Courtney A. Green

Heterogeneity of genetic modifiers ensures normal cardiac development

Background— Mutations of the transcription factor Nkx2-5 cause pleiotropic heart defects with incomplete penetrance. This variability suggests that additional factors can affect or prevent the mutant phenotype. We assess here the role of genetic modifiers and their interactions. Methods and Results— Heterozygous Nkx2-5 knockout mice in the inbred strain background C57Bl/6 frequently have atrial and ventricular septal defects. The incidences are substantially reduced in the Nkx2-5+/− progeny of first-generation (F1) outcrosses to the strains FVB/N or A/J. Defects recur in the second generation (F2) of the F1×F1 intercross or backcrosses to the parental strains. Analysis of >3000 Nkx2-5+/− hearts from 5 F2 crosses demonstrates the profound influence of genetic modifiers on disease presentation. On the basis of their incidences and coincidences, anatomically distinct malformations have shared and unique modifiers. All 3 strains carry susceptibility alleles at different loci for atrial and ventricular septal defects. Relative to the other 2 strains, A/J carries polymorphisms that confer greater susceptibility to atrial septal defect and atrioventricular septal defects and C57Bl/6 to muscular ventricular septal defects. Segregation analyses reveal that ≥2 loci influence membranous ventricular septal defect susceptibility, whereas ≥2 loci and at least 1 epistatic interaction affect muscular ventricular and atrial septal defects. Conclusions— Alleles of modifier genes can either buffer perturbations on cardiac development or direct the manifestation of a defect. In a genetically heterogeneous population, the predominant effect of modifier genes is health.

Complex Trait Analysis of Ventricular Septal Defects Caused by Nkx2-5 Mutation

Background— The occurrence of a congenital heart defect has long been thought to have a multifactorial basis, but the evidence is indirect. Complex trait analysis could provide a more nuanced understanding of congenital heart disease. Methods and Results— We assessed the role of genetic and environmental factors on the incidence of ventricular septal defects (VSDs) caused by a heterozygous Nkx2-5 knockout mutation. We phenotyped >3100 hearts from a second-generation intercross of the inbred mouse strains C57BL/6 and FVB/N. Genetic linkage analysis mapped loci with lod scores of 5 to 7 on chromosomes 6, 8, and 10 that influence the susceptibility to membranous VSDs in Nkx2-5 +/− animals. The chromosome 6 locus overlaps one for muscular VSD susceptibility. Multiple logistic regression analysis for environmental variables revealed that maternal age is correlated with the risk of membranous and muscular VSD in Nkx2-5 +/− but not wild-type animals. The maternal age effect is unrelated to aneuploidy or a genetic polymorphism in the affected individuals. The risk of a VSD is not only complex but dynamic. Whereas the effect of genetic modifiers on risk remains constant, the effect of maternal aging increases over time. Conclusions— Enumerable factors contribute to the presentation of a congenital heart defect. The factors that modify rather than cause congenital heart disease substantially affect risk in predisposed individuals. Their characterization in a mouse model offers the potential to narrow the search space in human studies and to develop alternative strategies for prevention.

Descending necrotizing mediastinitis: a modified algorithmic approach to define a new standard of care.

