Insights Into a “Negative” ICU Trial Derived From Gene Expression Profiling

Objectives: Randomized controlled trials in the ICU often fail to show differences in endpoints between groups. We sought to explore reasons for this at a molecular level by analyzing transcriptomic data from a recent negative trial. Our objectives were to determine if randomization successfully balanced transcriptomic features between groups, to assess transcriptomic heterogeneity among the study subjects included, and to determine if the study drug had any effect at the gene expression level. Design: Bioinformatics analysis of transcriptomic and clinical data collected in the course of a randomized controlled trial. Setting: Tertiary academic mixed medical-surgical ICU. Patients: Adult, critically ill patients expected to require invasive mechanical ventilation more than 48 hours. Interventions: Lactoferrin or placebo delivered enterally and via an oral swab for up to 28 days. Measurements and Main Results: We found no major imbalances in transcriptomic features between groups. Unsupervised analysis did not reveal distinct clusters among patients at the time of enrollment. There were marked differences in gene expression between early and later time points. Patients in the lactoferrin group showed changes in the expression of genes associated with immune pathways known to be associated with lactoferrin. Conclusions: In this clinical trial, transcriptomic data provided a useful complement to clinical data, suggesting that the reasons for the negative result were less likely related to the biological efficacy of the study drug, and may instead have been related to poor sensitivity of the clinical outcomes. In larger studies, transcriptomics may also prove useful in predicting response to treatment. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (https://ift.tt/29S62lw). Funding for the Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL) study was provided by the Southeastern Ontario Academic Medical Association Innovation Fund and the John Hechte Memorial Foundation. Funding for the genomics sub-study was provided by the McLaughlin Center, University of Toronto, and the Garfield Kelly Fund, Queen’s University. Ms. Hoekstra received funding and support for article research from Natural Sciences and Engineering Research Council of Canada (Undergraduate Student Research Award). Dr. Maslove disclosed off-label product use of lactoferrin of ICU. Dr. Muscedere’s institution received funding from Lotte and John Hechte Memorial Foundation Grant and Southeastern Academic Medical Association Grant, and he received funding from Poly- Phor Pharma. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: david.maslove@queensu.ca Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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IBCC chapter & cast: Acetaminophen toxicity

Acetaminophen is in everyone's medicine cabinet.  This makes it one of the more common intoxications.  At first blush, this might seem like an easy topic:  apply the nomogram, then give acetylcysteine.  Unfortunately, it's not quite that simple.  There are a variety of different presentations (e.g. acute, chronic, delayed), many of which will confound the nomogram.  […]

EMCrit Project by Josh Farkas.

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A Case of Splenic Laceration Presenting as a Delayed Complication of Colonoscopy

Publication date: Available online 28 February 2019

Source: The Journal of Emergency Medicine

Author(s): Nicholas Keeven, Pholaphat Charles Inboriboon

Abstract

Background

Colonoscopy is a frequently performed medical procedure; complications associated with this procedure often present to the emergency department (ED). Splenic laceration is a rare but life-threatening complication of colonoscopy. We report the unique case of a patient with a splenic laceration who presented after a recent colonoscopy and had no history of trauma.

Case Report

A 52-year-old man presented to our ED with abdominal pain and lightheadedness the day after a routine colonoscopy. Ultrasound demonstrated hemoperitoneum, and contrast-enhanced computed tomography of the abdomen revealed a large hemoperitoneum with active contrast extravasation from the laceration of the superior pole of the spleen. After resuscitation, the patient was managed with an emergency splenectomy.

Why Should an Emergency Physician Be Aware of This?

Colonoscopy complications are frequently identified and managed in the ED. Splenic laceration should be on the differential for patients that present with abdominal pain or hypotension after colonoscopy. Splenic injury carries a high mortality risk, and prompt, accurate diagnosis can be lifesaving.

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Perceived Electrical Injury: Misleading Symptomology Due to Multisensory Stimuli

Publication date: Available online 28 February 2019

Source: The Journal of Emergency Medicine

Author(s): Mark W. Kroll, Mollie B. Ritter, Peter E. Perkins, Ladan Shams, Chris J. Andrews

Abstract

Background

An electrical accident victim's recollection is often distorted by Bayesian inference in multisensory integration. For example, hearing the sound and seeing the bright flash of an electrical arc can create the false impression that someone had experienced an electrical shock. These subjects will often present to an emergency department seeking either treatment or reassurance.

