Recently Graduated Medical Students Lack Exposure to and Comfort with Chronic Liver Diseases.

BACKGROUND: The prevalence of chronic liver disease (CLD) is rising, but it remains unclear if medical school curricula are emphasizing CLD to reflect its growing epidemiology. AIMS: To assess comfort levels and knowledge of CLD among recently graduated medical students METHODS: An anonymous survey was distributed to incoming categorical Internal Medicine (IM) interns at a single academic institution during a 2-year period. The survey consisted of 38 Likert-like questions evaluating comfort levels and self-assessed knowledge for several general medicine and liver diseases, as well as 12 multiple-choice questions to objectively test knowledge. Wilcoxon ranked sum and Fisher's exact test were then used. RESULTS: There was a 100% (n = 65) completion rate. Only 14 (22%) of those surveyed reported exposure to a hepatology rotation in medical school. Highest mean comfort levels (1 = not at all comfortable, 5 = very comfortable) were for managing congestive heart failure (3.59) and chronic obstructive pulmonary disease (3.77). Mean comfort levels for various liver diseases were significantly lower (2.22-3.03, all p < 0.01). Mean self-rated knowledge (1 = no knowledge, 5 = strong knowledge) was also low (2.14-3.13). Although 98% agreed that hepatology is critical to IM training, only 42% agreed that their hepatology education during medical school was adequate. CONCLUSIONS: Recently graduated medical students are less comfortable managing liver diseases compared to other general medical conditions. Only a minority report satisfaction with hepatology education during medical school. These findings suggest that medical curricula need to be modified to better emphasize CLD.

Novel educational interventions in residency increase knowledge of chronic liver disease and career interest in hepatology.

There is an increasing burden of chronic liver disease (CLD) in the United States but a significant shortage of hepatologists. Thus, it is necessary to develop new recruitment strategies to the field of hepatology as well as ensure that non-gastroenterology-trained physicians are able to capably assist in the care of CLD. We established a novel, nonelective, inpatient hepatology rotation that uses required modules in the American Association for the Study of Liver Diseases Curriculum and Training-First Hepatitis B and C curriculums as well as in LiverLearning. A paper-based anonymous assessment was distributed to the inaugural 25 postgraduate years 2 and 3 internal medicine residents before and after the 2-week rotation over the course of 1 year. Both the prerotation and postrotation assessments included validated multiple-choice questions and Likert-type questions, which evaluated self-perceived knowledge and comfort with managing CLD. The mean comfort level (1 = not at all comfortable/strongly disagree, 5 = very comfortable/strongly agree) of managing several common liver diseases increased significantly after completion of the rotation (i.e., cirrhosis 2.8 versus 3.8, P < 0.001; hepatitis B 2.4 versus 3.4, P = 0.001; hepatitis C 2.6 versus 3.7, P = 0.002; nonalcoholic steatohepatitis 3.0 versus 4.0, P < 0.001; liver transplant care 2.1 versus 3.4, P < 0.001). There was also a significantly increased interest in hepatology as a career (2.6 versus 3.0, P = 0.03). Finally, the mean percentage of multiple-choice questions answered correctly on the pretest was 62% and posttest was 77% (P = 0.02). CONCLUSION: Our novel curriculum and nonelective hepatology rotation has effectively demonstrated improvement in internal medicine residents' comfort with and knowledge of CLD, and increased career interest in hepatology was also observed after completion of the curriculum, which suggests that more exposure to CLD could positively impact recruitment to the workforce; larger, multicenter studies are needed to validate these results. (Hepatology 2016;64:2210-2218).

Maternal asthma and microRNA regulation of soluble HLA-G in the airway.

BACKGROUND: We previously reported an interaction between maternal asthma and the child's HLA-G genotype on the child's subsequent risk for asthma. The implicated single nucleotide polymorphism at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect might be mediated by these miRs. OBJECTIVE: The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies. METHODS: We measured soluble HLA-G (sHLA-G) concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR-152 family (miR-148a, miR-148b, and miR-152) transcript levels in airway epithelial cells from the same subjects. RESULTS: miR-148b levels were significantly increased in airway epithelial cells from asthmatic subjects with an asthmatic mother compared with those seen in asthmatic subjects without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother but not among those with a nonasthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA). CONCLUSION: These combined results are consistent with +3142 allele-specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject's mother and the subject's genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of the mother's children persist into adulthood.

Nuclear import of serum response factor in airway smooth muscle.

We have previously shown that the transcription-promoting activity of serum response factor (SRF) is partially regulated by its extranuclear redistribution. In this study, we examined the cellular mechanisms that facilitate SRF nuclear entry in canine tracheal smooth muscle cells. We used in vitro pull-down assays to determine which karyopherin proteins bound SRF and found that SRF binds KPNA1 and KPNB1 through its nuclear localization sequence. Immunoprecipitation studies also demonstrated direct SRF-KPNA1 interaction in HEK293 cells. Import assays demonstrated that KPNA1 and KPNB1 together were sufficient to mediate rapid nuclear import of SRF-GFP. Our studies also suggest that SRF is able to gain nuclear entry through an auxiliary, nuclear localization sequence-independent mechanism.