Abstract Background: Descending necrotizing mediastinitis (DNM) is a highly morbid infectious process. This uncommon disease process has carried historically a substantial burden of morbidity and mortality. In this study we hypothesized that application of a prospective modified management algorithm would decrease the morbidity and mortality from this highly destructive process. Methods: We developed a systematic approach for managing DNM, focusing on serial debridement guided by imaging, in conjunction with the use of broad-spectrum antibiotics and modern principles of critical care. We reviewed all patients admitted with this disease process from 2007–2012. Data collected included demographic information, co-morbidities, laboratory data including culture results, operative details, imaging frequency and findings, complications, and survival. Continuous variables were reported as median values and ranges. Results: From 2007–2010, we treated eight patients with DNM. The median age of the patients was 33 y...BACKGROUND Descending necrotizing mediastinitis (DNM) is a highly morbid infectious process. This uncommon disease process has carried historically a substantial burden of morbidity and mortality. In this study we hypothesized that application of a prospective modified management algorithm would decrease the morbidity and mortality from this highly destructive process. METHODS We developed a systematic approach for managing DNM, focusing on serial debridement guided by imaging, in conjunction with the use of broad-spectrum antibiotics and modern principles of critical care. We reviewed all patients admitted with this disease process from 2007-2012. Data collected included demographic information, co-morbidities, laboratory data including culture results, operative details, imaging frequency and findings, complications, and survival. Continuous variables were reported as median values and ranges. RESULTS From 2007-2010, we treated eight patients with DNM. The median age of the patients was 33 y (range 28-63 y), and 63% were male. In accordance with our algorithm, the patients underwent serial imaging at regular intervals following operative debridement. The median number of imaging studies was 11 (range 4-19). The patients required a median of five operative debridements (range 1-15). In five patients, drainage was necessary through a cervical exploration. A thoracic approach was required in six patients (two thoracoscopic, four via thoracotomy). Additional procedures included thymectomy (n=2), anterior mediastinotomy, carotid sheath exploration and resections of the clavicle, first rib, manubrium, pectoralis major muscle, and sternocleidomastoid muscle. The most common etiologic agents were Peptostreptococcus spp. and Streptococcus anginosus. Study patients received a median of six different antibiotics (range 2-10) for a total of 42 d (range 34-55 d). These patients were hospitalized for a median of 29 days (range 16-56 d), with 15 d (range 7-48 d) spent in the intensive care unit. Remarkably, the rate of survival was 100% (median follow-up of 33 mo). The patients developed no major complications, required no re-admissions, and had no re-infections. CONCLUSIONS We applied an algorithmic approach to the treatment of DNM, consisting of aggressive operative debridement and enhanced by equally aggressive imaging. Our patients had excellent outcomes despite the widely known lethality of DNM. An aggressive approach may decrease complications and improve survival in this devastating disease process. Furthermore, our prospective experience with DNM suggests that this algorithm used in the present study should be the standard for managing patients with this challenging condition.

Current robotic curricula for surgery residents: A need for additional cognitive and psychomotor focus

BACKGROUND Current robot surgery curricula developed by industry were designed for expert surgeons. We sought to identify the robotic curricula that currently exist in general surgery residencies and describe their components. METHODS We identified 12 residency programs with robotic curricula. Using a structured coding form to identify themes including sequence, duration, emphasis and assessment, we generated a descriptive summary. RESULTS Curricula followed a similar sequence: learners started with online modules and simulation exercises, followed by bedside experience during R2-R3 training years, and then operative opportunities on the console in the final years of training. Consistent portions of the curricula reflect a device-dependent training paradigm; they defined the sequence of instruction. Most curricula lacked specifics on duration and content of training activities. None clearly described cognitive or psychomotor skills needed by residents and none required a proficiency assessment before graduation. CONCLUSIONS Resident-specific robotic curricula remain grounded in initial industrial efforts to train experienced surgeons, are non-specific regarding the type and nature of hands on experience, and do not include discussion of operative technique and surgical concepts.

Using Technological Advances to Improve Surgery Curriculum: Experience With a Mobile Application

OBJECTIVE Our previous home-video basic surgical skills curriculum required substantial faculty time and resources, and was limited by delayed feedback and technical difficulties. Consequently, we integrated that curriculum with a mobile application platform. Our purpose is to describe this application and learner satisfaction. MATERIALS AND METHODS The mobile platform incorporates a patented pedagogical design based on Ericssons deliberate practice and Banduras social learning theory. Instructors built step-wise skills modules. During the challenge phase, learners watched a video of surgical tasks completed by experts and uploaded a video of themselves performing the same task. In the Peer Review phase, they used a grading rubric to provide feedback. In the Recap stage, learners received individual feedback and could review their own videos. Two groups of learners, graduating medical students and matriculating surgical residents, participated in this independent learning platform, along with 2 to 4 laboratory sessions, and completed a survey about their experience. Survey responses were summarized descriptively and comments analyzed using content analysis. RESULTS Fifty learners submitted videos of assigned tasks and completed peer reviews. Learners reported positive experiences specifically for the Peer Review Stage, structured home practice, ease of mobile access to submit and review videos, and ongoing immediate feedback. Over half of the learners reported spending at least 10 to 30 minute practicing skills before recording their videos and over 80% rerecorded at least 2 times before submission. Content analysis revealed learners engaged with the educational concepts designed into the platform. CONCLUSION Learners easily used and were satisfied with a mobile-technology teaching platform that maintained the fundamental content, educational theories, and organizational structure of our previously effective surgical skills curriculum. Prior challenges were directly addressed through the mobile applications ease of use, support of deliberate practice, and improved timeliness of feedback.

