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The surgical process remains elusive to many. This paper presents two independent empirical investigations where psychomotor skill metrics were used to quantify elements of the surgical process in a procedural context during surgical tasks in a simulated environment. The overarching goal of both investigations was to address the following hypothesis: Basic motion metrics can be used to quantify specific aspects of the surgical process including instrument autonomy, psychomotor efficiency, procedural readiness, and clinical errors. Electromagnetic motion tracking sensors were secured to surgical trainees' (

Screening for blunt cardiac injury (BCI) includes obtaining a serum troponin level and an electrocardiogram for patients diagnosed with a sternal fracture. Our institution has transitioned to the use of a high sensitivity troponin I (hsTnI). The aim of this study was to determine whether hsTnI is comparable to troponin I (TnI) in identifying clinically significant BCI.Trauma patients presenting to a level I trauma center over a 24-mo period with the diagnosis of sternal fracture were screened for BCI. Any initial TnI more than 0.04 ng/mL or hsTnI more than 18 ng/L was considered positive for potential BCI. Clinically significant BCI was defined as a new-bundle branch block, ST wave change, echocardiogram change, or need for cardiac catheterization.Two hundred sixty five patients with a sternal fracture were identified, 161 underwent screening with TnI and 104 with hsTnI. For TnI, the sensitivity and specificity for detection of clinically significant BCI was 0.80 and 0.79, respectively. For hsTnI, the sensitivity and specificity for detection of clinically significant BCI was 0.71 and 0.69, respectively. A multivariate analysis demonstrated the odds ratio for significant BCI with a positive TnI was 14.4 (95% confidence interval, 3.9-55.8, P 0.0001) versus an odds ratio of 5.48 (95% confidence interval 1.9-15.7, P = 0.002) in the hsTnI group.The sensitivity of hsTnI is comparable to TnI for detection of significant BCI. Additional investigation is needed to determine the necessity and interval for repeat testing and the need for additional diagnostic testing.

This study investigated the possibility of using virtual reality perceptual-motor tasks as a screening tool for laparoscopic ability. We hypothesized that perceptual-motor skills assessed using virtual reality will correlate with the quality of simulated laparoscopic ventral hernia repair.Surgical residents (N = 37), performed 2 virtual reality perceptual-motor tasks: (1) force matching and (2) target tracking. Participants also performed a laparoscopic ventral hernia repair on a simulator and final product quality score, and endoscopic visualization errors were calculated. Correlational analysis was performed to assess the relationship between performance on virtual reality tasks and laparoscopic ventral hernia repair.Residents with poor performance on force matching in virtual reality-"peak deflection" (r = -0.34, P.05) and "summation distance" (r = -0.36, P.05)-had lower final product quality scores. Likewise, poor performance in virtual reality-based target tracking-"path length" (r = -0.49, P.05) and "maximum distance" (r = -0.37, P.05)-correlated with a lower final product quality score.Our findings support the notion that virtual reality could be used as a screening tool for perceptual-motor skill. Trainees identified as having poor perceptual-motor skill can benefit from focused curricula, allowing them to hone personal areas of weakness and maximize technical skill.

Background This paper explores a method for assessing intraoperative performance by modeling how surgeons integrate psychomotor, procedural, and cognitive skills to manage errors. Methods Audio-video data were collected from general surgery residents (N = 45) performing a simulated laparoscopic ventral hernia repair. Errors were identified using a standard checklist, and speech was coded for elements related to error recognition and management. Epistemic network analysis (ENA) was used to model the integration of error management skills. Results There was no correlation between number or type of errors committed and operative outcome. However, ENA models showed significant differences in the integration of error management skills between high-performing and low-performing residents. Conclusion These results suggest that error checklists and surgeons' speech can be used to model the integration of psychomotor, procedural, and cognitive aspects of intraoperative performance. Moreover, ENA can identify and quantify this integration, providing insight on performance gaps in both individuals and populations.

Background This study explores general surgery residents' decision making skills in uncommon, complex urinary catheter scenarios. Methods 40 residents were presented with two scenarios. Scenario A was a male with traumatic urethral injury and scenario B was a male with complete urinary blockage. Residents verbalized whether they would catheterize the patient and described the workup and management of suspected pathologies. Residents' decision paths were documented and analyzed. Results In scenario A, 45% of participants chose to immediately consult Urology. 47.5% named five diagnostic tests to decide if catheterization was safe. In scenario B, 27% chose to catheterize with a 16 French Coude. When faced with catheterization failure, participants randomly upsized or downsized catheters. Chi-square analysis revealed no measurable consensus amongst participants. Conclusions Residents need more training in complex decision making for urinary catheterization. The decision trees generated in this study provide a useful blueprint of residents' learning needs. Summary Exploration of general surgery residents' decision making skills in uncommon, complex urinary catheter scenarios revealed major deficiencies. The resulting decision trees reveal residents' learning needs.

