Xanthomonas immunity proteins protect against the cis-toxic effects of their cognate T4SS effectors.

Many bacteria kill rival species by translocating toxic effectors into target cells. Effectors are often encoded along with cognate immunity proteins that could (i) protect against "friendly-fire" (trans-intoxication) from neighboring sister cells and/or (ii) protect against internal cis-intoxication (suicide). Here, we distinguish between these two mechanisms in the case of the bactericidal Xanthomonas citri Type IV Secretion System (X-T4SS). We use a set of X. citri mutants lacking multiple effector/immunity protein (X-Tfe/X-Tfi) pairs to show that X-Tfis are not absolutely required to protect against trans-intoxication by wild-type cells. Our investigation then focused on the in vivo function of the lysozyme-like effector X-TfeXAC2609 and its cognate immunity protein X-TfiXAC2610. In the absence of X-TfiXAC2610, we observe X-TfeXAC2609-dependent and X-T4SS-independent accumulation of damage in the X. citri cell envelope, cell death, and inhibition of biofilm formation. While immunity proteins in other systems have been shown to protect against attacks by sister cells (trans-intoxication), this is an example of an antibacterial secretion system in which the immunity proteins are dedicated to protecting cells against cis-intoxication.

Ethanol endometrioma sclerotherapy: safety through 8 years of experience.

STUDY QUESTION: What are the complications of transvaginal ethanol sclerotherapy for the treatment of endometriomas? SUMMARY ANSWER: Sclerotherapy is a reliable, minimally invasive method applicable in outpatient procedures but with specific and potential life-threatening complications that need to be identified and prevented. WHAT IS KNOWN ALREADY: There are currently few data on the use of transvaginal ethanol sclerotherapy, and we mainly note septic complications. STUDY DESIGN, SIZE, DURATION: A retrospective observational cohort study was carried out. The study was conducted at an academic hospital and included 126 women aged 31.9 ± 5.5 years (mean ± SD), between November 2013 and June 2021. We analyzed a total of 157 ethanol sclerotherapy treatment (EST), treated by 131 EST procedures, in 126 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with an indication for transvaginal ethanol sclerotherapy. Indications were women with at least one endometrioma over 10 mm, isolated or associated with other endometriosis locations, requiring treatment for pain or infertility before assisted reproductive treatment. We followed a standardized transvaginal ethanol sclerotherapy procedure consisting of an ultrasound-guided transvaginal puncture of one or more endometriomas under general anesthesia. The cyst content was completely removed and flushed with saline solution. Ethanol (96%) was injected at 60% of the initial volume of the endometrioma, remained in the cyst for 10 min and was then completely removed. Ethanol loss was defined as a loss of 5 ml or more than 10% of the initial volume of the injected ethanol. Failure was defined by the contraindication of endometrioma puncture because of interposition of the digestive tract, ethanol loss in the previous endometrioma treated (in case of multiple ESTs), failure to aspirate the endometriotic fluid, contraindication to start ethanol injection owing to saline solution leakage, or contraindication to continue ethanol injection owing to suspicions of ethanol leakage at sonography. Intraoperative complications were defined by ethanol loss, positive blood alcohol level, and ethanol intoxication. Postoperative complications were defined by fever, biological inflammatory syndrome, and ovarian abscess. Complications were classified according to the Clavien and Dindo surgical classification, which is a system for classifying postoperative complications in five grades of increasing severity. MAIN RESULTS AND THE ROLE OF CHANCE: We reported a total of 17/157 (10.8%) transvaginal ethanol sclerotherapy failures during 14/131 (10.7%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. In the same sets of data, complication was reported for 15/157 (9.5%) transvaginal ethanol sclerotherapy in 13/131 (9.9%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. Nine of 126 women (7.1%) had a grade I complication, one (0.8%) had a grade II complication (medical treatment for suspicion of pelvic infection), two (1.6%) had a grade III complication (ovarian abscess) and one (0.8%) had a grade IV complication (ethanol intoxication). We did not observe any grade V complications. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study and pain assessment not considered. The benefit-risk balance of endometrioma transvaginal ethanol sclerotherapy was not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: Our study is the first to evaluate the complications of transvaginal ethanol sclerotherapy with such a large cohort of women in a standardized protocol. Transvaginal ethanol sclerotherapy seems to be an effective alternative to laparoscopic surgery in the management of endometriomas and limits the alteration of ovarian reserve. Transvaginal ethanol sclerotherapy is a reliable, minimally invasive method applicable on an outpatient basis. The majority of complications are Clavien-Dindo ≤IV, for which preventative measures, or at least early diagnosis and treatment, can be easily performed. The risk of ethanol intoxication is rare, but it is a life-threatening risk that must be avoided by appropriate implementation and promotion of the sclerotherapy procedures. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Aix Marseille University's ethics committee registration number 2021-06-03-01.

