Liver Transplantation in a Woman with Mahvash Disease.

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.

Prolonged Transcriptional Consequences in Survivors of Sepsis.

Survivors of sepsis often suffer from prolonged post-critical illness syndrome secondary to the immune system's reprogramming. It is unclear if this process is static and pervasive due to methodological difficulties studying long-term outcomes of sepsis. The purpose of this study is to evaluate transcriptional profiles longitudinally in Drosophila melanogaster in the aftermath of sepsis to provide preliminary data for targets playing a role in post-sepsis immunostasis. Adult Drosophila melanogaster were infected with E. coli, and survivors were euthanized at 7, 14, and 21 days. Control flies were subjected to sham stress. Gene profiling was done with RNA-seq, and potential miRNA factors were computed. Profiling identified 55 unique genes at seven days, 61 unique genes at 14 days, and 78 genes at 21 days in sepsis survivors vs. sham control. Each post-sepsis timepoint had a distinctive transcriptional pattern with a signature related to oxidative stress at seven days, neuronal signal transduction at 14 days, and metabolism at 21 days. Several potential miRNA patterns were computed as potentially affecting several of the genes expressed in sepsis survivors. Our study demonstrated that post-sepsis changes in the transcriptome profile are dynamic and extend well into the Drosophila melanogaster natural life span.

Access to internet, smartphone usage, and acceptability of mobile health technology among cancer patients.

PURPOSE: The use of mobile health (mHealth) technologies to augment patient care enables providers to communicate remotely with patients enhancing the quality of care and patient engagement. Few studies evaluated predictive factors of its acceptance and subsequent implementation, especially in medically underserved populations. METHODS: A cross-sectional study of 151 cancer patients was conducted at an academic medical center in the USA. A trained interviewer performed structured interviews regarding the barriers and facilitators of patients' current and desired use of mHealth technology for healthcare services. RESULTS: Of the 151 participants, 35.8% were male and ages ranged from 21 to 104 years. 73.5% of participants currently have daily access to internet, and 68.2% currently own a smartphone capable of displaying mobile applications. Among all participants, acceptability of a daily mHealth application was significantly higher in patients with a college-level degree (OR 2.78, CI95% 1.25-5.88) and lower in patients > 80 years of age (OR 0.05, CI95% 0.01-0.23). Differences in acceptability when adjusted for current smartphone use and daily access to internet were nonsignificant. Among smartphone users, the desire to increase cancer knowledge was associated with a higher likelihood of utilizing a mHealth application (OR 261.53, CI95% 10.13-6748.71). CONCLUSION: The study suggests that factors such as age, educational achievement, and access to internet are significant predictors of acceptability of a mHealth application among cancer patients. Healthcare organizations should consider these factors when launching patient engagement platforms.

Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF.

BACKGROUND: It has been shown that severe insult to the immune system may trigger prolonged macrophage characteristics associated with excessive release of monocyte colony stimulating factor (M-CSF). However, it is unclear how persistent is the macrophage-like characteristics in circulating monocytes (MO). In this study, 20 patients who underwent non-emergent cardiopulmonary bypass had their monocytes characterized before surgery and 3 months after surgery. METHODS: We assessed the macrophage characteristics of MO using cytokine production, surface marker expression, an ability to stimulate T cells, and methylation of the promoter region of the gene encoding PU.1, a critical component to M-CSF production. MO function as well as activation and differentiation potential were longitudinally assessed. RESULTS: At 3 months after cardiopulmonary bypass, monocytes exhibited increased expression of MRP8, transforming growth factor-ß/latency-associated peptide, suppressor of cytokine signaling 3 while phagocytic properties were increased. Concomitantly, we observed a decreased expression of CD86, a decreased ability to form regulatory dendritic cells, and a diminished ability to stimulate T cells. These characteristics were accompanied by a persistent increase in the secretion of M-CSF, over-activation of PU.1, and decreased methylation of the PU.1 promoter region. Serum levels of C-reactive protein and anti-cytomegalovirus IgG antibody titers were also elevated in some patients at 3 months after surgery. CONCLUSIONS: We concluded that at 3 months after cardiopulmonary bypass, monocytes continued to express a new macrophage-like milieu that was associated with the persistent activation of the PU.1/M-CSF pathway.

Content analysis of locum tenens recruitment emails for anesthesiologists.

