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AbstractBackgroundThe International Dermoscopy Society (IDS) recently released a set of five basic dermoscopic parameters (vessels, scales, follicular findings, “other structures,” and specific clues) encompassing a total of 31 subitems to standardize the use of dermoscopy in non‐neoplastic dermatoses, yet they have been developed taking into account Caucasian/Asian skin, with consequent possible limitations if used in dark skin.ObjectivesTo validate the abovementioned criteria for the use in dark‐skinned patients (phototypes IV–VI) through an expert consensus.MethodsThe two‐round Delphi method was adopted, with an iterative process consisting of two rounds of email questionnaires. Potential panelists were recruited via e‐mail from all over the world based on their expertise on dermoscopy of non‐neoplastic dermatoses in skin of color.ResultsTwenty‐two panelists took part in the validation process. All of the five originally proposed parameters and subitems reached agreement during the first round, aside from “follicular red dots.” Additionally, during round 1, five new subitems were proposed (perifollicular scales distribution, follicular openings obliteration, broken hairs, eccrine pigmentation, and eccrine ostia obliteration), along with the possibility to change the denomination of parameter 3 (from “follicular findings” to “follicular/eccrine findings”) and split it into two subparameters (“follicular findings” and “eccrine findings”). All such proposals reached agreement during the second round and therefore were included in the final list, for a total of 37 items.ConclusionsAlthough nearly all the dermoscopic criteria originally proposed by the IDS are applicable even to darker phototypes, several additional variables need to be assessed.

Background: Thrombelastography (TEG) is an established but labor intensive method for assessing global hemostasis for the management of bleeding and thrombotic risk in surgical, cardiovascular, and trauma patients. We performed the initial validation study of the first true point-of-care TEG, the CORA® (COagulation Resonance Analyzer or TEG-6S system). CORA uses resonance-frequency viscoelasticity measurements and a disposable multi-channel microfluidic cartridge to assess hemostasis and response to antiplatelet therapy. Methods: TEG assays (n=5,100) were performed from the blood of healthy volunteers (n=160) and patients undergoing coronary revascularization (n=300) collected at 3 hospitals. Quality controls were also assayed. The performance of the TEG-6S system was compared with the conventional TEG 5000 system in accordance with Clinical Laboratory Standards Institute Guidelines. Results: Regression analysis demonstrated a strong correlation (R) between the two systems by all standard measures and a lower coefficient of variation (CV %) with the CORA system at all hospitals (Table). Receiver operating characteristic (ROC) curve analysis showed an excellent correlation between platelet mapping methods (AUC≥0.90, p<0.001) and there was a substantial agreement for measuring antiplatelet response to aspirin (k=0.67, agreement=87%) and P2Y12 inhibitors (k=0.69, agreement=86%). Conclusion: The new point-of-care TEG-6S system is associated with improved precision, greater ease of use, and a strong correlation as compared to the conventional TEG 5000 system. The TEG-6S will facilitate future trials of personalized antiplatelet therapy and improve the assessment of bleeding and thrombotic risk in cardiovascular, surgical, and trauma patients.

0024 Background: There is evidence for the role of inflammation in the pathogenesis of coronary disease. Relative lymphocytopenia was reported for the diagnosis of myocardial infarction (MI), but little is known about its prognostic value. This study was undertaken to test the hypothesis that relative lymphocytopenia was associated with cardiac events (defined as recurrent MI, congestive heart failure or cardiac death) after MI among Olmsted County residents. Methods: MIs were validated using standard epidemiological criteria using enzymes, chest pain and Minnesota coding of the ECG. The entire community medical record, available via the Rochester Epidemiology Project, was reviewed to determine incident status and ascertain outcomes. Relative lymphocytopenia was defined as percent lymphocytes<20, 3%. Results: Between 1979 and 1994, an incidence cohort of 1653 validated MIs (mean age 67 ± 14, 43% women) was assembled. At the time of index MI, relative lymphocytopenia was present in 51% of the cases. After a mean follow-up of 6.9 ± 5.4 years, 471 pts had experienced recurrent MIs, 849 pts CHF and 602 cardiac deaths occurred. The 5-year event-free survival was 35% for cases with relative lymphocytopenia vs 52% for those without(p<0.001). After adjustment for age and current smoking, relative lymphocytopenia was associated with a 21% increase in the risk of cardiac event (RR 1.21, 95% CI 1.1-1.4; p=0.003). Conclusion: Relative lymphocytopenia is associated with cardiac events after incident MI. These data support the role of inflammation in the outcome of coronary disease.

Abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P &lt; .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P &lt; .001). Long-term relapse was lower with FM (HR = 0.65, P &lt; .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.