Ketone Supplementation Dampens Subjective and Objective Responses to Alcohol: Evidence From a Preclinical Rat Study and a Randomized, Cross-Over Trial in Healthy Volunteers.

BACKGROUND: Previous preclinical and human studies have shown that a high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal. However, the effects of KS on alcohol sensitivity are unknown. METHODS: In this single-blind, cross-over study, 10 healthy participants (3 females) were administered a single, oral dose of a KS (25 g of ketones from D-ß-hydroxybutyric acid and R-1,3-butanediol) or placebo 30 minutes before an oral alcohol dose (0.25 g/kg for women; 0.31 g/kg for men). Assessments of breath alcohol concentration and blood alcohol levels (BAL) and responses on the Drug Effect Questionnaire were repeatedly obtained over 180 minutes after alcohol consumption. In a parallel preclinical study, 8 Wistar rats (4 females) received an oral gavage of KS (0.42 g ketones/kg), water, or the sweetener allulose (0.58 g/kg) followed 15 minutes later by an oral alcohol dose (0.8 g/kg). BAL was monitored for 240 minutes after alcohol exposure. RESULTS: In humans, the intake of KS before alcohol significantly blunted breath alcohol concentration and BAL, reduced ratings of alcohol liking and wanting more, and increased disliking for alcohol. In rats, KS reduced BAL more than either allulose or water. CONCLUSION: KS altered physiological and subjective responses to alcohol in both humans and rats, and the effects were likely not mediated by the sweetener allulose present in the KS drink. Therefore, KS could potentially reduce the intoxicating effects of alcohol.

Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.

BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk. METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones. RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20). CONCLUSIONS: Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

GC-MS analysis of 4-hydroxyproline: elevated proline hydroxylation in metformin-associated lactic acidosis and metformin-treated Becker muscular dystrophy patients.

Metformin (N,N-dimethylbiguanide), an inhibitor of gluconeogenesis and insulin sensitizer, is widely used for the treatment of type 2 diabetes. In some patients with renal insufficiency, metformin can accumulate and cause lactic acidosis, known as metformin-associated lactic acidosis (MALA, defined as lactate ≥ 5 mM, pH < 7.35, and metformin concentration > 38.7 µM). Here, we report on the post-translational modification (PTM) of proline (Pro) to 4-hydroxyproline (OH-Pro) in metformin-associated lactic acidosis and in metformin-treated patients with Becker muscular dystrophy (BMD). Pro and OH-Pro were measured simultaneously by gas chromatography-mass spectrometry before, during, and after renal replacement therapy in a patient admitted to the intensive care unit (ICU) because of MALA. At admission to the ICU, plasma metformin concentration was 175 µM, with a corresponding lactate concentration of 20 mM and a blood pH of 7.1. Throughout ICU admission, the Pro concentration was lower compared to healthy controls. Renal excretion of OH-Pro was initially high and decreased over time. Moreover, during the first 12 h of ICU admission, OH-Pro seems to be renally secreted while thereafter, it was reabsorbed. Our results suggest that MALA is associated with hyper-hydroxyprolinuria due to elevated PTM of Pro to OH-Pro by prolyl-hydroxylase and/or inhibition of OH-Pro metabolism in the kidneys. In BMD patients, metformin, at the therapeutic dose of 3 × 500 mg per day for 6 weeks, increased the urinary excretion of OH-Pro suggesting elevation of Pro hydroxylation to OH-Pro. Our study suggests that metformin induces specifically the expression/activity of prolyl-hydroxylase in metformin intoxication and BMD.

