Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

An INAR(1) Time Series Model via a Modified Discrete Burr–Hatke with Medical Applications

This paper introduces a flexible discrete transmuted record type discrete Burr–Hatke (TRT-DBH) model that seems suitable for handling over-dispersion and equi-dispersion in count data analysis. Further to the elegant properties of the TRT-DBH, we propose, in the time series context, a first-order integer-valued autoregressive process with TRT-DBH distributed innovations [TRBH-INAR(1)]. The moment properties and inferential procedures of this new INAR(1) process are studied. Some Monte Carlo simulation experiments are executed to assess the consistency of the parameters of the TRBH-INAR(1) model. To further motivate its purpose, the TRBH-INAR(1) is applied to analyze the series of the COVID-19 deaths in Netherlands and the series of infected cases due to the Tularaemia disease in Bavaria. The proposed TRBH-INAR(1) model yields superior fitting criteria than other established competitive INAR(1) models in the literature. Further diagnostics related to the residual analysis and forecasting based on the TRBH-INAR(1) model are also discussed. Based on modified Sieve bootstrap predictors, we provide integer forecasts of future death of COVID-19 and infected of Tularemia.

Tularemia above the Treeline: Climate and Rodent Abundance Influences Exposure of a Sentinel Species, the Arctic Fox (Vulpes lagopus), to Francisella tularensis.

Tularemia is a zoonotic disease found throughout most of the northern hemisphere that may experience range expansion with warming temperatures. Rodents and lagomorphs are reservoirs for the disease, and outbreaks of tularemia often follow peaks in their abundance. As small mammals dominate the diet of arctic foxes (Vulpes lagopus), we determined whether they may serve as sentinels by identifying antibodies in live-captured and harvested foxes from northern Canada. Overall seroprevalence was 2% (CI95 1-2%) in 176 foxes harvested in 2018-2019 compared to 17% (CI95 12-22%) of 230 foxes captured live in 2011-2021. Prevalence was at an all-time high in 2018, following a peak in vole abundance in 2017. Antibodies were identified in fox pups born in 2018 and 2019, suggesting that F. tularensis was actively transmitted during the summers. High precipitation during the summer, increased snow cover and colder temperatures in May, and a higher abundance of voles were all associated with increased seroprevalence in live-captured foxes. Thus, exposure to F. tularensis is largely mediated through climate and rodent populations in the Canadian Arctic, and arctic foxes are useful sentinels for F. tularensis in northern ecosystems. Further studies should investigate whether infection impacts arctic fox survival and reproductive success in the circumpolar North.

An INAR(1) Time Series Model via a Modified Discrete Burr-Hatke with Medical Applications

This paper introduces a flexible discrete transmuted record type discrete Burr-Hatke (TRT-DBH) model that seems suitable for handling over-dispersion and equi-dispersion in count data analysis. Further to the elegant properties of the TRT-DBH, we propose, in the time series context, a first-order integer-valued autoregressive process with TRT-DBH distributed innovations [TRBH-INAR(1)]. The moment properties and inferential procedures of this new INAR(1) process are studied. Some Monte Carlo simulation experiments are executed to assess the consistency of the parameters of the TRBH-INAR(1) model. To further motivate its purpose, the TRBH-INAR(1) is applied to analyze the series of the COVID-19 deaths in Netherlands and the series of infected cases due to the Tularaemia disease in Bavaria. The proposed TRBH-INAR(1) model yields superior fitting criteria than other established competitive INAR(1) models in the literature. Further diagnostics related to the residual analysis and forecasting based on the TRBH-INAR(1) model are also discussed. Based on modified Sieve bootstrap predictors, we provide integer forecasts of future death of COVID-19 and infected of Tularemia.

