Severe Drug-Induced Liver Injury in the Military: A Retrospective Review.

OBJECTIVES: Drug-induced liver injury (DILI) is a significant cause of morbidity and mortality. Establishing a diagnosis is challenging due to the broad differential diagnosis of liver injury. We retrospectively reviewed patients with severe idiosyncratic DILI at Walter Reed National Military Medical Center in order to define the scope and patterns of injury in the military population. METHODS: Using the military health database, we identified a total of 110 patients who had an International Classification of Disease (ICD)-10 code for toxic liver injury in the electronic medical record at Walter Reed National Military Medical Center between 2016 and 2019. Each patient record was reviewed, and all pertinent data for included patients were recorded into a database for analysis. RESULTS: Twenty-seven out of 110 patients with a diagnostic code for toxic liver injury met inclusion criteria for severe idiosyncratic DILI. Nine cases were caused by supplements, including 5 active duty service members using synthetic anabolic steroids or preworkout supplements. The majority of patients were men and one-third were serving on active duty. The ranges of liver enzyme elevation and patterns of liver injury widely varied. CONCLUSION: Military service members are at particularly high risk for DILI given the frequent use of over-the-counter and other unregulated strength- and performance-enhancing supplements. These injuries not only have significant medical consequences but can profoundly impact military readiness and mission capability. Diagnosis of DILI among active duty service members requires a strong index of suspicion, and inquiry regarding all ingestions is crucial. Educating physicians, providers, and policy makers on the risks of supplement-induced liver injury among service members is crucial. These data will facilitate additional studies exploring susceptibility to severe idiosyncratic DILI among the military population.

Occult HBV Infection: A Case Series at a Military Treatment Facility.

Occult HBV infection (OBI) is defined as the presence of detectable hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg) negative individuals. Rarely, OBI is attributed to mutant HBV that cannot be detected by commercial assays, but most cases occur in the setting of chronic hepatitis B, particularly infection with wild-type viruses associated with strong HBV suppression. OBI is a high-risk diagnosis as it is associated with multiple complications: HBV reactivation in immunocompromised states, transmission of HBV, progression of liver disease, and hepatocellular carcinoma. The diagnosis is also easy to overlook, as the negative HBsAg in such cases can be falsely reassuring. This case series describes four male patients (mean age 51) who were diagnosed with OBI in the same military treatment facility between February 2018 and October 2018. Two of the four patients were active duty service members at the time of diagnosis. These patients had variable clinical presentations and outcomes. This case series illustrates the clinical significance of OBI and the importance of screening for OBI in HBsAg negative patients with signs of chronic or severe hepatic inflammation. It also prompts an intriguing question regarding the prevalence of both HBV and OBI in the United States military and whether or not routine screening for HBV should be implemented in this population. Further study is warranted to determine if adding HBV core antibody to a universally employed screening regimen would be beneficial.

Memantine-Induced Liver Injury With Probable Causality as Assessed Using the Roussel Uclaf Causality Assessment Method (RUCAM).

Presentations of drug-induced liver injury (DILI) are highly variable. Although biochemical evidence of cholestasis is common, the extent of aminotransferase elevations and patterns of liver injury vary. Patients may be asymptomatic, and many cases may never be diagnosed. We describe a case of memantine-induced hepatotoxicity in an elderly patient with Alzheimer's dementia, with probable causality for drug-induced liver injury, as assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score.

Clinical Reasoning in the Ward Setting: A Rapid Response Scenario for Residents and Attendings.

Introduction: There is a need for educational resources supporting the practice and assessment of the complex processes of clinical reasoning in the inpatient setting along a continuum of physician experience levels. Methods: Using participatory design, we created a scenario-based simulation integrating diagnostic ambiguity, contextual factors, and rising patient acuity to increase complexity. Resources include an open-ended written exercise and think-aloud reflection protocol to elicit diagnostic and management reasoning and reflection on that reasoning. Descriptive statistics were used to analyze the initial implementation evaluation results. Results: Twenty physicians from multiple training stages and specialties (interns, residents, attendings, family physicians, internists, surgeons) underwent the simulated scenario. Participants engaged in clinical reasoning processes consistent with the design, considering a total of 19 differential diagnoses. Ten participants provided the correct leading diagnosis, tension pneumothorax, with an additional eight providing pneumothorax and all participants offering relevant supporting evidence. There was also good evidence of management reasoning, with all participants either performing an intervention or calling for assistance and reflecting on management plans in the think-aloud. The scenario was a reasonable approximation of clinical practice, with a mean authenticity rating of 4.15 out of 5. Finally, the scenario presented adequate challenge, with interns and residents rating it as only slightly more challenging (means of 7.83 and 7.17, respectively) than attendings (mean of 6.63 out of 10). Discussion: Despite the challenges of scenario complexity, evaluation results indicate that this resource supports the observation and analysis of diagnostic and management reasoning of diverse specialties from interns through attendings.

Not Just Hocus POCUS: Implementation of a Point of Care Ultrasound Curriculum for Internal Medicine Trainees at a Large Residency Program.

