BAER-101, a selective potentiator of α2- and α3-containing GABAA receptors, fully suppresses spontaneous cortical spike-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS).

BAER-101 (formerly AZD7325) is a selective partial potentiator of α2/3-containing γ-amino-butyric acid A receptors (GABAARs) and produces minimal sedation and dizziness. Antiseizure effects in models of Dravet and Fragile X Syndromes have been published. BAER-101 has been administered to over 700 healthy human volunteers and patients where it was found to be safe and well tolerated. To test the extent of the antiseizure activity of BAER-1010, we tested BAER-101 in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model, a widely used and translationally relevant model. GAERS rats with recording electrodes bilaterally located over the frontal and parietal cortices were used. Electroencepholographic (EEG) signals in freely moving awake rats were analyzed for spike-wave discharges (SWDs). BAER-101 was administered orally at doses of 0.3-100 mg/kg and diazepam was used as a positive control using a cross-over protocol with a wash-out period between treatments. The number of SWDs was dose-dependently reduced by BAER-101 with 0.3 mg/kg being the minimally effective dose (MED). The duration of and total time in SWDs were also reduced by BAER-101. Concentrations of drug in plasma achieved an MED of 10.1 nM, exceeding the Ki for α2 or α3, but 23 times lower than the Ki for α5-GABAARs. No adverse events were observed up to a dose 300× MED. The data support the possibility of antiseizure efficacy without the side effects associated with other GABAAR subtypes. This is the first report of an α2/3-selective GABA PAM suppressing seizures in the GAERS model. The data encourage proceeding to test BAER-101 in patients with epilepsy.

Training Community Therapists in Core Elements of CBT and Family Therapy for Adolescent Externalizing Problems.

OBJECTIVE: This pilot study tested pragmatic methods for training therapists in core techniques of two evidence-based interventions (EBIs) for adolescent externalizing problems: cognitive-behavioral therapy (CBT) or family therapy (FT). Training methods were designed to help therapists accurately self-monitor their use of EBIs and increase delivery of EBIs with current clients. The study compared coder training only versus coder training plus fidelity-focused consultation. METHOD: Therapists (N = 42) from seven behavioral health clinics reported on 65 youth clients; four clinics elected to train in CBT and three in FT. Therapists were randomized to either coder training only, consisting of a 25-week observational coder training course (didactic instruction and mock session coding exercises in core EBI techniques); or coder training plus fidelity-focused consultation, consisting of direct-to-therapist fidelity measurement feedback along with fidelity-focused expert consultation. During the 25 weeks of training, therapists submitted self-report data on EBI use along with companion session audiotapes subsequently coded by observational raters. RESULTS: Compared to coder training only, coder training plus fidelity-focused consultation produced superior effects in therapist ability to judge the extensiveness of EBI techniques in online coding sessions, as well as therapist ability to self-rate use of EBI techniques with their own cases. In both conditions, therapists who trained in CBT showed a significant, though modest, increase in real-world delivery of core CBT techniques; this did not occur for FT. CONCLUSIONS: Pragmatic training and consultation methods show promise as viable and effective options for enhancing EBI fidelity monitoring and, for CBT, increasing EBI delivery.

Pilot Trial of Online Measurement Training and Feedback in Family Therapy for Adolescent Behavior Problems.