Oxytocin: physiology, pharmacology, and clinical application for labor management.

Oxytocin is a peptide hormone that plays a key role in regulating the female reproductive system, including during labor and lactation. It is produced primarily in the hypothalamus and secreted by the posterior pituitary gland. Oxytocin can also be administered as a medication to initiate or augment uterine contractions. To study the effectiveness and safety of oxytocin, previous studies have randomized patients to low- and high-dose oxytocin infusion protocols either alone or as part of an active management of labor strategy along with other interventions. These randomized trials demonstrated that active management of labor and high-dose oxytocin regimens can shorten the length of labor and reduce the incidence of clinical chorioamnionitis. The safety of high-dose oxytocin regimens is also supported by no associated differences in fetal heart rate abnormalities, postpartum hemorrhage, low Apgar scores, neonatal intensive care unit admissions, and umbilical artery acidemia. Most studies reported no differences in the cesarean delivery rates with active management of labor or high-dose oxytocin regimens, thereby further validating its safety. Oxytocin does not have a predictable dose response, thus the pharmacologic effects and the amplitude and frequency of uterine contractions are used as physiological parameters for oxytocin infusion titration to achieve adequate contractions at appropriate intervals. Used in error, oxytocin can cause patient harm, highlighting the importance of precise administration using infusion pumps, institutional safety checklists, and trained nursing staff to closely monitor uterine activity and fetal heart rate changes. In this review, we summarize the physiology, pharmacology, infusion regimens, and associated risks of oxytocin.

Implications of drug intoxication on donor utilization and outcomes in liver transplantation.

INTRODUCTION: This study evaluates the implications of drug intoxication (DI) on donor utilization and outcomes in liver transplantation (LT). METHODS: The UNOS STAR database was evaluated for all potential donors and adult, first-time, whole LT between 2005 and 2019. Logistic regression analyses evaluated liver utilization; proportional hazards modeling assessed risk of 1-year graft loss. RESULTS: A total of 132 783 potential donors (10 205, 7.7% from DI), and 90 612 adult LT were identified (7490, 8.3% from DI). DI donors had median age 32 years (IQR 26-40 years, p < .001), were 42.6% female (n = 4346), and 15.5% were DCD donors (n = 1583). Utilization of DI donors changed over time, such that by 2015-2019 they were the most likely donor cause of death (COD) to be utilized. Among LT recipients, there were insignificant differences (<2% variance) in age, gender, ethnicity, and etiology of liver disease according to donor COD. Recipients with MELD scores >30 more frequently received grafts from donors with trauma (23.8%) and DI (21.8%) versus cardiovascular (20.0%) and CVA/stroke (19.9%, p < .001). Among DBD donors, DI-COD was associated with superior 1-year graft survival compared to donors from trauma (HR 1.172, 95% CI 1.057-1.300) and CVA/stroke (HR 1.404, 95% CI 1.264-1.561, p < .001). Donor COD was not significantly associated with 1-year graft loss among DCD donors. CONCLUSIONS: There is an increased likelihood of donor utilization when COD is drug overdose and an increased likelihood of 1-year graft survival compared to donors from trauma, CVA/stroke, and other COD.

Death by accidental intravenous administration of gasoline.