Case Reports

We present seven cases in which the subjects were startled by an electrical shock (real or perceived) and injury was reported. Calculations of the current and path were used to allocate causality between the shock and a history of chronic disease or previous trauma. In all seven cases, our analysis suggests that no current was passed through the body.

Why Should an Emergency Physician Be Aware of This?

Symptomology seen as corroborating may actually be confounding. Witness and survivor descriptions of electrical shocks are fraught with subjectivity and misunderstanding. Available current is usually irrelevant and overemphasized, such as stress on a 100-ampere welding source, which is orders of magnitude beyond lethal limits. History can also be biased for a number of reasons. Bayesian inference in multisensory perception can lead to a subject sincerely believing they had experienced an electrical shock. Determination of the current pathway and calculations of the amplitude and duration of the shock can be critical for understanding the limits and potential causation of electrical injury.

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Seizure as the Presenting Symptom for Atypical Hemolytic Uremic Syndrome

Publication date: Available online 27 February 2019

Source: The Journal of Emergency Medicine

Author(s): Sandy Chan, Adam R. Weinstein

Abstract

Background

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated disease manifesting in thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. It has a higher incidence of extrarenal manifestations, including central nervous system findings like seizure or stroke, pancreatitis, and cardiac manifestations.

Case Report

We present a case of an unimmunized 14-month-old girl presenting with generalized seizure and ultimately diagnosed with aHUS.

Why Should an Emergency Physician Be Aware of This?

These atypical neurological symptoms can cause the diagnosis to be commonly missed in the emergency department. The etiology of approximately 60% of patients with aHUS can be attributed to genetic mutations in complement regulators including factor H, membrane cofactor protein, factor I, activator factor B, or C3. Although previously treated with plasma transfusion and immunosuppressants, eculizumab is a newer treatment that has been changing prognosis and management of aHUS, but it should be administered within 48 h of symptom onset for best efficacy.

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Arthus Reaction

Publication date: Available online 27 February 2019

Source: The Journal of Emergency Medicine

Author(s): Mei-Hua Wang, Alvin Hu, Yei-Soon Lee, Chih-Cheng Lai

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Bilateral Retinal Detachment in a Pediatric Patient

Publication date: Available online 27 February 2019

Source: The Journal of Emergency Medicine

Author(s): Caleb Cadis, Alex Wang, Maneesha Julakanti, Andrew Juergens

Abstract

Background

Pediatric retinal detachments occur rarely, and thus may be easily missed. Without treatment, this condition leads to permanent vision loss. Patients with Stickler syndrome, an inherited disorder of collagen synthesis, are more likely to have retinal detachments than the general population.

Case Report

We present a case of a 9-year-old boy who presented to the Emergency Department with blurry vision, and who was subsequently diagnosed with bilateral retinal detachments. The patient underwent successful operative intervention. He was eventually determined to have Stickler syndrome.

Why Should an Emergency Physician Be Aware of This?

It is important for emergency physicians to recognize pediatric visual problems such as retinal detachment, as their presentations may be unusual, and delay of definitive care could result in lifelong visual impairment.

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When Rest, Ice, Compression, and Elevation Fail: A Case of Chronic Wrist Pain

Publication date: Available online 27 February 2019

Source: The Journal of Emergency Medicine

Author(s): Matthew Streitz, Erica Simon

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Dr. U

Publication date: Available online 27 February 2019

Source: The Journal of Emergency Medicine

Author(s): Jeffrey Gardecki

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Pilot Study to Evaluate the Adjunct Use of a Povidone-Iodine Topical Antiseptic in Patients with Soft Tissue Abscesses

Publication date: Available online 27 February 2019

Source: The Journal of Emergency Medicine

Author(s): Adriana Segura Olson, Lauren Rosenblatt, Nicholas Salerno, Julie Odette, Ronnie Ren, Tatiana Emanuel, Joel Michalek, Qianqian Liu, Liem Du, Kourosh Jahangir, Gillian R. Schmitz

Abstract

Background

Povidone-iodine (PVP-I) antiseptic solutions have been shown to be effective against methicillin-resistant Staphylococcal aureus, a common cause of superficial skin abscesses.