Background Sedentary time has been shown to have deleterious effects on health. Today's workforce spends most of the day sitting. The objective of this study was to evaluate the effect of workplace interventions to decrease sedentary time on cardiometabolic risk factors. Methods Sedentary office workers (n=127; ages 22‐64; BMI=28.5±6.1 kg/m 2 ) were recruited from three Minnesota employers and randomized to one of four intervention groups for 6 months: 1) Control, 2) Move (蠅30 min of light activity during the workday), 3) Stand (standing 蠅50% of the workday using a sit‐stand workstation), or 4) Stand+Move (combined Stand and Move). A 'metabolic risk score' (MRS) was calculated at baseline and 6 months using the following cardiometabolic risk factors: blood pressure, fasting blood glucose, log of fasting triglycerides, and HDL‐cholesterol. A z‐score was computed for each risk factor for each subject [(subject value – sample mean)/sample SD]. The MRS was derived by summing the z‐scores (HDL‐z subtracted). Results There was a significant intervention effect on MRS (p<.01). A seasonal time trend was observed, with MRS increasing significantly in Control and Move groups (p<.001), but not for the Stand and Stand+Move. Results (mean±se) are shown in Figure 1. Conclusions Sit‐stand workstations combined with an intervention to increase light physical activity at work may be an effective tool to improve cardiometabolic risk. image

Mayo Clinic annually trains over 1000 predoctoral students and postdoctoral research fellows in medicine and biomedical sciences. However, training opportunities are limited for those interested in teaching and mentoring methodologies. Therefore, Mayo Clinic predoctoral students sought to provide trainee‐led learning opportunities for fellow trainees. A survey was sent to all Mayo Clinic predoctoral and postdoctoral trainees to determine preferences for pedagogy education formats. In response to survey results, the Twin Talk Series was developed. A Twin Talk is a set of one‐hour talks comprised of a Take‐in session and one or more Try‐out session(s). At the Take‐in session, a content expert discusses a pedagogical technique, and at the following Try‐out session(s), trainee volunteers practice the technique among themselves. Eight Twin Talks have been organized to date on several teaching techniques and pedagogical development topics. The impact of each Twin Talk, including understanding, format, and interest level, was evaluated through survey tools. Survey results suggested trainees favored in‐person pedagogy expert presenters during the Take‐in session over video conferences. Furthermore, modeling of the teaching technique by the expert presenter during the Take‐in session was well‐received. However, participation in the follow‐up Try‐out practice session was limited. Overall, the Twin Talk Series is a promising method for trainee‐led, peer‐to‐peer pedagogy education, particularly at institutions with limited access to pedagogical resources. The Twin Talk Series will continue to be refined to increase trainee participation, particularly in the follow‐up Try‐out sessions, and to provide relevant opportunities for trainees to practice teaching. Support or Funding Information Mayo Foundation of Medical Education and Research This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Cervical spinal hemisection at C2 (SH) paralyzes the diaphragm muscle by interrupting descending bulbospinal pathways to phrenic motoneurons. Signaling via the neurotrophin receptor TrkB in phrenic motoneurons enhances functional recovery after SH. However, it is not clear if the delay in gene expression resulting from adeno‐associated virus (AAV)‐mediated delivery would blunt the therapeutic efficacy of AAV delivered after SH. The goal of the present study was to examine the efficacy of intrapleurally‐delivered AAV7 encoding the full‐length TrkB receptor at 3 days post‐SH. Chronic diaphragm EMG recordings were conducted in adult male Sprague‐Dawley rats confirming absence of ipsilateral activity 3 days after SH. The proportion of animals displaying recovery of ipsilateral diaphragm EMG activity increased over time post‐SH and was greater in those treated with AAV‐TrkB (by 14 days post‐SH: AAV‐TrkB: 10/15 vs. AAV‐GFP: 2/11; p=0.01). Furthermore, peak root‐mean‐square amplitude of the diaphragm EMG activity increased progressively over time post‐SH. During eupnea, animals displaying recovery of ipsilateral diaphragm EMG activity that were treated with AAV‐TrkB achieved 40% of pre‐injury values (vs. 10% in those treated with AAV‐GFP). Targeting phrenic motoneurons via intrapleural delivery of AAV7‐TrkB promotes recovery of diaphragm activity when administered 3 days post‐injury. Grant Funding Source : Supported by R01 HL96750, T32 HL105355 and Mayo Clinic Center for Regenerative Medicine

Objectives: To understand how patients and family members experience dehumanizing or humanizing treatment when in the ICU. Design: Qualitative study included web-based focus groups and open-ended surveys posted to ICU patient/family social media boards. Focus groups were audio recorded and transcribed. Social media responses were collected and organized by stakeholder group. Data underwent qualitative analysis. Setting: Remote focus groups and online surveys. Patients: ICU patient survivors, family members, and ICU teams. Interventions: Not available. Measurements and Main Results: Semi-structured questions and open-ended survey responses. We enrolled 40 patients/family members and 31 ICU team members. Focus groups and surveys revealed three primary themes orienting humanizing/dehumanizing ICU experiences: 1) communication, 2) outcomes, and 3) causes of dehumanization. Dehumanization occurred during “communication” exchanges when ICU team members talked “over” patients, made distressing remarks when patients were present, or failed to inform patients about ICU-related care. “Outcomes” of dehumanization were associated with patient loss of trust in the medical team, loss of motivation to participate in ICU recovery, feeling of distress, guilt, depression, and anxiety. Humanizing behaviors were associated with improved recovery, well-being, and trust. “Perceived causes” of dehumanizing behaviors were linked to patient, ICU team, and healthcare system factors. CONCLUSIONS: Behaviors of ICU clinicians may cause patients and families to feel dehumanized when in the ICU. Negative behaviors are noticed by patients and families, possibly contributing to poor outcomes including mental health, recovery, and lack of trust in ICU teams. Supporting ICU clinicians may enable a more empathic environment and in turn more humanizing clinician-patient encounters.