Upadacitinib as Rescue Therapy for the Treatment of Acute Severe Colitis in an Acute Care Setting.

BACKGROUND: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. AIMS: We hypothesized that upadacitinib may be effective in treating acute severe colitis. METHODS: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. RESULTS: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. CONCLUSION: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.

Personalized Treatment for Crohn's Disease: Current Approaches and Future Directions.

Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.

Herbal and dietary supplement induced liver injury: Highlights from the recent literature.

Herbal-induced liver injury (HILI) is an important and increasingly concerning cause of liver toxicity, and this study presents recent updates to the literature. An extensive literature review was conducted encompassing September 2019 through March 2021. Studies with clinically significant findings were analyzed and included in this review. We emphasized those studies that provided a causality assessment methodology, such as Roussel Uclaf Causality Assessment Method scores. Our review includes reports of individual herbals, including Garcinia cambogia, green tea extract, kratom as well as classes such as performance enhancing supplements, Traditional Chinese medicine, Ayurvedic medicine and herbal contamination. Newly described herbals include ashwagandha, boldo, skyfruit, and 'Thermo gun'. Several studies discussing data from national registries, including the United States Drug-Induced Liver Injury (DILI) Network, Spanish DILI Registry, and Latin American DILI Network were incorporated. There has also been a continued interest in hepatoprotection, with promising use of herbals to counter hepatotoxicity from anti-tubercular medications. We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration. The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.

Drug-Induced Liver Injury: Highlights and Controversies in the Recent Literature.

Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice. Several new drugs were approved by the US Food and Drug Administration including a number of drugs implicated in causing DILI, particularly among the chemotherapeutic classes. The COVID-19 pandemic was also a major focus of attention in 2020 and we discuss some of the notable aspects of COVID-19-related liver injury and its implications for diagnosing DILI. Updates in diagnostic and causality assessments related to DILI such as the Roussel Uclaf Causality Assessment Method are included, mindful that there is still no single biomarker or diagnostic tool to unequivocally diagnose DILI. Glutamate dehydrogenase received renewed attention as being more specific than alanine aminotransferase. There were a few new reports of previously unrecognized hepatotoxins, including immune modulators and novel gene therapy drugs that we highlight. Updates and new developments of previously described hepatotoxins, such as immune checkpoint inhibitors and anti-tuberculosis drugs are reviewed. Finally, novel technologies such as organoid culture systems to better predict DILI preclinically may be coming of age and determinants of hepatocyte loss, such as calculating PALT are poised to improve our current means of estimating DILI severity and the risk of acute liver failure.

Office-Based Weight Loss Counseling Is Ineffective in Liver Transplant Recipients.

BACKGROUND: Weight gain after liver transplantation (LT) is a predictor of major morbidity and mortality post-LT; however, there are no data regarding weight loss following LT. The current study evaluates the effectiveness of standard lifestyle intervention in LT recipients. METHODS: All adult LT recipients with body mass index (BMI) ≥ 25 kg/m2 who followed up in post-LT clinic from January 2013 to January 2016 were given standard lifestyle advice based on societal recommendations which was reinforced at 24 weeks. Patients were followed for a total of 48 weeks to assess the impact of such advice on weight. Primary outcome was achieving weight loss ≥ 5% of the body weight after 48 weeks of follow-up. RESULTS: A total of 151 patients with 86 (56.0%) overweight and 65 (44.0%) obese patients were enrolled in the study. The mean BMI at baseline increased from 30.2 ± 3.7 to 30.9 ± 4.3 kg/m2 at 48-week follow-up (p = 0.001). Over the course of study, 58 (38.4%) patients lost any weight and weight loss greater than 5% and 10% occurred in only 18 (11.9%) and 8 (5.3%) of the entire cohort, respectively. Higher level of education was associated with increased likelihood of weight loss (OR 9.8, 95% CI 2.6, 36.9, p = 0.001), while nonalcoholic steatohepatitis as etiology of liver disease (HR 3.7, 95% CI 1.4, 9.7, p = 0.007) was associated with weight gain. CONCLUSION: The practice of office-based lifestyle intervention is ineffective in achieving clinically significant weight loss in LT recipients, and additional strategies are required to mitigate post-LT weight gain.

