Cell-Penetrating Anti-Protein Kinase C Theta Antibodies Act Intracellularly to Generate Stable, Highly Suppressive Regulatory T Cells.

Regulatory T cells maintain immunological tolerance and dampen inflammatory responses. Administering regulatory T cells can prevent the immune-mediated tissue destruction of graft-versus-host disease, which frequently accompanies hematopoietic stem cell transfer. Neutralizing the T cell-specific kinase, protein kinase C theta, which promotes T cell effector functions and represses regulatory T cell differentiation, augments regulatory T cell immunosuppression and stability. We used a synthetic, cell-penetrating peptide mimic to deliver antibodies recognizing protein kinase C theta into primary human CD4 T cells. When differentiated ex vivo into induced regulatory T cells, treated cells expressed elevated levels of the regulatory T cell transcriptional regulator forkhead box P3, the surface-bound immune checkpoint receptor programmed death receptor-1, and pro-inflammatory interferon gamma, previously ascribed to a specific population of stable, highly suppressive human induced regulatory T cells. The in vitro suppressive capacity of these induced regulatory T cells was 10-fold greater than that of T cells differentiated without antibody delivery. When administered at the time of graft-versus-host disease induction, using a humanized mouse model, antibody-treated regulatory T cells were superior to non-treated T cells in attenuating lethal outcomes. This antibody delivery approach may overcome obstacles currently encountered using patient-derived regulatory T cells as a cell-based therapy for immune modulation.

Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation.

Targeting cellular proteins with antibodies, to better understand cellular signaling pathways in the context of disease modulation, is a fast-growing area of investigation. Humanized antibodies are increasingly gaining attention for their therapeutic potential, but the collection of cellular targets is limited to those secreted from cells or expressed on the cell surface. This approach leaves a wealth of intracellular proteins unexplored as putative targets for antibody binding. Protein kinase Cθ (PKCθ) is essential to T cell activation, proliferation, and differentiation, and its phosphorylation at specific residues is required for its activity. Here we report on the design, synthesis, and characterization of a protein transduction domain mimic capable of efficiently delivering an antibody against phosphorylated PKCθ (Thr538) into human peripheral mononuclear blood cells and altering expression of downstream indicators of T cell activation and differentiation. We used a humanized, lymphocyte transfer model of graft-versus-host disease, to evaluate the durability of protein transduction domain mimic:Anti-pPKCθ modulation, when delivered into human peripheral mononuclear blood cells ex vivo. We demonstrate that protein transduction domain mimic:Antibody complexes can be readily introduced with high efficacy into hard-to-transfect human peripheral mononuclear blood cells, eliciting a biological response sufficient to alter disease progression. Thus, protein transduction domain mimic:Antibody delivery may represent an efficient ex vivo approach to manipulating cellular responses by targeting intracellular proteins.

Standardization in patient safety: the WHO High 5s project.

QUALITY PROBLEM: Despite its success in other industries, process standardization in health care has been slow to gain traction or to demonstrate a positive impact on the safety of care. INTERVENTION: The High 5s project is a global patient safety initiative of the World Health Organization (WHO) to facilitate the development, implementation and evaluation of Standard Operating Protocols (SOPs) within a global learning community to achieve measurable, significant and sustainable reductions in challenging patient safety problems. GOALS: The project seeks to answer two questions: (i) Is it feasible to implement standardized health care processes in individual hospitals, among multiple hospitals within individual countries and across country boundaries? (ii) If so, what is the impact of standardization on the safety problems that the project is targeting? METHOD: The two key areas in which the High 5s project is innovative are its use of process standardization both in hospitals within a country and in multiple participating countries, and its carefully designed multi-pronged approach to evaluation. STATUS: Three SOPs-correct surgery, medication reconciliation, concentrated injectable medicines-have been developed and are being implemented and evaluated in multiple hospitals in seven participating countries. Nearly 5 years into the implementation, it is clear that this is just the beginning of what can be seen as an exercise in behavior management, asking whether health care workers can adapt their behaviors and environments to standardize care processes in widely varying hospital settings.

Oxidized polyunsaturated fatty acid promotes colitis and colitis-associated tumorigenesis in mice.

