Impacts of United States Medical Licensing Examination Step 1 Scoring Change on Emergency Medicine Applicant Screening.

BACKGROUND: The U.S. Medical Licensing Examination (USMLE) Step 1 has been used as a screening tool for residency selection. In February 2020, Step 1 numerical scoring changed to pass/fail. OBJECTIVE: Our aim was to survey emergency medicine (EM) residency program attitudes towards the new Step 1 scoring change and to identify important applicant screening factors. METHODS: A 16-question survey was distributed through the Council of Residency Directors in Emergency Medicine listserv from November 11 through December 31, 2020. Given the Step 1 scoring change, the survey questioned the importance of EM rotation grades, composite standardized letters of evaluation (cSLOEs), and individual standardized letters of evaluation, using a Likert scale. Descriptive statistics of demographic characteristics and selection factors were performed along with a regression analysis. RESULTS: Of the 107 respondents, 48% were program directors, 28% were assistant or associate program directors, 14% were clerkship directors, and 10% were in other roles. Sixty (55.6%) disagreed with pass/fail Step 1 scoring change and, of those, 82% believed that numerical scoring was a good screening tool. The cSLOEs, EM rotation grades, and interview were the most important selection factors. Residencies with 50 or more residents had 5.25 odds (95% CI 1.25-22.1; p = 0.0018) of agreeing with pass/fail scoring and those who ranked cSLOEs as the most important selection factor had 4.90 odds (95% CI 1.125-21.37; p = 0.0343) of agreeing with pass/fail scoring. CONCLUSIONS: Most EM programs disagree with pass/fail scoring of Step 1 and will most likely use Step 2 score as a screening tool. The cSLOEs, EM rotation grades, and interview are considered the most important selection factors.

Phenytoin Toxicity After Transjugular Intrahepatic Portosystemic Shunt (TIPS).

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) alters portal blood flow and may impact drug metabolism and bioavailability. However, little evidence has been published to provide guidance on medication alterations after TIPS procedures. CASE REPORT: We report a patient who developed phenytoin toxicity requiring a prolonged readmission after a TIPS procedure. It is likely that the TIPS procedure altered phenytoin metabolism and led to toxicity in this patient. Phenytoin is an antiepileptic drug that is primarily eliminated by hepatic metabolism. It is possible that phenytoin toxicity may occur after TIPS, and that decreased dose requirements may be a durable effect of the procedure. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: TIPS is now the most common portal hypertension decompressive procedure performed by interventional radiologists and has become the primary portosystemic shunt (surgical or percutaneous) performed in the United States. Patients with a history of TIPS procedures commonly present to tertiary- and quaternary-care emergency departments with complex clinical presentations. Greater familiarity with the potential effects of TIPS on drug metabolism may help emergency physicians prevent adverse drug effects and optimize clinical outcomes.

Combined endogenous MR biomarkers to assess changes in tumor oxygenation induced by an allosteric effector of hemoglobin.

Hypoxia is a crucial factor in cancer therapy, determining prognosis and the effectiveness of treatment. Although efforts are being made to develop methods for assessing tumor hypoxia, no markers of hypoxia are currently used in routine clinical practice. Recently, we showed that the combined endogenous MR biomarkers, R1 and R2 *, which are sensitive to [dissolved O2 ] and [dHb], respectively, were able to detect changes in tumor oxygenation induced by a hyperoxic breathing challenge. In this study, we further validated the ability of the combined MR biomarkers to assess the change in tumor oxygenation induced by an allosteric effector of hemoglobin, myo-inositol trispyrophosphate (ITPP), on rat tumor models. ITPP induced an increase in tumor pO2 , as observed using L-band electron paramagnetic resonance oximetry, as well as an increase in both R1 and R2 * MR parameters. The increase in R1 indicated an increase in [O2 ], whereas the increase in R2 * resulted from an increase in O2 release from blood, inducing an increase in [dHb]. The impact of ITPP was then evaluated on factors that can influence tumor oxygenation, including tumor perfusion, saturation rate of hemoglobin, blood pH and oxygen consumption rate (OCR). ITPP decreased blood [HbO2 ] and significantly increased blood acidity, which is also a factor that right-shifts the oxygen dissociation curve. No change in tumor perfusion was observed after ITPP treatment. Interestingly, ITPP decreased OCR in both tumor cell lines. In conclusion, ITPP increased tumor pO2 via a combined mechanism involving a decrease in OCR and an allosteric effect on hemoglobin that was further enhanced by a decrease in blood pH. MR biomarkers could assess the change in tumor oxygenation induced by ITPP. At the intra-tumoral level, a majority of tumor voxels were responsive to ITPP treatment in both of the models studied.