BACKGROUND: Locum tenens continues to be an increasingly utilized employment option among healthcare organizations to cope with short-term provider vacancies. There exist no studies that explore the job characteristics of such assignments. The purpose of this study was to characterize the clinical responsibilities and compensation of anesthesiology locum tenens positions through content analysis of recruitment emails. Through this data, anesthesiologists interested in locum tenens will be better equipped to evaluate the merit of potential opportunities. METHODS: The study was conducted using a compiled database of unsolicited emails received by one of the authors. A total of 241 emails containing 794 assignments were included during the period of 1/09/17 to 1/26/18 (383 days in total). The information was extracted using a standardized template and was entered into a database. Additional validation of the content was done using a data mining tool. RESULTS: Most of the job opportunities originated from five staffing agencies. A total of 37, 25, and 17% of the assignments were allocated to hospitals, ambulatory surgical centers, and trauma centers respectively. The mean caseload for the assignments was between 8.5 and 11.1 cases per day. The mean daily work shift was 9.1 hours, and the average duration of the assignment was one week. The most frequently requested cases included general (74%), orthopedics (54%), and OB/GYN (51%). However, information regarding training qualifications and licensing was not routinely provided. Only 13.1% of assignments specified a system of medical documentation with paper charting being the most common. The mean hourly rate for locum anesthesiologists in our sample was $186.19, significantly higher than the national average of $127.88. Around 28% of staffing agencies covered the licensing expenses of specialists while 23% covered the expense of travels and 20% covered accommodation costs. CONCLUSIONS: Descriptions for locum tenens positions follow common anesthesiology practices and feature superior compensation to national estimates. However, vital information is often omitted from recruitment emails, and practice settings are highly variable. Anesthesiologists are urged to fully investigate opportunities before accepting based on recruitment emails. Managers should require more details to be provided in job offers.

Outcomes After Transcatheter Aortic Valve Implantation in Patients Excluded From Clinical Trials.

Background: The use of transcatheter aortic valve implantation (TAVI) in patients with aortic valve disease excluded from clinical trials has increased with no large-scale data on its safety. Objectives: The purpose of this study was to assess the trend of utilization and adjusted outcomes of TAVI in clinical trials excluded (CTE) vs clinical trials included TAVI (CTI-TAVI) patients. Methods: We used the National Readmission Database (2015-2019) to identify 15 CTE-TAVI conditions. A propensity score-matched analysis was used to calculate the adjusted odds ratio (aOR) of net adverse clinical events (composite of mortality, stroke, and major bleeding) in patients undergoing CTE-TAVI vs CTI-TAVI. Results: Among the 223,238 patients undergoing TAVI, CTE-TAVI was used in 41,408 patients (18.5%). The yearly trend showed a steep increase in CTE-TAVI utilization (P = 0.026). At index admission, the adjusted odds of net adverse clinical events (aOR: 1.83, 95% CI: 1.73-1.95) and its components, including mortality (aOR: 2.94, 95% CI: 2.66-3.24), stroke (aOR: 1.20, 95% CI: 1.07-1.34), and major bleeding (aOR: 1.49, 95% CI: 1.36-1.63) were significantly higher in CTE-TAVI compared with CTI-TAVI. Among the individual contraindications to clinical trial enrollment in the CTE-TAVI, patients with bicuspid aortic valve, leukopenia, and peptic ulcer disease appeared to have similar outcomes compared with CTI-TAVI, while patients with end-stage renal disease, bioprosthetic aortic valves, and coagulopathy had a higher readmission rate at 30 and 180 days. Conclusions: CTE-TAVI utilization has increased significantly over the 4-year study period. Patients undergoing CTE-TAVI have a higher likelihood of mortality, stroke, and bleeding than those undergoing CTI-TAVI.

Nocardiosis of the Central Nervous System: A rare complication of COVID management?

This case report examines a previously immunocompetent male that was treated with a prolonged course of corticosteroids for COVID pneumonia. He then returned with worsening headaches followed by flaccid paralysis of extremities due to cerebral and spinal cord abscesses secondary to Nocardia farcinica. A review of the literature on the mechanism of immunosuppression with COVID infection and corticosteroids is provided.

What Can COVID-19 Teach Us about Using AI in Pandemics?

The COVID-19 pandemic put significant strain on societies and their resources, with the healthcare system and workers being particularly affected. Artificial Intelligence (AI) offers the unique possibility of improving the response to a pandemic as it emerges and evolves. Here, we utilize the WHO framework of a pandemic evolution to analyze the various AI applications. Specifically, we analyzed AI from the perspective of all five domains of the WHO pandemic response. To effectively review the current scattered literature, we organized a sample of relevant literature from various professional and popular resources. The article concludes with a consideration of AI's weaknesses as key factors affecting AI in future pandemic preparedness and response.

The Impact of an International Elective on Anesthesiology Residents as Assessed by a Longitudinal Study.