Mandatory Hepatology Education for Internal Medicine Residents: Long-Term Effects and Implications for Workforce Needs.

We previously created a mandatory, inpatient, hepatology resident curriculum that immediately improved comfort, knowledge, and career interest in chronic liver disease (CLD). The durability of these effects needs to be known to use this intervention to address the hepatologist shortage. Thus, we aimed to assess this curriculum's long-term outcomes on internal medicine (IM) residents' CLD comfort, knowledge, and career interest. From 2015 to 2019 at a single institution, one IM resident was always assigned to the rotation. Similar anonymous assessments were administered to incoming postgraduate year (PGY)-1 residents and graduating PGY-3 residents, including a historic control cohort that graduated in June 2015. At residency completion, the intervention cohort (n = 61) had significantly higher comfort (1, not at all comfortable/strongly disagree; 5, very comfortable/strongly agree) with both hepatology (e.g., hepatitis C, 2.5 vs. 3.3, P < 0.001) and common IM topics (e.g., heart failure, 3.6 vs. 4.8, P < 0.001) but not specialty topics lacking curricula (e.g., inflammatory bowel disease, 2.8 vs. 2.7, P = 0.54). Compared to the historic cohort (n = 27), the intervention cohort was more comfortable in several CLD topics (e.g., cirrhosis, 3.2 vs. 3.8; P = 0.005) and answered more questions correctly (65% vs. 55%; P = 0.04), but career interest was unchanged (1.9 vs. 1.8; P = 0.45). Many residents (33%) would consider a hepatology career if training were separated from gastroenterology. Conclusion: With the completion of a mandatory hepatology curriculum, residents' CLD comfort and knowledge durably improved and exceeded that of historic counterparts. Initial career interest was not sustained, perhaps due to prerequisite gastroenterology training. These findings suggest IM educational initiatives may better address hepatology workforce needs by generating comanagers than by recruiting trainees.

Internal Medicine Residents' Retention of Knowledge and Skills in Bedside Ultrasound.

BACKGROUND: The long-term retention of knowledge and skills in bedside ultrasound by internal medicine residents after ultrasound training is not well understood. OBJECTIVE: We sought to determine whether knowledge and skills acquired from focused training in bedside ultrasound are retained over time, and whether retention is related to independent practice. METHODS: We conducted a prospective observational trial of 101 internal medicine residents at an academic medical center who participated in a bedside ultrasound workshop followed by 12 months of independent practice. Performance was measured on image-based knowledge and skills assessment using direct observation, both before the workshop and 12 months later. Individual usage data were obtained along with a survey on attitudes toward bedside ultrasound. RESULTS: Participants' mean knowledge assessment score increased from a baseline of 63.7% to 84.5% immediately after training (P < .001). At 12 months, mean knowledge score fell to 73.0%, significantly different from both prior assessments (P < .001). Despite knowledge decline, the mean skills assessment score improved from a baseline of 30.5% to 50.4% at 12 months (P < .001). Residents reporting more ultrasound use (> 25 examinations) had higher scores in baseline knowledge and skills assessments than those with lower usage (< 25 examinations). Change in knowledge and image acquisition skills between assessments was equal in both subgroups. CONCLUSIONS: Residents' knowledge of ultrasound improved after brief training but decayed over time, whereas skills showed marginal improvement over the study, with minimal support. Growth and retention of ultrasound abilities were not impacted by usage rates.

Piloting a Structured Practice Audit to Assess ACGME Milestones in Written Handoff Communication in Internal Medicine.

BACKGROUND: Written communication skills are integral to patient care handoffs. Residency programs require feasible assessment tools that provide timely formative and summative feedback, ideally linked to the Accreditation Council for Graduate Medical Education Milestones. OBJECTIVE: We describe the use of 1 such tool-UPDATED-to assess written handoff communication skills in internal medicine interns. METHODS: During 2012-2013, the authors piloted a structured practice audit at 1 academic institution to audit written sign-outs completed by 45 interns, using the UPDATED tool, which scores 7 aspects of sign-out communication linked to milestones. Intern sign-outs were audited by trained faculty members throughout the year. Results were incorporated into intern performance reviews and Clinical Competency Committees. RESULTS: A total of 136 sign-outs were audited (averaging 3.1 audits per intern). In the first trimester, 14 interns (31%) had satisfactory audit results. Five interns (11%) had critical deficiencies and received immediate feedback, and the remaining 26 (58%) were assigned future audits due to missing audits or unsatisfactory scores. In the second trimester, 21 interns (68%) had satisfactory results, 1 had critical deficiencies, and 9 (29%) required future audits. Nine of the 10 remaining interns in the final trimester had satisfactory audits. Faculty time was estimated at 10 to 15 minutes per sign-out audited. CONCLUSIONS: The UPDATED audit is a milestone-based tool that can be used to assess written sign-out communication skills in internal medicine residency programs. Future work is planned to adapt the tool for use by senior supervisory residents to appraise sign-outs in real time.