Impact of myo-inositol trispyrophosphate (ITPP) on tumour oxygenation and response to irradiation in rodent tumour models.

Tumour hypoxia is a well-established factor of resistance in radiation therapy (RT). Myo-inositol trispyrophosphate (ITPP) is an allosteric effector that reduces the oxygen-binding affinity of haemoglobin and facilitates the release of oxygen by red blood cells. We investigated herein the oxygenation effect of ITPP in six tumour models and its radiosensitizing effect in two of these models. The evolution of tumour pO2 upon ITPP administration was monitored on six models using 1.2 GHz Electron Paramagnetic Resonance (EPR) oximetry. The effect of ITPP on tumour perfusion was assessed by Hoechst staining and the oxygen consumption rate (OCR) in vitro was measured using 9.5 GHz EPR. The therapeutic effect of ITPP with and without RT was evaluated on rhabdomyosarcoma and 9L-glioma rat models. ITPP enhanced tumour oxygenation in six models. The administration of 2 g/kg ITPP once daily for 2 days led to a tumour reoxygenation for at least 4 days. ITPP reduced the OCR in six cell lines but had no effect on tumour perfusion when tested on 9L-gliomas. ITPP plus RT did not improve the outcome in rhabdomyosarcomas. In 9L-gliomas, some of tumours receiving the combined treatment were cured while other tumours did not benefit from the treatment. ITPP increased oxygenation in six tumour models. A decrease in OCR could contribute to the decrease in tumour hypoxia. The association of RT with ITPP was beneficial for a few 9L-gliomas but was absent in the rhabdomyosarcomas.

Characterization of a clinically used charcoal suspension for in vivo EPR oximetry.

OBJECTIVES: Electron paramagnetic resonance (EPR) oximetry using particulate materials allows repeatable measurements of oxygen in tissues. However, the materials identified so far are not medical devices, thus precluding their immediate use in clinical studies. The aim of this study was to assess the magnetic properties of Carbo-Rep®, a charcoal suspension used as a liquid marker for preoperative tumor localization. MATERIALS AND METHODS: Calibration curves (EPR linewidth as a function of pO2) were built using 9-GHz EPR spectrometry. The feasibility of performing oxygen measurements was examined in vivo by using a low-frequency (1 GHz) EPR spectrometer and by inducing ischemia in the gastrocnemius muscle of mice or by submitting rats bearing tumors to different oxygen-breathing challenges. RESULTS: Paramagnetic centers presenting a high oxygen sensitivity were identified in Carbo-Rep®. At 1 GHz, the EPR linewidth varied from 98 to 426 µT in L-band in nitrogen and air, respectively. The sensor allowed repeated measurements of oxygen over 6 months in muscles of mice. Subtle variations of tumor oxygenation were monitored in rats when switching gas breathing from air to carbogen. DISCUSSION: The magnetic properties of Carbo-Rep® are promising for its future use as oxygen sensor in clinical EPR oximetry.

Internet-purchased ibogaine toxicity confirmed with serum, urine, and product content levels.

UNLABELLED: Ibogaine, a psychotropic indole alkaloid, is gaining popularity among medical subcultures for its purported anti addictive properties. Its use has been associated with altered mental status, ataxia, gastrointestinal distress, ventricular arrhythmias, and sudden and unexplained deaths.Its pharmacokinetics in toxic states is not well understood. Case report:A 33-year-old man overdosed on ibogaine in an attempt to quit his use of heroin. He developed altered state of consciousness, tremor, ataxia,nausea, vomiting, and transient QT interval prolongation, which all remitted as he cleared the substance. Ibogaine was confirmed in his urine and serum with a peak serum concentration of 377 ng/mL. Nonlinear elimination kinetics and a formula match to its active metabolite noriobgaine were observed as well. CONCLUSION: This case presents the unique description of serial serum concentrations as well as urine and product-confirmed ibogaine toxicity with transient toxin-related QT interval prolongation.

Orbeez: the magic water absorbing bead--risk of pediatric bowel obstruction?