Background This study sought to compare general surgery research residents' survey information regarding self-efficacy ratings to their observed performance during a simulated small bowel repair. Their observed performance ratings were based on their leadership skills in directing their assistant. Methods Participants were given 15 min to perform a bowel repair using bovine intestines with standardized injuries. Operative assistants were assigned to help assist with the repair. Before the procedure, participants were asked to rate their expected skills decay, task difficulty, and confidence in addressing the small bowel injury. Interactions were coded to identify the number of instructions given by the participants to the assistant during the repair. Statistical analyses assessed the relationship between the number of directional instructions and participants' perceptions self-efficacy measures. Directional instructions were defined as any dialog by the participant who guided the assistant to perform an action. Results Thirty-six residents (58.3% female) participated in the study. Participants who rated lower levels of decay in their intraoperative decision-making and small bowel repair skills were noted to use their assistant more by giving more instructions. Similarly, a higher number of instructions correlated with lower perceived difficulty in selecting the correct suture, suture pattern, and completing the entire surgical task. Conclusions General surgery research residents' intraoperative leadership skills showed significant correlations to their perceptions of skill decay and task difficulty during a bowel repair. Evaluating resident's directional instructions may provide an additional individualized intraoperative assessment metric. Further evaluation relating to operative performance outcomes is warranted.

DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from long-term AYAHL survivors and their unaffected co-twins. Epigenetic aging (DNAm age) was calculated using previously described methods and compared between survivors and co-twins using paired t-tests and analyses were stratified by sample type, histology, sex, age at sample collection and time since diagnosis. Differences in blood DNAm age were observed between survivors and unaffected co-twins (64.1 vs. 61.3 years, respectively, p = .04), especially in females (p = .01); no differences in saliva DNAm age were observed. Survivors and co-twins had 74 (in blood DNA) and 6 (in saliva DNA) differentially methylated loci. Our results suggest persistent epigenetic aging in AYAHL survivors long after HL cure.

Simulators have been widely adopted to help surgical trainees learn procedural rules and acquire basic psychomotor skills, and research indicates that this learning transfers to clinical practice. However, few studies have explored the use of simulators to help more advanced learners improve their understanding of operative practices. To model how surgeons with different levels of experience use procedural simulators, we conducted a quantitative ethnographic analysis of small-group conversations in a continuing medical education short course on laparoscopic hernia repair. Our research shows that surgeons who had less experience with laparoscopic surgery tended to use the simulators to learn and rehearse the basic procedures, while more experienced surgeons used the simulators as a platform for exploring a range of hernia presentations and operative approaches based on their experiences. Thus simple, inexpensive simulators may be effective with both novice and more experienced learners.

Neoplasms derived from lymphoid cells include precursor lymphoid neoplasms, mature B-cell neoplasms, plasma cell myeloma, mature T- and NK-cell neoplasms, and Hodgkin lymphoma. The morphology and immunophenotype of B-cell neoplasms correlate with various stages of normal B-cell differentiation and are currently used as a basis for their classification and nomenclature. Alterations in the major physiologic pathways in B cells such as the B-cell receptor signaling pathway, T-cell receptor pathway, NF-kB pathway, MAPK pathway, PI3K/AKT1, MTOR pathway, NOTCH signaling pathway, inhibition of apoptosis, impairment of differentiation to plasma cells, and epigenetic alterations play a major role in neoplastic transformation. Advances in understanding of the molecular pathogenesis of lymphomas in recent years, especially using next-generation sequencing, have enabled identification of novel diagnostic, prognostic, and predictive molecular biomarkers. Novel-targeted therapies based on these biomarkers have revolutionized the therapeutic landscape for relapsed and refractory lymphomas.

Background The aim of this study was to investigate whether junior surgical residents had successfully mastered bladder catheterization. Our hypothesis was that surgical residents would be overly confident in their abilities and underestimate the potential for case complexity. Materials and methods PGY 2-4 surgery residents ( n = 44) were given 15 min. to complete three of four bladder catheterization simulations. Participants reported their mastery by rating confidence using a 5-point Likert scale. Multiple linear regression analysis was used to test predictors of procedure performance. Results Participants made a total of 228 errors with an average of 5.1 errors (standard deviation = 2.6) per participant. The most common errors included not maintaining the sterile field (52.0%), failure to get urine return (20.3%), and inflating the catheter balloon before urine return (8.4%). Some residents committed the same error more than once. Presimulation confidence ratings ranged from “1” being not confident to “5” being extremely confident. Average presimulation confidence was 4.42 (range 1-5, standard deviation = 0.85). Sixteen (36%) residents ranked their presimulation confidence in problem-solving abilities as “moderately confident” or below, whereas 28 (64%) were “very confident” or above. The lower the resident's presimulation confidence in problem-solving, the more errors they committed during the simulation (beta = −0.33, t = −2.15, P = 0.04). Conclusions The residents did not perform as well as they anticipated when presented with more complicated bladder catheterization scenarios. Simulation can be used to identify and expose potential errors that may occur during complex presentations of basic procedures. This type of training and assessment may facilitate mastery.