INTRODUCTION: Participation of anesthesiology residents in international electives may lead to the acquisition of skills as described in the Accreditation Council for Graduate Medical Education (ACGME) competencies. There is great interest in participating in such electives, but it is not clear there are educational or professional benefits. The purpose of this study was to evaluate the educational benefits of participating in overseas electives among anesthesiology residents. METHODS: A longitudinal study design was used between 2010 and 2015 to survey all anesthesiology residents selected to participate in the nationally competitive Society for Education in Anesthesia-Health Volunteers Overseas (SEA-HVO) Traveling Fellowship Program in which third-year residents receive scholarships and ABA credit for 1-month teaching electives in a low-resource country. Pre-elective and post-elective surveys were sent via de-identified e-mails during the third year of residency. We investigated residents' expectations, plans, and comfort level with teaching techniques prior to the elective and after and asked about perceived benefits. RESULTS: The response rate was 68.8% of the 45 residents who received the survey. Participants were motivated by professional and humanitarian goals. Residents reported improved comfort with teaching techniques, especially lecturing and giving feedback. Participants acquired better skills in assessing the learning needs of students. There was a slight but nonsignificant increased comfort dealing with cultural and language barriers. The major self-perceived unique benefit of international electives was improvement in intercultural communication. The systems' changes reported by residents as the most important to improve were those that affected patient safety. CONCLUSION: Global health electives have a small positive effect on teaching, cultural proficiency, and systems assessment skills. Residents improve in their ability to identify educational needs and to give feedback. Patient safety during anesthetic care is appreciated as the most important systems' need.

Self-Assessment of Preparedness among Critical Care Trainees Transitioning from Fellowship to Practice.

This study evaluated the subjective assessment of preparedness needs of critical care trainees and recent graduates between 2013 and 2014. A questionnaire was developed and validated by the subcommittee of the In-Training Section of Society of Critical Care Medicine (SCCM). The survey was deployed twice between December 2013 and January 2014 via email to any trainee or individual graduated from a critical care fellowship within the previous three years. Six percent (180) of all individuals completed the survey, and 67% of respondents had recently interviewed for a job. Northeast was the preferred location for a job (47%), and academia was favored over private practice (80% vs. 15%). Of the respondents that secured an interview, 55% felt prepared for the interview, 67% felt prepared to build an adequate job portfolio, 33% received formal guidance from their mentor/training program. 89% of total respondents agreed it is important to participate in a formal training course in job search, portfolio development, and interviewing process. The preferred sources of training were equally distributed between their home institution, webinars, and SCCM. There is an ongoing need in education regarding the transition period from fellowship to practice.

Global Brain Drain: How Can the Maslow Theory of Motivation Improve Our Understanding of Physician Migration?

The migration of physicians from low-resource to high-resource settings is a prevalent global phenomenon that is insufficiently understood. Most low-income countries are severely understaffed with physicians, and the emigration of the already limited number of physicians to other countries can significantly reduce access to healthcare in the source country. Despite a growing interest in global capacity building in these countries by academic and non-governmental organizations in high-income countries, efforts to stem physician migration have been mostly unsuccessful. The authors reviewed the current literature for the motivational factors leading to physician migration in the context of Maslow's hierarchy of human needs. Our study found that financial safety needs were major drivers of physician emigration. However, factors related to self-actualization such as the desire for professional development through training opportunities and research, were also major contributors. These findings highlight the multifactorial nature of physician motivations to emigrate from low-resource countries. Maslow's Theory of Motivation may provide a useful framework for future studies evaluating the concerns of physicians in low-income countries and as a guide to incentivize retention.

Implications of Chronic Opioid Therapy on Perioperative Complications and Long-Term Surgical Recovery.

With chronic opioid use becoming an increasingly common occurrenceamong the general population, perioperative specialties must adapt to the physiologic changes caused by long-term opioids. However, data on the clinicalanesthetics implications of long-term opioid use is scarce. This review intends to survey the literature addressing the molecular mechanisms of long-term opioid use as well as their interaction with various organ systems.

Observational study of long-term persistent elevation of neurodegeneration markers after cardiac surgery.

