Utility of Recipient Cardiothoracic Ratio in Predicting Delayed Chest Closure after Heart Transplantation.

BACKGROUND: Predicted cardiac mass (PCM) has been well validated for size matching donor hearts to heart transplantation recipients. We hypothesized that cardiothoracic ratio (CTR) could be reflective of recipient-specific limits of oversizing, and sought to determine the utility of donor to recipient PCM ratio (PCMR) and CTR in predicting delayed chest closure after heart transplantation. METHODS: A retrospective review of prospectively collected data on 38 consecutive heart transplantations performed at our institution from 2017 to 2020 was performed. Donor and recipient PCM were estimated using Multi-Ethnic Study of Atherosclerosis predictive models. Receiver operating characteristic analysis was performed to determine the discriminatory power of the ratio of PCMR to CTR in predicting delayed sternal closure. RESULTS: Of the 38 patients, 71.1% (27/38) were male and the median age at transplantation was 58 (interquartile range [IQR]: 47-62) years. Ischemic cardiomyopathy was present in 31.6% of recipients (12/38). Median recipient CTR was 0.63 [IQR: 0.59-0.66]. Median donor to recipient PCMR was 1.07 [IQR: 0.96-1.19], which indicated 7% oversizing. Thirteen out of 38 (34.2%) underwent delayed sternal closure. Primary graft dysfunction occurred in 15.8% (6/38). PCMR/CTR showed good discriminatory power in predicting delayed sternal closure [area under the curve: 80.4% (65.3-95.6%)]. PCMR/CTR cut-off of 1.7 offered the best trade-off between the sensitivity (69.6%) and specificity (91.7%). CONCLUSION: CTR could be helpful in guiding the recipient-specific extent of oversizing donor hearts. Maintaining the ratio of PCMR to CTR below 1.7 could avoid excessive oversizing of the donor heart.

Microaxial circulatory support for percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Microaxial circulatory support devices have been used to support patients treated with percutaneous coronary intervention (PCI) for acute myocardial infarction complicated by cardiogenic shock (AMICS). The purpose of this systematic review and meta-analysis was to pool and analyze the existing evidence on the baseline characteristics, periprocedural data, and outcomes of microaxial support before and after PCI in AMICS. METHODS: An electronic database search was performed to identify all cohort studies on Impella and PCI for cardiogenic shock in the English language. A total of five articles comprising 543 patients were included. These patients received microaxial support either before (pre-PCI) or after (post-PCI) undergoing PCI. Comparative analyses were done between both groups. RESULTS: The mean patient age was 66 years [95% Confidence Interval (58-74)], and 22% (89/396) of patients were female. ST-elevation myocardial infarctions (MI) comprised 64% (44-80) of MIs and 50% (44-56) of MIs involved the left anterior descending artery. The mean number of diseased vessels was 2.21 (1.62-2.80). The mean left ventricular ejection fraction was 31% (23.4-38.6). The mean arterial pressure was 66.3 mm Hg (54.1-78.5). Mean serum lactate [6.1 mmol/L (3.3-8.9)] and serum creatinine [1.4 mg/dl (1.0-1.7)] were similar between groups. 30-day mortality was lower in the pre-PCI group [41% (34%-49%)] compared to the post-PCI group [61% (42%-77%), p < 0.01]. Pooled Kaplan-Meier analysis showed better early survival in the pre-PCI group (p < 0.001). CONCLUSION: Patients presenting with AMICS were similar at baseline in both pre-PCI and post-PCI groups. Nevertheless, pre-PCI group showed better early survival compared to post-PCI group.

Frequency of Statin Prescription Among Individuals with Coronary Artery Calcifications Detected Through Lung Cancer Screening.

Individuals eligible for lung cancer screening (LCS) are at risk for atherosclerotic cardiovascular disease (ASCVD) due to smoking history. Coronary artery calcifications (CAC), a common incidental finding on low-dose CT (LDCT) for LCS, is a predictor of cardiovascular events. Despite findings of high ASCVD risk and CAC, a substantial proportion of LCS patients are not prescribed primary preventive statin therapy for ASCVD. We assessed the frequency of statin prescription in LCS patients with moderate levels of CAC. Among 259 individuals with moderate CAC, 95% had ASCVD risk ≥ 7.5%. Despite this, 27% of patients were statin-free prior to LDCT and 21.2% remained statin-free after LDCT showing moderate CAC. Illustratively, while a substantial proportion of LCS patients are statin-eligible, many lack a statin prescription, even after findings of CAC burden. CAC reporting should be standardized, and interdisciplinary communication should be optimized to ensure that LCS patients are placed on appropriate preventive therapy.