OBJECTIVE: Pragmatic procedures for sustaining high-fidelity delivery of evidence-based interventions are needed to support implementation in usual care. This study tested an online therapist training system, featuring observational coder training and self-report fidelity feedback, to promote self-report acumen and routine use of family therapy (FT) techniques for adolescent behavior problems. METHOD: Therapists (N = 84) from nine substance use and mental health treatment sites reported on 185 adolescent clients. Therapists submitted baseline data on FT technique use with clients, completed a workshop introducing the 32-week training system, and were randomly assigned by site to Core Training versus Core Training + Consultation. Core Training included a therapist coder training course (didactic instruction and mock session coding exercises in 13 FT techniques) and fidelity feedback procedures depicting therapist-report data on FT use. Consultation convened therapists and supervisors for one-hour monthly sessions with an external FT expert. During the 32 weeks of training, therapists submitted self-report data on FT use along with companion session audiotapes subsequently coded by observational raters. RESULTS: Therapist self-report reliability and accuracy both increased substantially during training. Observers reported no increase over time in FT use; therapists self-reported a decrease in FT use, likely an artifact of their improved self-report accuracy. Consultation did not enhance therapist self-report acumen or increase FT use. CONCLUSIONS: Online training methods that improve therapist-report reliability and accuracy for FT use may confer important advantages for treatment planning and fidelity monitoring. More intensive and/or different training interventions appear needed to increase routine FT delivery.

Therapist Self-Report of Fidelity to Core Elements of Family Therapy for Adolescent Behavior Problems: Psychometrics of a Pragmatic Quality Indicator Tool.

Therapist-report measures of evidence-based interventions have enormous potential utility as quality indicators in routine care; yet, few such tools have shown strong psychometric properties. This study describes reliability and validity characteristics of a therapist-report measure of family therapy techniques for treating adolescent conduct and substance use problems: Inventory of Therapy Techniques for Core Elements of Family Therapy (ITT-CEFT). Study participants included 31 staff therapists treating 68 adolescent clients in eight community-based mental health and substance use clinics. Therapists submitted ITT-CEFT checklists and companion audio recordings for 189 sessions. The ITT-CEFT contains 13 techniques identified as core elements of three manualized family therapy models that are empirically supported for the target group. Therapists also reported on their use of three motivational interventions, and independent observers coded the submitted recordings. ITT-CEFT factor validity was shown via confirmatory factor analyses of the tool's theoretical structure. Derived modules were: Family Engagement (four items; Cronbach's α = .72); Relational Orientation (five items; α = .74); and Interactional Change (four items; α = .66). Concurrent validity analyses showed fair-to-excellent therapist reliability compared to observer ratings (ICCs range .64-.75); they showed moderate therapist accuracy compared to observer mean scores, reflecting a tendency to overestimate delivery of the techniques. Discriminant validity analyses showed tool differentiation from motivational interventions. Results offer provisional evidence for the feasibility of using the therapist-report ITT-CEFT to anchor quality procedures for family therapy interventions in real-world settings.Trial Registration: The parent clinical trial is registered at www.ClinicalTrials.gov , ID: NCT03342872 (registration date: 11.10.17).

Online Training of Community Therapists in Observational Coding of Family Therapy Techniques: Reliability and Accuracy.

A foundational strategy to promote implementation of evidence-based interventions (EBIs) is providing EBI training to therapists. This study tested an online training system in which therapists practiced observational coding of mock video vignettes demonstrating family therapy techniques for adolescent behavior problems. The study compared therapists ratings to gold-standard scores to measure therapist reliability (consistency across vignettes) and accuracy (approximation to gold scores); tested whether reliability and accuracy improved during training; and tested therapist-level predictors of overall accuracy and change in accuracy over time. Participants were 48 therapists working in nine community behavioral health clinics. The 32-exercise training course provided online instruction (about 15 min/week) in 13 core family therapy techniques representing three modules: Family Engagement, Relational Orientation, Interactional Change. Therapist reliability in rating technique presence (i.e., technique recognition) remained moderate across training; reliability in rating extensiveness of technique delivery (i.e., technique judgment) improved sharply over time, from poor to good. Whereas therapists on average overestimated extensiveness for almost every technique, their tendency to give low-accuracy scores decreased. Therapist accuracy improved significantly over time only for Interactional Change techniques. Baseline digital literacy and submission of self-report checklists on use of the techniques in their own sessions predicted coding accuracy. Training therapists to be more reliable and accurate coders of EBI techniques can potentially yield benefits in increased EBI self-report acumen and EBI use in daily practice. However, training effects may need to improve from those reported here to avail meaningful impact on EBI implementation.Trial Registration: The parent clinical trial is registered at www.ClinicalTrials.gov , ID: NCT03342872 (registration date: 11.10.17).