TULAREMIA PRESENTING AS LARGE GI ULCERATION AND HEMORRHAGE

SESSION TITLE: Critical Care Infections SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Francisella tularensis is a zoonotic disease by an aerobic, gram negative coccobacillus. It is transmitted by exposure to infected animal or vectors in individuals who landscape or camp. Common symptoms are fever, chills, anorexia, and headache. Abdominal tularemia can present with abdominal pain, emesis, diarrhea, and rarely intestinal ulceration and hemorrhage. It is treated with aminoglycosides, fluoroquinolones and tetracycline. CASE PRESENTATION: 38-year-old male presented with fever, cough, anorexia, and black stool for 5 days. Patient worked as a landscaper. He has no pets, travel history or sick contacts. He does not take any medications at home. Physical exam was significant for sinus tachycardia and rhonchi of right upper lobe. Significant labs include WBC of 9.8 with 41% bands, hemoglobin 15.5, sodium 125, procalcitonin 27.3, and lactic acid 1.8. COVID-19, MRSA, Legionella and Pneumococcal urine antigen were negative. CTA chest revealed mass-like opacity in right upper lobe with multiple bilateral pulmonary nodules. Lower respiratory culture showed Candida albicans. Patient was empirically started on ceftriaxone and azithromycin. He was transferred to intensive care for worsening respiratory status and was placed on non-invasive ventilation on hospital day 1. Antibiotics were broadened to ceftaroline and levofloxacin due to suspicion of tularemia. Amphotericin B was added. Labs for Histoplasma, Blastomyces, TB, Leptospira, and HIV were negative. Patient then suffered a cardiac arrest on hospital day 2 after having large brown secretions pouring from his mouth. Cardiopulmonary resuscitation was initiated and patient was intubated and started on vasopressors with return of spontaneous circulation. Massive blood transfusion protocol was initiated. Emergent bedside upper endoscopy showed large blood clot adherent to duodenal ulcer. Interventional radiology planned on performing gastric duodenal artery embolization. However, patient suffered two more cardiac arrest with resuscitation efforts terminated per family request. Karius Digital Culture later was positive for Francisella tularensis. Autopsy revealed diffuse alveolar hemorrhage, hilar lymphadenopathy, and perforated duodenal ulceration with large adherent clot. DISCUSSION: Gastrointestinal tularemia is rare and usually from drinking contaminated water or oral inoculation of bacteria. Intestinal tract involvement can present with mesenteric lymphadenopathy and ulcerative lesions resulting in gastrointestinal bleeding with case fatality rate of 50%. Even though this is noted in the literature, to our knowledge no case reports have been published. CONCLUSIONS: Careful history taking and early identification of risk factors are important when severe tularemia infection is suspected such as in individuals with extensive outdoor activities. Treatment should be empirically initiated in high risk patients. Reference #1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585636/ Reference #2: https://casereports.bmj.com/content/2017/bcr-2017-22125. Reference #3: Altman GB, Wachs JE. Tularemia: A pathogen in nature and a biological weapon. Aaohn Journal. 2002 Aug;50(8):373-9. DISCLOSURES: No relevant relationships by Maria Haider Baig