Outcomes of percutaneous temporary biventricular mechanical support: a systematic review.

Percutaneous biventricular assist devices (BiVAD) are a recently developed treatment option for severe cardiogenic shock. This systematic review sought to identify indications and outcomes of patients placed on percutaneous BiVAD support. An electronic search was performed to identify all appropriate studies utilizing a percutaneous BiVAD configuration. Fifteen studies comprising of 20 patients were identified. Individual patient survival and outcomes data were combined for statistical analysis. All 20 patients were supported with a microaxial LVAD, 12/20 (60%) of those patients were supported with a microaxial (RMA) right ventricular assist device (RVAD), and the remaining 8/20 (40%) patients were supported with a centrifugal extracorporeal RVAD (RCF). All patients presented with cardiogenic shock, and of these, 12/20 (60%) presented with a non-ischemic etiology vs 8/20 (40%) with ischemic disease. For the RMA group, RVAD support was significantly longer [RMA 5 (IQR 4-7) days vs RCF 1 (IQR 1-2) days, p = 0.03]. Intravascular hemolysis post-BiVAD occurred in three patients (27.3%) [RMA 3 (33.3%) vs RCF 0 (0%), p = 0.94]. Five patients received a durable left ventricular assist device, one patient received a total artificial heart, and one patient underwent a heart transplantation. Estimated 30-day mortality was 15.0%, and 78.6% were discharged alive. Both strategies for percutaneous BiVAD support appear to be viable options for severe cardiogenic shock.

Computational sentiment analysis of an online left ventricular assist device support forum: positivity predominates.

BACKGROUND: The impact of left ventricular assist device (LVAD) complications on the individual patient, overall sentiment, and its effect on referral patterns, is not fully understood. We sought to better understand patient attitudes towards LVAD therapy using a computational sentiment analysis approach. METHODS: Posts, comments, and titles were parsed from MyLVAD.com's HTML as a text file using custom Python scripts (version 3.6). Individual word frequency was computed with word classification as 'positive', 'negative', or 'neutral'. Data transformation and cleaning, sentiment determination, and analysis was performed with a binary dictionary package using R software (version 3.6). RESULTS: Sixty-six thousand eight hundred and twenty-one unique words were noted, including 4,623 (6.9%) with positive sentiment and 3,248 (4.8%) with negative sentiment. Net sentiment ratio [(number of positive words - number of negative words)/(number of total words)] was 2.1%. Positive sentiment dominated the 20 most commonly used words. Odds ratio of non-neutral words [(number of positive words/number of negative words)] was 1.42, indicating a less obvious disparity in sentiment when expanding analysis beyond the top 20 words. Word cloud analysis of positive and negative sentiments was performed, indicating common use of "infection" (208 mentions) compared to other complications such as "stroke" (29 mentions), "bleeding" (30 mentions), and "thrombosis" or "clot" (32 mentions). CONCLUSIONS: Positive sentiment dominates the most frequently used words, yet this disparity decreases when considering the totality of words. "Infection" is mentioned a disproportionate number of times compared to other LVAD complications. Further research is required to address analysis limitations, including selection bias.

Tricuspid regurgitation associated with implantable electrical device insertion: A systematic review and meta-analysis.