Early cardiac arrest in patients hospitalized with pneumonia: a report from the American Heart Association's Get With The Guidelines-Resuscitation Program.

BACKGROUND: Pneumonia is the leading infectious cause of death. Early deterioration and death commonly result from progressive sepsis, shock, respiratory failure, and cardiac complications. Recent data suggest that cardiac arrest may also be common, yet few previous studies have addressed this. Accordingly, we sought to characterize early cardiac arrest in patients who are hospitalized with coexisting pneumonia. METHODS: We performed a retrospective analysis of a multicenter cardiac arrest database, with data from > 500 North American hospitals. We included in-hospital cardiac arrest events that occurred in community-dwelling adults with pneumonia within the first 72 h after hospital admission. We compared patient and event characteristics for patients with and without pneumonia. For patients with pneumonia, we also compared events according to event location. RESULTS: We identified 4,453 episodes of early cardiac arrest in patients who were hospitalized with pneumonia. Among patients with preexisting pneumonia, only 36.5% were receiving mechanical ventilation and only 33.3% were receiving infusions of vasoactive drugs prior to cardiac arrest. Only 52.3% of patients on the ward were receiving ECG monitoring prior to cardiac arrest. Shockable rhythms were uncommon in all patients with pneumonia (ventricular tachycardia or fibrillation, 14.8%). Patients on the ward were significantly older than patients in the ICU. CONCLUSIONS: In patients with preexisting pneumonia, cardiac arrest may occur in the absence of preceding shock or respiratory failure. Physicians should be alert to the possibility of abrupt cardiopulmonary collapse, and future studies should address this possibility. The mechanism may involve myocardial ischemia, a maladaptive response to hypoxia, sepsis-related cardiomyopathy, or other phenomena.

Inhibition of transforming growth factor beta-enhanced serum response factor-dependent transcription by SMAD7.

Transforming growth factor (TGF)-beta is present in large amounts in the airways of patients with asthma and with other diseases of the lung. We show here that TGFbeta treatment increased transcriptional activation of SM22alpha, a smooth muscle-specific promoter, in airway smooth muscle cells, and we demonstrate that this effect stems in part from TGFbeta-induced enhancement of serum response factor (SRF) DNA binding and transcription promoting activity. Overexpression of Smad7 inhibited TGFbeta-induced stimulation of SRF-dependent promoter function, and chromatin immunoprecipitation as well as co-immunoprecipitation assays established that endogenous or recombinant SRF interacts with Smad7 within the nucleus. The SRF binding domain of Smad7 mapped to the C-terminal half of the Smad7 molecule. TGFbeta treatment weakened Smad7 association with SRF, and conversely the Smad7-SRF interaction was increased by inhibition of the TGFbeta pathway through overexpression of a dominant negative mutant of TGFbeta receptor I or of Smad3 phosphorylation-deficient mutant. Our findings thus reveal that SRF-Smad7 interactions in part mediate TGFbeta regulation of gene transcription in airway smooth muscle. This offers potential targets for interventions in treating lung inflammation and asthma.

Can we differentiate between airway and vascular smooth muscle?

1. Airway smooth muscle (ASM) has recently been termed the 'frustrated' cell of the lung given that contraction of ASM has no proven useful physiological function in adults and yet is indelibly associated with pathological conditions by virtue of its unwanted airflow-limiting actions in asthma. In contrast, pulmonary vascular smooth muscle contraction plays an essential role in the control of blood flow through the lung. 2. Little is known of the differences in phenotype between human ASM and pulmonary vascular smooth muscle (VSM) tissues, but differences in contractile protein and transcription factor expression and regulation of contractile protein promoter activity have been documented. Similarly, the embryological signals in mice required for differentiation of ASM versus pulmonary VSM are distinct. 3. Bronchoconstriction in asthma is currently treated with beta2-adrenoceptor agonists, which relax contracted ASM cells. An additional approach may be to use gene therapy to render ASM unable to contract (via disruption of their contractile apparatus organization). 4. Application of ASM-specific gene therapies would rely on minimal actions on other lung smooth muscle tissues, including pulmonary and bronchial vascular smooth muscle. The combination of mRNA analysis of laser-captured microdissected tissue with in situ immunohistochemical staining for protein should be very useful in terms of being able to characterize definitively the differences in mRNA and protein expression between the smooth muscle species of the lung. Any discovery of an ASM-selective target could provide a novel lead for ASM-directed anti-asthma therapy.