The Impact of Coronary Artery Disease and Statins on Survival After Liver Transplantation.

Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n = 495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50 years were evaluated via coronary angiography. The impact of pre-LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new-onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3 ± 9.3 years at the time of LT, and median follow-up was 4.5 years. CAD was noted in 129 (26.1%) patients during the pre-LT evaluation. The presence or severity of pre-LT CAD did not impact post-LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new-onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new-onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5 years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12-0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre-LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre-LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.

Training and Assessing Critical Airway, Breathing, and Hemorrhage Control Procedures for Trauma Care: Live Tissue Versus Synthetic Models.

INTRODUCTION: Optimal teaching and assessment methods and models for emergency airway, breathing, and hemorrhage interventions are not currently known. The University of Minnesota Combat Casualty Training consortium (UMN CCTC) was formed to explore the strengths and weaknesses of synthetic training models (STMs) versus live tissue (LT) models. In this study, we compare the effectiveness of best in class STMs versus an anesthetized caprine (goat) model for training and assessing seven procedures: junctional hemorrhage control, tourniquet (TQ) placement, chest seal, needle thoracostomy (NCD), nasopharyngeal airway (NPA), tube thoracostomy, and cricothyrotomy (Cric). METHODS: Army combat medics were randomized to one of four groups: 1) LT trained-LT tested (LT-LT), 2) LT trained-STM tested (LT-STM), 3) STM trained-LT tested (STM-LT), and 4) STM trained-STM tested (STM-STM). Participants trained in small groups for 3 to 4 hours and were evaluated individually. LT-LT was the "control" to which other groups were compared, as this is the current military predeployment standard. The mean procedural scores (PSs) were compared using a pairwise t-test with a Dunnett's correction. Logistic regression was used to compare critical fails (CFs) and skipped tasks. RESULTS: There were 559 subjects included. Junctional hemorrhage control revealed no difference in CFs, but LT-tested subjects (LT-LT and STM-LT) skipped this task more than STM-tested subjects (LT-STM and STM-STM; p < 0.05), and STM-STM had higher PSs than LT-LT (p < 0.001). For TQ, both STM-tested groups (LT-STM and STM-STM) had more CFs than LT-LT (p < 0.001) and LT-STM had lower PSs than LT-LT (p < 0.05). No differences were seen for chest seal. For NCD, LT-STM had more CFs than LT-LT (p = 0.001) and lower PSs (p = 0.001). There was no difference in CFs for NPA, but all groups had worse PSs versus LT-LT (p < 0.05). For Cric, we were underpowered; STM-LT trended toward more CFs (p = 0.08), and STM-STM had higher PSs than LT-LT (p < 0.01). Tube thoracostomy revealed that STM-LT had higher CFs than LT-LT (p < 0.05), but LT-STM had lower PSs (p < 0.05). An interaction effect (making the subjects who trained and tested on different models more likely to CF) was only found for TQ, chest seal, and Cric; however, of these three procedures, only TQ demonstrated any significant difference in CF rates. CONCLUSION: Training on STM or LT did not demonstrate a difference in subsequent performance for five of seven procedures (junctional hemorrhage, TQ, chest seal, NPA, and NCD). Until STMs are developed with improved anthropomorphic and tissue fidelity, there may still be a role for LT for training tube thoracostomy and potentially Cric. For assessment, our STM appears more challenging for TQ and potentially for NCD than LT. For junctional hemorrhage, the increased "skips" with LT may be explained by the differences in anatomic fidelity. While these results begin to uncover the effects of training and assessing these procedures on various models, further study is needed to ascertain how well performance on an STM or LT model translates to the human model.

Validation of an Assessment Tool for Field Endotracheal Intubation.

