Background Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a potentially life-threatening clinical condition characterized by bradycardia, renal ...failure, atrioventricular (AV) node blocking, shock, and hyperkalemia. It constitutes a vicious circle in which the accumulation of pharmacologically active compounds and hyperkalemia lead to hemodynamic instability and heart failure. Case presentation A 66-year-old Caucasian female patient was admitted to the emergency department presenting with fatigue and bradycardia. Upon examination, the patient was found to be anuric and hypotensive. Laboratory investigations revealed metabolic acidosis and hyperkalemia. Clinical evaluation suggested signs of digoxin toxicity, with serum digoxin concentrations persistently elevated over several days. Despite the implementation of antikalemic measures, the patient's condition remained refractory, necessitating renal dialysis and administration of digoxin immune fab. Conclusion Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a life-threatening condition that requires prompt management. It is important to also consider potential coexisting clinical manifestations indicative of intoxication from other pharmacological agents. Specifically, symptoms associated with the accumulation of drugs eliminated via the kidneys, such as digoxin. These manifestations may warrant targeted therapeutic measures. Keywords: Digoxin toxicity, BRASH syndrome, Bradycardia, Hyperkalemia, Case report
Glutathione transferases (GSTs) are dimeric enzymes involved in cell detoxification versus many endogenous toxic compounds and xenobiotics. In addition, single monomers of GSTs appear to be involved ...in particular protein−protein interactions as in the case of the pi class GST that regulates the apoptotic process by means of a GST−c-Jun N-terminal kinase complex. Thus, the dimer−monomer transition of GSTs may have important physiological relevance, but many studies reached contrasting conclusions both about the modality and extension of this event and about the catalytic competence of a single subunit. This paper re-examines the monomer−dimer question in light of novel experiments and old observations. Recent papers claimed the existence of a predominant monomeric and active species among pi, alpha, and mu class GSTs at 20−40 nM dilution levels, reporting dissociation constants (K d) for dimeric GST of 5.1, 0.34, and 0.16 μM, respectively. However, we demonstrate here that only traces of monomers could be found at these concentrations since all these enzymes display K d values of ≪1 nM, values thousands of times lower than those reported previously. Time-resolved and steady-state fluorescence anisotropy experiments, two-photon fluorescence correlation spectroscopy, kinetic studies, and docking simulations have been used to reach such conclusions. Our results also indicate that there is no clear evidence of the existence of a fully active monomer. Conversely, many data strongly support the idea that the monomeric form is scarcely active or fully inactive.
Abstract
Background
Nomograms are easy-to-handle clinical tools which can help in estimating the risk of adverse outcome in certain population. This multi-center study aims to create and validate a ...simple and usable clinical prediction nomogram for individual risk of post-traumatic Intracranial Hemorrhage (ICH) after Mild Traumatic Brain Injury (MTBI) in patients treated with Direct Oral Anticoagulants (DOACs).
Methods
From January 1, 2016 to December 31, 2019, all patients on DOACs evaluated for an MTBI in five Italian Emergency Departments were enrolled. A training set to develop the nomogram and a test set for validation were identified. The predictive ability of the nomogram was assessed using AUROC, calibration plot, and decision curve analysis.
Results
Of the 1425 patients in DOACs in the study cohort, 934 (65.5%) were included in the training set and 491 (34.5%) in the test set. Overall, the rate of post-traumatic ICH was 6.9% (7.0% training and 6.9% test set). In a multivariate analysis, major trauma dynamic (OR: 2.73, p = 0.016), post-traumatic loss of consciousness (OR: 3.78, p = 0.001), post-traumatic amnesia (OR: 4.15, p < 0.001), GCS < 15 (OR: 3.00, p < 0.001), visible trauma above the clavicles (OR: 3. 44, p < 0.001), a post-traumatic headache (OR: 2.71, p = 0.032), a previous history of neurosurgery (OR: 7.40, p < 0.001), and post-traumatic vomiting (OR: 3.94, p = 0.008) were independent risk factors for ICH. The nomogram demonstrated a good ability to predict the risk of ICH (AUROC: 0.803; CI95% 0.721–0.884), and its clinical application showed a net clinical benefit always superior to performing CT on all patients.
Conclusion
The Hemorrhage Estimate Risk in Oral anticoagulation for Mild head trauma (HERO-M) nomogram was able to predict post-traumatic ICH and can be easily applied in the Emergency Department (ED).