Core Elements of CBT for Adolescent Conduct and Substance Use Problems: Comorbidity, Clinical Techniques, and Case Examples.

Adolescent externalizing problems (AEPs), including serious conduct problems, delinquency, and substance misuse, are the most common adolescent behavioral issues in specialty care. High rates of comorbidity between conduct and substance use problems necessitate multidomain treatment strategies that can effectively address the AEP spectrum. One strategy to increase delivery of evidence-based interventions for multiproblem youth in usual care is to focus on core elements of empirically supported treatments that can be judiciously applied to clients presenting with diverse clinical profiles. This article describes six core practice elements of the cognitive-behavioral treatment (CBT) approach for AEPs: (1) Functional Analysis of Behavior Problems; (2) Prosocial Activity Sampling; (3) Cognitive Monitoring and Restructuring; (4) Emotion Regulation Training; (5) Problem-solving Training; (6) Communication Training. Integrated delivery of these core CBT elements is illustrated in two case examples, and implications for treatment planning for youth with AEPs are discussed.

Effects of extended-release niacin/laropiprant on correlations between apolipoprotein B, LDL-cholesterol and non-HDL-cholesterol in patients with type 2 diabetes.

BACKGROUND: LDL-C, non-HDL-C and ApoB levels are inter-correlated and all predict risk of atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes mellitus (T2DM) and/or high TG. These levels are lowered by extended-release niacin (ERN), and changes in the ratios of these levels may affect ASCVD risk. This analysis examined the effects of extended-release niacin/laropiprant (ERN/LRPT) on the relationships between apoB:LDL-C and apoB:non-HDL-C in patients with T2DM. METHODS: T2DM patients (n = 796) had LDL-C ≥1.55 and <2.97 mmol/L and TG <5.65 mmol/L following a 4-week, lipid-modifying run-in (~78 % taking statins). ApoB:LDL-C and apoB:non-HDL-C correlations were assessed after randomized (4:3), double-blind ERN/LRPT or placebo for 12 weeks. Pearson correlation coefficients between apoB:LDL-C and apoB:non-HDL-C were computed and simple linear regression models were fitted for apoB:LDL-C and apoB:non-HDL-C at baseline and Week 12, and the correlations between measured apoB and measured vs predicted values of LDL-C and non-HDL-C were studied. RESULTS: LDL-C and especially non-HDL-C were well correlated with apoB at baseline, and treatment with ERN/LRPT increased these correlations, especially between LDL-C and apoB. Despite the tighter correlations, many patients who achieved non-HDL-C goal, and especially LDL-C goal, remained above apoB goal. There was a trend towards greater increases in these correlations in the higher TG subgroup, non-significant possibly due to the small number of subjects. CONCLUSIONS: ERN/LRPT treatment increased association of apoB with LDL-C and non-HDL-C in patients with T2DM. Lowering LDL-C, non-HDL-C and apoB with niacin has the potential to reduce coronary risk in patients with T2DM.

Family Support Protocol for Adolescent Internalizing Disorders: Protocol for a Pre-Post Quantitative Treatment Development Study.

