Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies

Les sous-types de récepteurs de transmission de l'angiotensine II: caractérisation, distribution et mécanisme de transmission du signal

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

EXPLORATION HORMONALE DES HYPOGONADISMES CHEZ L'HOMME ADULTE

GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Inactivation of β-adrenergic receptors by N-ethylmalmeimide: Permissive role of β-adrenergic agents in relation to adenylate cyclase activation

The β1-adrenergic receptors of turkey erythrocyte membranes have been identified by the specific binding of the radiolabeled antagonist (-)-[3H]dihydroalprenolol. Binding of β-adrenergic agonists to these receptors sites sensitizes them to inactivation by the alkylating agent N-ethylmaleimide. A dose- and time-dependent decrease of 45 to 60% of the sites is commonly observed. Binding of (-)-3H-dihydroalprenolol and β-adrenergic agonists to the remaining sites occurs with the same characteristics as for the untreated receptor population. Kinetic experiments reveal that the rate of inactivation is proportional to the concentration of N-ethylmaleimide (between 5.5 and 450μM). In contrast, the rate of inactivation reaches a plateau value when increasing the concentration of the agonist. The rate of inactivation is half-maximal in presence of 1.3 μM (-)-epinephrine or 20μM (+)-epinephrine. This marked stereospecificity, along with the close identity of the above concentrations with the equilibrium dissociation constant (K(D)) of the epinephrine isomers for binding to the β-receptor (i.e. 2.0 μM for (-)-epinephrine and 21 μM for (+)-epinephrine) indicate that N-ethylmaleimide inactivates the agonist-bound form of the receptor. The second-order rate constant (k2) of the inactivation process, in the presence of 15 β-adrenergic ligands, was found to correlate with their capability to stimulate the adenylate cyclase activity, i.e. 'intrinsic activity'. Since all tested ligands were able to cause a complete and dose-dependent displacement of bound (-)-[3H]dihydroalprenolol, it is likely that both the intrinsic activity and k2 of each adrenergic ligand reflect an inherent property of the ligand-bound receptor. The proportionality between k2 and the intrinsic acid activity further suggests that β-adrenergic agonists 'induce' or 'favor' a conformational change of the receptor, resulting in adenylate cyclase activation and the uncovering of an alkylable group which becomes exposed to N-ethylmaleimide in the active conformation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Identification and characterization of α1-adrenergic receptors in human myometrium by [3H]prazosin binding

α1-adrenergic receptors can be directly characterized in myometrial membranes using the specific α1-adrenergic radioligand [3H]prazosin. Compared to the previous approach, this allows a more precise determination of the α1-adrenergic receptor number and of their agonist and antagonist binding properties. Use of this radioligand might prove to be a powerful tool in distinguishing α1-receptors from the total amount of α-adrenergic receptors. As a practical application, it becomes now possible to determine whether the reported influence of sex steroid hormones on the total α-adrenergic receptor population in animal uteri does also apply to the α1-subpopulation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Identification and characterization of α2-adrenergic receptors in human myometrium by [3H]rauwolscine binding

Human myometrium contains α3-adrenergic receptors which can be identified by binding of the α2-adrenergic antagonist [3H]rauwolscine. Scatchard analysis of saturation binding data on myometrial membranes revealed that [3H]rauwolscine bound to a single class on noncooperative sites (262 ± 89 fmol/mg of membrane protein) with high affinity (i.e. with an equilibrium dissociation constant of 5.3 ± 2.2 nM). The α2-adrenergic nature of these sites was derived from the order of potencies and stereospecificity of α-adrenergic agonists and antagonists to compete with [3H]rauwolscine binding.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Differential regulation of α-adrenergic receptor subclasses by gonadal steroids in human myometrium

Adrenergic receptors have been shown to be involved in uterine contractility. α-Adrenergic receptors cause uterine contraction, whereas β-adrenergic receptors induce relaxation. In animals, myometrial α-adrenergic receptors are regulated by gonadal steroids. We have identified α1- and α2-adrenergic receptors in myometrial membranes using the newly developed radiolabeled specific antagonists [3H]prazosin and [3H]rauwolscine. This allowed characterization of both receptor subclasses individually and study of them in various physiological and pharmacological conditions in the human, i.e. during different phases of the menstrual cycle, in postmenopausal women, term pregnancy, and during depo-progestin (medroxyprogesterone acetate) therapy. The affinity and number of α1-adrenergic receptors were unchanged in all conditions, whereas the number of α2-adrenergic receptors increased concomitantly with circulating plasma estradiol levels. However, this latter effect was counteracted by progesterone. These results are an example of the heteroregulation of membrane receptors by estrogens and progesterone and throw new light on the regulatory mechanisms involved in uterine contractility in the human.SCOPUS: ar.jinfo:eu-repo/semantics/publishe