Is Robotic Surgery Highlighting Critical Gaps in Resident Training

I ntegrating robotic surgery into resident training is challenging. The robotic environment requires reconsideration of the apprenticeship model for surgical training and development of new curricula and instructional approaches to ensure skill acquisition. The surgical literature has mentioned the need to improve resident training in robotic surgery. This article highlights components of the robotic teaching environment that limit the efficacy of current training models. By targeting these components, educators can begin to develop more effective curricula and instructional strategies for surgical residents. The robotic learning environment is complex. It incorporates a physically distant operative field, separating the trainer and the trainee; it makes the surgeon less dependent on assistance from a resident; and it necessitates acquisition of perceptual expertise without tactile information. At teaching hospitals, residents are exposed to an increasing number of robotic procedures, yet this often occurs in the context of observers, not participants. This has resulted in an emerging training gap. By considering relevant cognitive learning theories, we can guide surgical educators to new approaches to reduce this gap. While recent literature highlighted the feasibility and safety of implementing robotic curricula in residency, few studies have evaluated their efficacy, or described curricular components in detail. Surgical educators need a deep understanding of the robotic environment to appropriately evaluate the efficacy of resident integration in the operating room. Robotic technology provides independence for surgeons. Using the robot, 1 surgeon controls 4 robotic arms and manipulates the camera independently, decreasing the need for residents as assistants. While beneficial to hospitals with limited staffing, this aspect of robotic surgery presents challenges in teaching settings. Typically, in open or laparoscopic operations, residents obtain technical skills as surgical assistants, providing retraction and tissue manipulation essential for creating a functional operative field. This experience allows learners to understand how the surgeon’s movements (degree of tension or retraction) affect the operative field. Residents stand across from, or adjacent to, the attending surgeon throughout the procedure—often with arms entangled in an effort to create adequate visualization. Residents directly observe the attending physician’s physical movements, including minute details of individual digit placement, while performing each operative step. Robotic surgery technology is entirely different. It creates a physical distance between the operating surgeon, the operative field, and any assistants or learners. Residents are positioned at the bedside assisting with instrument exchange, or seated at a console distant from the sterile operative field. They cannot see the attending’s physical movements, and cannot appreciate when the attending surgeon ‘‘clutches,’’ repositioning the hands, maximizing economy of motion. Residents also are unaware when the attending reaches for the foot pedal to swap robotic arms or activate electrocautery. Residents are limited to observing the movements of the robotic arms, either extracorporeally from the bedside or intracorporeally from a console or monitor. To learn to perform the movements as they appear on the screen, the resident must recreate the movements of the surgeon seated at the console. In contrast, in open and laparoscopic surgery, the operating surgeon’s movements are open and visible. In the robotic environment, the operating surgeon’s movements cannot be fully appreciated. How will residents understand what physical movements on the console are needed to translate into the same observed actions seen on the screen? The frequent experiential instruction that occurs in surgical training becomes complicated by a physically separated operative field (described by Zemel and Koschmann as the combination of instructional demonstration, creation of referential practices, and embodied procedures). DOI: http://dx.doi.org/10.4300/JGME-D-17-00802.1

Guided Laparoscopic Video Tutorials for Medical Student Instruction in Abdominal Anatomy

