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We show that hypertension is evident in female 5-HT-deficient TPH2−/− rats when sex hormones are controlled, an effect most evident upon the transition to REM sleep. In addition, our data strongly suggest that increased sympathetic vascular tone contributes to the hypertension present in this 5-HT-deficient model of neurogenic hypertension.

Mastocytosis is a rare neoplastic disorder of the mast cell lineage resulting in unregulated proliferation and activation of mast cells. Symptoms worsen in about one-third of pregnant patients. Treatment focuses on management of symptoms with antimediator therapy (H1H2 antihistamines, glucocorticoids, and epinephrine, if required). Medication selection requires care during labor and delivery. Although it is generally considered safe to use a medication patient tolerated before, some common medications may need to be avoided or used with caution (eg, codeine, morphine, nonsteroidal antiinflammatory drugs, vancomycin) if the patient does not have any history of exposure to them.

Anaphylaxis in pregnancy is a rare event, but has important implications for the pregnant patient and fetus. The epidemiology, pathophysiology, diagnosis, and treatment all carry important considerations unique to the pregnant patient. Common culprits of anaphylaxis are primarily medications, particularly antibiotics and anesthetic agents. Diagnosis can be difficult given the relative lack of cutaneous symptoms, and normal physiologic changes in pregnancy such as low blood pressure and tachycardia. Apart from patient positioning, treatment is similar to that of the general population, with a focus on prompt epinephrine administration.

Background: The aim of this study is to compare the effects of %4 articaine and %2 lidocaine on inferior alveolar nerve block (IANB) for implant surgery in the posterior mandible.Material and Methods: The patients who have inserted implants in the posterior mandible were divided into 2 groups for IANB: lidocaine and articaine. VAS = visual analog scale, pain during surgery and injection, lip numb-ness time, mandibular canal-implant apex distance, age, gender, bone density, implant number, release incision, adjacent teeth, and duration of surgery were analyzed using t-test, Mann-Whitney U test, Spearman's coefficient, and, Pearson's chi-squared test. This trial followed the recommendations of the Consort Statement for reporting randomized controlled trials. Results: 577 patients were included and 1185 dental implants were analyzed. There was no significant difference between the two groups in terms of injection and surgery VAS values (p>0.05). The lip numbness time of lido-caine was 3.06 +/- 3.22min while articaine was found to be 2.96 +/- 3.09min (p>0.05). Mandibular canal-implant apex distance was found to be 2.28 +/- 0.75mm in the articaine and 2.45 +/- 0.86mm in the lidocaine group (p

A university student with a background of atopy presented to her general practitioner (GP) 2 weeks following an episode of throat tightening and dizziness occurring after touching cashew nut to her lip. She took antihistamine medication immediately and went to sleep, fearing for her life. On waking, she felt astounded to be alive. Her symptoms resolved gradually over the following week. She waited 2 weeks for an appointment with her GP, who referred her to allergy clinic. Eight months later, she was still waiting for her clinic appointment, and was left fearing a future fatal reaction, having been provided with no interim treatment. Not all patients who have severe allergic reactions present to the emergency department. Living with the constant fear of anaphylaxis can be overwhelming for patients and their families, and it can negatively impact mental health. Therefore, we advise early allergy counselling and early EpiPen prescription.

Management of fluid refractory pediatric shock requires prompt administration of vasoactive agents. Although delivery of vasoactive therapy is generally provided via a central venous catheter, their placement can delay drug administration and is associated with complications. We characterize peripheral vasoactive administration in a cohort of critically ill children with shock, evaluate progression to central venous catheter placement, and describe complications associated with extravasation.Retrospective cohort study.Single-center, quaternary PICU (January 2010 to December 2015).Children (31 d to 18 yr) who received epinephrine, norepinephrine, or dopamine.None.We compared patients based on the initial site of vasoactive infusion: peripheral venous access (PVA) or central venous access (CVA) and, within the PVA group, compared patients based on subsequent placement of a central catheter for vasoactive infusion. We also characterized peripheral extravasations. We evaluated 756 patients: 231 (30.6%) PVA and 525 (69.4%) CVA patients. PVA patients were older, had lower illness severity, and more frequently had vasoactive therapy initiated at night compared with CVA patients. In PVA patients, 124 (53.7%) had a central catheter placed after a median of 140 minutes (interquartile range, 65-247 min) of peripheral treatment. Patients who avoided central catheter placement had lower illness severity. Of the 93 patients with septic shock, 44 (47.3%) did not have a central catheter placed. Extravasations occurred in four of 231 (1.7% [95% CI, 0.03-3.4]) PVA patients, exclusively in the hand. Three patients received pharmacologic intervention, and none had long-term disabilities.In our experience, peripheral venous catheters can be used for vasoactive administration. In our series, the upper limit of the 95% CI for extravasation is approximately 1-in-30, meaning that this route may be an appropriate option while evaluating the need for central access, particularly in patients with low illness severity.

Epinephrine is the principal resuscitation therapy for pediatric cardiac arrest (CA). Clinical data suggest that although epinephrine increases the rate of resuscitation, it fails to improve neurological outcome, possibly secondary to reductions in microvascular flow. We characterized the effect of epinephrine vs. placebo administered at resuscitation from pediatric asphyxial CA on microvascular and macrovascular cortical perfusion assessed using

To compare the levels of different urinary catecholamines amongst paediatric patients with and without sleep-disordered breathing (SDB).Literature searches were conducted on PubMed and EMBASE until 25/06/2022. Inclusion criteria were original human studies, English language, paediatric subjects diagnosed with SDB/obstructive sleep apnoea (OSA). The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The registered number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42022332939. The main outcome measured was standardised mean difference (SMD) of urinary catecholamine between subjects with and without SDB, between those with and without OSA, and also between subjects with mild OSA and those with moderate/ severe OSA. Sensitivity analyses were performed to avoid bias.9 studies (8 cross-sectional and 1 cohort study) with a total of 838 subjects, were included in the quantitative analysis. Urine level of noradrenaline was higher in patients with SDB, which included primary snoring (PS), when compared to controls: SMD = 0.86 (95%CI=0.32-1.41; IUrinary noradrenaline was higher in all patients with SDB. Subjects with OSA, a more severe form of SDB, had higher urine levels of noradrenaline and adrenaline. Hence, noradrenaline and adrenaline may be markers of sympathetic overtone in patients with SDB and could potentially act as surrogate markers for SDB complications. Further studies are needed to assess this association.