OBJECTIVES: Endotracheal intubation (ETI) is an important skill for all emergency providers; our ability to train and assess our learners is integral to providing optimal patient care. The primary aim of this study was to assess the inter-rater reliability (IRR) and discriminant validity of a novel field ETI assessment tool using a checklist-derived performance score (PS) and critical failure (CF) rate. METHODS: Forty-three participants (18 paramedic students, 11 paramedics, and 14 emergency physicians [EPs]) performed ETI during a simulated trauma scenario on a pseudo-ventilated cadaver. Each participant was assessed by two experienced raters. IRR was calculated using the intraclass correlation coefficient. Regarding discriminant validity, a Kruskal-Wallis test was used to analyze PSs and a χ2 test was used for CFs. Mean global rating scale (GRS) scores were compared using an analysis of variance. RESULTS: The ETI assessment tool had excellent IRR, with an intraclass correlation coefficient of 0.94. There was a significant difference in PSs, CFs, and GRSs (p < 0.05) between cohorts. CONCLUSION: The novel field ETI assessment tool has excellent reliability among trained raters and discriminates between experienced ETI providers (EPs) and less experienced ETI performers using PSs, CFs, and GRSs on a fresh cadaveric model.

Literature Evidence on Live Animal Versus Synthetic Models for Training and Assessing Trauma Resuscitation Procedures.

There are many models currently used for teaching and assessing performance of trauma-related airway, breathing, and hemorrhage procedures. Although many programs use live animal (live tissue [LT]) models, there is a congressional effort to transition to the use of nonanimal- based methods (i.e., simulators, cadavers) for military trainees. We examined the existing literature and compared the efficacy, acceptability, and validity of available models with a focus on comparing LT models with synthetic systems. Literature and Internet searches were conducted to examine current models for seven core trauma procedures. We identified 185 simulator systems. Evidence on acceptability and validity of models was sparse. We found only one underpowered study comparing the performance of learners after training on LT versus simulator models for tube thoracostomy and cricothyrotomy. There is insufficient data-driven evidence to distinguish superior validity of LT or any other model for training or assessment of critical trauma procedures.

Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure.

Patients with heart failure (HF) have evidence of chronic systemic inflammation. Whether inflammation contributes to the exercise intolerance in patients with HF is, however, not well established. We hypothesized that the levels of C-reactive protein (CRP), an established inflammatory biomarker, predict impaired cardiopulmonary exercise performance, in patients with chronic systolic HF. We measured CRP using high-sensitivity particle-enhanced immunonephelometry in 16 patients with ischemic heart disease (previous myocardial infarction) and chronic systolic HF, defined as a left ventricular ejection fraction ≤ 50% and New York Heart Association class II-III symptoms. All subjects with CRP >2 mg/L, reflecting systemic inflammation, underwent cardiopulmonary exercise testing using a symptom-limited ramp protocol. CRP levels predicted shorter exercise times (R = -0.65, p = 0.006), lower oxygen consumption (VO2) at the anaerobic threshold (R = -0.66, p = 0.005), and lower peak VO2 (R = -0.70, p = 0.002), reflecting worse cardiovascular performance. CRP levels also significantly correlated with an elevated ventilation/carbon dioxide production slope (R = +0.64, p = 0.008), a reduced oxygen uptake efficiency slope (R = -0.55, p = 0.026), and reduced end-tidal CO2 level at rest and with exercise (R = -0.759, p = 0.001 and R = -0.739, p = 0.001, respectively), reflecting impaired gas exchange. In conclusion, the intensity of systemic inflammation, measured as CRP plasma levels, is associated with cardiopulmonary exercise performance, in patients with ischemic heart disease and chronic systolic HF. These data provide the rationale for targeted anti-inflammatory treatments in HF.

Bite force and feeding kinematics in the eastern North Pacific Kyphosidae.