Urinary catheter insertion is a common procedure performed in hospitals. Improper catheterization can lead to unnecessary catheter-associated urinary tract infections and urethral trauma, increasing patient morbidity. To prevent such complications, guidelines were created on how to insert and troubleshoot urinary catheters. As nurses have an increasing responsibility for catheter placement, resident responsibility has shifted to more complex scenarios. This study examines the clinical decision-making skills of surgical residents during simulated urinary catheter scenarios. We hypothesize that during urinary catheterization, residents will make inconsistent decisions relating to catheter choices and clinical presentations.Forty-five general surgery residents (postgraduate year 2-4) in Midwest training programs were presented with three of four urinary catheter scenarios of varying difficulty. Residents were allowed 15 min to complete the scenarios with five different urinary catheter choices. A chi-square test was performed to examine the relation between initial and subsequent catheter choices and to evaluate for consistency of decision-making for each scenario.Eighty-two percent of residents performed scenario A; 49% performed scenario B; 64% performed scenario C, and 82% performed scenario D. For initial attempt for scenario A-C, the 16 French Foley catheter was the most common choice (38%, 54%, 50%, P's 0.001), whereas for scenario D, the 16 French Coude was the most common choice (37%, P 0.01). Residents were most likely to be successful in achieving urine output in the initial catheterization attempt (P 0.001). Chi-square analyses showed no relationship between residents' first and subsequent catheter choices for each scenario (P's 0.05).Evaluation of clinical decision-making shows that initial catheter choice may have been deliberate based on patient background, as evidenced by the most popular choice in scenario D. Analyses of subsequent choices in each of the catheterization models reveal inconsistency. These findings suggest a possible lack of competence or training in clinical decision-making with regard to urinary catheter choices in residents.

The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 26 centers in 24 countries using the World Health Organization classification, and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males than females in the developing regions compared to the developed world (P

Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low-grade (LG) B-NHL (34·3%) and a higher proportion of high-grade (HG) B-NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High-grade Burkitt-like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60·4%) and a lower frequency of HG B-NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B-NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences.

Comparative data regarding the distribution of non-Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly-diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91·7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male-to-female ratio was significantly higher in NAF/ME/IN (1·8) compared to NA (1·1; P< 0·05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B-NHL (28·4%) and a higher proportion of HG B-NHL (58·4%) were found compared to NA (56·1% and 34·3%, respectively). Diffuse large B-cell lymphoma was more common in NAF/ME/IN (49·4%) compared to NA (29·3%), whereas follicular lymphoma was less common in NAF/ME/IN (12·4%) than in NA (33·6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences.

Problem The current obstacles to paediatric junior doctors engaging in patient safety include poor compliance with the safety reporting process (Datix – only 2% completed by doctors locally) and lack of understanding in what the process is trying to achieve. There is also a ‘fear of failure culture’ so doctors are more likely not to admit to mistakes. High turnover of staff leads to problems with team dynamics and lack of ‘buy in’ into the departmental safety culture. Aims The aim is to foster an open safety culture, remove this fear of blame mentality and promote collective learning from error. I want to double the number of Datix reported by junior doctors within 6 months. Methods The interventions are going to be: departmental induction, monthly clinical governance meetings, and interprofessional simulation. Outcomes are going to be measured through a pre and post placement questionnaire and the numbers of Datix logged by paediatric junior doctors six months pre and six months post-intervention. Results 100% of doctors stated patient safety was ‘important’ or ‘very important’ to clinical care. 100% knew what a Datix was, but only 16% had filled one in during the previous six months. This was reflected in only 5 out of 139 Datix (3.6%) being filled in by junior doctors. After the planned interventions Datix completion by paediatric junior doctors improved to 10/126 (8.1%) – over a 2 fold increase from the previous six months. The aim for the next 12 months is to expand this safety engagement across the whole hospital establishing a ‘safety board’ to which an elected trainee from each speciality will be a part and establish a monthly grand round looking at a clinical incident or datix to promote an open ‘no blame’ approach that will become part of the hospital culture.

Background This study explores the long-term effectiveness of a newly developed clinical skills curriculum. Methods Students (N = 40) were exposed to a newly developed, simulation-based, clinical breast exam (CBE) curriculum. The same students returned one year later to perform the CBE and were compared to a convenience sample of medical students (N = 15) attending a national conferences. All students were given a clinical vignette and performed the CBE. CBE techniques were video recorded. Chi-squared tests were used to assess differences in CBE technique. Results Students exposed to a structured curriculum performed physical examination techniques more consistent with national guidelines than the random, national student sample. Structured curriculum students were more organized, likely to use two hands, a linear search pattern, and include the nipple-areolar complex during the CBE compared to national sample (p Conclusions Students exposed to a structured skills curriculum more consistently performed the CBE according to national guidelines. The variability in technique compared with the national sample of students calls for major improvements in adoption and implementation of structured skills curricula.