Introduction As technological advances present new forms of media to anatomy educators involved in medical education, there is opportunity to expand on traditional dissection of embalmed cadavers. At the University of California, San Francisco School of Medicine, the surgery and anatomy departments collaborated to create guided video tutorials using laparoscopic surgical footage to teach the anatomy of the lesser sac and gastroesophageal junction. Methods These tutorials are instructional adjuncts to a laparoscopy session on fresh cadavers with first-year medical students. Students view the videos on their own before attending the anatomy lab. The anatomy lab includes six 30-minute sessions, in which approximately 22 students at a time leave their cadaver lab to participate in this laparoscopy session taught by colorectal surgeons and general surgery residents. Results Learner interest and satisfaction was measured through a postsession survey. Nearly all respondents indicated that the videos helped them learn the anatomy of the gastroesophageal junction and lesser sac, and were a valuable addition to dissection of embalmed cadavers. A second session was conducted with first-year medical students in which a pretest and posttest were administered before and after a screening of the tutorial on the gastroesophageal junction. Learners’ average scores on the test improved from 39% to 88% after watching the video. Discussion These data indicate that learners appreciate the incorporation of laparoscopy and video tutorials into anatomy education. These data further corroborate the measures of student enthusiasm, and support the value of the tutorials in short-term acquisition of anatomic knowledge.

Descending necrotizing mediastinitis

Abstract Background: Descending necrotizing mediastinitis (DNM) is a highly morbid infectious process. This uncommon disease process has carried historically a substantial burden of morbidity and mortality. In this study we hypothesized that application of a prospective modified management algorithm would decrease the morbidity and mortality from this highly destructive process. Methods: We developed a systematic approach for managing DNM, focusing on serial debridement guided by imaging, in conjunction with the use of broad-spectrum antibiotics and modern principles of critical care. We reviewed all patients admitted with this disease process from 2007–2012. Data collected included demographic information, co-morbidities, laboratory data including culture results, operative details, imaging frequency and findings, complications, and survival. Continuous variables were reported as median values and ranges. Results: From 2007–2010, we treated eight patients with DNM. The median age of the patients was 33 y...BACKGROUND Descending necrotizing mediastinitis (DNM) is a highly morbid infectious process. This uncommon disease process has carried historically a substantial burden of morbidity and mortality. In this study we hypothesized that application of a prospective modified management algorithm would decrease the morbidity and mortality from this highly destructive process. METHODS We developed a systematic approach for managing DNM, focusing on serial debridement guided by imaging, in conjunction with the use of broad-spectrum antibiotics and modern principles of critical care. We reviewed all patients admitted with this disease process from 2007-2012. Data collected included demographic information, co-morbidities, laboratory data including culture results, operative details, imaging frequency and findings, complications, and survival. Continuous variables were reported as median values and ranges. RESULTS From 2007-2010, we treated eight patients with DNM. The median age of the patients was 33 y (range 28-63 y), and 63% were male. In accordance with our algorithm, the patients underwent serial imaging at regular intervals following operative debridement. The median number of imaging studies was 11 (range 4-19). The patients required a median of five operative debridements (range 1-15). In five patients, drainage was necessary through a cervical exploration. A thoracic approach was required in six patients (two thoracoscopic, four via thoracotomy). Additional procedures included thymectomy (n=2), anterior mediastinotomy, carotid sheath exploration and resections of the clavicle, first rib, manubrium, pectoralis major muscle, and sternocleidomastoid muscle. The most common etiologic agents were Peptostreptococcus spp. and Streptococcus anginosus. Study patients received a median of six different antibiotics (range 2-10) for a total of 42 d (range 34-55 d). These patients were hospitalized for a median of 29 days (range 16-56 d), with 15 d (range 7-48 d) spent in the intensive care unit. Remarkably, the rate of survival was 100% (median follow-up of 33 mo). The patients developed no major complications, required no re-admissions, and had no re-infections. CONCLUSIONS We applied an algorithmic approach to the treatment of DNM, consisting of aggressive operative debridement and enhanced by equally aggressive imaging. Our patients had excellent outcomes despite the widely known lethality of DNM. An aggressive approach may decrease complications and improve survival in this devastating disease process. Furthermore, our prospective experience with DNM suggests that this algorithm used in the present study should be the standard for managing patients with this challenging condition.