BACKGROUND AND AIMS: Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD. Here, we aim to compare the effects of unoxidized PUFA vs. oxidized PUFA on the development of IBD and associated colorectal cancer. METHODS: We evaluated the effects of unoxidized and oxidized PUFA on dextran sodium sulfate (DSS)- and IL-10 knockout-induced colitis, and azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Additionally, we studied the roles of gut microbiota and Toll-like receptor 4 (TLR4) signaling involved. RESULTS: Administration of a diet containing oxidized PUFA, at human consumption-relevant levels, increases the severity of colitis and exacerbates the development of colitis-associated colon tumorigenesis in mice. Conversely, a diet rich in unoxidized PUFA doesn't promote colitis. Furthermore, oxidized PUFA worsens colitis-associated intestinal barrier dysfunction and leads to increased bacterial translocation, and it fails to promote colitis in Toll-like receptor 4 (TLR4) knockout mice. Finally, oxidized PUFA alters the diversity and composition of gut microbiota, and it fails to promote colitis in mice lacking the microbiota. CONCLUSIONS: These results support that oxidized PUFA promotes the development of colitis and associated tumorigenesis in mouse models via TLR4- and gut microbiota-dependent mechanisms. Our findings highlight the potential need to update regulation policies and industrial standards for oxidized PUFA levels in food.

LKB1 isoform expression modulates T cell plasticity downstream of PKCθ and IL-6.

Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as colitis, in which high levels of IL-6 promote plasticity between regulatory T (Treg) cells and Th17 cells. Protein Kinase C theta (PKCθ) is a T cell-specific serine/threonine kinase that promotes Th17 differentiation while negatively regulating Treg differentiation. Liver kinase B1 (LKB1), also a serine/threonine kinase and encoded by Stk11, is necessary for Treg survival and function. Stk11 can be alternatively spliced to produce a short variant (Stk11S) by transcribing a cryptic exon. However, the contribution of Stk11 splice variants to Th cell differentiation has not been previously explored. Here we show that in Th17 cells, the heterogeneous ribonucleoprotein, hnRNPLL, mediates Stk11 splicing into its short splice variant, and that Stk11S expression is diminished when Hnrnpll is depleted using siRNA knock-down approaches. We further show that PKCθ regulates hnRNPLL and, thus, Stk11S expression in Th17 cells. We provide additional evidence that exposing induced (i)Tregs to IL-6 culminates in Stk11 splicing downstream of PKCθAltogether our data reveal a yet undescribed outside-in signaling pathway initiated by IL-6, that acts through PKCθ and hnRNPLL to regulate Stk11 splice variants and facilitate Th17 cell differentiation. Furthermore, we show for the first time, that this pathway can also be initiated in developing iTregs exposed to IL-6, providing mechanistic insight into iTreg phenotypic stability and iTreg to Th17 cell plasticity.

Effects of Linoleic Acid-Rich Diet on Plasma Profiles of Eicosanoids and Development of Colitis in Il-10-/- Mice.

Dietary intake of linoleic acid (LA, 18:2ω-6) has risen dramatically in recent decades. Previous studies have suggested a high intake of LA could increase tissue concentrations of proinflammatory and protumorigenic ω-6-series eicosanoid metabolites, increasing risks of inflammation and associated diseases. However, the effects of a LA-rich diet on in vivo profiles of eicosanoids and development of inflammatory diseases are understudied. Here, we treated spontaneous colitis-prone (Il-10-/-) mice with a control diet (∼3 Cal% LA) or a LA-rich diet (∼9 Cal% LA) for 18 weeks and analyzed the effects of the LA-rich diet on profiles of eicosanoids and development of colitis. We found that treatment with the LA-rich diet increased the tissue level of LA: the liver levels of LA were 5.8 ± 0.6% in the control diet-treated mice versus 11.7 ± 0.7% in the LA-rich diet-treated mice (P < 0.01). The plasma concentrations of a series of LA-derived metabolites, including 9-hydroxyoctadecadienoic acid (HODE), 9,10-dihydroxyoctadecenoic acid (DiHOME), 12,13-DiHOME, and 13-HODE were significantly increased by treatment with the LA-rich diet (P < 0.05). However, the LA-rich diet had little effect on the severity of colitis in the treated Il-10-/- mice. These results suggest a limited role of increased consumption of dietary LA on promoting colitis in the Il-10-/- model.

Triclocarban Exposure Exaggerates Spontaneous Colonic Inflammation in Il-10-/- Mice.