OBJECTIVES: In December 2012, the U.S. Consumer Product Safety Commission recalled the water-absorbing toy WaterBalz after reports of small intestine obstruction after ingestion by children. Orbeez, another water-absorbing bead, remains available and is marketed as a children's toy. We sought to determine the extent to which Orbeez enlarge in various liquid media and the potential risk for bowel obstruction. METHODS: Three Orbeez beads were added to 210 mL of the following liquid media: room temperature tap water, whole milk, simulated gastric fluid, GoLytely (polyethelyelene glycol, 3350 and electrolytes), and vodka (40% ethanol by volume). Diameters before exposure to media were measured using a caliper to the nearest 0.1 mm and again at 1, 2, 4, 6, 12, and 24 hours. Ten beads were then added to the beads already immersed in simulated gastric fluid and water and observed for an additional 72 hours (96 hours total) for clumping or increase in diameter. Clumping was defined as two or more beads remaining persistently adherent to one another despite gentle circular movement (swirling) of the liquid. RESULTS: Growth in each of the media was observed. Growth in simulated gastric fluid was minimal, whereas the beads were observed to be the largest after 24 hours in vodka. Clumping of the beads was not observed to occur. CONCLUSIONS: Orbeez beads enlarge to a different extent in different liquid media. It is unlikely that Orbeez beads would expand to sizes or demonstrate clumping that would be concerning for intestinal obstruction.

Methane oxidation by an extremely acidophilic bacterium of the phylum Verrucomicrobia.

Aerobic methanotrophic bacteria consume methane as it diffuses away from methanogenic zones of soil and sediment. They act as a biofilter to reduce methane emissions to the atmosphere, and they are therefore targets in strategies to combat global climate change. No cultured methanotroph grows optimally below pH 5, but some environments with active methane cycles are very acidic. Here we describe an extremely acidophilic methanotroph that grows optimally at pH 2.0-2.5. Unlike the known methanotrophs, it does not belong to the phylum Proteobacteria but rather to the Verrucomicrobia, a widespread and diverse bacterial phylum that primarily comprises uncultivated species with unknown genotypes. Analysis of its draft genome detected genes encoding particulate methane monooxygenase that were homologous to genes found in methanotrophic proteobacteria. However, known genetic modules for methanol and formaldehyde oxidation were incomplete or missing, suggesting that the bacterium uses some novel methylotrophic pathways. Phylogenetic analysis of its three pmoA genes (encoding a subunit of particulate methane monooxygenase) placed them into a distinct cluster from proteobacterial homologues. This indicates an ancient divergence of Verrucomicrobia and Proteobacteria methanotrophs rather than a recent horizontal gene transfer of methanotrophic ability. The findings show that methanotrophy in the Bacteria is more taxonomically, ecologically and genetically diverse than previously thought, and that previous studies have failed to assess the full diversity of methanotrophs in acidic environments.

Severe alcohol withdrawal in an adolescent male.

Ethanol remains one of the most frequently abused agents by adolescents, exceeding all others except for vaping nicotine, and use is rising. With increased ethanol use comes a greater risk for dependence and potential for alcohol withdrawal syndromes (AWS). Pediatric AWS is extremely rare and poorly characterized in the literature. Pediatric acute care practitioners may have limited exposure to AWS. We report the case of a 16-year-old male with a history of polysubstance abuse who presented with mild AWS and progressed rapidly to delirium tremens. His withdrawal was initially refractory to high dose benzodiazepine therapy but responded well to phenobarbital. This case highlights how rapidly and dangerously AWS can progress if not aggressively treated. Given the rise in adolescent alcohol use and potential for life threatening symptoms, practitioners, especially in acute care specialties such as emergency medicine, critical care, and hospital medicine, would benefit from additional familiarity with AWS diagnoses and management strategies.

Spectrophotometric analysis of purple urine secondary to methylene blue and hydroxocobalamin co-administration.

BACKGROUND: The development of purple urine after methylene blue (methylthioninium chloride) and hydroxocobalamin co-administration is a rare clinical entity that has not been fully elucidated. A 47-year-old male presented to the emergency department with hypotension, cyanosis, and depressed mental status. The patient was noted to have profound peripheral and central cyanosis, as well as chocolate-colored arterial blood. He was treated with both methylene blue and hydroxocobalamin and developed purple urine for approximately 1 week. METHODS: Color chromatography was performed by placing the patient's urine directly onto absorbent filter paper. Urine spectrophotometry was performed utilizing the NanoDrop One/One C UV-Vis Spectrophotometer. RESULTS: Color chromatography of the urine was demonstrated clear separation of distinct red and blue phases. Urine spectrophotometry demonstrated near perfect overlap between the methylene blue + hydroxocobalamin absorbance spectrum and the patient's purple urine absorbance spectrum. CONCLUSION: Purple urine secondary to methylene blue and hydroxocobalamin co-administration is due to combined urinary excretion of methylene blue (blue) and hydroxocobalamin (red), and not a novel purple metabolite. We anticipate that this is going to be an increasingly common clinical entity as the roles of both hydroxocobalamin and methylene blue expand from toxicologic antidotes to adjunct therapies for vasoplegia, poor cardiac output, and sepsis.

