consensus exists. These studies focus on two subtypes of HLA-B*57 prevalent in Caucasian and African populations, HLA-B*57:01 and HLA-B*57:03, respectively. These alleles appear equally protective against HIV disease progression. The CTL epitopes presented are in many cases identical, and the dominant response in chronic infection in each case is to the Gag epitope KF11. However, there the similarity ends. This study sought to better understand the reasons for these differences and what they teach us about which immune responses contribute to immune control of HIV infection.

Peripheral nerve catheters in children: an analysis of safety and practice patterns from the pediatric regional anesthesia network (PRAN).

BACKGROUND: Peripheral nerve catheters (PNCs) are used with increasing frequency in children. Although adult studies have demonstrated safety with this technique, there have been few safety studies in children. The main objective of the current investigation was to examine the incidence of PNC complications in children undergoing surgery. METHODS: This is an observational, multi-institutional study using the Pediatric Regional Anesthesia Network (PRAN) database. Data pertaining to PNCs were entered prospectively into a secure, online database by each participating centre. Patient characteristics, anatomic location, localization techniques, medications used, and complications were recorded for each catheter. All complications and any sequelae were followed until resolution. RESULTS: There were 2074 PNCs included in the study. 251 adverse events and complications were recorded, resulting in an overall incidence (95% CI) of complications of 12.1% (10.7-13.5%). The most common complications were catheter malfunction, block failure, infection, and vascular puncture. There were no reports of persistent neurologic problems, serious infection, or local anaesthetic systemic toxicity, resulting in an estimated incidence (95% CI) of 0.04% (0.001-0.2%). Patients who developed an infection had used the catheters for a greater number of days, median (IQR) of 4.5 (3-7) days compared with 3 (1-3) days in the patients who did not develop an infection, P<0.0001. CONCLUSIONS: Our data support the safety of placing PNCs in children, with adverse event rates similar to adult studies. Catheter problems are common, yet minor, in severity.

Efficacy of antifungal PACT in an in vitro model of onychomycosis.

BACKGROUND: The difficulty of antifungal substances to penetrate keratin and slow nail growth limit the efficacy of topical therapy in onychomycosis. One promising alternative is photodynamic antimicrobial chemotherapy, or PACT: an irradiated photosensitizer creates singlet oxygen molecules which destroy pathogens without damaging human cells. OBJECTIVE: As PACT has demonstrated strong antifungal capabilities, we wanted to investigate its efficacy in an in vitro model of onychomycosis. METHODS: PACT was tested in a microdilution assay, in an in vitro onychomycosis model as well as in a patient. RESULTS: PACT inhibited fungal growth in the microdilution assay with no colonies of T. rubrum detectable. Fungal growth was also inhibited in an onychomycosis model, after 30 min of LED irradiation. Subsequently, a patient with distolateral onychomycosis was treated on three consecutive days and showed significant and durable improvement of nail morphology 6 months after. CONCLUSION: PACT appears to be an effective treatment of onychomycosis in vitro. The promising results need to be validated by clinical trials.  

Effects of acute glucocorticoid blockade on metabolic dysfunction in patients with Type 2 diabetes with and without fatty liver.

To investigate the potential of therapies which reduce glucocorticoid action in patients with Type 2 diabetes we performed a randomized, double-blinded, placebo-controlled crossover study of acute glucocorticoid blockade, using the glucocorticoid receptor antagonist RU38486 (mifepristone) and cortisol biosynthesis inhibitor (metyrapone), in 14 men with Type 2 diabetes. Stable isotope dilution methodologies were used to measure the rates of appearance of glucose, glycerol, and free fatty acids (FFAs), including during a low-dose (10 mU·m⁻² ·min⁻¹) hyperinsulinemic clamp, and subgroup analysis was conducted in patients with high or low liver fat content measured by magnetic resonance spectroscopy (n = 7/group). Glucocorticoid blockade lowered fasting glucose and insulin levels and improved insulin sensitivity of FFA and glycerol turnover and hepatic glucose production. Among this population with Type 2 diabetes high liver fat was associated with hyperinsulinemia, higher fasting glucose levels, peripheral and hepatic insulin resistance, and impaired suppression of FFA oxidation and FFA and glycerol turnover during hyperinsulinemia. Glucocorticoid blockade had similar effects in those with and without high liver fat. Longer term treatments targeting glucocorticoid action may be useful in Type 2 diabetes with and without fatty liver.