Objective:Despite the common clinical impression that patients with a history of drug use are challenging to anesthetize with local anesthesia, literature on this clinical phenomenon is sparse. The objective of this pilot study was to assess if differences in local anesthetic efficacy for dental treatment exist between marijuana users and nonusers.Methods:Subjects were healthy adult males and females who qualified as either chronic marijuana users or nonusers. All subjects had an asymptomatic, vital maxillary lateral incisor that responded to an electric pulp test (EPT). A standard maxillary infiltration injection technique was employed using 1.7 mL 2% lidocaine with 1:100,000 epinephrine over the test tooth, and the tooth was tested with an EPT at 3-minute intervals.Results:A total of 88% of nonusers (15/17) and 61% of users (11/18) were successfully anesthetized, defined as anesthesia onset within 10 minutes and lasting at least 15 minutes. The difference in the proportion of anesthetized subjects was not statistically significant (P = .073). For subjects with successful anesthesia, there was no significant difference between nonusers and users in the onset or duration of anesthesia.Conclusion:No significant differences in local anesthetic efficacy with respect to local anesthetic success, onset, or duration of action were found between chronic marijuana users and nonusers. However, larger studies are likely needed to provide more definitive evidence.

This study aimed to develop a mobile web-based food allergy (FA) and anaphylaxis management educational program for parents of school-aged children with food allergies and evaluate its effectiveness.A mobile program was developed based on a web-based teaching-learning system model. Its effectiveness was subsequently evaluated using a parallel, randomized controlled pre- and post-test design. This study included 73 parents of school-aged children with food allergies. These parents were randomly assigned to either the experimental (n = 37) or control (n = 36) groups. The experimental group participated in a 2-week mobile web-based educational program that covered major topics in FA and anaphylaxis management. These topics included an understanding of food allergies and anaphylaxis, learning techniques for using an epinephrine auto-injector, and developing an emergency action plan. An educational booklet was provided to the control group. Participants completed a pre-test and two post-test questionnaires to evaluate the impact of the program. The assessment tools were the Food Allergy Knowledge Test, Food Allergy Self-Efficacy for Parents, and Food Management and Adaptation Scale. The data were analyzed using descriptive statistics, a test of homogeneity for the pre-test, an independent t-test, and repeated measures ANOVA.The experimental group experienced greater improvement in the knowledge of FA (post-intervention t = 14.51, p .001; 2 weeks post-intervention, t = 16.15, p .001), FA self-efficacy (post-intervention t = 77.99, p .001; 2 weeks post-intervention, t = 76.09, p .001), and practice behavior in FA management (post-intervention t = 28.10, p .001; 2 weeks post-intervention, t = 27.98, p .001) after web-based FA education.This study revealed improvements in the knowledge, self-efficacy, and practice behaviors of parents regarding FA and anaphylaxis management. Therefore, the mobile web-based educational program can contribute to the effective management of food allergies and anaphylaxis for parents of school-aged children. CRIS registration: KCT0007491.

Tranexamic acid (TXA) has been used surgically to decrease blood loss. The ability of TXA to improve arthroscopic visualization and allow for reduction in pump pressure is unknown. The purpose of this study was to determine the effect of intravenous (IV) TXA on change in pump pressure and visualization during arthroscopic rotator cuff repair.This was a single-center, prospective, randomized, double-anonymized controlled trial. Patients with full-thickness rotator cuff tears undergoing operative repair were enrolled. Patients were randomized to receive 1 g of IV TXA preoperatively or no TXA (control group). All patients underwent arthroscopy using saline irrigation fluid with 3 mL epinephrine injected into the first 1000-mL saline bag. Total operative time, final pump pressure, number of increases in pump pressure, total amount of irrigation fluid used, blood pressure and anesthesia medical interventions for blood pressure were recorded. Visualization was measured by a visual analog scale (VAS) completed by the surgeon at the end of the case. Postoperative VAS pain scores were obtained 24 hours after surgery. The primary aim of this study was to investigate the effect that IV TXA has on change in pump pressure (ΔP) during shoulder arthroscopy, with a ΔP of 15 mm Hg set as a threshold for clinical significance.There were 50 patients randomized to the TXA group and 50 patients in the no TXA group. No significant differences were found between the TXA group and the control group regarding any measure of pump pressure, including the final arthroscopic fluid pump pressure (44.5 ± 8.1 mm Hg vs. 42.0 ± 8.08 mm Hg, P = .127), the mean ΔP (20.9 ± 10.5 mm Hg vs. 21.8 ± 8.5 mm Hg, P = .845), or the number of times a change in pump pressure was required (1.7 ± 0.9 vs. 1.7 ± 0.8, P = .915). Overall arthroscopic visualization was not significantly different between the TXA group and the control group (7.2 ± 1.8 vs. 7.4 ± 1.6, P = .464). No significant difference existed between the TXA and control groups regarding postoperative pain scores assessed by VAS pain scale (4.1 ± 2.0 vs. 4.3 ± 1.9, P = .519) at 24 hours after surgery.The use of IV TXA demonstrated no measurable improvement in surgeon ability to maintain a lower pump pressure during arthroscopic rotator cuff repair. Additionally, there was no measurable improvement in arthroscopic visualization or early pain scores.

Objective. To investigate the clinical application of preoperative adductor canal block combined with general anaesthesia in elderly patients with total knee arthroplasty. Methods. Seventy-four patients scheduled for elective TKA in Shaanxi Nuclear Industry Hospital No. 215 were selected and were assigned into group A (continuous ACB prior to the induction of anaesthesia) and group B (continuous ACB after extraction of the tracheal catheter post-operatively) according to the random number table method. Pre and postoperative plasma adrenaline and noradrenaline levels were measured; mean arterial pressure (MAP) and heart rate (HR) were recorded at the admission and the surgical skin incision; intraoperative sufentanil dosage, number of analgesic pump presses at 48 h postoperatively; postoperative adverse effects and length of stay were recorded; resting and active VAS pain scores were assessed at 4, 8, 12, 24, and 48 h postoperatively. Results. Group B experienced a substantial increase in MAP and HR at the time of surgical skin incision, while group A registered a smaller change and a stable haemodynamic profile ( P < 0.05 ). The plasma adrenaline and norepinephrine concentrations in group B were elevated compared to the preoperative period, differentially with group A. Group A received less intraoperative sufentanil than Group B ( P < 0.05 ). Conclusion. Collectively, postoperative resting VAS scores and active VAS scores remained lower in TKA patients who were subjected to preoperative and postoperative ACB, while preoperative ACB in conjunction with general anaesthesia decreased intraoperative sufentanil dosage, contained the surgical stress response, and maintained a stable intraoperative haemodynamic state, in what is probably a preferable option for elderly patients undergoing TKA. This study has served as a reference for postoperative patients to reduce their medication and for clinicians in the treatment going forward.