Herein, we present the case of accidental intravenous injection of gasoline in a 62-year-old male who was admitted to a dialysis center for his regular hemodialysis. Due to previous contact with another SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) positive patient, the hemodialysis was conducted in an isolated room. At the end of the procedure, the nurse, wearing all necessary personal protective equipment (PPE), in the intent to clean the dialysis catheter, applied medical gasoline, instead of 0.9% sodium chloride, intravenously to the patient. Soon afterwards, the patient's clinical condition deteriorated, and cardiopulmonary resuscitation was started. Despite the immediate reaction of the medical staff, after two successful cardiopulmonary reanimation and necessary intensive care measures, the patient suffered respiratory, metabolic, and lactic acidosis, hypotension, and tachyarrhythmia and ultimately died 7 h after the incident. The autopsy was conducted under the order of the district attorney. Main autopsy findings were marked congestion; right pleural and pericardial effusion; brain and lung edema; enlarged heart with left ventricle thickening and mild perivascular fibrosis; nephrosclerosis; tubular thyroidization; and interstitial fibrosis with inflammation. Gasoline presence was indisputably proven by conducted toxicology analysis in lung, bile, and brain samples. Traces of gasoline could be noted in the patient's blood sample in comparison to the blood that did not contain gasoline, but it was not possible to confidently claim that gasoline was present in the blood. Based on relevant findings, we concluded that the death of the patient was violent and that the cause of death was acute intoxication by gasoline.

First evidence in an oversea French department of the deadly risk of protonitazene use: about 5 post mortem cases.

Protonitazene is a synthetic benzoimidazole opioid of the nitazenes class, developed in the 1950s as an effective analgesic, but never released in the market due to severe side effects and major risk of dependence. The laboratory was involved in the determination of the cause of death for 5 subjects deceased in a French department of the Indian Ocean. The 5 victims were male, aged between 20 and 35 years. The first 2 victims were found dead in their prison cell and the 3 other victims were found dead in a squat. Therefore, we have developed and validated a specific procedure to identify and quantify the drug in post mortem specimens using LC-MS/MS. The procedure involves extraction of 0.5 mL fluid at pH 9.5 with a mixture of organic solvents in presence of 20 ng fentanyl-d5 used as internal standard. Linearity of the method was verified from 0.1 to 20 ng/mL in both whole blood and urine (r2 = 0.9983 and 0.9993, respectively). The limit of detection was estimated at 0.05 ng/mL in each matrix. Protonitazene was identified at < LOQ to 0.8 ng/mL, 0.4 to 2.9 ng/mL and 3.0 to 8.0 ng/mL in femoral blood, urine and bile, respectively. Post mortem concentrations were very low, which is consistent with reported high toxicity of protonitazene. As nitazenes represent a growing threat to public health in various parts of the world, this method seems to be a good response to the challenges posed by the identification of this class of substances.

Alpha-methyltryptamine and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) fatal co-intoxication: case report and review of literature.

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

Is ethyl chloride the new nitrous oxide? A case report.

BACKGROUND: Over the last decade, there has been an emerging trend of recreational misuse of several drugs and inhaled solvent including ethyl chloride. This case report follows CARE guidelines and highlights, with supporting video, the neurological features of ethyl chloride intoxication. CASE PRESENTATION: A 48-year-old man was seen for the sudden occurrence of an unsteady gait with dizziness. His only medical history was a chronic and treated HIV infection without any complications. Clinical examination revealed a cerebellar syndrome associated with impairment of short-term memory. Biological and radiological workups were normal. After several days, the patient recalled ethyl chloride inhalation. He fully recovered after being discharged from hospital. CONCLUSION: Clinicians should recognise the clinical features and neurological manifestations of ethyl chloride intoxication due to the potential fatal cardiovascular complications of this intoxication.

Impact of a Divided Phenobarbital Load and Taper Compared With Lorazepam Symptom Triggered Therapy in Hospitalized Patients.