Many details of oxidative folding of proteins remain obscure, in particular, the role of oxidized glutathione (GSSG). This study reveals some unknown aspects. When a reduced ribonuclease A refolds in ...the presence of GSSG, most of its eight cysteines accomplish a very fast glutathionylation. In particular, one single cysteine, identified as Cys95 by mass spectrometry, displays 3600 times higher reactivity when compared with an unperturbed protein cysteine. Furthermore, the other five cysteines show 40-50 times higher reactivity toward GSSG. This phenomenon is partially due to a low p
value of most of these cysteines (average p
= 7.9), but the occurrence of a reversible GSSG-ribonuclease complex (
= 0.12 mM) is reasonably responsible for the extraordinary hyper-reactivity of Cys95. Neither hyper-reactivity nor some protein-disulfide complexes have been found by reacting a reduced ribonuclease with other natural disulfides i.e., cystine, cystamine, and homocystine. Hyper-reactivity of all cysteines was observed toward 5,5'-dithiobis-(2-nitrobenzoic acid). Given that GSSG is present in high concentrations in the endoplasmic reticulum, this property may shed light on the early step of its oxidative folding. The ultra-rapid glutathionylation of cysteines, only devoted to form disulfides, is a novel property of the molten globule status of the ribonuclease.
During the first months of the COVID-19 pandemic, local health authorities in most Italian regions prescribed a reduction of ordinary outpatient and community mental health care. The aim of this ...study was to assess the impact of the COVID-19 pandemic on access to the emergency departments (ED) for psychiatric consultation in the pandemic years 2020 and 2021 compared to 2019.
This is a retrospective study conducted by using routinely collected administrative data of the two EDs of the Verona Academic Hospital Trust (Verona, Italy). All ED psychiatry consultations registered from 01.01.2020 to 31.12.2021 were compared with those registered in the pre-pandemic year (01.01.2019 to 31.12.2019). The association between each recorded characteristic and the year considered was estimated by chi-square or Fisher's exact test.
A significant reduction was observed between 2020 and 2019 (-23.3%) and between 2021 and 2019 (-16.3%). This reduction was most evident in the lockdown period of 2020 (-40.3%) and in the phase corresponding to the second and third pandemic waves (-36.1%). In 2021, young adults and people with diagnosis of psychosis showed an increase in requests for psychiatric consultation.
Fear of contagion may have been an important factor in the overall reduction in psychiatric consultations. However, psychiatric consultations for people with psychosis and for young adults increased. This finding underlines the need for mental health services to implement alternative outreach strategies aimed to support, in times of crisis, these vulnerable segments of the population.
Nerium oleander is a toxic plant containing cardiac glycosides throughout all its parts, thereby posing severe health risks upon ingestion. The clinical manifestations of oleander poisoning closely ...resemble those of digoxin toxicity, encompassing a spectrum of gastrointestinal symptoms, neuropsychiatric disorders, and cardiac disturbances. This scientific case report describes a case of accidental intoxication resulting from the consumption of an oleander leaves infusion misidentified as bay laurel leaves.
An 84-year-old patient consumed an oleander leaves infusion, and after four hours experienced gastrointestinal symptoms. He contacted the poison control center (PCC) and was advised to go to the emergency department (ED). Upon arrival, the patient presented stable vital signs without cardiac irregularities. The PCC recommended the administration of activated charcoal, vigilant monitoring, including electrocardiography (ECG). Subsequent ECGs assessments revealed the presence of third-degree atrioventricular block; in consultation with the PCC, digoxin-specific antibodies and external pacing were necessary. The patient was discharged on the eighth day in good hemodynamic condition, and outpatient follow-up visits showed clinical stability.
This study offers insights for the management of similar cases. The limitations of conventional assays in measuring oleander cardiac glycosides were observed, emphasizing reliance on clinical evaluation. The patient's trajectory, remaining asymptomatic despite severe ECG changes post-ingestion, underscores the importance of prolonged clinical monitoring.
•Standard digoxin tests don't accurately detect oleander cardiac glycosides.•Prolonged clinical monitoring with frequent ECGs in oleander intoxication is imperative.•Involving specialized poison response units is crucial for an integrated treatment approach in case of oleander intoxication.