After weaning from cardiopulmonary bypass (CPB), the radial artery pressure is frequently lower than the central pressure as reflected by femoral pressure. This discrepancy may cause improper blood pressure management. In this study, we aimed to evaluate the risk factors related to developing a significant postbypass femoral-to-radial pressure gradient, including the incidence of complications related to femoral pressure monitoring.From January 2017 to May 2021, we studied consecutive adult cardiovascular surgical patients undergoing CPB in a historical cohort study. Patients were divided into two groups according to developing a significant femoral-to-radial pressure gradient, which was defined as a difference of ≥ 25 mm Hg for systolic pressure or ≥ 10 mm Hg for mean pressure, lasting ≥ 5 minutes for 30 minutes after CPB weaning. Factors associated with a significant pressure gradient and femoral pressure monitoring-related complications were analyzed.Among 2,019 patients, 677 (34%) showed a significant postbypass femoral-to-radial pressure gradient. Multivariable logistic regression analysis revealed the following factors related to the pressure gradient development: age (adjusted odds ratio [aOR] for an increase in 10 years, 1.09; 95% confidence interval [CI], 1.04 to 1.09; P0.001), body surface area (BSA) (aOR for an increase in 1 mOur study showed that old age, smaller BSA, prolonged aortic cross-clamping time, and intraoperative epinephrine use were associated with developing a significant postbypass femoral-to-radial pressure gradient in cardiovascular surgery. Considering monitoring-related complications occurred very infrequently, it might be helpful to monitor both radial and femoral pressure simultaneously in patients with these risk factors for appropriate blood pressure management. Nevertheless, further studies are needed to confirm our findings because our results are limited by a retrospective design and residual confounding factors.RéSUMé: OBJECTIF: Après le sevrage de la circulation extracorporelle (CEC), la pression dans l’artère radiale est souvent inférieure à la pression centrale, comme en témoigne la pression fémorale. Cette divergence peut provoquer une gestion inadaptée de la tension artérielle. Dans cette étude, nous avons cherché à évaluer les facteurs de risque liés au développement d’un gradient de pression significatif fémoro-radial post CEC, y compris l’incidence des complications liées à la surveillance de la pression fémorale. MéTHODES: Nous avons étudié consécutivement, de janvier 2017 à mai 2021, des patients adultes de chirurgie cardiovasculaire subissant une CEC dans une étude de cohorte historique. Les patients ont été séparés en deux groupes en fonction de la survenue d’un gradient de pression fémoro-radial significatif qui était défini ainsi : différence de ≥ 25 mmHg pour la pression systolique ou ≥ 10 mmHg pour la pression moyenne, durant ≥ 5 minutes pendant les 30 minutes suivant le sevrage de la CEC. Les facteurs associés à un gradient de pression significatif et aux complications liées à la surveillance de la pression fémorale ont été analysés. RéSULTATS: Parmi les 2 019 patients, 677 (34 %) ont présenté un gradient de pression fémoro-radial significatif post CEC. Une analyse par régression logistique multifactorielle a révélé que les facteurs suivants étaient liés à la survenue du gradient de pression : l’âge (rapport de cotes ajusté [aOR] pour une augmentation en dix ans, 1,09; intervalle de confiance [IC] à 95 % : 1,04 à 1,09; P0,001), la surface corporelle (SC) (aOR pour une augmentation dans 1 m

To review the current literature regarding the health disparities in the prevalence, diagnosis, and management of pediatric food allergy and discuss possible interventions.Literature search of PubMed and Google Scholar databases regarding pediatric food allergy and health disparities.Original research articles, reviews, and guidelines on health disparities in pediatric food allergy were included in this review.The overall prevalence of food allergy appears to be increasing and disproportionately affecting minority groups. Racial and socioeconomic disparities are evident across all aspects of food allergy care: diagnosis, prevention, acute management (eg, access to epinephrine autoinjectors, visits to emergency department), and long-term management (eg, oral immunotherapy). Children of minority populations and those of low socioeconomic status are at a greater risk of food insecurity, which is further exacerbated by the high cost of allergen-free foods and limited support from food assistance programs.Racial, ethnic, and socioeconomic disparities in food allergy among children in the United States are evident and negatively affect the outcomes of children with food allergies. Active efforts to decrease racial and socioeconomic disparities, through education, research, and advocacy, will be important to help improve health outcomes in food allergy for all children, regardless of their race, ethnicity, or socioeconomic status.

The objective of this single-blind randomized study is to compare local infiltration of bupivacaine or liposomal bupivacaine (LipoB) in narcotic naïve patients undergoing minimally invasive lobectomy for early stage lung cancer.Adult patients without previous lung surgery undergoing minimally invasive lobectomy (robotic or thoracoscopic) for early stage lung cancer were randomly assigned to bupivacaine (with epinephrine 0.25%, 1:200 000) or LipoB 1.3%. Pain level was documented using the visual analog scale and morphine equivalents for narcotic pain medications. Inhospital treatment cost and pharmacy cost were compared.The study enrolled 50 patients (bupivacaine, 24; LipoB, 26). The mean age of patients was 66 years, 94% were non-Hispanic white, and 48% were male. There was no difference in baseline characteristics and comorbidities. Duration of surgery (105 vs 137 minutes, P = .152), chest tube duration (49 vs 55 hours, P = .126), and length of stay (2.45 vs 3.28 days, P = .326) were similar between treatments. Inhospital morphine equivalents were 42.7 mg vs 48 mg (P = .714), and the median pain score was 5.2 vs 4.75 (P = .602) for bupivacaine vs LipoB, respectively. There was no difference in narcotic use at 2 to 4 weeks (57.1% [12 of 21] vs 54.5% [12 of 22], P = 1.00), and at 6 months (5.9% [1 of 17] vs 9.5% [2 of 21], P = 1.00) after surgery. The overall cost ($20 252 vs $22 775, P = .225) was similar; however, pharmacy cost for LipoB was higher ($1052 vs $596, P = .0001).In narcotic naïve patients undergoing minimally invasive lobectomy, short-term narcotic use, postoperative pain scores, length of stay, and long-term narcotic use were similar between bupivacaine and LipoB.

We describe emergency medical services (EMS) protocols and prehospital practice patterns related to traumatic cardiac arrest (TCA) management in the U.S.We examined EMS management of TCA by 1) assessing variability in recommended treatments in state EMS protocols for TCA and 2) analyzing EMS care using a nationwide sample of EMS activations. We included EMS activations involving TCA in adult (≥18 years) patients where resuscitation was attempted by EMS. Descriptive statistics for recommended and actual treatments were calculated and compared between blunt and penetrating trauma using χThere were 35 state EMS protocols publicly available for review, of which 16 (45.7%) had a specific TCA protocol and 17 (48.5%) had a specific termination of resuscitation protocol for TCA. Recommended treatments varied. We then analyzed 9,565 EMS activations involving TCA (79.1% blunt, 20.9% penetrating). Most activations (93%) were managed by advanced life support. Return of spontaneous circulation was achieved in 25.5% of activations, and resuscitation was terminated by EMS in 26.4% of activations. Median prehospital scene time was 16.4 minutes; scene time was shorter for penetrating mechanisms than blunt (12.0 vs 17.0 min, p 0.001). Endotracheal intubation was performed in 32.0% of activations, vascular access obtained in 66.6%, crystalloid fluids administered in 28.8%, and adrenaline administered in 60.1%.Actual and recommended approaches to EMS treatment of TCA vary nationally. These variations in protocols and treatments highlight the need for a standardized approach to prehospital management of TCA in the U.S.