Large and systematic studies of non-Hodgkin lymphoma (NHL) in the Far East (FE) with good comparative data are scarce in the literature. In this study, five expert hematopathologists classified 730 consecutive cases of newly-diagnosed NHL from four sites in the FE (excluding Japan) using the World Health Organization classification. The results were compared to 399 cases from North America (NA). We found a significantly higher male to female ratio in the FE compared to NA (1.7 versus 1.1; p

Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd.

The World Health Organization classification of lymphoma recommends the subdivision of follicular lymphoma (FL) into 3 grades (FL1-3) based on the average number of centroblasts per high-power field in the neoplastic follicles, but does not recognize a form of FL characterized by a predominance of large cleaved cells (centrocytes) without enough centroblasts to meet the World Health Organization criteria for FL3. We have classified such cases as follicular large cleaved cell lymphoma (FLC) and, herein, describe the pathologic and clinical features of 72 cases of this entity. The features of FLC include a follicular growth pattern with pale follicles at low magnification and frequent follicular and/or interfollicular fibrosis. Cytologically, the cells are predominantly large cleaved cells with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear diameter of the large cleaved cells was 10.1μ, approximately twice that of small lymphocytes and similar to centroblasts. The t(14;18) was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%) and had high Ki67 proliferation (81%). The clinical features of patients with FLC were similar to those with other types of FL, and survival was excellent with anthracycline-based chemotherapy plus rituximab. FLC is a variant of follicular lymphoma which should be recognized in future lymphoma classifications because the diagnosis of FLC may be important for the selection of therapy.

Background The aim was to validate the potential use of a single, early procedure, operative task as a predictive metric for overall performance. The authors hypothesized that a shortcut psychomotor assessment would be as informative as a total procedural psychomotor assessment when evaluating laparoscopic ventral hernia repair performance on a simulator. Methods Using electromagnetic sensors, hand motion data were collected from 38 surgery residents during a simulated laparoscopic ventral hernia repair procedure. Three time-based phases of the procedure were defined: Early Phase (start time through completion of first anchoring suture), Mid Phase (start time through completion of second anchoring suture), and Total Operative Time. Correlations were calculated comparing time and motion metrics for each phase with the final laparoscopic ventral hernia repair score. Results Analyses revealed that execution time and motion, for the first anchoring suture, predicted procedural outcomes. Greater execution times and path lengths correlated to lesser laparoscopic ventral hernia repair scores (r = -0.56, P = .0008 and r = -0.51, P = .0025, respectively). Greater bimanual dexterity measures correlated to Greater LVH repair scores (r = + 0.47, P = .0058). Conclusions This study provides validity evidence for use of a single, early operative task as a shortcut assessment to predict resident performance during a simulated laparoscopic ventral hernia repair procedure. With the continued development and decreasing costs of motion technology, faculty should be well-versed in the use of motion metrics for performance measurements. The results strongly support the use of dexterity and economy of motion (path length + execution time) metrics as early predictors of operative performance.

Background Type I diabetes mellitus (DM) has been associated with abnormalities of T cells. Our objective was to assess whether antibody responses to T-cell-dependent and -independent antigens in children with DM are lower than those of children without DM. Methods We performed a case-control study matching children with DM to children without DM by age and by assessing antibody levels to pneumococcal serotypes, Haemophilus influenzae, and tetanus and diphtheria toxoids and reassessing antibody levels in patients with antibody levels below protective thresholds after booster immunisation. Results We recruited 36 children with DM and 36 age-matched controls. The mean age was 10 years. There was no difference between groups in antibody levels against the antigens tested. Pneumococcal antibody levels below the protective threshold were found in 35.9% of DM patients after conjugate pneumococcal vaccination with no difference between groups. Booster immunisation with unconjugated pneumococcal vaccine resulted in a median level against pneumococcal serotypes of 2.3 mg/ml (range, 0.05 to 664.7 mg/ml) in children with DM and 6.1 mg/ml (0.12 to 203.36 mg/ml) in children without DM (p=0.013). Over 85% of children had levels above the protective threshold after booster immunisation with no difference between groups. Conclusions There was no evidence for a reduced antibody response to T-cell-dependent antigens given during childhood immunizations in children with DM. There was a reduced antibody response to antigens of pneumococcal strains in children with DM given unconjugated pneumococcal polysaccharide vaccine compared with that of children without DM without being associated with a difference in percentage of antibody levels below the protective threshold between groups.