BACKGROUND: Internalizing disorders (IDs), primarily depression and anxiety, are highly prevalent among adolescents receiving community-based treatment for substance use disorders (SUDs). For such clients, interventions that do not holistically address both SUDs and IDs are less effective. OBJECTIVE: This pilot treatment development study aims to develop and test a modular treatment protocol for addressing cooccurring IDs among adolescents (aged 13 to 18 years) enrolled in routine care for substance use problems: Family Support Protocol for Adolescent Internalizing Disorders (Fam-AID). As an adjunctive protocol, Fam-AID will not require clinicians to markedly alter existing base practices for SUD. It will be anchored by 3 evidence-based foundations for treating cooccurring adolescent IDs: family engagement techniques, transdiagnostic individual cognitive behavioral therapy techniques, and family psychoeducation and safety planning. METHODS: This quasi-experimental study will proceed in 2 stages. The pilot stage will use rapid-cycle prototyping methods in collaboration with end-user stakeholders to draft protocol delivery and fidelity guidelines adapted from existing resources, solicit provider and client input on protocol content and delivery via cognitive interviewing, and pilot prototype components on 4 to 6 cases. The second stage will be an interrupted time series study for 60 comorbid SUD+ID cases across 2 sites serving diverse adolescents: 30 will receive treatment as usual (TAU); following clinician training in the protocol, 30 new cases will receive TAU enhanced by Fam-AID. For aim 1, the focus is on evaluating the acceptability of the Fam-AID protocol through therapist and client interviews as well as assessing fidelity benchmarks using therapist- and observer-reported protocol fidelity data. For aim 2, the plan is to compare the effects of TAU only cases versus TAU+Fam-AID cases on family treatment attendance and on adolescent ID and substance use symptoms, with measurements taken at baseline and at 3-month and 6-month follow-ups. RESULTS: Study recruitment will begin in April 2025. CONCLUSIONS: We anticipate that Fam-AID will contain 5 treatment modules that can be delivered in any sequence to meet client needs: family engagement of primary supports in treatment planning and services; relational reframing of family constraints, resiliencies, and social capital connected to the adolescent's ID symptoms; functional analysis of the adolescent's ID symptoms and related behaviors; cognitive behavioral therapy to address the adolescent's ID symptoms and functional needs, featuring 3 core techniques (emotion acceptance, emotional exposure, and behavioral activation) to address negative affect and emotional dysregulation; and family psychoeducation and safety planning focused on education about comorbid SUD+ID and prevention of adolescent self-harm. If the abovementioned modules are found to be feasible and effective, Fam-AID will offer a set of pragmatic interventions to SUD clinicians for treating cooccurring IDs in adolescent clients. TRIAL REGISTRATION: ClinicalTrials.gov NCT06413979; https://www.clinicaltrials.gov/study/NCT06413979. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/64332.

Standard Versus Family-Based Screening, Brief Intervention, and Referral to Treatment for Adolescent Substance Use in Primary Care: Protocol for a Multisite Randomized Effectiveness Trial.

BACKGROUND: Screening, brief intervention, and referral to treatment for adolescents (SBIRT-A) is widely recommended to promote detection and early intervention for alcohol and other drug (AOD) use in pediatric primary care. Existing SBIRT-A procedures rely almost exclusively on adolescents alone, despite the recognition of caregivers as critical protective factors in adolescent development and AOD use. Moreover, controlled SBIRT-A studies conducted in primary care have yielded inconsistent findings about implementation feasibility and effects on AOD outcomes and overall developmental functioning. There is urgent need to investigate the value of systematically incorporating caregivers in SBIRT-A procedures. OBJECTIVE: This randomized effectiveness trial will advance research and scope on SBIRT-A in primary care by conducting a head-to-head test of 2 conceptually grounded, evidence-informed approaches: a standard adolescent-only approach (SBIRT-A-Standard) versus a more expansive family-based approach (SBIRT-A-Family). The SBIRT-A-Family approach enhances the procedures of the SBIRT-A-Standard approach by screening for AOD risk with both adolescents and caregivers; leveraging multidomain, multireporter AOD risk and protection data to inform case identification and risk categorization; and directly involving caregivers in brief intervention and referral to treatment activities. METHODS: The study will include 2300 adolescents (aged 12-17 y) and their caregivers attending 1 of 3 hospital-affiliated pediatric settings serving diverse patient populations in major urban areas. Study recruitment, screening, randomization, and all SBIRT-A activities will occur during a single pediatric visit. SBIRT-A procedures will be delivered digitally on handheld tablets using patient-facing and provider-facing programming. Primary outcomes (AOD use, co-occurring behavior problems, and parent-adolescent communication about AOD use) and secondary outcomes (adolescent quality of life, adolescent risk factors, and therapy attendance) will be assessed at screening and initial assessment and 3-, 6-, 9-, and 12-month follow-ups. The study is well powered to conduct all planned main and moderator (age, sex, race, ethnicity, and youth AOD risk status) analyses. RESULTS: This study will be conducted over a 5-year period. Provider training was initiated in year 1 (December 2023). Participant recruitment and follow-up data collection began in year 2 (March 2024). We expect the results from this study to be published in early 2027. CONCLUSIONS: SBIRT-A is widely endorsed but currently underused in pediatric primary care settings, and questions remain about optimal approaches and overall effectiveness. In particular, referral to treatment procedures in primary care remains virtually untested among youth. In addition, whereas research strongly supports involving families in interventions for adolescent AOD, SBIRT-A effectiveness trial testing approaches that actively engage family members in primary care are absent. This trial is designed to help fill these research gaps to inform the critical health decision of whether and how to include caregivers in SBIRT-A activities conducted in pediatric primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05964010; https://www.clinicaltrials.gov/study/NCT05964010. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54486.