BACKGROUND: Implantable cardioverter defibrillator (ICD) and permanent pacemaker (PPM) lead placement may worsen or result in tricuspid regurgitation (TR). While the association between lead placement and the incidence of TR has been established, current understanding of this problem remains incomplete. This systematic review and meta-analysis sought to pool the existing evidence to better understand the occurrence and severity of TR associated with cardiac implantable electrical device (CIED) insertion. METHODS: An electronic search was performed to identify all relevant studies published from 2000 to 2018. Overall, 15 studies were selected for the analysis comprising 4019 patients with data reported on TR development following ICD or PPM lead placement. Demographic information, perioperative clinical variables, and clinical outcome measures, including pre and postoperative echocardiographic TR grade changes, were extracted and pooled for systematic review. RESULTS: Mean patient age was 69 years [95% CI: 64.62-73.59], and 63% [95% CI: 57-68] were male. Devices implanted included ICD in 57% [95%CI: 43-70] and PPM in 41% [95%CI: 31-52]. The most common indications for pacemaker implantation were sick sinus syndrome in 22% [95% CI: 22-37] and AV block in 21% [95%CI:12-34. The commonest indications for ICD implantation were primary and secondary prevention of sudden cardiac death. Atrial fibrillation was present in 37% [95%CI: 28-46] and congestive heart failure in 15% [95%CI: 2-57]. Baseline distribution of TR grades were as follows: grade 0/1 TR in 89% [95%CI: 82-93], grade 2 TR in 8% [95%CI: 5-13], grade 3 TR in 2% [95%CI: 0-7] and grade 4 TR in 2% [95%CI: 1-4]. Post-procedure, grade 0/ 1 TR decreased to 68% [95% CI: 51-81] (p < 0.01), grade 2 TR increased to 21% [15-28] (p < 0.01), grade 3 TR increased to 13% [95%CI: 5-32] (p = 0.02), and grade 4 TR increased to 7% [95%CI: 5-9] (p < 0.01). CONCLUSION: ICD and PPM lead placement is associated with increased TR post-procedure. Further studies are warranted to evaluate changes in TR grade in the long term.

Evidence-Based Alignment of Pathology Residency With Practice II: Findings and Implications.

This article presents findings from a 4-year series of surveys of new-in-practice pathologists, and a survey of physician employers of new pathologists, assessing how pathology graduate medical education prepares its graduates for practice. Using the methodology described in our previous study, we develop evidence for the importance of residency training for various practice areas, comparing findings over different practice settings, sizes, and lengths of time in practice. The principal findings are (1) while new-in-practice pathologists and their employers report residency generally prepared them well for practice, some areas-billing and coding, laboratory management, molecular pathology, and pathology informatics-consistently were identified as being important in practice but inadequately prepared for in residency; (2) other areas-autopsy pathology, and subspecialized apheresis and blood donor center blood banking services-consistently were identified as relatively unimportant in practice and excessively prepared for in residency; (3) the notion of a single comprehensive model for categorical training in residency is challenged by the disparity between broad general practice in some settings and narrower subspecialty practice in others; and (4) the need for preparation in some areas evolves during practice, raising questions about the appropriate mode and circumstance for training in these areas. The implications of these findings range from rebalancing the emphasis among practice areas in residency, to reconsidering the structure of graduate medical education in pathology to meet present and evolving future practice needs.

Continuous-flow LVAD exchange to a different pump model: Systematic review and meta-analysis of the outcomes.

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.

Utilization of extracorporeal life support for diffuse alveolar damage and diffuse alveolar hemorrhage: A systematic review.

Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.

Very High-Dose Furosemide Continuous Infusions: A Case Series.

BACKGROUND: There is paucity of data evaluating the efficacy and safety of very high-dose furosemide continuous infusions (≥40 mg/h) for volume removal. This infusion is a novel strategy of loop diuretic administration that may add valuable data to current literature. METHODS AND RESULTS: This was a retrospective chart review. Patients were eligible for inclusion if prescribed a very high-dose furosemide infusion (defined as ≥40 mg/h, up to 240 mg/h) from April 1, 2017, to January 1, 2019, at Thomas Jefferson University Hospital. Data collected included the change in cumulative urine output, net urine output, incidence of acute kidney injury, occurrences of hypotension, electrolyte abnormalities, body weight, and ototoxicity. Twenty-two patients were included in this analysis. The median change in 24-hour urine output from before to after very high-dose continuous furosemide infusion increased from 1193 mL at 24 hours before infusion initiation to 3518 mL at 24 hours after infusion initiation (P < .01). Serum creatinine increased 24 hours after infusion initiation but decreased within 48 hours. There were no electrolyte abnormalities. Out of 22 patients, only 2 had an occurrence of hypotension. No patients were reported to have ototoxicity. CONCLUSIONS: Very high-dose furosemide continuous infusions provide a significant increase in diuresis without worsening renal function, disturbing electrolytes, or increasing the risk of ototoxicity. Further studies are necessary to examine the efficacy and safety of this novel strategy.