Allergic reactions to the coronavirus disease 2019 (COVID-19) vaccines have raised concerns, particularly as repeated doses are required. Skin tests with the vaccines excipient were found to be of low value, whereas the utility of skin tests with the whole vaccine is yet to be determined.To evaluate a panel of skin tests and the outcomes of subsequent doses of immunization among subjects who suffered an immediate allergic reaction to the BioNTech (BNT162b2) COVID-19 vaccine.Between March and December 2021, patients who experienced symptoms consistent with immediate allergic reactions to the BNT162b2 vaccine and were referred to the Sheba Medical Center underwent skin testing with polyethylene glyol (PEG)-containing medicines, Pfizer-BNT162b2, and Oxford-AstraZeneca vaccine (AZD1222). Further immunization was performed accordingly and under medical observation.A total of 51 patients underwent skin testing for suspected allergy to the COVID vaccines, of which 38 of 51 (74.5%) were nonreactive, 7 of 51(13.7%) had no skin sensitization but suffered a clinical reaction during skin testing (mainly cough), and 6 of 51 (11.7%) exhibited immediate skin sensitization. Both skin sensitization and cough during testing were related to a higher use of adrenaline following immunization (P = .08 and P = .024, respectively). Further immunization with the BNT162b2 vaccine was recommended unless sensitization or severe reaction to previous immunization was evident. The latter were referred to be tested/receive the alternative AZD1222 vaccine. Ten patients underwent skin testing with AZD1222: 2 of 10 (20%) demonstrated skin sensitization to both vaccines; thus, 8 of 10 were immunized with the AZD1222, of which 2 of 8 (25%) had allergic reactions.Immediate allergic reactions to COVID-19 vaccines are rare but can be severe and reoccur. Intradermal testing with the whole vaccine may discriminate sensitized subjects, detect cross-sensitization between vaccines, and enable estimation of patients at higher risk.

For patients with colorectal cancer, minimally invasive surgical methods, particularly laparoscopic methods, are now the preferred course of therapy. This research is performed to investigate the effects of laparoscopic radical resection on patients with colorectal cancer. A total of 100 colorectal cancer patients treated in our hospital from January 2017 to January 2019 were enrolled. The subjects were divided into observation ( n = 50 ) and control ( n = 50 ) groups and treated with laparoscopic surgery and laparotomy, respectively. As well as postoperative complications and survival rates, the levels of inflammatory substances, stress response, immunological function, and perioperative markers were compared between the two groups. There was no significant difference in the postoperative exhaust time between the two groups ( P > 0.05 ). Compared with the control group, the observation group showed longer operation time, faster recovery of intestinal function, shorter hospital stay, and less intraoperative bleeding amount ( P < 0.05 ). The serum contents of hs-CRP, TNF-α, IL-6, norepinephrine, adrenaline, and cortisol at 1 d, 3 d, and 5 d after surgery were significantly higher than before in both groups ( P < 0.05 ). Moreover, the serum contents of hs-CRP, TNF-α, IL-6, norepinephrine, adrenaline, and cortisol in the observation group were significantly lower than that in the control group ( P < 0.05 ). At 10 days following surgery, immune index levels had dramatically increased in both groups, with noticeably higher immune index levels in the observation group than in the control group ( P < 0.05 ). There were no appreciable differences in the two groups’ 2-year survival rates ( P > 0.05 ), but the complication rate was much greater in the control group ( P < 0.05 ). To sum up, after laparoscopic surgery, patients had fewer complications, shorter hospital stay, lower inflammatory factor expression, less stress response, better immune function, less trauma, faster recovery, and improved quality of life.

Pain from dental injections is a common reason why people fear dentistry and avoid dental treatment. Thus, researchers have attempted to find methods to decrease dental injection pain.Considering the analgesic effect of the photobiomodulation therapy (PBMT), the aim of this study was to evaluate the effects of PBMT on the pain caused by dental anesthetic injections.This randomized, split-mouth, triple-blind clinical trial evaluated 60 bilateral canine teeth in 30 dental students. After the random selection of the test (laser) quadrant, the injection site was irradiated with a 940 nm diode laser. Buccal infiltration anesthesia was then administered by injecting lidocaine plus epinephrine with a short needle. The level of pain experienced during the injection was determined using a 100-millimeter visual analog scale (VAS). The same procedure was performed for the control (no laser) quadrant, with the difference being that the laser handpiece was turned on, but no radiation was administered. The 2 groups were compared using the non-parametric Wilcoxon signed-rank test.The mean VAS pain scores were 21.2 ±15.7 for the laser quadrant and 27.9 ±18.9 for the control quadrant; this difference was statistically significant (p = 0.030), but did not seem to be clinically relevant.The photobiomodulation therapy prior to dental anesthetic injections has no clinical advantage for reducing injection pain.

BACKGROUND AND PURPOSE: Nausea is associated with the hormonal secretion of vasopressin and adrenaline, although their actions in inducing nausea is poorly understood. Here, we have investigated their actions on human stomach muscle. EXPERIMENTAL APPROACH: Muscle strips were suspended in tissue baths and neuronal-/non-neuronally-mediated contractions were measured. Custom software analysed eight motility parameters defining spontaneous phasic non-neuronally mediated contractions. Receptor distributions were assessed by qPCR and immunofluorescence. KEY RESULTS: V1A receptors and α1 -adrenoceptors were located on muscle as well as interstitial cells of Cajal (ICCs). Myogenic contractions of human proximal and distal stomach (respectively, 2.6 ± 0.1 and 2.7 ± 0.0 per minute; n = 44) were larger in the distal area (1.1 ± 0.1 and 5.0 ± 0.1 mN), developing relatively slowly (proximal) or rapidly (distal). Vasopressin caused tonic (proximal) or short-lived (distal) increases in muscle tone and increased myogenic contraction amplitude, frequency and rate (acting at V1A receptors; thresholds 10-11 -10-10 M); by contrast, cholinergically mediated contractions were unaffected. Oxytocin acted similarly to vasopressin but less potently, at OT receptors). Adrenaline increased (10-10 -10-5 M; α1 -adrenoceptors) and decreased (≥10-6 M; β-adrenoceptors) muscle tone and enhanced/reduced myogenic contractions. Cholinergically mediated contractions were reduced (α2 -adrenoceptors). Combined, vasopressin (10-9 M) and adrenaline (10-8 M) increased muscle tone and phasic myogenic activity in a synergistic manner. CONCLUSIONS AND IMPLICATIONS: Vasopressin and adrenaline increased human gastric tone and myogenic contraction amplitude, rate of contraction and frequency. In combination, their actions were further increased in a synergistic manner. Such activity may promote nausea.