Surgery and anesthesia induce inflammatory changes in the central nervous system, which ultimately lead to neuronal damage concomitant with an increase in the level of neurodegeneration markers. Despite some experimental data showing prolonged activation of the immune system post-surgery, no study has determined the extent of long-term elevation of neurodegeneration markers. The purpose of this study was to investigate the serum levels of tau protein, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), neurofilament light (NF-L), and glial fibrillary acidic protein (GFAP) after elective cardiac surgery with the implementation of cardiopulmonary bypass (CPB). The serum levels of these markers from 30 patients were compared longitudinally to the baseline (pre-surgery or t0), at 24 hours (t+24), at 7 days (t+7d), and at 3 months (t+3m). The secondary outcome was the production of macrophage-colony stimulating factor (M-CSF) and tumor necrosis factor-α (TNF-α) in vitro by isolated monocytes in response to lipopolysaccharide (LPS) as the measure of immune system activation. The tertiary outcome was the serum level of C-reactive protein (CRP), serum amyloid P (SAP), and α-2-macroglobulin (A2M). Serum levels of tau protein increased 24 hours after surgery (p = 0.0015) and remained elevated at 7 days (p = 0.0017) and three months (p = 0.036). Serum levels of UCH-L1 peaked at 24 hours (p = 0.00055) and normalized at 3 months. In vitro secretion of M-CSF by LPS-stimulated peripheral monocytes, but not TNFα, correlated highly (r = 0.58; p = 0.04) with persistent elevation of serum tau levels at 3 months. The serum CRP and SAP increases correlated with tau post-CPB levels significantly at 3 months. We demonstrated that elevation of serum tau levels at 24 hours, 7 days, and 3 months after heart surgery is concomitant with some traits of inflammation after CPB. The elevation of tau several weeks into recovery is significantly longer than expected.

Behavioural patterns of electrolyte repletion in intensive care units: lessons from a large electronic dataset.

Repletion of electrolytes often depends on provider-specific behavior and hospital policy. We examined the pattern of electrolyte repletion across several intensive care units (ICU) in a large healthcare system from 2010-2015. This included 109 723 potassium repletions, 51 833 magnesium repletions, 2 306 calcium repletions, 8 770 phosphate repletions, and 3 128 249 visit-days over 332 018 visits. Potassium, magnesium, and calcium were usually repleted within the institutional reference range. In contrast, the bulk of phosphate repletion was done with pre-repletion serum level below the reference range. The impact of repletion on post-repletion levels was significant but uniformly small. The pre-repletion serum level had a significant inverse correlation with the post-repletion level of each electrolyte. Potassium, magnesium and phosphate follow-up labs were scheduled in 9-10 hours after their repletion. In contrast, calcium was rechecked in less than 20 minutes. Routine repletion of potassium, magnesium and calcium had no effect on the incidence of tachyarrhythmias. We estimated the expense from electrolyte repletion within the reference range was approximately $1.25 million. Absent a specific clinical indication, repleting electrolytes when the serum concentration are within normative values may represent an avenue for cost savings, staff burden unload and potential reduction in frequency of complications in the ICUs.

Potential Pitfalls of the Humanized Mice in Modeling Sepsis.

Humanized mice are a state-of-the-art tool used to study several diseases, helping to close the gap between mice and human immunology. This review focuses on the potential obstacles in the analysis of immune system performance between humans and humanized mice in the context of severe acute inflammation as seen in sepsis or other critical care illnesses. The extent to which the reconstituted human immune system in mice adequately compares to the performance of the human immune system in human hosts is still an evolving question. Although certain viral and protozoan infections can be replicated in humanized mice, whether a highly complex and dynamic systemic inflammation like sepsis can be accurately represented by current humanized mouse models in a clinically translatable manner is unclear. Humanized mice are xenotransplant animals in the most general terms. Several organs (e.g., bone marrow mesenchymal cells, endothelium) cannot interact with the grafted human leukocytes effectively due to species specificity. Also the interaction between mice gut flora and the human immune system may be paradoxical. Often, grafting is performed utilizing an identical batch of stem cells in highly inbred animals which fails to account for human heterogeneity. Limiting factors include the substantial cost and restricting supply of animals. Finally, humanized mice offer an opportunity to gain knowledge of human-like conditions, requiring careful data interpretation just as in nonhumanized animals.

Factors Underlying Racial Disparities in Sepsis Management.

Sepsis, a syndrome characterized by systemic inflammation during infection, continues to be one of the most common causes of patient mortality in hospitals across the United States. While standardized treatment protocols have been implemented, a wide variability in clinical outcomes persists across racial groups. Specifically, black and Hispanic populations are frequently associated with higher rates of morbidity and mortality in sepsis compared to the white population. While this is often attributed to systemic bias against minority groups, a growing body of literature has found patient, community, and hospital-based factors to be driving racial differences. In this article, we provide a focused review on some of the factors driving racial disparities in sepsis. We also suggest potential interventions aimed at reducing health disparities in the prevention, early identification, and clinical management of sepsis.