Background The aim of this study was to assess performance measurement validity of our newly developed robotic surgery task trainer. We hypothesized that residents would exhibit wide variations in their intercohort performance as well as a measurable difference compared to surgeons in fellowship training. Materials and methods Our laboratory synthesized a model of a pelvic tumor that simulates unexpected bleeding. Surgical residents and fellows of varying specialties completed a demographic survey and were allowed 20 minutes to resect the tumor using the da Vinci robot and achieve hemostasis. At a standardized event in the simulation, venous bleeding began, and participants attempted hemostasis using suture ligation. A motion tracking system, using electromagnetic sensors, recorded participants' hand movements. A postparticipation Likert scale survey evaluated participants' assessment of the model's realism and usefulness. Results Three of the seven residents (postgraduate year 2-5), and the fellow successfully resected the tumor in the allotted time. Residents showed high variability in performance and blood loss (125-700 mL) both within their cohort and compared to the fellow (150 mL blood). All participants rated the model as having high realism and utility for trainees. Conclusions The results support that our bleeding pelvic tumor simulator has the ability to discriminate resident performance in robotic surgery. The combination of motion, decision-making, and blood loss metrics offers a multilevel performance assessment, analyzing both technical and decision-making abilities.

Background Nearly one-third of surgical residents will enter into academic development during their surgical residency by dedicating time to a research fellowship for 1-3 y. Major interest lies in understanding how laboratory residents' surgical skills are affected by minimal clinical exposure during academic development. A widely held concern is that the time away from clinical exposure results in surgical skills decay. This study examines the impact of the academic development years on residents' operative performance. We hypothesize that the use of repeated, annual assessments may result in learning even without individual feedback on participants simulated performance. Methods Surgical performance data were collected from laboratory residents (postgraduate years 2-5) during the summers of 2014, 2015, and 2016. Residents had 15 min to complete a shortened, simulated laparoscopic ventral hernia repair procedure. Final hernia repair skins from all participants were scored using a previously validated checklist. An analysis of variance test compared the mean performance scores of repeat participants to those of first time participants. Results Twenty-seven (37% female) laboratory residents provided 2-year assessment data over the 3-year span of the study. Second time performance revealed improvement from a mean score of 14 (standard error = 1.0) in the first year to 17.2 (SD = 0.9) in the second year, (F[1, 52] = 5.6, P = 0.022). Detailed analysis demonstrated improvement in performance for 3 grading criteria that were considered to be rule-based errors. There was no improvement in operative strategy errors. Conclusions Analysis of longitudinal performance of laboratory residents shows higher scores for repeat participants in the category of rule-based errors. These findings suggest that laboratory residents can learn from rule-based mistakes when provided with annual performance-based assessments. This benefit was not seen with operative strategy errors and has important implications for using assessments not only for performance analysis but also as a learning experience.

Summary In nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), little is known about the presence of intranodular clusters of cytologically activated lymphoid cells producing a moth-eaten pattern histologically. This pilot study of 32 NLPHL cases from Finland ascertained (1) the frequency of the intranodular clusters of activated lymphoid cells, (2) the immunophenotype of the activated cells, (3) the size and immunophenotype of the rosetting cells, and (4) the clinical significance of the activated cells. Histologically, intranodular clusters of activated cells produced a moth-eaten pattern in 100% (32 cases; subtle in 62.5%, overt in 37.5%). In immunostains, activated cells in subtle clusters (20 cases) were very difficult to identify. Twelve cases had overt clusters of activated cells, which were positive with CD3, CD4, PD1, CXCL13 (T follicular helper [T FH ] phenotype), but rarely with Ki-67 and BCL2. Most activated rosetting cells had the same immunophenotype as the nonrosetting cells, except for CXCL13. Clinical presentation for all 32 Finnish patients was distinctive: 97% men, 97% with peripheral lymphadenopathy and 35.5% with stage III/IV disease. Only 22% relapsed; 97% were in remission. There was no significant clinical difference between cases with overt and subtle clusters. Intranodular activated T FH cells in NLPHL appeared to be nonproliferating and not long-living, and they were not associated with any adverse clinical outcome. Although most activated cells were T FH cells, it seemed that they were unable to increase the number of malignant cells. The pathogenetic role of the intranodular activated T FH and the small T cells in NLPHL needs further investigation.

Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV-encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi-squared statistics, and Student's t-test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0-19, 20-34, 35-59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0-19 to 55% in age group 20-34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one-third of tumors and it was strongly associated with race and HIV status, and marginally with age-group.

Background: Adolescent/young adult Hodgkin lymphoma (AYAHL) survivors report fewer exposures to infections during childhood compared with controls, and they have functional lymphocyte aberrations. The gut microbiota plays a central role in immunity. Methods: We investigated whether fecal microbial diversity differed between 13 AYAHL survivors and their unaffected co-twin controls. Pyrosequencing of fecal bacterial 16S rRNA amplicons yielded 252 943 edited reads that were assigned to species-level operational taxonomic units (OTUs) and standardised for sequencing depth by random sampling. Microbial diversity was compared within vs between twin pairs and by case–control status. Results: The number of unique OTUs was more similar within twin pairs compared with randomly paired participants (P=0.0004). The AYAHL cases had fewer unique OTUs compared with their co-twin controls (338 vs 369, P=0.015); this difference was not significant (169 vs 183, P=0.10) when restricted to abundant OTUs. Conclusion: In this small study, AYAHL survivors appear to have a deficit of rare gut microbes. Further work is needed to determine if reduced microbial diversity is a consequence of the disease, its treatment, or a particularly hygienic environment.