False-positive urine phencyclidine immunoassay screen result caused by interference by tramadol and its metabolites.

Phencyclidine is one of the drugs of abuse included in qualitative urine drug screens that are frequently ordered in the emergency department despite concerns about specificity and clinical utility. Many drugs have been described to cause false-positive results for phencyclidine. We present 2 cases of false-positive phencyclidine qualitative urine drug screen results in patients with seizures from tramadol misuse or abuse. The involvement of tramadol and its active metabolite, N-desmethyltramadol, was confirmed by in vitro testing. These cases illustrate that tramadol and its metabolites can trigger a false-positive phencyclidine urine drug screen result in nonfatal cases and highlight the lack of specificity of the phencyclidine qualitative urine drug screen.

Mass sociogenic illness initially reported as carbon monoxide poisoning.

BACKGROUND: Mass sociogenic illness (MSI) is a rare occurrence involving a constellation of physical signs and symptoms in a group of individuals that are exhibited subconsciously and have no corresponding organic etiology. OBJECTIVES: To describe an outbreak of MSI initially attributed to carbon monoxide (CO) poisoning. CASE REPORTS: While attending a church service, one child fainted, followed by another. This led to multiple individuals reporting a constellation of symptoms. A total of 22 individuals presented to emergency departments (EDs) with neurologic, gastrointestinal, and respiratory complaints. The onset of symptoms followed evacuation in most of these patients. Prehospital personnel obtained carboxyhemoglobin (COHb) levels with a portable oximeter device, identifying levels up to 19% in 6 patients; 17 were taken to a tertiary hospital with a hyperbaric oxygen chamber, and the other 5 to a local ED. All other attendees were asymptomatic. Within the 15-min transport time, all patients were asymptomatic and had normal physical examinations. The mean age of patients was 13 years; 7 were male and 10 were female. Venous blood gas identified normal COHb levels in all patients. Pulse oximetry in the ED was normal. Another handheld oximeter device in the ED found normal COHb and methemoglobin levels. CONCLUSION: Varying complaints with onset after removal from the church suggest MSI. The hazardous materials team reproduced the scenario and no toxic gases were detected. Escalation of symptoms and an increased number of persons being affected along with increasing ambulance presence are common in MSI. We suspect that field oximeter readings were either aberrant from an inexperienced operator or were false-positive COHb readings. Clinicians should consider MSI after mass outbreaks of illness, particularly with rapid onset, rapid resolution of symptoms, and normal physical examinations and laboratory analyses. However, the diagnosis of MSI should be entertained only after potential toxicologic etiologies have been excluded.

"Spice" girls: synthetic cannabinoid intoxication.

BACKGROUND: "Spice" refers to various synthetic cannabinoid-containing products that seem to have rapidly become popular recreational drugs of abuse. Very little medical literature currently exists detailing the adverse effects and emergency department (ED) presentations associated with "spice" use. OBJECTIVES: To describe the presentation of 2 patients who recreationally used a "spice" product and to briefly summarize what is known about "spice" and synthetic cannabinoids. CASE REPORT: Two patients presented to the ED with, predominantly, anxiety after recreationally using a "spice" product that we subsequently confirmed to contain the synthetic cannabinoids, JWH-018 and JWH-073. CONCLUSION: We suspect that use of "spice" products may increase. Although anxiety was a prominent presentation in both of the patients described here, undoubtedly, future studies will describe the manifestations of intoxication and toxicity with the various synthetic cannabinoids.

Prolonged coma in a child due to hashish ingestion with quantitation of THC metabolites in urine.

BACKGROUND: Cannabinoid-containing substances are commonly abused worldwide. Significant toxicity from these substances is uncommon in adults but can result in significant symptoms in children; these symptoms are usually short-lived. OBJECTIVES: To report a case of prolonged mental status alteration of more than 2 days in a child who ingested hashish. CASE REPORT: A 14-month-old child presented comatose to a pediatric emergency department after ingestion of hashish; she did not regain consciousness for more than 48 h. Quantitative testing of the child's urine for a tetrahydrocannabinol metabolite revealed a markedly elevated level, the decline of which coincided with the child's clinical improvement. CONCLUSIONS: Significant ingestion of cannabinoid-containing substances is capable of causing prolonged symptoms (including coma) in children.

The impact of particulate electron paramagnetic resonance oxygen sensors on fluorodeoxyglucose imaging characteristics detected via positron emission tomography.