Objectives

Our objective was to study the feasibility of using PVP-I as a treatment adjunct in patients with superficial skin abscesses and determine if it confers any benefit over incision and drainage (I&D) alone.

Methods

This was a randomized controlled pilot study of adult patients with an uncomplicated skin abscess. Patients were randomized to PVP-I or standard treatment. All patients had I&D and abscess packing. Patients randomized to PVP-I were instructed on daily application of the agent to hands, wound, and surrounding skin with dressing changes. Subjects returned at 48–72 h and 7–10 days and followed-up by phone at 30 days. The primary outcome was clinical cure 7–10 days after I&D. The secondary outcomes were rate of development of new skin lesions and spread in household contacts within 30 days.

Results

Clinical cure occurred in 91.3% of patients in the standard group vs. 88.2% of patients in the PVP-I group (difference, 3.1%; 95% confidence interval [CI] −10.7 to 16.8; p = 0.53). There was a significantly higher adverse event rate in the group who received PVP-I (59.6%) vs. standard care (26.5%) (difference 33.1%, 95% CI 13.2–50.2; p < 0.001).

Conclusions

There was no difference in clinical cure rates among patients using PVP-I (88.2%) vs. standard care (91.3%) after I&D. There were no major adverse events, but the addition of PVP-I was commonly associated with local skin irritation.

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IBCC chapter & cast: Acetaminophen toxicity

Acetaminophen is in everyone's medicine cabinet.  This makes it one of the more common intoxications.  At first blush, this might seem like an easy topic:  apply the nomogram, then give acetylcysteine.  Unfortunately, it's not quite that simple.  There are a variety of different presentations (e.g. acute, chronic, delayed), many of which will confound the nomogram.  […]

EMCrit Project by Josh Farkas.

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Mesenchymal stem cell transplantation in polytrauma: Evaluation of bone and liver healing response in an experimental rat model

Abstract

Purpose

Trauma is the most common cause of death of young people in the world. As known, mesenchymal stem cells (MSCs) accelerate tissue regeneration mechanisms. In our study, we aimed to investigate the effects of MSCs transplantation on the healing of liver and bone tissue by considering trauma secondary inflammatory responses.

Methods

56 adult Wistar-albino rats were divided into two groups: the polytrauma (liver and bone) (n = 28), and the liver trauma group (n = 28). At 36 h and 5th day after surgery, both rats with polytrauma and with isolated liver injury received either intravenous (IV) or intraperitoneal (IP) injections of MSCs (one million cells per kg body weight). Untreated groups received IV and IP saline injections. At day 21 after surgery, liver, tibia and fibula of the subjects were excised and evaluated for histopathologic and histomorphometric examination. Additionally, whole blood count (white blood cells, hemoglobin and platelets), C-reactive protein (CRP), glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, blood gas, and trauma markers interleukin-1B (IL-1B), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) levels were investigated.

Results

In general, MSC transplantations were well tolerated by the subjects. It was found that ALT, CRP, albumin were significantly lower in rats which received MSCs (p < 0.001). Inflammation of the liver and bone tissue in the MSC-injected rats were significantly lower than that of the untreated groups.

Conclusions

Herewith we have shown that MSC infusion in posttraumatic rats leads to less aggressive and more effective consequences on liver and bone tissue healing. Human MSC treatment for trauma is still in early stages of development; thus standard protocols, and patient inclusion criteria should be established beforehand clinical trials.

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Total knee arthroplasty for distal femoral fractures in osteoporotic bone: a systematic literature review

Abstract

Purpose

Distal femoral fractures in the elderly are associated with high morbidity and mortality and their incidence is increasing with an ageing population. Management of these fractures has evolved over recent decades and there is now an accepted recognition of the important role that acute arthroplasty may have in treatment of these fractures. Our purpose was to systematically review the evidence available in the literature for arthroplasty as a treatment option for distal femoral fractures.

Methods

This systematic review was conducted in accordance with the PRISMA reporting guidelines. We searched CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded (until October 2018) for studies and case series. Furthermore, clinical trial registries were searched for ongoing studies. We included all studies or case series that described total knee arthroplasty for distal femoral fractures irrespective of language, publication status, sample size, or follow-up period due to limited studies available in the literature. Exclusion criteria included single patient case reports, isolated tibia fractures, and periprosthetic fractures. Two authors independently identified trials for inclusion and independently extracted the data. Outcome measures included mortality, peri-operative complications (excluding mortality), anaesthetic time, blood loss, time to mobilisation, length of hospital stay, functional scores, radiological loosening, and revision rate.