Triclocarban (3,4,4'-trichlorocarbanilide, TCC) is a high-volume chemical used as an antimicrobial ingredient in many consumer and personal care products. In 2016, the Food and Drug Administration removed TCC from over-the-counter hand washing products. However, TCC remains approved to use in many other products and is a ubiquitous contaminant in the environment; furthermore, many common food crops can efficiently accumulate environmental TCC, resulting in potential human exposure through oral ingestion of contaminated food products. Therefore, human exposure to TCC could be a long-lasting and serious problem. A better understanding of its impact on human health could lead to important impact for public health and regulatory policy. Using a spontaneous colonic inflammation model in Il-10-/- mice, here we demonstrate that exposure to TCC, at doses relevant to human exposure, exaggerates spontaneous colonic inflammation in Il-10-/- mice, with reduced colon length, increase fecal concentration of lipocalin 2, enhanced gene expression of Il-6 and Ifn-γ in the colon, and exaggerated crypt damage in the colon. Collectively, these results support that TCC could be a potential environmental risk factor of colitis and associated gut diseases.

CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells.

Notch signaling provides an important cue in the mammalian developmental process. It is a key player in T cell development and function. Notch ligands such as Delta-like ligands (DLL) 1, 3, 4, and JAG1, 2 can impact Notch signaling positively or negatively, by trans-activation or cis-inhibition. Trans and cis interactions are receptor-ligand interaction on two adjacent cells and interaction on the same cell, respectively. The former sends an activation signal and the later, a signal for inhibition of Notch. However, earlier reports suggested that Notch is activated in the absence of Notch ligand-expressing APCs in a purified population of CD4 T cells. Thus, the role of ligands in Notch activation, in a purified population of CD4 T cells, remains obscure. In this study, we demonstrate that mature CD4 T cells are capable of expressing Notch ligands on their surface very early upon activation with soluble antibodies against CD3 and CD28. Moreover, signaling solely through CD28 induces Notch ligand expression and CD3 signaling inhibits ligand expression, in contrast to Notch which is induced by CD3 signaling. Additionally, by using decoys, mimicking the Notch extracellular domain, we demonstrated that DLL1, DLL4, and JAG1, expressed on the T cells, can cis-interact with the Notch receptor and inhibit activation of Notch. Thus, our data indicate a novel mechanism of the regulation of Notch ligand expression on CD4 T cells and its impact on activated Notch.

Towards an International Classification for Patient Safety: a Delphi survey.

OBJECTIVE: Interpretation and comparison of patient safety information have been compromised by the lack of a common understanding of the concepts involved. The World Alliance set out to develop an International Classification for Patient Safety (ICPS) to address this, and to test the relevance and acceptability of the draft ICPS and progressively refine it prior to field testing. DESIGN: Two-stage Delphi survey. Quantitative and qualitative analyses informed the review of the ICPS. SETTING: International web-based survey of expert opinion. PARTICIPANTS: Experts in the fields of patient safety, health policy, reporting systems, safety and quality control, classification theory and development, health informatics, consumer advocacy, law and medicine; 253 responded to the first round survey, 30% of whom responded to the second round. RESULTS: In the first round, 14% felt that the conceptual framework was missing at least one class, although it was apparent that most respondents were actually referring to concepts they felt should be included within the classes rather than the classes themselves. There was a need for clarification of several components of the classification, particularly its purpose, structure and depth. After revision and feedback, round 2 results were more positive, but further significant changes were made to the conceptual framework and to the major classes in response to concerns about terminology and relationships between classes. CONCLUSIONS: The Delphi approach proved invaluable, as both a consensus-building exercise and consultation process, in engaging stakeholders to support completion of the final draft version of the ICPS. Further refinement will occur.

Towards an International Classification for Patient Safety: key concepts and terms.

BACKGROUND: Understanding the patient safety literature has been compromised by the inconsistent use of language. OBJECTIVE: To identify key concepts of relevance to the International Patient Safety Classification (ICPS) proposed by the World Alliance For Patient Safety of the World Health Organization (WHO), and agree on definitions and preferred terms. METHODS: Six principles were agreed upon-that the concepts and terms should: be applicable across the full spectrum of healthcare; be consistent with concepts from other WHO Classifications; have meanings as close as possible to those in colloquial use; convey the appropriate meanings with respect to patient safety; be brief and clear, without unnecessary or redundant qualifiers; be fit-for-purpose for the ICPS. RESULTS: Definitions and preferred terms were agreed for 48 concepts of relevance to the ICPS; these were described and the relationships between them and the ICPS were outlined. CONCLUSIONS: The consistent use of key concepts, definitions and preferred terms should pave the way for better understanding, for comparisons between facilities and jurisdictions, and for trends to be tracked over time. Changes and improvements, translation into other languages and alignment with other sets of patient safety definitions will be necessary. This work represents the start of an ongoing process of progressively improving a common international understanding of terms and concepts relevant to patient safety.