The efferent branches of the splanchnic sympathetic nerves that enhance interleukin-10 (IL-10) and suppress tumour necrosis factor-α (TNF) levels in the reflex response to systemic immune challenge were investigated in anaesthetized, ventilated rats. Plasma levels of TNF and IL-10 were measured 90 min after intravenous lipopolysaccharide (LPS, 60 µg/kg). Splanchnic nerve section, ganglionic blockade with pentolinium tartrate or β

Justyna Hajtuch,1 Eliza Iwicka,1 Anna Szczoczarz,1 Damian Flis,1 El&zdot;bieta Megiel,2 Piotr Cieciórski,2 Marek Witold Radomski,3 Maria Jose Santos-Martinez,4 Iwona Inkielewicz-Stepniak1 1Department of Pharmaceutical Pathophysiology, Medical University of Gdansk, Gdansk, Poland; 2Faculty of Chemistry, University of Warsaw, Warsaw, Poland; 3Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 4School of Pharmacy and Pharmaceutical Sciences and School of Medicine, Trinity College Dublin, Dublin, Dublin 2, IrelandCorrespondence: Iwona Inkielewicz-Stepniak, Tel +48 58 349 1516, Fax +48 58 349 1517, Email iwona.inkielewicz-stepniak@gumed.edu.plPurpose: In the search for new drug delivery platforms for cardiovascular diseases and coating of medical devices, we synthesized eptifibatide-functionalized silver nanoparticles (AgNPs-EPI) and examined the pharmacological activity of AgNPs-EPI on platelets and endothelial cells in vitro and ex vivo.Methods: Spherical AgNPs linked to eptifibatide were synthesized and characterized. Cytotoxicity was measured in microvascular endothelial cells (HMEC-1), platelets and red blood cells. Platelet mitochondrial respiration was measured using the Oxygraph-2k, a high-resolution modular respirometry system. The effect of AgNPs-EPI on the aggregation of washed platelets was measured by light aggregometry and the ex vivo occlusion time was determined using a reference laboratory method. The surface amount of platelet receptors such as P-selectin and GPIIb/IIIa was measured. The influence of AgNPS-EPI on blood coagulation science was assessed. Finally, the effect of AgNPs-EPI on endothelial cells was measured by the levels of 6-keto-PGF1alpha, tPa, cGMP and vWF.Results: We describe the synthesis of AgNPs using eptifibatide as the stabilizing ligand. The molecules of this drug are directly bonded to the surface of the nanoparticles. The synthesized AgNPs-EPI did not affect the viability of platelets, endothelial cells and erythrocytes. Preincubation of platelets with AgNPs-EPI protected by mitochondrial oxidative phosphorylation capacity. AgNPs-EPI inhibited aggregation-induced P-selectin expression and GPIIb/IIIa conformational changes in platelets. AgNPs-EPI caused prolongation of the occlusion time in the presence of collagen/ADP and collagen/adrenaline. AgNPs-EPI regulated levels of 6-keto-PGF1alpha, tPa, vWf and cGMP produced in thrombin stimulated HMEC-1 cells.Conclusion: AgNPs-EPI show anti-aggregatory activity at concentrations lower than those required by the free drug acting via regulation of platelet aggregation, blood coagulation, and endothelial cell activity. Our results provide proof-of-principle evidence that AgNPs may be used as an effective delivery platform for antiplatelet drugs.Graphical Abstract: Keywords: drug delivery, antiplatelet, RGD, aggregation, coagulation system, biocompatibility

Background and objective: The incidence of food allergy among children is on the rise. Children who are diagnosed with a food allergy receive long-term treatment for allergy management from allergy specialists, nurses and dieticians. This management may include the prescription of an adrenaline autoinjector (AAI) if the child is at risk of a severe allergic reaction (anaphylaxis). Therefore, it is important that parents of children with allergies are trained in the recognition of anaphylaxis and in the correct administration of an AAI. However, many parents are unable to correctly administer an AAI when assessed. The aim of this study is to review the current literature on caregiver’s and paediatric patients’ ability to use an AAI. Methodology: An electronic search to evaluate AAI technique in caregivers and children with food allergy was conducted. A total of 323 articles were screened in which 10 studies were reviewed. Results: Seventy-eight percent of parents who had never been trained in the use of an AAI were unable to trigger it. In studies where paediatric patients’ ability to use an AAI was assessed, a mean score of 7.78/9 was derived for AAI knowledge among adolescents. Conclusion: Caregivers and patient’s ability to use an AAI was inconclusive, and further research should address the validation of an assessment tool for AAI use. A significant improvement in AAI use was found after an educational intervention. This highlights the need for improved education for allergic individuals and their caregivers, and further study should explore what are the best educational methods to meet these needs.

While adrenal venous sampling (AVS) differentiates between the unilateral and bilateral disease in patients with primary aldosteronism (PA), it is unknown if AVS can determine laterality of pheochromocytoma in patients with bilateral adrenal masses. This study analyzes adrenal vein (AV) epinephrine and norepinephrine levels in nonpheochromocytoma patients to determine the "normal" range.We reviewed patients who underwent AVS for PA between 2009 and 2019 at a single institution; pheochromocytoma was excluded. Aldosterone, cortisol, epinephrine, and norepinephrine levels were obtained from the inferior vena cava (IVC), left adrenal vein (LAV), and right adrenal vein (RAV). Successful AV cannulation was defined by an AV/IVC cortisol ratio of ≥3:1 or an AV epinephrine level ≥364 pg/mL. Plasma measurements (pg/mL) are median values with interquartile ranges; normal ranges for epinephrine and norepinephrine are 10-200 pg/mL and 80-520 pg/mL, respectively.AVS was performed in 172 patients in 405 AVs (173 LAV and 232 RAV). Median epinephrine levels were IVC = 19 (14 and 34), LAV = 3811 (1870 and 6915), and RAV = 2897 (1500 and 5288). Median norepinephrine levels were IVC = 325 (186 and 479), LAV = 1450 (896 and 2050), and RAV = 786 (436 and 1582). There was a difference between LAV and RAV epinephrine levels (P = 0.024) and between LAV and RAV norepinephrine (P = 0.002) levels.This extensive experience with AVS demonstrated a wide range of "normal" AV catecholamine levels in patients without pheochromocytoma, which suggests that the utility of AVS to determine disease laterality in patients with pheochromocytoma and bilateral adrenal nodules is likely to be limited.