Some fishes that feed on attached food items possess an intramandibular joint (IMJ), which is thought to increase maximum gape and facilitate contact between the tooth-bearing surface and the substrate. However, the mechanical consequences of using an IMJ to remove attached food items from the substrate are still poorly understood. We examined the most prominent eastern North Pacific kyphosid, the scraper: Girella nigricans and two other kyphosids, Medialuna californiensis and Hermosilla azurea, which occupy similar habitats. Of the three species, G. nigricans had the highest theoretical bite force per unit length. We examined the feeding mechanics of G. nigricans in two different feeding scenarios: a scraping behavior elicited on a block of brine shrimp gelatin and a picking behavior elicited on Ulva sp. We measured cranial elevation, lower jaw rotation, premaxillary protrusion, premaxillary rotation, gape maximum, and intramandibular rotation. Ulva treatments produced significantly greater cranial rotation, when compared to gelatin treatments. Gelatin treatments were associated with greater lower jaw rotation and larger gape. Premaxillary rotation and premaxillary protrusion did not differ between treatments. Intramandibular rotation occurred only when G. nigricans physically contacted the gelatin, suggesting the IMJ is a passive joint with no associated musculature. We also noted that G. nigricans do not appear to use suction to draw food into the mouth. The lack of suction and the presence of the IMJ suggest that the jaws of G. nigricans are specialized for maximizing jaw force when scraping.

Reliability and validity of a test designed to assess combat medics' readiness to perform life-saving procedures.

OBJECTIVES: Reducing preventable deaths because of uncontrolled hemorrhage, tension pneumothorax, and airway loss is a priority. As part of a research initiative comparing different training models, this study evaluated the reliability and validity of a test that assesses combat medic performance during a polytrauma scenario using live animal models. METHODS: Nine procedural checklists and seven global rating scales were piloted with four cohorts of soldiers (n = 94) at two U.S. training sites. Cohorts represented "novice" to "proficient" trainees. Procedure scores and a mean global score were calculated per subject. The intraclass correlation was calculated per procedure, with 0.70 as the threshold for acceptability. An overall difference among cohorts was hypothesized: Cohort 4 (proficient) > Cohort 3 (competent) > Cohort 2 (beginners) > Cohort 1 (novice) trainees. Data were analyzed using Kruskal-Wallis and analysis of variance. RESULTS: At Site A, intraclass correlation coefficients ranged from 74% to 93% for 6 of 9 procedures. Cohorts differed significantly on hemorrhage control, needle decompression, cricothyrotomy, amputation management, chest tube insertion, and mean global scores. Cohort 4 outperformed the others, and Cohorts 2 and 3 outperformed Cohort 1. CONCLUSION: The test differentiates novices from beginners, competent, and proficient trainees on difficult procedures and overall performance.

Prehospital chemical restraint of a noncommunicative autistic minor by law enforcement.

When responders are dealing with an agitated patient in the field, safety for all involved may sometimes only be accomplished with physical or chemical restraints. While experiences using chemical restraint in the prehospital setting are found in the medical literature, the use of this by law enforcement as a first-response restraint has not previously been described. We report a case of successful law enforcement-administered sedation of a noncommunicative, autistic, and violent minor using intramuscular droperidol and diphenhydramine. Although this case has some unique characteristics that allowed chemical restraint to be given by the law enforcement agency, it calls attention to some specific prehospital issues that need to be addressed when dealing with autistic patients with extreme agitation.

Introduction of the conducted electrical weapon into a hospital setting.

BACKGROUND: The TASER(®) X26 Conducted Electrical Weapon (CEW) provides painful stimuli and neuromuscular incapacitation to potentially violent persons. Use by law enforcement in society is common. Presenting a CEW is known to de-escalate some situations. Health care personnel sometimes encounter violent persons within the confines of the hospital. CEW use by health care security personnel has not been described. OBJECTIVE: The objective is to describe results from the introduction of the CEW into a hospital environment. METHODS: Upon introducing the CEW into an urban hospital campus, standardized reports were made describing all CEW use by hospital security. Reports were retrospectively reviewed for the first 12 months of CEW use. Collected data included force options used, potential injuries avoided, witness comments, outcomes, and whether the CEW required full activation or if inactive presentation was sufficient to control the situation. Rates of security personnel injuries were also gathered. Descriptive analysis was applied. RESULTS: Twenty-seven CEW deployments occurred: four were inactive presentation, 20 were presentation with LASER sight activation, and three were probe deployments with a 5-s delivery of electrical current. Two persons required evaluation for minor injuries not related to CEW use. Witnesses reported that in all incidents, injuries were likely avoided due to CEW presentation or use. CEW use aborted one suicide attempt. Personnel injury rates decreased during the study period. CONCLUSION: CEW introduction into a health care setting demonstrated the ability to avert and control situations that could result in further injury to subjects, patients, and personnel. This correlates with a decrease in injury for hospital personnel. Further study is recommended for validation.