BACKGROUND: Benzodiazepines are the preferred treatment for alcohol withdrawal. Phenobarbital is an alternative in the setting of prescriber expertise or benzodiazepine contraindication. OBJECTIVE: To evaluate the efficacy and safety of a phenobarbital dosing strategy aimed at treating a spectrum of alcohol withdrawal symptoms across various patient populations. METHODS: Retrospective review of patients admitted with concerns of alcohol withdrawal between May 2018 and November 2022. Patients were separated into a before-after cohort of lorazepam or phenobarbital. The primary outcome was hospital length of stay (LOS). Secondary outcomes were intensive care unit (ICU) LOS, escalation of respiratory support, increased level of care (LOC), and incidence of delirium tremens and/or seizures. RESULTS: Two hundred and seventy-seven patients received lorazepam and 198 received phenobarbital. Hospital LOS was longer in the phenobarbital cohort compared with the lorazepam cohort (6.9 vs 9.3 days). There was no difference in ICU LOS. Level of care increases were fewer in the phenobarbital cohort (4 events vs 19 events). There were higher rates of non-invasive respiratory interventions in the lorazepam cohort and higher rates of mechanical ventilation in the phenobarbital cohort. Utilization of phenobarbital was attributed to a reduction in delirium tremens and seizures. CONCLUSION AND RELEVANCE: This study is novel because of the broad application of a phenobarbital order set across multiple levels of care and patient admission diagnoses. A risk targeted split load intravenous phenobarbital order set can safely be administered to patients with fewer escalations of care, seizures, delirium tremens, and respiratory care escalation.

Water insecurity among seasonal agriculture workers: perspectives from Spanish professionals.

BACKGROUND: Migrant seasonal agricultural workers face conditions of material vulnerability such as inadequate housing difficulties prevent access to running water supplies. The purpose of this study is to explore the perceptions of professionals involved in the care and support of seasonal migrant agricultural workers, as it relates to water access and water consumption and their impact on these workers' health, in a context of COVID-19 pandemic. METHODS: A qualitative exploratory and descriptive study was conducted in 2021 as part of a larger research project, based on 63 personal semi-structured interviews with professionals who provided support to seasonal migrant agricultural workers in three Spanish autonomous regions. COREQ checklist was used for reporting. The interviews were recorded, transcribed, and imported into ATLAS.ti-9 for an inductive thematic analysis. RESULTS: The results have been structured into two main themes: (1) Accessing and obtaining water; and (2) Health problems related to water consumption. Seasonal migrant agricultural workers experience barriers to obtaining safe water for hygiene, cleaning, food preparation and drinking. The implementation of regulations to reduce COVID-19 transmission resulted in improved hygiene levels in the migrants' quarters, including access to safe drinking water. CONCLUSION: This study suggests that water insecurity experienced by migrant seasonal agricultural workers in Spain results from their poor living conditions and causes health problems related to a lack of hygiene and the use of unsafe water. Sustainable solutions are needed beyond the pandemic in order to provide migrant workers with adequate living conditions and ensure their water needs are fulfilled.

Blood lead levels in an endangered vulture decline following changes in hunting activity.

Lead ammunition stands out as one of the most pervasive pollutants affecting wildlife. Its impact on bird populations have spurred efforts for the phase-out of leaded gunshot in several countries, although with varying scopes and applications. Ongoing and future policy changes require data to assess the effectiveness of adopted measures, particularly in the current context of biodiversity loss. Here, we assessed the long-term changes in blood lead (Pb) levels of Egyptian vultures from the Canary Islands, Spain, which have been severely affected by Pb poisoning over the past two decades. During this period, the reduction in hunting pressure and changes in legislation regarding firearms usage for small game hunting likely contributed to a decrease in environmental Pb availability. As anticipated, our results show a reduction in Pb levels, especially after the ban on wild rabbit hunting with shotgun since 2010. This effect was stronger in the preadult fraction of the vulture population. However, we still observed elevated blood Pb levels above the background and clinical thresholds in 5.6% and 1.5% of individuals, respectively. Our results highlight the positive impact of reducing the availability of Pb from ammunition sources on individual health. Nonetheless, the continued use of Pb gunshot remains an important source of poisoning, even lethal, mainly affecting adult individuals. This poses a particular concern for long-lived birds, compounding by potential chronic effects associated with Pb bioaccumulation. Our findings align with recent studies indicating insufficient reductions in Pb levels among European birds of prey, attributed to limited policy changes and their uneven implementation. We anticipated further reductions in Pb levels among Egyptian vultures with expanded restrictions on hunting practices, including a blanket ban on Pb shot usage across all small game species.