The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences.

Objective Previous studies have found that both resident and staff surgeons highly value postoperative feedback; and that such feedback has high educational value. However, little is known about how to consistently deliver this feedback. Our aim was to understand how often surgical residents should receive feedback and what barriers are preventing this from occurring. Design Surveys were distributed to resident and attending surgeons. Questions focused on the current frequency of postoperative feedback, desired frequency and methods of feedback, and perceived barriers. Quantitative data were analyzed with descriptive statistics, and text responses were examined using coding. Setting University-based general surgery department at a Midwestern institution. Participants General surgery residents ( n = 23) and attending surgeons ( n = 22) participated in this study. Results Residents reported receiving and staff reported giving feedback for procedure-specific performance after 25% versus 34% of cases, general technical feedback after 36% versus 32%, and nontechnical performance after 17% versus 18%. Both perceived procedure-specific and general technical feedback should be given more than 80% of the time, and nontechnical feedback should happen for nearly 60% of cases. Verbal feedback immediately after the operation was rated as best practice. Both parties identified time, conflicting responsibilities, lack of privacy, and discomfort with giving and receiving meaningful feedback as barriers. Conclusions Both resident and staff surgeons agree that postoperative feedback is given far less often than it should. Future work should study intraoperative and postoperative feedback to validate resident and attending surgeons’ perceptions such that interventions to improve and facilitate this process can be developed.

The main purpose of this study is to find possible relationships between the smoothness of hand function during laparoscopic ventral hernia (LVH) repair and psychomotor skills in a defined virtual reality (VR) environment. Thirty four surgical residents N = 34 performed two scenarios. First, participants were asked to perform a simulated LVH repair during which their hand movement was tracked using electromagnetic sensors. Subsequently, the smoothness of hand function was calculated for each participant's dominant and non-dominate hand. Then participants performed two modules in a defined VR environment, which assessed their force matching and target tracking capabilities. More smooth hand function during the LVH repair correlated positively with higher performance in VR modules. Also, translational smoothness of dominant hand is found as the most informative smoothness metric in the LVH repair scenario. Therefore, defined force matching and target tracking assessments in VR can potentially be used as an indirect assessment of fine motor skills in the LVH repair.

Cyclin D1 is an important regulator of the cell cycle and overexpression of this protein by immunohistochemistry is characteristically seen in mantle cell lymphoma as well as other B-cell neoplasms. However, little is known about the expression of this protein in T-cell lymphomas. Cyclin-dependent kinase pathway inhibitors are in development, therefore identifying cyclin D1-positive T-cell lymphomas may provide a therapeutic target in a disease where novel treatments are urgently needed. We collected 200 peripheral T-cell lymphomas from three institutions including the following types of cases: 34 anaplastic large cell lymphoma, ALK+, 44 anaplastic large cell lymphoma, ALK negative, 68 peripheral T-cell lymphomas, not otherwise specified, 24 angioimmunoblastic T-cell lymphomas, 7 extranodal NK/T-cell lymphomas, 4 enteropathy associated T-cell lymphomas, 3 hepatosplenic T-cell lymphomas, 12 cutaneous T-cell lymphomas, and 4 large granular lymphocytic leukemias. Immunohistochemical stains for cyclin D1 protein (SP4 clone) were performed on paraffin-embedded tissue. In a subset of cases, IGH/CCND1 fluorescence in situ hybridization analysis was also performed. Cyclin D1 staining was predominantly seen in anaplastic large cell lymphoma, including 8 of 34 cases with ALK+ anaplastic large cell lymphoma (24%), and 3 of 44 cases of ALK negative (7%) anaplastic large cell lymphoma. Three cases of peripheral T-cell lymphoma, not otherwise specified, were also positive (3/68, 4%). All other T-cell lymphomas were negative for cyclin D1. In four of the cyclin D1-positive T-cell lymphomas by immunohistochemistry, fluorescence in situ hybridization analysis was negative for IGH/CCND1 translocation or extra copies of the CCND1 gene. Cyclin D1 overexpression by immunohistochemistry is not limited to B-cell lymphomas and is also observed in some peripheral T-cell lymphomas, particularly in anaplastic large cell lymphoma, ALK+. Cyclin D1 expression was not associated with extra copies or translocation of the CCND1 gene. Cyclin D1 over-expression may be the result of a post-translational phenomenon and may represent a potential therapeutic target using agents that target the cyclin-dependent kinase pathway.