Relationship-Oriented Recovery System for Youth (RORSY): Clinical Protocol for Transition-Age Youth with Opioid Use Disorders.

This article introduces the Relationship-Oriented Recovery System for Youth (RORSY) protocol, which is designed to increase uptake of Medications for Opioid Use Disorder (MOUD) and related services among adolescents and young adults. Youth exhibit alarmingly poor rates of MOUD initiation and adherence, OUD services involvement and long-term recovery success. RORSY attends to three developmentally unique recovery needs of this age group: assess and bolster youth recovery capital, prioritize involvement of concerned significant others, and use digital direct-to-consumer recovery supports. RORSY contains five evidence-informed intervention modules that can be flexibly tailored to meet the individual and relationship needs of a given youth: Relational Orientation, Youth Recovery Management Planning, Relational Recovery Management Planning, Relationship Skills Building, and Digital Recovery Support Planning. The article concludes with practice and policy recommendations for making relationship-building a top clinical priority for addressing youth OUD.

Launching Relationship-Oriented Behavioral Services for Youth Opioid Use Disorder: Innovations in Medication Decision-Making and Adherence Planning.

This article presents behavioral interventions designed to enhance uptake and retention on medication for opioid use disorder (MOUD) among transition-age youth (16-25 years) enrolled in treatment services. The article describes three relationship-oriented interventions designed to address barriers to MOUD uptake, enhance MOUD adherence planning, and strengthen OUD recovery among youth: Relational Orientation; Medication Education and Decision-making Support, and Family Leadership and Ownership of Adherence to Treatment. These interventions are inter-connected can be delivered flexibly. The article concludes with three case examples that illustrate how these modular interventions can be tailored to meet the needs of diverse client profiles.

Couple and family therapy for substance use disorders: Evidence-based update 2010-2019.

This article updates the evidence-based on couple and family therapy interventions for substance use disorders (SUD) since publication of the previous JMFT reviews in 2012. It first summarizes previous reviews along with findings from more recent reviews and meta-analytic studies. It then presents study design and methods criteria used to select 13 studies of couple and family therapy for level of support evaluation. Cumulative level of support designations are then determined for identified treatment approaches. Findings indicate that systemic family therapy is well-established as a standalone treatment, and behavioral family therapy and behavioral couple therapy are probably efficacious as standalone treatments and well-established as part of a multicomponent treatment. The article then suggests practice guidelines with regard to treatment modality considerations and implementation challenges. It concludes with future directions for delivering couple and family interventions in routine systems of care for SUD.

Measurement training and feedback system for implementation of evidence-based treatment for adolescent externalizing problems: protocol for a randomized trial of pragmatic clinician training.