Abomasitis associated with halofuginone intoxication in pre-weaned calves.

BACKGROUND: In this case series abomasitis as a consequence of halofuginone intoxication is suspected. CASE PRESENTATION: Seven Belgian-Blue calves with complaints of anorexia and weight loss were presented to an university clinic. Ultrasonography showed thickening and edema of the abomasal wall in all cases, suggesting abomasitis. Abomasitis was confirmed on necropsy in three cases. Retrospective analysis clarified the uptake of an overdose of halofuginone lactate (348-421 µg/kg/day). Four animals fully recovered after removal of halofuginone lactate administration, therapy for comorbidities (pneumonia, diarrhoea) and supportive therapy. CONCLUSION: To the authors' knowledge, this case series is the first report associating halofuginone lactate use with abomasitis. This was suspected after clinical improvement of four of the presented animals after terminating the administration of a high dose of halofuginone lactate, and exclusion of other possible causes. Underlying mechanisms are still unclear.

Impact of Acute Alcohol Consumption on Sexuality: A Look at Psychological Mechanisms.

Alcohol's link with sexuality is long-standing and prominent. While research continues to document robust associations between drinking and sexual behavior, scientific attention now centers primarily on evaluating mechanisms and attendant theoretical frameworks to advance our understanding of how alcohol exerts a causal impact. We describe four domains with reliable evidence of alcohol effects: sexualized social perceptions, sexual arousal, sexual risk taking, and sexual assault. We consider three contextual frames: distal factors associated with encountering opportunities for alcohol-involved sex, proximal factors associated with alcohol's acute effects, and distal-proximal interactions. We then examine the empirical support for mechanisms embedded within four theoretical frameworks: alcohol disinhibition, alcohol expectancy, alcohol myopia, and emotion regulation. Support for disinhibition mechanisms is evident with sexual arousal only. Expectancy and myopia mechanisms enjoy support across domains and make up bases for integrative expectancy-myopia causal explanations. Emotion regulation mechanisms evidence preliminary support in risk taking and sexual assault. Implications and future directions are considered.

A case of lethal suicidal intoxication with propafenone and diazepam.

Diazepam poisoning is a common emergency situation, but propafenone poisoning is relatively rare. We reported a case of propafenone poisoning combined with diazepam. An 18-year-old female patient was admitted to our hospital with an overdose of oral propafenone and diazepam. The patient was treated with medication that proved to be useful, but the sinus rhythm could not be recovered, and cardiac arrest occurred. A bipolar temporary pacemaker and extracorporeal membrane oxygenation (ECMO) were installed. However, even with multiple electrode positions, effective capture could not be achieved. The patient eventually died. We should be alert to the possibility of co-poisoning.

The efficacy of intermittent hemodialysis in severe bromovalerylurea poisoning.

Bromvalerylurea (BVU) is a sedative-hypnotic drug with a high risk of acute poisoning. In the present case, hemodialysis (HD) was introduced in a patient with severe BVU poisoning who later demonstrated respiratory arrest, and then HD clearances (CLHD) were assessed in detail. A 20-year-old female was transported to the emergency department by ambulance, an estimated two to four hours after orally ingesting 144 tablets of Utto® (12,000 mg BVU) in a suicide attempt. The patient was comatose on arrival. After intratracheal intubation, 50 g of activated charcoal was administered through nasogastric tube. She was then transferred to the intensive care unit. Ten hours after arrival at the hospital, her light reflex, contralateral light reflex, corneal reflex, and spontaneous respiration disappeared, resulting in an introduction of HD 16 h after arrival. Eighteen hours after arrival, her light reflex, contralateral light reflex, and corneal reflexes had recovered. Twenty-one hours after arrival, her consciousness level improved and the patient was weaned from HD. During HD treatment, blood samples were collected pre-HD and post-HD every hour. Serum BVU concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median CLHD was 133.61 mL/min, and the systemic clearance (CLSYS) was 117.77 mL/min. Higher CLHD of BVUs over CLSYS suggests that HD may play an important role in the treatment of severe BVU poisoning.