Outcomes of Extracorporeal Life Support Use in Accidental Hypothermia: A Systematic Review.

BACKGROUND: Extracorporeal life support (ECLS) has been used in the treatment of accidental hypothermia with hemodynamic instability, with promising outcomes. This systematic review examines ECLS treatment of accidental hypothermia to assess outcomes. METHODS: An electronic search was performed to identify articles reporting ECLS use for treatment of accidental hypothermia. Only reports describing patients aged more than 16 years after January 1, 2005, were included. Nineteen studies were identified comprising 47 patients. Demographic information, perioperative variables, and outcomes were extracted for analysis. RESULTS: Median patient age was 48 years (interquartile range (IQR), 29 to 56), and 72.3% (34 of 47) were male. On presentation, median body temperature was 24.6°C (IQR, 22.2° to 26°C), median potassium level 4.3 mmol/L (IQR, 3.4 to 4.6 mmol/L), and median Glasgow Coma Scale score 3 (IQR, 3 to 7). Cardiac arrest occurred in 35 of 47 patients (74.5%). Median time to ECLS initiation from scene was 155 minutes (IQR, 113 to 245). Median ECLS duration was 18 hours (IQR, 4 to 27), with median rewarming rate of 2°C per hour (IQR, 1.5° to 4°). Median intensive care unit stay and hospital length of stay were 8 days (IQR, 2 to 16) and 17 days (IQR, 10 to 36), respectively. Inhospital mortality was 19.1% (9 of 47). Median discharge Glasgow Coma Scale score was 15 (IQR, 15 to 15) with minor long-term cognitive impairments noted in 6 of 47 patients (19.4%). Survival was significantly associated with potassium on presentation (P < .001), initial body temperature (P < .001), and ECLS rewarming rate (P < .001). CONCLUSIONS: Extracorporeal life support is a viable cardiac support option for rewarming patients with accidental hypothermia, and initial potassium level, initial body temperature, and ECLS rewarming rate appear to be significantly associated with survival.

Domino heart transplant following heart-lung transplantation: a systematic review and meta-analysis.

BACKGROUND: The domino-donor operation occurs when a "conditioned" heart from the heart-lung transplant (HLT) recipient is transplanted into a separate heart transplant (HT) recipient. The purpose of this systematic review was to investigate the indications and outcomes associated with the domino procedure. METHODS: An electronic search was performed to identify all prospective and retrospective studies on the domino procedure in the English literature. Eight studies reported 183 HLT recipients and 263 HT recipients who were included in the final analysis. RESULTS: HLT indications included cystic fibrosis in 58% (95% CI: 27-84%) of recipients, primary pulmonary hypertension (PPH) in 17% (95% CI: 12-24%), bronchiectasis in 5% (95% CI: 3-10%), emphysema in 5% (95% CI: 0-45%), and Eisenmenger's syndrome in 4% (95% CI: 2-8%). HT indications included ischemic heart disease in 40% (95% CI: 33-47%), non-ischemic disease in 39% (95% CI: 25-56%), and re-transplantation in 10% (95% CI: 1-59%). The pooled mean pulmonary vascular resistance (PVR) in HT recipients was 3.05 Woods units (95% CI: 0.14-5.95). The overall mortality in the HLT group was 28% (95% CI: 18-41%) at an average follow-up of 15.68 months (95% CI: 0.82-30.54), and 35% (95% CI: 17-58%) in the HT group at an average follow-up of 37.26 months (95% CI: 6.68-67.84). Freedom from rejection in HT was 94% (95% CI: 75-99%) at 1 month, 77% (95% CI: 30-96%) at 6 months, and 41% (95% CI: 33-50%) at 1 year. CONCLUSIONS: The domino procedure appears to be a viable option in properly selected patients that can be performed safely with acceptable outcomes.

Cell Line-, Protein-, and Sialoglycosite-Specific Control of Flux-Based Sialylation in Human Breast Cells: Implications for Cancer Progression.