UNDERSTANDING THE NEED FOR A BROAD DIFFERENTIAL DIAGNOSIS: A CASE OF PNEUMONIC TULAREMIA

SESSION TITLE: Disseminated Bacterial Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Tularemia is a rare infectious disease caused by Francisella Tularensis that typically affects the skin, eyes, lymph nodes, and lungs. There are a variety of forms of tularemia with varying rates of contagiousness and mortality. Respiratory tularemia has a high mortality rate if left untreated and presents with non-specific viral like symptoms occurring in conjunction with respiratory symptoms: cough, hemoptysis, and pleuritic chest pain. In this COVID ARDS era, it is important to evaluate a broad differential diagnosis. Therefore, the authors describe a patient presenting with flu-like respiratory symptoms whom was ultimately was diagnosed with acute respiratory distress syndrome (ARDS) due to F. Tulerensis. CASE PRESENTATION: A 44-year-old male presented with a four-day history of night sweats, shortness of breath, a productive cough which progressed to hemoptysis, and oliguria. Prior to admission, his initial symptoms were treated as chronic sinusitis with varied antibiotics. Social history including tobacco abuse and deer hunting 1 month prior to presentation. Vitals were stable except for tachycardia, hypoxia, and tachypnea. Laboratory findings were significant for AKI, lactic acidosis, mild transaminitis, hyperbilirubinemia, and leukocytosis with predominant neutrophilia. Thoracic CTA showed bilateral diffused pulmonary edema without evidence of pulmonary embolism. Due to the patient's worsening respiratory status, he was intubated for support. The patient progressed to Severe ARDS per Berlin Criteria eventually requiring pronation and continuous paralyzing. Bronchoscopy was performed with bronchial lavage. Bacterial, viral, and fungal cultures did not show growth while vasculitic work-up was negative. Empiric antibiotic treatment did not show improvement until the patient was diagnosed with F. Taularensis via serological testing with an IgM of 20 U/mL, and patient was transitioned to gentamycin. Ultimately, the patient was extubated, transitioned to oral doxycycline, and discharged home. DISCUSSION: Approximately 250 cases of tularemia are reported to CDC each year. Respiratory tularemia has a mortality rate up to 30% if not treated. For this reason, F. tularensis is a potential biological weapon and is categorized as a Group A pathogenic agent. Serological testing may be negative early in disease progression;therefore, early inflammatory markers with clinical suspicion are essential to diagnose the disease early in its course. DNA microarray has high specificity and sensitivity for rapid diagnosis of tularemia while being cost effective. After prompt diagnosis, intravenous aminoglycosides;such as gentamycin or streptomycin;must be started. CONCLUSIONS: In the above case, we illustrate the gradual onset and rapid patient deterioration when treatment is delayed;yet, there is rapid recovery once appropriate treatment is used. Reference #1: 1. Ranjbar, Reza, Payam Behzadi, and Caterina Mammina. "Respiratory tularemia: Francisella tularensis and microarray probe designing.” The open microbiology journal 10 (2016): 176. Reference #2: 2. Akhvlediani, N., I. Burjanadze, D. Baliashvili, T. Tushishvili, M. Broladze, A. Navdarashvili, S. Dolbadze et al. "Tularemia transmission to humans: a multifaceted surveillance approach.” Epidemiology & Infection 146, no. 16 (2018): 2139-2145. Reference #3: 3. Tularemia in British Columbia: A case report and review. Issue: BCMJ, vol. 52, No. 6, July August 2010 (Pages 303- 307). Megan Isaac-Renton, BSc, Muhammad Morshed, PhD, SCCM Eleni Galanis, MD, MPH, FRCPC Sunny Mak, MSc Vicente Loyola, MD, FRCPC, Linda M.N. Hoang, MD, MHSc, FRCPC DISCLOSURES: No relevant relationships by Munish Adhikari No relevant relationships by Ashma Ul Husna No relevant relationships by Yan Jiang No relevant relationships by Divya Kharel No relevant relationships by Gregory Polcha

Ulceroglandular form of tularemia after squirrel bite: a case report.

BACKGROUND: The diagnosis of tularemia is not often considered in Germany as the disease is still rare in this country. Nonetheless, Francisella tularensis, the causative agent of tularemia, can infect numerous animal species and should, therefore, not be neglected as a dangerous pathogen. Tularemia can lead to massively swollen lymph nodes and might even be fatal without antibiotic treatment. To our knowledge, the case described here is the first report of the disease caused by a squirrel bite in Germany. CASE PRESENTATION: A 59-year-old German woman with a past medical history of hypothyroidism and cutaneous lupus erythematosus presented at the emergency room at St. Katharinen Hospital with ongoing symptoms and a swollen right elbow persisting despite antibiotic therapy with cefuroxime for 7 days after she had been bitten (right hand) by a wild squirrel (Eurasian red squirrel). After another 7 days of therapy with piperacillin/tazobactam, laboratory analysis using real-time polymerase chain reaction (PCR) confirmed the suspected diagnosis of tularemia on day 14. After starting the recommended antibiotic treatment with ciprofloxacin, the patient recovered rapidly. CONCLUSION: This is the first report of a case of tularemia caused by a squirrel bite in Germany. A naturally infected squirrel has recently been reported in Switzerland for the first time. The number of human cases of tularemia has been increasing over the last years and, therefore, tularemia should be taken into consideration as a diagnosis, especially in a patient bitten by an animal who also presents with headache, increasing pain, lymphadenitis, and fever, as well as impaired wound healing. The pathogen can easily be identified by a specific real-time PCR assay of wound swabs and/or by antibody detection, for example by enzyme-linked immunosorbent assay (ELISA), if the incident dates back longer than 2 weeks.