Obesity is independently associated with disturbances in lipid and lipoprotein metabolism, oxidative stress, and is a well-established independent risk factor for cardiovascular diseases (CVD). Human ...paraoxonase 1 (PON1) is a pleotropic high-density lipoprotein (HDL)-associated enzyme with antioxidant and anti-inflammatory proprieties that have been suggested to contribute to the athero-protective function of the lipoprotein. The aim of this study was to investigate whether obesity is associated with PON1 activity and whether this association is influenced by oxidative stress, inflammation and HDL cholesterol (HDL-C) concentration. The promiscuous activities, arylesterase and paraoxonase, and the putative physiological activity, lactonase, of PON1 were assessed in the serum of 214 obese and severely obese, 101 overweight and 129 normal-weight women. Levels of high-sensitivity C-reactive protein (hs-CRP), hydroperoxides (by-products of lipid oxidative damage) and lipid profiles were also evaluated. Arylesterase activity was the only activity that significantly differed across the groups (ANOVA, p < .01), with the greatest decrease observed in individuals with body mass index (BMI) > 40 kg/m
2
compared to controls (p < .001). This activity was also inversely, although weakly (r = −0.160, p < .001) correlated with the BMI, and the association was independent of age and levels of oxidative stress and inflammation, but not of HDL-C concentration. In conclusion, our results suggest that the apparent obesity-associated decrement of PON1 activity might simply reflect the decrease in concentration of its plasmatic carrier.
Particulate matter (PM) air pollution has been associated with cardiovascular and respiratory disease. Recent studies have proposed also a link with venous thromboembolism (VTE) risk. This study was ...aimed to evaluate the possible influence of air pollution-related changes on the daily flux of patients referring to the Emergency Department (ED) for VTE, dissecting the different effects of coarse and fine PM. From July 1(st), 2007, to June 30(th), 2009, data about ED accesses for VTE and about daily concentrations of PM air pollution in Verona district (Italy) were collected. Coarse PM (PM(10-2.5)) was calculated by subtracting the finest PM(2.5) from the whole PM(10). During the index period a total of 302 accesses for VTE were observed (135 males and 167 females; mean age 68.3 ± 16.7 years). In multiple regression models adjusted for other atmospheric parameters PM(10-2.5), but not PM(2.5), concentrations were positively correlated with VTE (beta-coefficient = 0.237; P = 0.020). During the days with high levels of PM(10-2.5) (≥ 75(th) percentile) there was an increased risk of ED accesses for VTE (OR 1.69 with 95%CI 1.13-2.53). By analysing days of exposure using distributed lag non-linear models, the increase of VTE risk was limited to PM(10-2.5) peaks in the short-term period. Consistently with these results, in another cohort of subjects without active thrombosis (n = 102) an inverse correlation between PM(10-2.5) and prothrombin time was found (R = -0.247; P = 0.012). Our results suggest that short-time exposure to high concentrations of PM(10-2.5) may favour an increased rate of ED accesses for VTE through the induction of a prothrombotic state.
More clinical data are required on the safety of direct oral anticoagulants (DOACs). Although patients treated with warfarin and DOACs have a similar risk of bleeding, short-term mortality after a ...gastrointestinal bleeding (GIB) episode in DOAC-treated patients has not been clarified. The objective of this study was to assess differences in 30-day mortality in patients treated with DOACs or warfarin admitted to the emergency department (ED) for GIB. This was a multicentre retrospective study conducted over 2 years. The study included patients evaluated at three different EDs for GIB. The baseline characteristics were included. Subsequently, we assessed the differences in past medical history and clinical data between the two study groups (DOAC and warfarin users). Differences between the two groups were evaluated using Kaplan–Meier curves. Among the 284 patients presenting GIB enrolled in the study period, 39.4% (112/284) were treated with DOACs and 60.6% (172/284) were treated with warfarin. Overall, 8.1% (23/284) of patients died within 30 days. Among the 172 warfarin-treated patients, 8.7% (15/172) died within 30 days from ED evaluation. In the 112 DOAC-treated patients, the mortality rate was 7.1% (8/112). The Cox regression analysis, adjusted for possible clinical confounders, and the Kaplan–Meier curves did not outline differences between the two treatment groups. The present study shows no differences between DOACs and warfarin in short-term mortality after GIB.
There is limited literature on managing chronic lead exposure from non-removable sources such as lead fragments. In this case report, we present the complexities and clinical considerations involved ...in treating an elderly patient who sustained a comminuted knee fracture due to a gunshot wound, complicated by retained lead fragments. This case highlights the absence of comprehensive guidelines for managing chronic lead exposure when complete fragment removal is impractical. It also emphasizes the importance of a multidisciplinary approach to decision-making, while considering patient autonomy in such unique clinical scenarios.
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•Lead toxicity is an underestimated medical concern in cases of gunshot injuries.•The cessation of lead exposure is the primary focus of clinical treatment.•Monitoring of blood lead levels and chelation treatments are recommended.•If surgical removal is not feasible, involve the patient in the therapeutic decision-making process.
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