In this study new metrics were developed for assessing the performance of surgical knots. By adding sensors to a knot tying simulator we were able to measure the forces used while performing this basic and essential skill. Data were collected for both superficial tying and deep tying of square knots using the one hand and two hands techniques. Participants used significantly more force when tying a deep knot compared to a superficial knot (3.79N and 1.6N respectively). Different patterns for upward and downward forces were identified and showed that although most of the time upward forces are used (72% of the time), the downward forces are just as large. These data can be crucial for improving the safeness of knot tying. Combing these metrics with known metrics based on knot tensiometry and motion data may help provide feedback and objective assessment of knot tying skills.

Background Due to the increased use of peripherally inserted central catheter lines, central lines are not performed as frequently. The aim of this study is to evaluate whether a virtual reality (VR)–based assessment of fine motor skills can be used as a valid and objective assessment of central line skills. Methods Surgical residents (N = 43) from 7 general surgery programs performed a subclavian central line in a simulated setting. Then, they participated in a force discrimination task in a VR environment. Hand movements from the subclavian central line simulation were tracked by electromagnetic sensors. Gross movements as monitored by the electromagnetic sensors were compared with the fine motor metrics calculated from the force discrimination tasks in the VR environment. Results Long periods of inactivity (idle time) during needle insertion and lack of smooth movements, as detected by the electromagnetic sensors, showed a significant correlation with poor force discrimination in the VR environment. Also, long periods of needle insertion time correlated to the poor performance in force discrimination in the VR environment. Conclusions This study shows that force discrimination in a defined VR environment correlates to needle insertion time, idle time, and hand smoothness when performing subclavian central line placement. Fine motor force discrimination may serve as a valid and objective assessment of the skills required for successful needle insertion when placing central lines.

Extranodal NK/T-cell lymphoma, nasal type, is a rare type of non-Hodgkin lymphoma that is most common in Asia and is driven by Epstein-Barr virus infection. These tumors usually arise in the nasal region; in rare cases they can involve extranasal sites, most often skin, with involvement of the breast being rare. Lymphomas arising adjacent to breast implants are rare, and most cases reported to date have been anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Here we report a 41-year-old white woman with bilateral saline breast implants placed for cosmetic reasons who almost 9 years later developed painful swelling at the right-breast implant site. Excisional biopsy revealed lymphoma composed of monomorphic large cells associated with necrosis and angioinvasion. Immunohistochemical analysis showed an aberrant, NK/T-cell immunophenotype with the lymphoma cells being CD2+, CD3+, CD56+, partial CD30+, granzyme B, TIA-1+, CD4+, CD5+, CD7+, and CD8+. In situ hybridization analysis showed Epstein-Barr virus-encoded RNA within the neoplastic cells. Polymerase chain reaction analysis showed monoclonal T-cell receptor-γ chain gene rearrangement. These findings support the diagnosis of extranodal NK/T-cell lymphoma, nasal type. On the basis of our review of the literature, this case is unique. In addition, we believe this case is important to report, because it expands the spectrum of T-cell lymphomas that can be associated with breast implants and may be a forerunner of additional cases to follow.

Langerhans cell histiocytosis (LCH) is a well-known but rare disease that may occur at any age with markedly variable clinical features: self-regressive, localized, multiorgan, aggressive, or fatal outcome. Congenital LCH is rare and often clinically benign. While LCH is characterized by a clonal proliferation of Langerhans cells, its etiology is unknown. Although BRAF V600E mutations were recently identified as a recurrent genetic alteration in LCH cases, the clinical significance of this mutation within the heterogeneous spectrum of LCH is also currently unknown. We studied a cutaneous, benign form of congenital LCH that occurred in a newborn male, without recurrence for 8 years. Histopathologically, the skin lesion excised after birth showed the typical cytologic and immunophenotypic features of LCH. Sequencing analysis of Exon 15 of the BRAF gene revealed the V600D mutation, with an allelic abundance of 25-30%, corresponding to the LCH cells being hemizygous for the mutant allele. BRAF V600E-specific polymerase chain reaction was negative. Our report is the first to identify the rare, variant BRAF V600D mutation in LCH, and provides support for constitutively activated BRAF oncogene-induced cell senescence as a mechanism of regression in congenital, benign LCH. Further, our clinicopathologic findings provide proof for the first time that the V600D mutation can also occur in the absence of ultraviolet light, and can occur in a clinically benign proliferation, similar to the V600E mutation. Additional clinicopathologic studies in larger numbers of LCH patients may be valuable to ascertain the pathophysiologic role of BRAF mutations in LCH.

Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P = 5.35 × 10−10), rs204999 (P = 1.44 × 10−9), and rs2858870 (P = 1.69 × 10−8). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 × 10−10). rs204999 and rs2858870 were weakly correlated (r2 = 0.257), and the remaining pairs of SNPs were not correlated (r2 < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 × 10−6; GAATC, OR = 0.4, P = 1.16 × 10−4). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology.

The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long-term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development.