INTRODUCTION: In 2018, the American College of Physicians formally acknowledged the importance of Point of Care Ultrasound (POCUS) to the practice of internal medicine (IM). For the military internist, POCUS training is critical for care of the trauma patient in austere environments, mass casualty events and natural disasters. While emergency medicine and critical care training programs have adopted POCUS education, few IM programs have integrated POCUS into their core curricula. We designed and implemented an iterative POCUS curriculum for trainees at a large military IM residency program over a two-year period. METHODS: In collaboration with our critical care and simulation departments, we developed a pilot curriculum consisting of five, 60-minute courses offered on a voluntary basis at monthly intervals throughout 2017. Based on the pilot's success we incorporated a POCUS curriculum into the core academics received by all IM trainees during the 2017-2018 academic year. Trainees attended seven, 3-hour sessions during their scheduled academic time taught by subspecialists with POCUS expertise in an on-site simulation center. Baseline surveys and knowledge assessment examinations were administered during orientation and repeated at the end of the academic year. Comparison of results before and after the POCUS curriculum was the primary outcome evaluated. RESULTS: Intervention #1: Pilot, 2016-2017 Academic Year45 trainees attended at least one course with an average of 1.8 sessions per trainee. Baseline survey data showed 91% of trainees believe POCUS is quite or extremely beneficial for their patients, but 73% feel slightly or not at all confident in POCUS knowledge. The pre-test mean and median scores were 71% and 77% respectively, which both increased to a post-test mean and median of 81%. Post-test mean percentage correct for trainees attending 1, 2, or 3 courses was 74%, 82%, and 91% respectively. Intervention #2: Incorporation of POCUS into Core Academics, 2017-2018 Academic YearAll 75 trainees participated in training with an average of 3.77 sessions attended per trainee. Survey analysis revealed significant improvement in confidence of performing ultrasound-guided procedures (p = 0.0139), and a 37% absolute increase in respondents who anticipate using ultrasound in their clinical practice (p = 0.0003). The mean pre-test score was 67.8% with median of 63.6% while mean and median post-test scores were 82.1% and 81.8%, with an absolute improvement of 14.3% and 18.2% respectively (p = 0.0004). CONCLUSION: A structured POCUS curriculum was successfully incorporated at a large multiservice military IM residency program, with demonstrated retention of knowledge, improved confidence in performance of ultrasound guided invasive procedures, and increased interest in the use of POCUS in future clinical practice. Similar programs should be implemented across all IM programs in military graduate medical education to enhance operational readiness and battlefield care.

POEMS syndrome: diagnostic delay and successful treatment with lenalidomide, cyclophosphamide and prednisone followed by autologous peripheral stem cell transplantation.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a rare systemic disease, often unrecognised in the primary care setting. POEMS syndrome is associated with plasma cell dyscrasias and upregulation of vascular endothelial growth factor leading to systemic oedema, papilloedema and pulmonary hypertension. A wide constellation of presenting symptoms often leads to late diagnosis. Unrecognised and untreated disease rapidly leads to death from neuropathic exhaustion or cardiopulmonary failure. Treatment is extrapolated from other plasma cell dyscrasias such as multiple myeloma. Autologous peripheral blood stem cell transplantation (PBSCT) is often an important component of treatment. There is no established standard of care for POEMS syndrome. Therapies include lenalidomide, bortezomib and targeted monoclonal antibodies. We present a patient with POEMS syndrome who achieved rapid complete response to triple therapy consisting of lenalidomide, cyclophosphamide and prednisone, followed by high-dose chemotherapy and PBSCT.

Successful perioperative management in a patient with factor XI deficiency.

Factor XI (FXI) deficiency is an autosomal disorder which manifests as bleeding of varying severity. While homozygotes typically experience more dramatic bleeding symptoms, heterozygotes may experience clinically significant bleeding following surgical procedures or trauma, and therefore the condition is not purely recessive. The clinical significance of FXI deficiency is complicated in that FXI levels do not correlate well with bleeding severity, and in fact the bleeding risk is variable even for an individual in response to different haemostatic challenges. We present the case of a 74-year-old man of Ashkenazi Jewish heritage with a family and personal history of bleeding during surgical procedures, who presented with excessive bleeding following total thyroidectomy. He was found to have a FXI level of 52% (low normal). Genetic testing revealed that he was heterozygous for the c.403G>T mutation. This case demonstrates successful work-up and perioperative management of a patient with FXI deficiency.

Factors influencing decisions about a career in hepatology: A survey of gastroenterology fellows.

Despite an unmet need for hepatologists in the United States, every year transplant hepatology (TH) fellowship positions remain unfilled. To address this, we investigated factors that influence trainee decisions about pursuing a career in hepatology. We invited current gastroenterology (GI) and TH fellows from all Accreditation Council for Graduate Medical Education-accredited programs for the academic year 2014-2015 to participate in an online survey about factors influencing decisions to train in hepatology. The same paper-based survey was distributed at a nationally recognized GI board review course. The survey was completed by 180 participants of which 91% were current GI or TH fellows and 24% were not aware of the pilot 3-year combined GI and TH training program. A majority of respondents (57%) reported that a shorter time (3 versus 4 years) to become board certification eligible would influence their decisions to pursue TH. The most common reasons for not pursuing hepatology were less endoscopy time (67%), additional length of training (64%), and lack of financial compensation (44%). Personal satisfaction (66%), management of complex multisystem disease (60%), and long-term relationships with patients (57%) were the most attractive factors. Sixty-one percent of participants reported having a mentor, and 94% of those with mentors reported that their mentors influenced their career decisions. Conclusion: We have identified several factors that affect fellows' decision to pursue TH. Shorter training, increased financial compensation, and increased endoscopy time are potentially modifiable factors that may increase the number of trainees seeking careers in hepatology and help alleviate the deficit of hepatologists. (Hepatology Communications 2017;1:347-353).