Results

Fourteen papers were included for subsequent quantitative and qualitative synthesis incorporating a total of 181 patients. The highest level of evidence identified was a single cohort study (level III), the remaining 13 papers consisted of multi- or single-centre case series (level IV). The mean mortality rate was 3.34% (range 0–10) at 30 days and 18.4% (range 0–42) at 1 year. The mean revision rate was 3.43% (range 0–25) at 1 year. The mean time to mobilisation was 3.90 days (range 2.5–6) with a mean time to discharge from the acute ward being 16.6 days (range 8–33).

Conclusions

Although there is limited evidence in the literature available, our review suggests that there is a role for acute knee arthroplasty in distal femoral fractures. This mode of treatment has satisfactory mortality and revision rates, and may result in faster time to mobilisation and discharge. There is a need for a higher level of evidence to delineate this issue further.

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Factors predicting adverse outcome in complete intra-articular distal radius fractures

Abstract

Purpose

To determine risk factors associated with adverse functional and radiological outcome in complete intra-articular distal radius fractures (AO 23 C2–3) with a minimum follow-up of 1 year.

Methods

Retrospective case series of 87 consecutive patients with a complete intra-articular distal radius fracture (AO/OTA 23 C2–3) and a minimum follow-up of 1 year between 2012 and 2016. Risk factors for adverse clinical [using the Patient-Rated Wrist Evaluation (PRWE) score] and radiological outcome (positive ulnar variance 1 year postoperative) were analysed in a linear regression model.

Results

PRWE scored a median of 4.5 points (range 0–72.5) after a median follow-up of 31 months (range 12–70 months). A concomitant polytrauma was associated with a worse PRWE (β = 23.34, p < 0.01) and was also significantly associated with the use of a temporary external fixator (χ² = 11.93; p < 0.01) and high-energy trauma (χ² = 19.39; p < 0.01). Radiological outcome measures 1 year postoperative did not correlate with clinical outcome measures.

Conclusion

This cohort of complete intra-articular distal radius fractures (AO/OTA 23 C2–3) shows a good clinical outcome at medium-term follow-up independent of the radiological outcome. A concomitant polytrauma was associated with worse functional outcome and a higher complication rate. This is most likely due to the associated injury severity. These factors help the treating physician in decision-making and informing patients when treating displaced intra-articular radius fractures.

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Hot off the Press: LOw dose MAGnesium sulfate versus HIgh dose in the early management of rapid atrial fibrillation: randomised controlled double‐blind study

Abstract

Atrial fibrillation is the most common cardiac dysthrymia. Several rate‐control strategies have been used, and magnesium sulfate has been investigated as an adjunct. In this review, we look at a trial by Bouida et al in which magnesium sulfate was studied in two different doses for rate control in atrial fibrillation. In addition, we review the social media commentary in response to the Skeptics Guide of Emergency Medicine Hot of the Press podcast.

This article is protected by copyright. All rights reserved.

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The use of polymeric clips in securing the appendiceal stump during laparoscopic appendicectomy: a systematic review

Abstract

Purpose

A key step during laparoscopic appendicectomy is securing the appendiceal stump. This has traditionally been achieved using vicryl endoloops, but increasing evidence suggests that the use of polymeric clips (Hem-o-lok) may be a safe and viable method. Current evidence for its clinical use in laparoscopic appendicectomy is unknown. We performed a systematic review of the literature examining the clinical outcomes of laparoscopic appendicectomy using polymeric clips compared to other methods of stump closure.

Methods

A systematic literature review based on PRISMA guidelines was performed using MEDLINE, PubMed, EMBASE and Cochrane library databases between 2000 and 2017. All studies analysing appendiceal stump closure during laparoscopic appendicectomy using polymeric clips compared to other methods of stump closure were included. The methodological quality of the included studies was assessed using the Cochrane Handbook for Systematic Reviews. The review was registered with the PROSPERO register of systematic reviews.

Results

Ten studies were included, involving 702 patients, 7 of which were prospective studies and 1 a randomised control trial. Polymeric clips were found to be the cheapest method (€20.47 average per patient) and also had the lowest rate of complications (2.7%) compared to other commonly used closure methods. Meanwhile, operative time and duration of in-patient stay were similar between groups.