Anaphylaxis is a potentially life-threatening event in children, commonly encountered in the prehospital and emergency department settings. Recently published clinical guidelines emphasize early recognition of anaphylaxis and administration of epinephrine as the mainstay of management. Literature regarding adjuvant therapies, biphasic reactions, observation times, and disposition of patients with anaphylaxis remains controversial. In this article, we will review the background and pathophysiology of anaphylaxis, as well as the diagnostic approach, management, and future directions of anaphylaxis in children.

We examined the effect of intermittent hypoxia (IH, a hallmark feature of sleep apnea) on adipose tissue lipolysis and the role of endothelin-1 (ET-1) in this response. We hypothesized that IH can increase ET-1 secretion and plasma free fatty acid (FFA) concentrations. We further hypothesized that inhibition of ET-1 receptor activation with bosentan could prevent any IH-mediated increase in FFA. To test this hypothesis, 16 healthy male participants (32 ± 5 yr, 26 ± 2 kg/m2) were exposed to 30 min of IH in the absence (control) and presence of bosentan (62.5 mg oral twice daily for 3 days prior). Arterial blood samples for ET-1, epinephrine, and FFA concentrations, as well as abdominal subcutaneous adipose tissue biopsies (to assess transcription of cellular receptors/proteins involved in lipolysis), were collected. Additional proof-of-concept studies were conducted in vitro using primary differentiated human white preadipocytes (HWPs). We show that IH increased circulating ET-1, epinephrine, and FFA ( P < 0.05). Bosentan treatment reduced plasma epinephrine concentrations and blunted IH-mediated increases in FFA ( P < 0.01). In adipose tissue, bosentan had no effect on cellular receptors and proteins involved in lipolysis ( P > 0.05). ET-1 treatment did not directly induce lipolysis in differentiated HWP. In conclusion, IH increases plasma ET-1 and FFA concentrations. Inhibition of ET-1 receptors with bosentan attenuates the FFA increase in response to IH. Based on a lack of a direct effect of ET-1 in HWP, we speculate the effect of bosentan on circulating FFA in vivo may be secondary to its ability to reduce sympathoadrenal tone.

Data are sparse regarding tree nut-induced anaphylaxis (TNA).To characterize rate, clinical characteristics, and management of TNA in children (0-17 years old) across Canada and evaluate factors associated with severe reactions and epinephrine use.Between April 2011 and May 2020, data were collected on children presenting to 5 emergency departments in Canada. Multivariate logistic analysis was used to evaluate factors associated with severe reactions (stridor, cyanosis, circulatory collapse, or hypoxia) and epinephrine use.Among 3096 cases of anaphylaxis, 540 (17%) were induced by tree nut. The median age was 5.2 (interquartile range, 2.5-9.5) years and 65.4% were of male sex. Among all reactions, 7.0% were severe. The major tree nuts accounting for anaphylaxis were cashew (32.8%), hazelnut (20.0%), and walnut (11.5%). Cashew-induced anaphylaxis was more common in British Columbia (14.0% difference [95% confidence interval (CI), 1.6-27.6]) vs Ontario and Quebec, whereas pistachio-induced anaphylaxis was more common in Ontario and Quebec (6.3% difference [95% CI, 0.5-12.2]). Prehospital and emergency department intramuscular epinephrine administration was documented in only 35.2% and 52.4% of cases, respectively. Severe reactions were more likely among of male sex (adjusted odds ratio [aOR], 1.05 [95% CI, 1.01-1.10]), older children (aOR, 1.00 [95% CI, 1.00-1.01]), and in reactions triggered by macadamia (aOR, 1.27 [95% CI, 1.03-1.57]).Different TNA patterns in Canada may be because of differences in lifestyle (higher prevalence of Asian ethnicity in British Columbia vs Arabic ethnicity in Ontario and Quebec). Intramuscular epinephrine underutilization urges for epinephrine autoinjector stocking in schools and restaurants, patient education, and consistent policies across Canada.

The appropriate at-home management of anaphylaxis begins with patient education on recognition and treatment, especially when and how to use epinephrine. Delayed administration of epinephrine as well as having severe symptoms and needing multiple doses of epinephrine to treat symptoms are risk factors for biphasic anaphylaxis. The successful implementation of at-home management of anaphylaxis requires appropriate patient selection and an algorithmic approach that recommends activation of emergency medical services (EMS) when the patient does not adequately respond to at-home administration of epinephrine or there are extenuating patient-related circumstances. Fortunately, approximately 98% of anaphylactic episodes respond to 2 or fewer doses of epinephrine, the standard prescription used for epinephrine autoinjectors; fatal anaphylaxis is very rare, as low as 0.002 deaths/million person-years; and biphasic reactions are uncommon (∼5%), and only extremely rarely lethal. Thus, most common concerns leading to recommended EMS activation and emergency department visits after epinephrine administration are generally unsubstantiated. Furthermore, emergency department visits do not always lead to better treatment and drive health care costs higher. Open communications with patients and families regarding risks and benefits of at-home management and observation versus EMS activation and emergency department evaluation after epinephrine administration for anaphylaxis are essential. However, we believe the data indicate that it is time to reconsider the often used and taught approach that recommends EMS activation whenever epinephrine is used.

Sesame can cause severe allergic reactions and is a priority allergen in Canada.To assess clinical characteristics and management of pediatric sesame-induced anaphylaxis and identify factors associated with epinephrine treatment.Between 2011 and 2021, children with sesame-induced anaphylaxis presenting to 7 emergency departments (ED) in 4 Canadian provinces and 1 regional emergency medical service were enrolled in the Cross-Canada Anaphylaxis Registry. Standardized recruitment forms provided data on symptoms, severity, triggers, and management. Multivariate logistic regression evaluated associations with epinephrine treatment pre-ED and multiple epinephrine dosages.Of all food-induced anaphylactic reactions (n = 3279 children), sesame accounted for 4.0% (n = 130 children), of which 61.5% were boys, and the average (SD) age was 5.0 (4.9) years. Hummus containing sesame paste triggered 58.8% of reactions. In the pre-ED setting, 32.3% received epinephrine, and it was more likely to be used in boys (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.08-1.50) and those with a known food allergy (aOR, 1.36; 95% CI, 1.11-1.68]). In the ED, 47.7% of cases received epinephrine, with older children more likely to receive multiple epinephrine doses (aOR, 1.00; 95% CI, 1.00-1.02).In Canada, hummus is the major trigger of sesame-induced anaphylaxis. Knowledge translation focused on prompt epinephrine use and product-labeling policies are required to limit sesame reactions in communities.