Sialylation, a post-translational modification that impacts the structure, activity, and longevity of glycoproteins has been thought to be controlled primarily by the expression of sialyltransferases (STs). In this report we explore the complementary impact of metabolic flux on sialylation using a glycoengineering approach. Specifically, we treated three human breast cell lines (MCF10A, T-47D, and MDA-MB-231) with 1,3,4-O-Bu3ManNAc, a "high flux" metabolic precursor for the sialic acid biosynthetic pathway. We then analyzed N-glycan sialylation using solid phase extraction of glycopeptides (SPEG) mass spectrometry-based proteomics under conditions that selectively captured sialic acid-containing glycopeptides, referred to as "sialoglycosites." Gene ontology (GO) analysis showed that flux-based changes to sialylation were broadly distributed across classes of proteins in 1,3,4-O-Bu3ManNAc-treated cells. Only three categories of proteins, however, were "highly responsive" to flux (defined as two or more sialylation changes of 10-fold or greater). Two of these categories were cell signaling and cell adhesion, which reflect well-known roles of sialic acid in oncogenesis. A third category-protein folding chaperones-was unexpected because little precedent exists for the role of glycosylation in the activity of these proteins. The highly flux-responsive proteins were all linked to cancer but sometimes as tumor suppressors, other times as proto-oncogenes, or sometimes both depending on sialylation status. A notable aspect of our analysis of metabolically glycoengineered breast cells was decreased sialylation of a subset of glycosites, which was unexpected because of the increased intracellular levels of sialometabolite "building blocks" in the 1,3,4-O-Bu3ManNAc-treated cells. Sites of decreased sialylation were minor in the MCF10A (<25% of all glycosites) and T-47D (<15%) cells but dominated in the MDA-MB-231 line (~60%) suggesting that excess sialic acid could be detrimental in advanced cancer and cancer cells can evolve mechanisms to guard against hypersialylation. In summary, flux-driven changes to sialylation offer an intriguing and novel mechanism to switch between context-dependent pro- or anti-cancer activities of the several oncoproteins identified in this study. These findings illustrate how metabolic glycoengineering can uncover novel roles of sialic acid in oncogenesis.

Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue following Stroke, 6th edition update 2019.

The 2019 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Mood, Cognition and Fatigue following Stroke is a comprehensive set of evidence-based guidelines addressing three important issues that can negatively impact the lives of people who have had a stroke. These include post-stroke depression and anxiety, vascular cognitive impairment, and post-stroke fatigue. Following stroke, approximately 20% to 50% of all persons may be affected by at least one of these conditions. There may also be overlap between conditions, particularly fatigue and depression. If not recognized and treated in a timely matter, these conditions can lead to worse long-term outcomes. The theme of this edition of the CSBPR is Partnerships and Collaborations, which stresses the importance of integration and coordination across the healthcare system to ensure timely and seamless care to optimize recovery and outcomes. Accordingly, these recommendations place strong emphasis on the importance of timely screening and assessments, and timely and adequate initiation of treatment across care settings. Ideally, when screening is suggestive of a mood or cognition issue, patients and families should be referred for in-depth assessment by healthcare providers with expertise in these areas. As the complexity of patients treated for stroke increases, continuity of care and strong communication among healthcare professionals, and between members of the healthcare team and the patient and their family is an even bigger imperative, as stressed throughout the recommendations, as they are critical elements to ensure smooth transitions from acute care to active rehabilitation and reintegration into their community.

Age of initiation of cigarette smoking and smokeless tobacco use among western Alaska Native people: Secondary analysis of the WATCH study.

OBJECTIVE: This study examined self-reported age of tobacco initiation (cigarette smoking and smokeless tobacco [ST] use) and explored potential sex and generational group influences on tobacco use onset among Alaska Native (AN) adult ever tobacco users. METHODS: Secondary analysis of consolidated data from the Western Alaska Tribal Collaborative for Health (WATCH) study comprised 2800 AN adult ever tobacco users (1490 women, 1310 men; mean age = 39.2 years) from two rural western Alaska regions. ST use data were limited to one region. Logistic regression was used to examine potential sex and generational group (age 18-29, 30-49, ≥50) effects on initiation at ≤13 years of age. RESULTS: Thirty-seven percent of the sample reported using any tobacco product by age 13 years. Initiation of any ST use by age 13 was greater than for cigarette smoking (52.7% vs. 18.2%), and women were more likely than men to report initiation of any ST use at ≤13 years (52.6% vs. 38.4%). Nearly one-third of ever smokers (31%) initiated in young adulthood (ages 18-29). For ST use, logistic regression analyses revealed significant sex differences (women more likely to initiate by 13 years of age than men) and generational group effects with younger and middle age groups more likely to report initiation ≤13 years compared to the eldest participants. For smoking, no sex differences were observed but the youngest generational group was more likely to report initiation by age 13 compared to the eldest group. CONCLUSIONS: Earlier age of tobacco initiation is found among younger generations of AN people. Findings highlight the need to focus prevention efforts on initiation of smoking in young adulthood and uptake of ST use among girls.