Conclusions

Current evidence suggests that polymeric clips are an effective and cost-efficient method for stump closure in laparoscopic appendicectomy for acute appendicitis. Further high-quality evidence is required before polymeric clips can be recommended as the gold standard for appendiceal stump closure.

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EMCrit CQiR – IV Bolus Epinephrine for Anaphylaxis: A Double-Edged Sword

Is IM still the way to go with epi in anaphylaxis?

EMCrit Project by Ashley Mogul.

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EMCrit CQiR – IV Bolus Epinephrine for Anaphylaxis: A Double-Edged Sword

Is IM still the way to go with epi in anaphylaxis?

EMCrit Project by Ashley Mogul.

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Comparison of fracture healing and long-term patient-reported functional outcome between dorsal and volar plating for AO C3-type distal radius fractures

Abstract

Purpose

This study aimed to evaluate the differences in long-term functional outcome and radiographic fracture healing between volar and dorsally approached comminuted intra-articular distal radius fractures (DRF) (AO C3-type).

Methods

A retrospective, age-matched, case–control study with a 1:2 allocation ratio was conducted in 84 patients C3-type DRFs patients who underwent either dorsal locking plating (DLP) group (n = 28) or volar locking plating (VLP) group (n = 56). Standardized wrist radiographs (posterior–anterior and 15° lateral) were assessed immediately postoperative and at final follow. To evaluate for loss of reduction standard radiographic measurements were performed. Fracture healing was assessed radiologically. Patient-reported outcomes were assessed with the patient-related wrist evaluation and the EQ-5D-3L for health-related quality of life. Patient satisfaction was assessed with the use of a numeric analog scale ranging from 0 (not satisfied) to 100 (very satisfied).

Results

All fractures united within 3 months postoperatively. Average age was 59 ± 12 years. Fifty-five patients (66%) participated in the follow-up survey at an average of 76.6 ± 23.8 months. DLP group showed a significant change in sagittal tilt compared with VLP group (3.4 ± 3.0° vs − 0.4 ± 4.1°, p < 0.001). No significant difference in other radiographic and long-term functional outcome was found between both groups (p > 0.05).

Conclusion

Dorsal locking plating fixation in C3-type DRFs resulted in a minimal, but statistically significant, volar collapse of sagittal tilt compared with volar locking plating fixation. However, this difference in volar collapse did not significantly influence the long-term clinical outcome.

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Man With Sudden Paralysis: Insidious Spinal Cord Infarction due to a Non-Ruptured Abdominal Aortic Aneurysm

Publication date: Available online 26 February 2019

Source: The Journal of Emergency Medicine

Author(s): Hyunjoo Lee, Dimitrios Papanagnou, Mitchell Berman, Xiao Chi Zhang

Abstract

Background

Acute infarctions of the spinal cord are rare events characterized by sudden paralysis or sensory deficits below the level of injury. Etiologies include spinal cord trauma, vascular injury, arterial dissection, thromboembolic disease, chronic inflammatory conditions, or mass effect on the spinal cord.

Case Report

A 63-year-old male presented to the emergency department with sudden-onset bilateral leg numbness and weakness. His physical examination was notable for decreased light touch and temperature sensation and bilateral lower-extremity paresis. Initial magnetic resonance imaging (MRI) of his spine did not show cord injuries. Computed tomography angiography of his chest, abdomen, and pelvis demonstrated a 7.5-cm non-ruptured infrarenal abdominal aortic aneurysm (AAA) extending into bilateral iliac arteries. The patient was diagnosed with clinical spinal cord infarction secondary to a thromboembolic event from his AAA. A repeat MRI 15 h later showed spinal cord infarction from T8 down to the conus. He received an endovascular aortic repair and was ultimately discharged to rehabilitation with slightly improved lower-extremity strength.

Why Should an Emergency Physician Be Aware of This?

Atraumatic cord syndrome is exceedingly rare and is associated with dissection or complication of aortic aneurysm repair. There are very few reported cases of thrombotic events leading to ischemic cord syndrome. When presented with a patient with symptoms consistent with cord syndrome in the absence of trauma or mass effect on the spinal cord, providers should work up for vascular etiology.

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