BACKGROUND: Innovations in clinical training and support that enhance fidelity to evidence-based treatment (EBT) for adolescent behavior problems are sorely needed. This study will develop an online training system to address this gap: Measurement Training and Feedback System for Implementation (MTFS-I). Using procedures intended to be practical and sustainable, MTFS-I is designed to increase two aspects of therapist behavior that are fundamental to boosting EBT fidelity: therapist self-monitoring of EBT delivery, and therapist utilization of core techniques of EBTs in treatment sessions. This version of MTFS-I focuses on two empirically supported treatment approaches for adolescent conduct and substance use problems: family therapy and cognitive behavioral therapy (CBT). METHODS/DESIGN: MTFS-I expands on conventional measurement feedback systems for client outcomes by adding training in observational coding to promote EBT self-monitoring and focusing on implementation of EBT treatment techniques. It has two primary components. (1) The training component, delivered weekly in two connected parts, involves self-monitored learning modules containing brief clinical descriptions of core EBT techniques and mock session coding exercises based on 5-8 min video segments that illustrate delivery of core techniques. (2) The feedback component summarizes aggregated therapist-reported data on EBT techniques used with their active caseloads. MTFS-I is hosted online and requires approximately 20 min per week to complete for each treatment approach. This randomized trial will first collect data on existing delivery of family therapy and CBT techniques for youth in outpatient behavioral health sites (Baseline phase). It will then randomize site clinicians to two study conditions (Implementation phase): Training Only versus Training + Feedback + Consultation. Therapists will choose whether to train in family therapy, CBT, or both. Study aims will compare clinician performance across study phase and between study conditions on MTFS-I uptake, reliability and accuracy in EBT self-monitoring, and utilization of EBT techniques in treatment sessions (based on observer coding of audiotapes). DISCUSSION: Study contributions to implementation science and considerations of MTFS-I sustainability are discussed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03722654. Registered on 29 October 2018.

Devastating consequences of subway accidents: traumatic amputations.

The efficiencies of the subway system are tempered by the occurrence of accidents, some with devastating injuries. The purpose of this study is to examine our experience with traumatic amputations after subway accidents. A retrospective trauma registry review (1989-2003) of 41 patients who presented to Bellevue Hospital, New York City, with amputations from subway accidents was undertaken to examine the following end points: age, sex, Injury Severity Score, time and mechanism of accident, history of psychiatric disorders and alcohol use, admission vital signs, Glasgow Coma Scale score, amputation type, associated injuries, limb salvage rate, operative procedures, mortality, and disposition. Elevated alcohol levels and prior psychiatric diagnoses were present in 39 per cent and 17 per cent of the patients, respectively. Patients were stable on admission with a mean systolic blood pressure of 114 mmHg, hematocrit of 32, and Glasgow Coma Scale score range of 13 to 15. The most common amputation was below knee, and patients underwent an average of three operative procedures. Limb salvage was attempted in eight patients with no successes. Amputation wound infection rate was 32 per cent and mortality rate was 5 per cent. Victims of subway trauma who arrive at the hospital with devastating amputations have an excellent chance of surviving to discharge.

Bivalirudin in peripheral interventions.

The discovery of heparin and its eventual incorporation into many therapeutic and diagnostic procedures has made this agent ubiquitous in the fields of cardiac and vascular medicine. Heparin however does have a significant complication and side-effect profile that includes both bleeding as well as vessel thrombosis through the development of heparin-induced thrombocytopenia. The recent addition of direct thrombin inhibitors, for example, bivalirudin, to the anticoagulation armaterium has produced favorable outcomes. Most of the experience with bivalirudin has been in coronary interventions and only recently have more interventionalists been turning to this agent as the sole anticoagulant for peripheral interventions even in patients who could tolerate heparin. In this review, we describe our experience with bivalirudin in peripheral interventions emphasizing how we dose and monitor this drug. In addition, this article discusses the findings in existing clinical trials involving bivalirudin.