During a first-in-humans clinical trial investigating electron paramagnetic resonance tumor oximetry, a patient injected with the particulate oxygen sensor Printex ink was found to have unexpected fluorodeoxyglucose (FDG) uptake in a dermal nodule via positron emission tomography (PET). This nodule co-localized with the Printex ink injection; biopsy of the area, due to concern for malignancy, revealed findings consistent with ink and an associated inflammatory reaction. Investigations were subsequently performed to assess the impact of oxygen sensors on FDG-PET/CT imaging. A retrospective analysis of three clinical tumor oximetry trials involving two oxygen sensors (charcoal particulates and LiNc-BuO microcrystals) in 22 patients was performed to evaluate FDG imaging characteristics. The impact of clinically used oxygen sensors (carbon black, charcoal particulates, LiNc-BuO microcrystals) on FDG-PET/CT imaging after implantation in rat muscle (n = 12) was investigated. The retrospective review revealed no other patients with FDG avidity associated with particulate sensors. The preclinical investigation found no injected oxygen sensor whose mean standard uptake values differed significantly from sham injections. The risk of a false-positive FDG-PET/CT scan due to oxygen sensors appears low. However, in the right clinical context the potential exists that an associated inflammatory reaction may confound interpretation.

Recurrent coagulopathy and thrombocytopenia in children treated with crotalidae polyvalent immune fab: a case series.

OBJECTIVES: Recurrent signs and symptoms after initial treatment and control of coagulopathy and thrombocytopenia after American pit viper (crotaline) envenomations have been previously described in patients treated with Crotalidae polyvalent immune Fab antivenom (FabAV). The significance and necessity of treatment of these recurrent abnormalities are uncertain. Our goal was to further characterize recurrent coagulopathy or thrombocytopenia in pediatric patients. METHODS: All cases presenting to our Toxicology Consult Service, which covers 6 hospitals in a metropolitan area, from May 2007 to April 2008 with recurrent coagulopathy after initial control with FabAV were included and retrospectively reviewed. RESULTS: Four cases of pediatric patients are presented who presented with recurrent coagulopathy and/or thrombocytopenia after initial control with FabAV. The patients were all treated with delayed administration of FabAV with variable results. Blood products administered without concurrent FabAV were of limited use. The laboratory abnormalities took up to 18 days to resolve in one case. One patient developed hemodynamically significant spontaneous bleeding. CONCLUSIONS: The cases presented here suggest administration of FabAV may correct delayed coagulopathy associated with crotaline envenomations. The first 3 cases illustrate that in the face of severe derangements in laboratory values, most envenomated patients treated with FabAV do not develop significant bleeding. These cases may respond to additional antivenom alone. However, case 4 illustrates that hemodynamically significant spontaneous bleeding can occur. Until more data are available, readministration of FabAV is a reasonable first-line therapy for delayed coagulopathy associated with crotaline envenomations.

A retrospective poison center review of varenicline-exposed patients.

BACKGROUND: Varenicline was approved by the Food and Drug Administration (FDA) as a prescription smoking cessation aid in May 2006. Varenicline is both a partial nicotine agonist and an antagonist. Recent reports by the Institute of Safe Medication Practices identified safety problems associated with varenicline use, and the FDA recently issued a boxed warning. These safety concerns regarding varenicline use prompted this study. OBJECTIVE: To characterize varenicline-exposed patients as reported to a poison control system. METHODS: We performed a retrospective search of the California Poison Control System electronic database from August 2006 through August 2008, using the term varenicline or Chantix. Cases matching these results were reviewed. All ages were included. Excluded were patients with coingestants and unknown outcomes. Clinical parameters and medical outcomes were extracted from the database. RESULTS: Thirty-six cases met inclusion criteria and 17 cases were excluded, Ten cases involved nonpediatric patients; 9 cases involved patients less than 6 years old, which were defined as pediatric patients. The median duration of poison center follow-up for pediatric patients was 253 minutes; median duration of follow-up for nonpediatric patients with unintentional exposures was 28.5 minutes. The majority of exposures were unintentional and included all the pediatric patients and 6 nonpediatric patients who had unintentional medication errors. Gastrointestinal and neuropsychiatric adverse events were most frequently reported. The majority of these patients were managed at home. Among those evaluated at a healthcare facility, only 1 pediatric patient was admitted. Of the remaining patients, 1 nonpediatric patient reported a deliberate exposure and 3 nonpediatric patients experienced adverse effects at therapeutic doses. Median duration of follow-up for these patients was 308 minutes. CONCLUSIONS: Patients exposed to varenicline in our study had favorable outcomes. Gastrointestinal and neuropsychiatric effects were the most commonly reported adverse events. A dose-response relationship could not be determined and triage criteria to a healthcare facility remain undetermined.