Clinical Medical Librarian Licensure: Pros versus Cons.

In hospitals and clinics, anyone who "touches" a patient has a license authorizing them to do so-from the phlebotomist to the cardiologist, from the genetic counselor to the social worker, and so on, except for the clinical medical librarian. This column discusses the intent versus the realities of occupational licensure for clinical medical librarians and provides recommendations for next steps.

Evidence-Based Alignment of Pathology Residency With Practice: Methodology and General Consideration of Results.

Few medical specialties engage in ongoing, organized data collection to assess how graduate medical education in their disciplines align with practice. Pathology educators, the American Board of Pathology, and major pathology organizations undertook an evidence-based, empirical assessment of what all pathologists need to learn in categorical residency. Two challenges were known when we commenced and we encountered 2 others during the project; all were ultimately satisfactorily addressed. Initial challenges were (1) ensuring broad representation of the new-in-practice pathologist experience and (2) adjusting for the effect on this experience of subspecialty fellowship(s) occurring between residency and practice. Additional challenges were (3) needing to assess and quantify degree and extent of subspecialization in different practice settings and (4) measuring changing practice responsibilities with increasing time in practice. We instituted annual surveys of pathologists who are relatively new (<10 years) in practice and a survey of physician employers of new pathologists. The purpose of these surveys was to inform (1) the American Board of Pathology certification process, which needs to assess the most critical knowledge, judgment, and skills required by newly practicing pathologists, and (2) pathology graduate medical education training requirements, which need to be both efficient and effective in graduating competent practitioners. This article presents a survey methodology to evaluate alignment of graduate medical education training with the skills needed for new-in-practice physicians, illustrates an easily interpreted graphical format for assessing survey data, and provides high-level results showing consistency of findings between similar populations of respondents, and between new-in-practice physicians and physician-employers.

Integration of genetic and metabolic features related to sialic acid metabolism distinguishes human breast cell subtypes.

In this report we use 'high-flux' tributanoyl-modified N-acetylmannosamine (ManNAc) analogs with natural N-acetyl as well as non-natural azido- and alkyne N-acyl groups (specifically, 1,3,4-O-Bu3ManNAc, 1,3,4-O-Bu3ManNAz, and 1,3,4-O-Bu3ManNAl respectively) to probe intracellular sialic acid metabolism in the near-normal MCF10A human breast cell line in comparison with earlier stage T-47D and more advanced stage MDA-MB-231 breast cancer lines. An integrated view of sialic acid metabolism was gained by measuring intracellular sialic acid production in tandem with transcriptional profiling of genes linked to sialic acid metabolism. The transcriptional profiling showed several differences between the three lines in the absence of ManNAc analog supplementation that helps explain the different sialoglycan profiles naturally associated with cancer. Only minor changes in mRNA transcript levels occurred upon exposure to the compounds confirming that metabolic flux alone can be a key determinant of sialoglycoconjugate display in breast cancer cells; this result complements the well-established role of genetic control (e.g., the transcription of STs) of sialylation abnormalities ubiquitously associated with cancer. A notable result was that the different cell lines produced significantly different levels of sialic acid upon exogenous ManNAc supplementation, indicating that feedback inhibition of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE)-generally regarded as the 'gatekeeper' enzyme for titering flux into sialic acid biosynthesis-is not the only regulatory mechanism that limits production of this sugar. A notable aspect of our metabolic glycoengineering approach is its ability to discriminate cell subtype based on intracellular metabolism by illuminating otherwise hidden cell type-specific features. We believe that this strategy combined with multi-dimensional analysis of sialic acid metabolism will ultimately provide novel insights into breast cancer subtypes and provide a foundation for new methods of diagnosis.