Past, present, and future endograft devices.

Since the original descriptions of endovascular grafts for treatment of aneurysms, a number of devices and approaches have been developed. The following is a discussion summarizing the number of devices which have been developed and used in patients, as well as chosen the directions of this technology. The diversity of approach from an engineering and materials point of view speaks of the fact that opportunity exists for continued development in the future.

Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control.

BACKGROUND: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM) may alter lipid levels and may alter the efficacy of lipid-modifying agents. OBJECTIVE: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT) in subgroups of patients with T2DM with better or poorer glycemic control. METHODS: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796), examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. RESULTS: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a), compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. CONCLUSION: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758).

Interleukin 10 gene transfection of donor lungs ameliorates posttransplant cell death by a switch from cellular necrosis to apoptosis.

BACKGROUND: We have previously shown that cell death is a pathophysiologic consequence of ischemia-reperfusion and that interleukin-10 gene therapy improves the function of transplanted lungs. Interleukin-10 downregulates the inflammatory response and can inhibit apoptosis. The objective was to determine whether donor lung transfection with the interleukin-10 gene ameliorates lung dysfunction by decreasing cell death after transplantation. METHODS: Single lung transplants were performed in 3 groups of rats (n = 5 each): AdhIL-10, transtracheal administration of Ad5E1RSVhIL-10 (5 x 10(9) pfu); EV, empty vector; and VD, vector diluent (3% sucrose). After in vivo transfection, donor lungs were excised, stored at 4 degrees C for 24 hours, and then transplanted. After 2 hours of reperfusion, lungs were flushed with trypan blue and fixed. TUNEL staining was used for the detection of apoptosis. This combined staining technique allows one to determine the mode of cell death by distinguishing apoptotic dead cells from necrotic dead cells. RESULTS: Lung function was superior in the interleukin-10 group (P =.0001) vs the EV and VD group (Pao(2): 240 +/- 31 mm Hg vs 98 +/- 17 mm Hg vs 129 +/- 11 mm Hg, respectively). Although the total number of dead cells (as percent of total cells) was similar in all groups (32.7% +/- 3.2%, 30.2% +/- 2.5%, and 30.3% +/- 3.8%), interestingly, apoptosis was highest in interleukin-10 lungs (9.7 +/- 1.9 vs 2 +/- 1.9 and 1.8 +/- 2, P =.0001), and necrosis was lowest in the interleukin-10 group (20.6 +/- 5.7 vs 28.3 +/- 3.1 and 30.3 +/- 4.2, P =.01). CONCLUSIONS: AdhIL-10 gene transfection improves function of transplanted lungs. Although the total number of cells dying as a result of the transplant process did not change, the mode of cell death appears to have been modified. It is possible that AdhIL-10, by decreasing proinflammatory cytokine production, ameliorates the overall injury and preserves the ability of damaged cells to undergo a more quiescent and less tissue-damaging mode of cell death-apoptosis, rather than necrosis.

Abdominal wall necrotizing fasciitis from dislodged percutaneous endoscopic gastrostomy tubes: a case series.

We report three cases of abdominal wall necrotizing fasciitis that occurred as a result of leakage from displaced percutaneous endoscopic gastrostomy tubes. This is the first report of such a series. Patients underwent extensive operative excisions of their abdominal walls down to their posterior fascia. All patients tolerated their initial surgery, however, two patients ultimately expired from respiratory complications. The surviving patient underwent multiple repeat debridements and reconstructive abdominal wall surgery. We review the epidemiology of patients at risk for this complication and discuss its presentation, as well as the appropriate workup and management. We also address the issues of closure of large abdominal wall defects and future alimentation in this patient group. Finally, abdominal wall necrotizing faciitis from gastrostomy tube leakage is a devastating complication, and the development of preventative strategies for patients at risk is of paramount importance.