Towards an International Classification for Patient Safety: the conceptual framework.

Global advances in patient safety have been hampered by the lack of a uniform classification of patient safety concepts. This is a significant barrier to developing strategies to reduce risk, performing evidence-based research and evaluating existing healthcare policies relevant to patient safety. Since 2005, the World Health Organization's World Alliance for Patient Safety has undertaken the Project to Develop an International Classification for Patient Safety (ICPS) to devise a classification which transforms patient safety information collected from disparate systems into a common format to facilitate aggregation, analysis and learning across disciplines, borders and time. A drafting group, comprised of experts from the fields of patient safety, classification theory, health informatics, consumer/patient advocacy, law and medicine, identified and defined key patient safety concepts and developed an internationally agreed conceptual framework for the ICPS based upon existing patient safety classifications. The conceptual framework was iteratively improved through technical expert meetings and a two-stage web-based modified Delphi survey of over 250 international experts. This work culminated in a conceptual framework consisting of ten high level classes: incident type, patient outcomes, patient characteristics, incident characteristics, contributing factors/hazards, organizational outcomes, detection, mitigating factors, ameliorating actions and actions taken to reduce risk. While the framework for the ICPS is in place, several challenges remain. Concepts need to be defined, guidance for using the classification needs to be provided, and further real-world testing needs to occur to progressively refine the ICPS to ensure it is fit for purpose.

Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease.

The immune-mediated tissue destruction of graft-vs-host disease (GvHD) remains a major barrier to greater use of hematopoietic stem cell transplantation (HSCT). Mesenchymal stem cells (MSCs) have intrinsic immunosuppressive qualities and are being actively investigated as a therapeutic strategy for treating GvHD. We characterized Cymerus™ MSCs, which are derived from adult, induced pluripotent stem cells (iPSCs), and show they display surface markers and tri-lineage differentiation consistent with MSCs isolated from bone marrow (BM). Administering iPSC-MSCs altered phosphorylation and cellular localization of the T cell-specific kinase, Protein Kinase C theta (PKCθ), attenuated disease severity, and prolonged survival in a humanized mouse model of GvHD. Finally, we evaluated a constellation of pro-inflammatory molecules on circulating PBMCs that correlated closely with disease progression and which may serve as biomarkers to monitor therapeutic response. Altogether, our data suggest Cymerus iPSC-MSCs offer the potential for an off-the-shelf, cell-based therapy to treat GvHD.

Rotenone Treatment Reveals a Role for Electron Transport Complex I in the Subcellular Localization of Key Transcriptional Regulators During T Helper Cell Differentiation.

Recent advances in our understanding of tumor cell mitochondrial metabolism suggest it may be an attractive therapeutic target. Mitochondria are central hubs of metabolism that provide energy during the differentiation and maintenance of immune cell phenotypes. Mitochondrial membranes harbor several enzyme complexes that are involved in the process of oxidative phosphorylation, which takes place during energy production. Data suggest that, among these enzyme complexes, deficiencies in electron transport complex I may differentially affect immune responses and may contribute to the pathophysiology of several immunological conditions. Once activated by T cell receptor signaling, along with co-stimulation through CD28, CD4 T cells utilize mitochondrial energy to differentiate into distinct T helper (Th) subsets. T cell signaling activates Notch1, which is cleaved from the plasma membrane to generate its intracellular form (N1ICD). In the presence of specific cytokines, Notch1 regulates gene transcription related to cell fate to modulate CD4 Th type 1, Th2, Th17, and induced regulatory T cell (iTreg) differentiation. The process of differentiating into any of these subsets requires metabolic energy, provided by the mitochondria. We hypothesized that the requirement for mitochondrial metabolism varies between different Th subsets and may intersect with Notch1 signaling. We used the organic pesticide rotenone, a well-described complex I inhibitor, to assess how compromised mitochondrial integrity impacts CD4 T cell differentiation into Th1, Th2, Th17, and iTreg cells. We also investigated how Notch1 localization and downstream transcriptional capabilities regulation may be altered in each subset following rotenone treatment. Our data suggest that mitochondrial integrity impacts each of these Th subsets differently, through its influence on Notch1 subcellular localization. Our work further supports the notion that altered immune responses can result from complex I inhibition. Therefore, understanding how mitochondrial inhibitors affect immune responses may help to inform therapeutic approaches to cancer treatment.