Rat isolated vas deferens releases 6-nitrodopamine (6-ND), and the spasmogenic activity of this novel catecholamine is significantly reduced by tricyclic compounds such as amitriptyline, desipramine, and carbamazepine and by antagonists of the αsub1/sub-adrenergic receptors such as doxazosin, tamsulosin, and prazosin.To investigate the liberation of 6-ND by human epididymal vas deferens (HEVDs) and its pharmacological actions.The in vitro liberation of 6-ND, dopamine, noradrenaline, and adrenaline from human vas deferens was evaluated by LC-MS/MS. The contractile effect of the catecholamines in HEVDs was investigated in vitro. The action of tricyclic antidepressants was evaluated on the spasmogenic activity ellicited by the catecholamines and by the electric-field stimulation (EFS). The tissue was also incubated with the inhibitor of nitric oxide (NO) synthase L-NAME and the release of catecholamines and the contractile response to EFS were assessed.6-ND is the major catecholamine released from human vas deferens and its synthesis/release is inhibited by NO inhibition. The spasmogenic activity elicited by EFS in the human vas deferens was blocked by tricyclic antidepressants only at concentrations that selectively antagonize 6-ND induced contractions of the human vas deferens, without affecting the spasmogenic activity induced by dopamine, noradrenaline, and adrenaline in this tissue. Incubation of the vas deferens with L-NAME reduced both the 6-ND release and the contractions induced by EFS.6-ND should be considered a major endogenous modulator of human vas deferens contractility and possibly plays a pivotal role in the emission process of ejaculation. It offers a novel and shared mechanism of action for tricyclic antidepressants and αsub1/sub-adrenergic receptor antagonists.

N-stearoylethanolamine (NSE), a lipid mediator that belongs to the N-acylethanolamine (NAE) family, has anti-inflammatory, antioxidant, and membranoprotective actions. In contrast to other NAEs, NSE does not interact with cannabinoid receptors. The exact mechanism of its action remains unclear. The aim of this study is to evaluate the action of NSE on activation, aggregation, and adhesion of platelets that were chosen as a model of cellular response. Aggregation of platelets was measured to analyze the action of NSE (10sup-6/sup-10sup-10/supM) on platelet reactivity. Changes in granularity and shape of resting platelets and platelets stimulated with ADP in the presence of NSE were monitored by flow cytometry, and platelet deganulation was monitored by spectrofluorimetry. In vivo studies were performed using obese insulin-resistant rats. Binding of fibrinogen to the GPIIb/IIIa receptor was estimated using indirect ELISA and a scanning electron microscopy (SEM). It was found that NSE inhibits the activation and aggregation of human platelets. Our results suggest that NSE may decrease the activation and subsequent aggregation of platelets induced by ristocetin, epinephrine, and low doses of ADP. NSE also reduced the binding of fibrinogen to GPIIb/IIIa on activated platelets. These effects could be explained by the inhibition of platelet activation mediated by integrin receptors: the GPIb-IX-V complex for ristocetin-induced activation and GPIIb/IIIa when epinephrine and low doses of ADP were applied. The anti-platelet effect of NSE complements its anti-inflammatory effect and allows us to prioritize studies of NSE as a potent anti-thrombotic agent. SIGNIFICANCE STATEMENT: N-stearoylethanolamine (NSE) was shown to possess inhibitory action on platelet activation, adhesion, and aggregation. The mechanism of inhibition possibly involves integrin receptors. This finding complements the known anti-inflammatory effects of NSE.

Background Postoperative hemodynamic deterioration among cardiac surgical patients can indicate or lead to adverse outcomes. Whereas prediction models for such events using electronic health records or physiologic waveform data are previously described, their combined value remains incompletely defined. The authors hypothesized that models incorporating electronic health record and processed waveform signal data (electrocardiogram lead II, pulse plethysmography, arterial catheter tracing) would yield improved performance versus either modality alone. Methods Intensive care unit data were reviewed after elective adult cardiac surgical procedures at an academic center between 2013 and 2020. Model features included electronic health record features and physiologic waveforms. Tensor decomposition was used for waveform feature reduction. Machine learning–based prediction models included a 2013 to 2017 training set and a 2017 to 2020 temporal holdout test set. The primary outcome was a postoperative deterioration event, defined as a composite of low cardiac index of less than 2.0 ml min˗1 m˗2, mean arterial pressure of less than 55 mmHg sustained for 120 min or longer, new or escalated inotrope/vasopressor infusion, epinephrine bolus of 1 mg or more, or intensive care unit mortality. Prediction models analyzed data 8 h before events. Results Among 1,555 cases, 185 (12%) experienced 276 deterioration events, most commonly including low cardiac index (7.0% of patients), new inotrope (1.9%), and sustained hypotension (1.4%). The best performing model on the 2013 to 2017 training set yielded a C-statistic of 0.803 (95% CI, 0.799 to 0.807), although performance was substantially lower in the 2017 to 2020 test set (0.709, 0.705 to 0.712). Test set performance of the combined model was greater than corresponding models limited to solely electronic health record features (0.641; 95% CI, 0.637 to 0.646) or waveform features (0.697; 95% CI, 0.693 to 0.701). Conclusions Clinical deterioration prediction models combining electronic health record data and waveform data were superior to either modality alone, and performance of combined models was primarily driven by waveform data. Decreased performance of prediction models during temporal validation may be explained by data set shift, a core challenge of healthcare prediction modeling. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Purpose: Macular edema including cystoid macular edema is one of the main causes of unfavorable visual outcomes after cataract surgery. The macular thickness and the occurrence of macular edema after uncomplicated cataract surgery was evaluated using optical coherence tomography (OCT) in this study.Methods: Macular map images were taken by OCT before surgery and at 1 week, 1 month, and 2 months postsurgery. The subjects were classified into two groups (group 1, patients with no macular edema; group 2, patients with macular edema). Group 2 was defined as increase in central macular thickness (CMT) by 30% compared with that before surgery. The risk factors for macular edema were evaluated. Group 2 was divided into two subgroups: subclinical macular edema (group 2A) and cystoid macular edema (group 2B) and they were assessed in terms of the clinical course of best-corrected visual acuity and CMT.Results: A total of 376 patients were enrolled in this study, of which 36 (9.57%, group 2) showed macular edema measured by OCT after the surgery. Univariate analysis for group 1 and 2 revealed that intracameral injection of epinephrine during phacoemulsification was associated with the development of macular edema. In group 2, five patients (1.33%) developed cystoid macular edema. Statistically significant differences in the clinical course of CMT were observed at 2 months (201.2 ± 23.1, 250.0 ± 29.8, and 371.0 ± 160.3 in group 1, group 2A, and group 2B, respectively; p < 0.001) and 1 month postoperatively (198.5 ± 23.6, 237.8 ± 40.9, and 314.0 ± 104.5 in group 1, group 2A, and group 2B, respectively; p < 0.001). Group 2B required additional treatment and eventually achieved best-corrected visual acuity of >0.2 with CMT in the normal range.Conclusions: The intracameral injection of epinephrine may cause macular edema after uncomplicated cataract surgery. Examination of CMT using OCT is recommended for the early detection of macular edema.