The aim of this study is to report the relative frequencies of non-Hodgkin lymphoma (NHL) subtypes in Guatemala. A panel of five hematopathologists reviewed 226 consecutive biopsies and classified them according to the 2001 World Health Organization (WHO) classification. The 83 cases of diffuse large B-cell lymphoma (DLBCL) were further subclassified into germinal center B-cell-like (GCB) and non-GCB subtypes. Of the 226 cases, 194 (86%) were confirmed as NHL, including 169 (87%) B-cell and 25 (13%) T- or natural killer (NK)-cell NHL. The most common subtype was DLBCL (44.3%), and the most frequent subtype among T- and NK-cell NHL was extranodal NK/T-cell lymphoma, nasal type (7.8% of all NHL). A comparison of the frequencies of NHL subtypes between Guatemala and other parts of the world showed that Guatemala is most similar to the Middle East and Asia. However, there is no significant difference in the frequency of the DLBCL subtypes compared to North America and Europe.

Fifty-five consecutive cases of Hodgkin's lymphoma (HL), collected between 1996 and 1998 from Cairo, Egypt, were histologically subtyped, phenotyped, and then studied for the presence of Epstein-Barr virus (EBV). We used immunohistochemical stains for EBV latent membrane protein 1 (LMP-1) and in situ hybridization stains for EBV-encoded small RNA (EBER-1) transcripts. Forty-five cases (82%) had classic HL (cHL), and ten cases (18%) had nodular lymphocyte predominant HL (NLPHL), with each group expressing its typical phenotype. LMP-1 stains were positive in 63% and 0% of cHL and NLPHL cases, respectively. EBER-positive Reed-Sternberg cells and variants were also present in 62% and 0% of each group, respectively. The cHL cases showed variable EBER positivity: nodular sclerosis, 58%; mixed cellularity, 100%; lymphocyte depletion, 100%; and unclassifiable, 67%. Our findings are similar to those from other developing countries and point towards a pathogenic role of EBV in cHL.

The role of histologic examination in lymphoma diagnosis has been called into question by proponents of new technologies, such as genomics and proteomics. We review the history and salient features of morphologic evaluation in lymphoid diseases, and discuss the general and specific limitations of mature ancillary techniques, such as immunohistochemistry, flow cytometry, and molecular studies. We then speculate on the future relationship between morphology and the new genomic and proteomic technologies as they become integrated into clinical practice.

S100 T-cell lymphomas are infrequent, and except 1 all have been CD4 negative. On the basis of an index case of CD4 S100 T-cell prolymphocytic leukemia (T-PLL), we studied S100 protein expression in 19 additional T-PLLs and 56 other T-cell lymphomas that are usually CD4, including 15 angioimmunoblastic T-cell lymphomas, 24 anaplastic large cell lymphomas (16 ALK and 8 ALK), 7 mycosis fungoides/Sezary syndrome, and 10 peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). Two additional S100 CD4 PTCL, NOS cases were also reviewed. Thirty percent (6/20) of T-PLLs were S100 compared with 0/56 other T-cell lymphomas with previously unstudied S100 reactivity (40 CD4, 2 CD8, 11 CD4/CD8, 3 unknown) (P=0.0007). There were no significant differences between the S100 and S100 T-PLLs with regard to the male:female ratio (2:1 vs. 1:1), age (71.6±7.7 vs. 65.4±9.3), peripheral blood lymphocyte count (67.2±116.6 vs. 101.1±159.7×10/L), or median survival (463 vs. 578 d, where known). The 2 S100 PTCL, NOS cases occurred in a 7-year-old boy and a 45-year-old woman. Both had involvement of the bone marrow and peripheral blood but were morphologically unlike T-PLL and lacked TCL1 gene rearrangement. These results demonstrate that S100 T-cell lymphomas include a subset that are CD4 and most often, but not exclusively, are T-PLL. Although having diagnostic implications, there were no documented clinical differences between the S100 and S100 T-PLLs.

Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John WileySons, Ltd.

The distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world, but a systematic study of South-eastern Europe (SEEU) has never been done. Therefore, we evaluated the relative frequencies of NHL subtypes in three SEEU countries--Croatia, Romania and Macedonia. Five expert haematopathologists reviewed 632 consecutive cases of newly diagnosed NHL from the three SEEU countries using the World Health Organization classification. The results were compared to 399 cases from North America (NA) and 580 cases from Western Europe (WEU). The proportions of B- and T-cell NHL and the sex distribution in SEEU were similar to WEU and NA. However, the median ages of patients with low- and high-grade B-NHL in SEEU (60 and 59 years, respectively) were significantly lower than in NA (64 and 68 years, respectively; P < 0·05). SEEU had a significantly lower proportion of low-grade B-NHL (46·6%) and higher proportion of high-grade B-NHL (44·5%) compared to both WEU (54·5% and 36·4%, respectively) and NA (56·1% and 34·3%, respectively). There were no significant differences in the relative frequencies of T-NHL subtypes. This study provides new insights into differences in the relative frequencies of NHL subtypes in different geographic regions. Epidemiological studies are needed to better characterize and explain these differences.