Ultrasound study of elbow ulnar collateral ligament changes in collegiate baseball players: A pilot study.

OBJECTIVE: To assess changes in elbow ulnar collateral ligament length in college baseball pitchers over the course of a single season. DESIGN: Cohort Feasibility Study. METHODS: Diagnostic ultrasound was used to assess both the dominant and non-dominant medial elbow joint space in four pitchers and five fielders and compared to in-game pitching data. Shoulder, elbow, wrist, hip, knee, and ankle range of motion measurements were also taken. RESULTS: Mean trends for both the pitching and fielding groups showed no increases in dominant arm medial elbow joint space. Range of motion (ROM) increases were seen in both groups, and neither ultrasound nor ROM changes correlated to number of pitches thrown. CONCLUSION: It is feasible that shoulder and hip range of motion changes directly affect stresses at the elbow in baseball pitching (Wilk et al., 2014) (Sauers et al., 2014). Further research is needed to investigate whether UCL injuries are related to increased laxity of the ligament.

Teaching pediatrics residents how to obtain informed consent.

BACKGROUND: Few physicians view informed consent as a critical component of the physician-patient relationship or as a way to improve individual and population health. We hypothesized that formal education about informed consent would affect first-year pediatrics residents' knowledge and attitudes. METHOD: Twenty-seven first-year pediatrics residents participated in a randomized controlled trial with a wait-list control group. The one-hour interactive intervention consisted of a lecture, video, and small-group discussion. Outcomes were measured after randomization at baseline and after the intervention group received the intervention. Data were analyzed using multivariate analysis and between and within group t tests. Qualitative data were obtained after the wait-list control group's exposure to the intervention. RESULTS: The quantitative analyses demonstrated that the intervention yielded statistically significant improvements in the measured outcomes. The qualitative analyses confirm the quantitative findings. CONCLUSION: A formal session on informed consent in the pediatrics residency educational program positively affects residents' knowledge and attitudes about informed consent.

Recognizing clinical faculty's contributions in education.

OBJECTIVE: A faculty productivity profile system was designed to recognize faculty's contributions to administrative, educational, and research activities. It has long been recognized that clinical faculty receive little recognition or compensation for their efforts in education. Our surgery department previously had in place a recognition program for research achievements, but not for educational contributions. The new system was designed to recognize and reward all aspects of faculty contributions, including education. DESCRIPTION: The faculty productivity profile is a simple Excel document sent to each faculty member once a year. We piloted the program for the first time in 2001, recognizing faculty's contributions for the previous year. The pilot began with the formation of a committee whose first function was to identify all possible opportunities for faculty to participate as educators at our institution. This included giving lectures, participating in faculty development programs, serving as mentors, interviewing student or resident candidates, serving in administrative educational roles (e.g., clerkship or residency director), giving oral exams, or attending conferences and journal club. The committee then developed a point scale assigning each activity or contribution a value on a scale of 0-25. Each activity was then listed on the Excel form. Faculty were to fill in the number of times each activity was performed and this was multiplied by the points to obtain a weighted value. Point values for conferences were determined by percentage of conferences attended for a year (i.e., for grand rounds, those attending 0-49%, 50-75%, 75-90%, and more than 90% received 0, 20, 40, and 60 points, respectively). Points were also assigned for teaching awards and high scores on student and resident evaluations. After approval by the committee and the department chairman, the form was presented at a faculty meeting. Each faculty member then received a floppy disk with the form and was asked to complete the form and attach a supporting copy of his or her CV. The form required only input of numbers or a "yes" or "no." After submission, the clerkship coordinator input additional data from a database of conference attendance and student evaluations. Points were then calculated for each faculty member based upon his or her contributions and each activity's weighted value. A dinner was held to recognize outstanding faculty contributions. All faculty completing the form were invited and recognized and those with outstanding contributions received awards. DISCUSSION: Teaching medical students and residents is a rewarding experience; however, it requires significant time and effort. Faculty who feel their contributions are unrecognized may be more likely to burn out and less likely to continue contributing. We believe it is worthwhile to recognize faculty contributions in all areas, including education. Our pilot program had excellent participation due to the ease of using the form. We believe it has improved faculty morale and willingness to participate. We are continuing the program and plan to evaluate its impact on encouraging continued participation in teaching.