Historical epidemics and the effects of COVID-19 restrictions on human health

In historical and prehistoric times, various pathogens from human origin or from animals to humans have affected millions of people as diseases such as plague, smallpox, and tularemia. It is known that epidemic diseases played a role in the historical records on the way to the collapse of the Hittite state. There are many records of epidemics in ancient Greek and Roman states. Geographical discoveries have opened up new opportunities for the spread of diseases. The corona virus epidemic, which emerged in China at the end of 2019 and spread from there to the whole world, was named COVID-19 by the World Health Organization. It causes problems in many parts of the body in addition to the respiratory tract. COVID-19 has become the biggest epidemic of recent years, affecting millions of people. Restrictions against COVID-19 have raised concerns about health problems in people as well as economy. Psychological problems, anxiety and sleep disorders related to decreased sociality have been reported in many studies. Possible problems due to inactivity are areas where more data can be revealed in the future. The purpose of this review is to gather historical information on past outbreaks and present some of the selected effects of the current Covid-19 outbreak on human health.

A case report of ulceroglandular tularemia caused by Francisella tularensis subsp. Holarctica in Iran.

BACKGROUND: Tularemia is a zoonotic disease that has been reported in many countries of the Northern Hemisphere. However, in some countries, such as Iran, this disease has been neglected by the health care system, and it is under-reported. CASE PRESENTATION: Here we report an unusual case of ulceroglandular tularemia occurring in a 35-year-old woman who presented with a skin lesion of the left flank, inguinal lymphadenopathy, and an abdominal abscess. The serological and real-time PCR tests for tularemia were positive for this patient, and infection by Francisella tularensis subsp. holarctica was confirmed. CONCLUSIONS: It is necessary to implement various educational programs to increase the awareness of physicians with tularemia.

Advances and applications of dextran-based nanomaterials targeting inflammatory respiratory diseases

Dextran, a hydrophilic polysaccharide consists essentially of α-1,6 linked glucopyranoside residues that form the parent chain, along with α-1,2/3/4 linked residues that constitute its side chain. A considerable biocompatibility, stability under mildly acidic and basic conditions, solubility in water, non-immunogenicity, and presence of chemically modifiable –OH groups make dextran an ideal candidate for development of drug delivery vehicles and excipients. The presence of α-1,6 linkages in the parent chain provides enhanced chain mobility that determines the aqueous solubility of dextran, while its metabolism by the digestive enzymes to generate physiologically harmless degradation products validates its biocompatibility. Native dextran can be tuned for the development of pH-sensitive delivery systems by chemical modification that ensure an optimal drug concentration at the target site, and lowered dosing frequency that may ensure an overall improved patient compliance. The physicochemical properties of dextran can be changed by performing a chemical modification predominantly at the –OH group to obtain ester, ether, acetal, and dialdehyde of dextran. The review presented by us is a comprehensive account of the chemical modification strategies for native dextran and their clinical applications in containing pulmonary diseases. Furthermore, the presented review highlights the importance of nanomaterials derived from chemically modified dextran for the management of an optimal respiratory health by containing the inflammatory respiratory diseases.

EFSA and ECDC publishes EU One Health 2020 zoonoses report

The European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC) have published the EU One Health 2020 Zoonoses Report. Campylobacteriosis was the most reported zoonosis in the EU in 2020, with 120,946 cases compared to more than 220,000 the previous year. This was followed by salmonellosis, which affected 52,702 people, compared to 88,000 in 2019. The number of reported foodborne outbreaks fell by 47%, with the report acknowledging the impact of the COVID-19 pandemic in the drop in reported zoonotic diseases in humans. The next most commonly reported diseases were yersiniosis, with 5,668 cases, and infections caused by Shiga toxin-producing Escherichia coli, with 4,446 cases. Listeriosis was the fifth most reported zoonosis, mainly affecting people over the age of 64. Listeriosis and West Nile virus (WNV) infections were the diseases with the highest case fatality and hospitalisation rates, with most locally acquired human infections of WNV reported in Greece, Spain and Italy. The report also monitors foodborne outbreaks in the EU, events during which at least two people contract the same illness from the same contaminated food. A total of 3,086 foodborne outbreaks were reported in 2020, with Salmonella remaining the most frequently detected agent, causing around 23% of outbreaks. The most common sources of salmonellosis outbreaks were eggs, egg products and pig meat. The report also includes data on Mycobacterium bovis, Mycobacterium caprae, Brucella, Trichinella, Echinococcus, Toxoplasma gondii, rabies, Q fever and tularaemia.