An impedance threshold device increases blood pressure in hypotensive patients.

BACKGROUND: The impedance threshold device (ITD-7) augments the vacuum created in the thorax with each inspiration, thereby enhancing blood flow from the extrathoracic venous systems into the heart. OBJECTIVES: To the best of our knowledge, the ITD-7 has not previously been investigated in hypotensive patients in the emergency department (ED) or the prehospital setting. The objective of this study was to determine whether the ITD-7 would increase systolic arterial pressures in hypotensive spontaneously breathing patients. METHODS: The ED study was a prospective, randomized, double-blind, sham control design. Patients with a systolic blood pressure ≤ 95 mm Hg were randomized to breathe for 10 min through an active or sham ITD. The primary endpoint was the change in systolic blood pressure measured non-invasively. The prehospital study was a prospective, non-blinded evaluation of the ITD-7 in hypotensive patients. RESULTS: In the ED study, the mean ± standard deviation rise in systolic blood pressure was 12.9 ± 8.5 mm Hg for patients (n = 16) treated with an active ITD-7 vs. 5.9 ± 5.9 mm Hg for patients (n = 18) treated with a sham ITD-7 (p < 0.01). In the prehospital study, the mean systolic blood pressure before the ITD-7 was 79.4 ± 10.2 mm Hg and 107.3 ± 17.6 mm Hg during ITD-7 use (n = 47 patients) (p < 0.01). CONCLUSION: During this clinical evaluation of the ITD-7 for the treatment of hypotensive patients in the ED and in the prehospital setting, use of the device significantly increased systolic blood pressure and was safe and generally well tolerated.

Hospital response to a major freeway bridge collapse.

BACKGROUND: We describe the hospital system response to the Interstate 35W bridge collapse in Minneapolis into the Mississippi River on August 1, 2007, which resulted in 13 deaths and 127 injuries. Comparative analysis of response activities at the 3 hospitals that received critical or serious casualties is provided. METHODS: First-hand experiences of hospital physicians, issues identified in after-action reports, injury severity scores, and other relevant patient data were collected from the 3 hospitals that received seriously injured patients, including the closest hospitals to the collapse on each side of the river. RESULTS/DISCUSSION: Injuries were consistent with major acceleration/deceleration force injuries. The most critical patients arrived first at each hospital, suggesting appropriate prehospital triage. Capacity of the health care system was not overwhelmed and the involved hospitals generally reported an overresponse by staff. Communication and patient tracking problems occurred at all of the hospitals. Situational awareness was limited due to the scope of structural collapse and incomplete information from the scene. CONCLUSIONS: Hospitals were generally satisfied with their surge capacity and incident management plan activation. Issues such as communications, patient tracking, and staff overreporting that have been identified in past incidents also were problematic in this event. Hospitals will need to address deficiencies and build on successful actions to cope with future, potentially larger incidents.

Emergency medical services response to a major freeway bridge collapse.

BACKGROUND: The Interstate 35W Bridge in Minneapolis collapsed into the Mississippi River on August 1, 2007, killing 13 people and injuring 127. METHODS: This article describes the emergency medical services response to this incident. RESULTS/DISCUSSION: Complexities of the event included difficult patient access, multiple sectors of operation, and multiple mutual-aid agencies. Patient evacuation and transportation was rapid, with the collapse zone cleared of victims 95 minutes after the initial 9-1-1 call. A common regional emergency medical service incident management plan that was exercised was critical to the success of the response. CONCLUSIONS: Communication and patient tracking difficulties could be improved in future responses.