Questioning skills: the effect of wait time on accuracy of medical student responses to oral and written questions.

BACKGROUND: Pauses (wait time) after asking questions in pre-college classes result in improved discussion and answer accuracy. The authors hypothesized that this would extend to medical students. METHOD: Third-year surgery clerks were randomized to three-second or six-second wait times after questions asked of them during a scripted lecture. Students were randomized within each session to answer 21 scripted questions. Students also completed a post-lecture written examination. RESULTS: Correct responses ranged from 17% to 100% for oral and 22% to 100% for written questions. Answer accuracy could not be distinguished between three- and six-second wait times for oral or written questions. CONCLUSIONS: The benefit of increasing wait times from three to six seconds appears not to extend to medical students. This may represent evolution of learning or different learning modes in medical students. Alternatively, maximum benefit may be achieved in medical students with shorter wait times.

A critical evaluation of the morbidity and mortality conference.

BACKGROUND: This study was designed to evaluate the impact of changes made to our morbidity and mortality (M&M) conference. METHODS: A 23-item survey using corresponding Likert-type scales was created. Faculty and residents were asked to anonymously complete the surveys in June 1999. Based on this information, specific modifications were made to the conference. The same survey was administered to faculty and residents in the Fall of 2000. Analysis was performed using Student t tests. RESULTS: Postsurvey findings showed residents felt eight components improved significantly (P <0.05). Faculty noted nonsignificant improvement in nine survey items and decline in nine items (five unchanged). CONCLUSIONS: Changes in content and structure made to enhance our M&M conference's educational value resulted in significant improvements as perceived by the surgical residents. Interestingly, these changes had only minimal impact on faculty perceptions.

Residents seeking informed consent: Are they adequately knowledgeable?

PURPOSE: The purpose of this study was to determine the extent to which first-year surgical residents are prepared to obtain informed consent from patients. The study was designed to answer the following research questions: 1) Are first-year residents who are asked to obtain informed consent sufficiently knowledgeable about the risks, benefits, and alternatives of the procedures? 2) Can first-year residents accurately answer the questions patients may pose about these procedures? METHODS: First-year residents (n = 18) were asked to list the risks, benefits, and alternatives for open inguinal hernia repair, laparoscopic cholecystectomy, total thyroidectomy, esophagogastrectomy, and abdominal aortic aneurysm repair, assuming the procedures were elective on otherwise healthy individuals. Residents were also asked to answer questions that patients may pose about each of the procedures. The basic minimum risks, benefits, and alternatives to be listed and answers to the questions were validated by asking faculty representing general (n = 6) and vascular (n = 3) surgery to complete the questionnaires. RESULTS: Few residents were able to correctly list all risks, benefits, and alternatives of any of the procedures. Less than one-half of the questions that patients may ask about the procedures were correctly answered. CONCLUSIONS: Even though first-year residents are commonly obtaining consent for surgical procedures, many are unable to provide patients with the correct descriptions of the risks, benefits, and alternatives. Nor were they able to correctly answer common questions. Surgical faculty must take more time to educate first-year residents on the appropriate issues in informed consent for the procedures being performed.

Impact of a structured skills laboratory curriculum on surgery residents' intraoperative decision-making and technical skills.

BACKGROUND: This project sought to study the effectiveness of a curriculum to enhance the intraoperative clinical judgment and procedural skill of surgical residents. METHOD: A multiinstitutional, prospective, randomized study was performed. A cognitive task analysis of laparoscopic cholecystectomy (LC) was conducted on which instructional activities and measurement instruments were designed. Residents were randomly assigned to a control or intervention group. Subjects took written pre- and posttests examining procedure-related judgment and knowledge. The intervention group participated in a three-session curriculum emphasizing LC critical decisions and error prevention. All subjects were evaluated performing the procedure on a cadaveric model. Scores from written and practical exams were compared using independent-sample and paired Student t tests. RESULTS: Written examination scores increased for both groups. The intervention group scored significantly higher (P < .05) on the written posttest than the control group. There were no differences between groups on the practical examination. Reliability coefficients for the written examination ranged from .65 to .75. Reliability coefficients for the oral exam, technical skill, and error items on the porcine practical exam were .83, .90, and .53. CONCLUSIONS: The curriculum resulted in enhanced performance on a written exam designed to assess intraoperative judgment, but no differences in technical skills, showing important implications for future skills lab curriculum formats.