The impact of recreational cannabis legalization on ED visit rates for acute cannabis intoxication.

BACKGROUND: In December 2018 the Michigan Regulation and Taxation of Marihuana Act legalized the recreational use of cannabis in Michigan. There are now high potency forms of cannabis readily available in the state, which could result in increased emergency department (ED) visit rates due to intoxication in adults and children. Although cannabis related visits account for a small percentage of all adult and pediatric ED visits, they impose a significant burden on the health care system's resources. This study aimed to assess the impact of the legalization of recreational marijuana on the rate of ED visits for acute cannabis intoxication. METHODS AND DESIGN: We utilized the legalization of marijuana in the state of Michigan to conduct a natural experiment utilizing a retrospective observational cohort design of ED visits for acute intoxication before and after legalization. The study was conducted at a health system composed of eight hospitals in southeast Michigan, including both academic and community hospitals serving a diverse patient population. We estimated monthly cannabis-related ED visits based on cannabis-related ICD-10 discharge codes and total ED visits using electronic health record data from 2016 to 2022. A negative-binomial (NB) regression model was used to estimate the immediate and cumulative changes in cannabis-related ED visit rate after legalization. RESULTS: There were a total of 2177 ED visits from 2066 patients for cannabis intoxication in our study cohort. Of the 2177 visits, 671 were before and 1506 were after legalization. In the univariate analysis, recreational cannabis legalization was associated with an increase in the average cannabis-related ED visit rate (Rate Ratio [RR]:1.70, 95% CI: (1.49, 1.94), p-value <0.001). In the multivariate analysis adjusting for age, results remain significant (RR 1.47, 95% CI (1.29, 1.70), p-value <0.001). The increased visit rate occurred in the first month after legalization; however, the slope of the increasing rate of ED visits were similar before and after cannabis legalization (RR, 1.28, 95% CI (1.07, 1.54), p-value <0.001). CONCLUSIONS: The legalization of recreational cannabis in Michigan was associated with an immediate increase in ED visit rates for acute cannabis intoxications across all ages, especially among middle-aged adults, in the context of an stably increasing ED visit rate.

Intoxication and Glasgow coma scale scores in patients with head trauma.

INTRODUCTION: The Glasgow Coma Scale (GCS) is an assessment tool commonly used by emergency department (ED) clinicians to objectively describe level of consciousness, especially in trauma patients. This study aims to assess the effect of drug and alcohol intoxication on GCS scores in cases of traumatic head injury. METHODS: In this retrospective chart review study, data were extracted from The Pennsylvania Trauma Systems Foundation Data Base Collection System. Eligible subjects included trauma patients aged 18 years and older, with head trauma, who presented between January 2019 and August 2023. Subjects were matched to controls who did not test positive for drugs or alcohol, matched by Injury Severity Score (ISS) category. RESULTS: Among 1088 subjects, the mean age was 63 (95% CI 62-64). The mean Injury Severity Score was 21 (95% CI 21-22). The median GCS among all subjects was 14 (IQR 6-15). Cases with alcohol or drug use were matched to controls without alcohol or drug use, and were matched by categories of Injury Severity Score. Cases with alcohol or drug use had lower GCS (median 13; IQR 3-15), compared to cases without alcohol or drug use (median 15; IQR 13-15) (p < 0.0001, Wilcoxon Rank Sum Test). CONCLUSIONS: Among patients with head trauma, intoxicated patients had statistically significant lower GCS scores as compared to matched patients with similar Injury Severity Scores.