Systemic administration of drugs that activate the noradrenergic or glucocorticoid system potentiates aversive memory consolidation and reconsolidation. The opposite happens with the stimulation of endocannabinoid signaling under certain conditions. An unbalance of these interacting neurotransmitters can lead to the formation and maintenance of traumatic memories, whose strength and specificity attributes are often maladaptive. Here we aimed to investigate whether originally low-intensity and precise contextual fear memories would turn similar to traumatic ones in rats systemically administered with adrenaline, corticosterone, and/or the cannabinoid type-1 receptor antagonist/inverse agonist AM251 during consolidation or reconsolidation. The high dose of each pharmacological agent evaluated significantly increased freezing times at test in the conditioning context one and nine days later when given alone post-acquisition or post-retrieval. Their respective low dose produced no relative changes when given separately, but co-treatment of adrenaline with corticosterone or AM251 and the three drugs combined, but not corticosterone with AM251, produced results equivalent to those mentioned initially. Neither the high nor the low dose of adrenaline, corticosterone, or AM251 altered freezing times at test in a novel, neutral context two and ten days later. In contrast, animals receiving the association of their low dose exhibited significantly higher freezing times than controls. Together, the results indicate that newly acquired and destabilized threat memory traces become more intense and generalized after a combined interference acting synergistically and mimicking that reported in patients presenting stress-related psychiatric conditions.

The extraction of a tooth exacerbates the stress in diabetic patients leading to diabetic complications so the aim was to evaluate the changes in blood cortisol, glucose, and oxygen saturation in type 2 diabetic patients during tooth extraction to pay special attention during a routine surgical procedure.The research included 40 patients with type 2 diabetes with indications of tooth extraction. They were divided into two subgroups by 20 participants and split according to local anesthesia (lidocaine with additional adrenaline or lidocaine only). Cortisol, blood sugar, blood pressure, arterial pulse, and blood oxygen saturation were measured. Patients were also evaluated for their sensitivity to pain through the Visual Analog Scale (VAS).Cortisol and glucose levels scientifically increased throughout the procedure. Meanwhile, systolic, and diastolic blood pressure and saturation showed no difference between the measurements during and after tooth extraction (p = .280; p = .090; p = .590, respectively). Most patients (60.0%) felt no pain during/after the procedure. None of the subjects was feeling more pain than 30 points by VAS. The comparison between groups receiving lidocaine showed no statistical differences when adding adrenaline to lidocaine. Evaluation of pain by VAS showed that more patients felt pain when they were receiving lidocaine without adrenaline.Diabetic patients require a more cautious approach when undergoing teeth extractions despite it being a routine procedure.

International audience; Background: there is a lack of population-based studies of anaphylaxis from low-and middle-income countries. This hampers public health planning and investments and may influence availability of adrenaline auto-injectors.Objective: we conducted the first national population-based study of anaphylaxis hospitalization in Brazil.Methods: descriptive study using routinely reported data to the Brazilian Hospital Information System for the years 2011-2019. Information available is coded based on the International Classification of Diseases (ICD)-10 and covers main cause of hospitalization (primary cause) and any conditions contributing to it (secondary cause).Results: over 9 years, we identified 5716 admissions due to anaphylaxis for all causes. The average hospitalization rate related to anaphylaxis was 0.71/100,000 population per year, with a 2.4% (95% CI 1.9%, 2.9%) increase per annum over the study period. Admissions were more frequent among females (52.8%), except for cases due to insect sting. Most admissions occurred in adulthood, from 30 to 59 years (36.3%) but 13.8% in preschool children (0-4 years). There were more young children admitted for food-related anaphylaxis, and more adults admitted for drug/iatrogenic-related anaphylaxis. There were 334 cases (5.8% of admissions) of fatal anaphylaxis over the study period, with increased case fatality rate over time.Conclusions and clinical relevance: this is the first study of anaphylaxis hospital admissions using nation-wide data from a low- or middle-income country. Hospital admissions and fatalities from anaphylaxis in Brazil appear to be increasing.

BACKGROUND AND IMPORTANCE There has been much discussion of the results of the PARAMEDIC2 trial, as resuscitation outcome rates are considerably lower in this trial than in country-level registries on out-of-hospital cardiac arrest (OHCA). Here, we developed a statistical framework to investigate this gap and to examine possible sources for observed discrepancies in outcome rates. DESIGN Summary data from the PARAMEDIC2 trial were used as available in the publication of this study. We developed a modelling framework based on logistic regression to compare data from this randomized controlled trial and registry data from the German Resuscitation Registry (GRR), where we considered 26 019 patients treated with epinephrine for OHCA in the GRR. To account and adjust for differences in patient characteristics and baseline variables predictive for outcomes after OHCA between the GRR cohort and the PARAMEDIC2 study sample, we included all available variables determined at the arrival of EMS personnel in the modelling framework: age, sex, initial cardiac rhythm, cause of cardiac arrest, witness of cardiac arrest, CPR performed by a bystander, and the interval between emergency call and arrival of the ambulance at the scene (baseline model). In order to find possible explanations for the discrepancies in outcome between PARAMEDIC2 and GRR, in a second (baseline plus treatment) model, we additionally included all available variables related to the interventions of the EMS personnel (type of airway management, type of vascular access, and time to administration of epinephrine). MAIN RESULTS A patient cohort with baseline variables as in the PARAMEDIC2 trial would have survived to hospital discharge in 7.7% and survived with favourable neurological outcome in 5.0% in an EMS and health care system as in Germany, compared with 3.2 and 2.2%, respectively, in the Epinephrine group of the trial. Adding treatment-related variables to our logistic regression model, the rate of survival to discharge would decrease from 7.7 (for baseline variables only) to 5.6% and the rate of survival with favourable neurological outcome from 5.0 to 3.4%. CONCLUSION Our framework helps in the medical interpretation of the PARAMEDIC2 trial and the transferability of the trial's results for other EMS systems. Significantly higher rates of survival and favourable neurological outcome than reported in this trial could be possible in other EMS and health care systems.

Benzonatate is a local anesthetic-like sodium channel antagonist that is widely prescribed as an antitussive. While it may be reasonable to assume that patients would present with a prolonged QRS interval following benzonatate overdose, the published literature does not support this. We report a case of a patient presenting following a benzonatate overdose with a prolonged QRS on her initial electrocardiograph (ECG) rhythm strip with rapid normalization of QRS duration.A 14-year-old girl presented in cardiac arrest following a benzonatate overdose. The patient was found in cardiac arrest within minutes of last being known well. Bystanders immediately provided cardiopulmonary resuscitation (CPR), and she was in asystole on emergency medical services (EMS) arrival. Return of spontaneous circulation (ROSC) was obtained following administration of intraosseous epinephrine and naloxone. EMS obtained an ECG rhythm strip following ROSC demonstrating a sinus rhythm with a QRS duration of 160 ms. Over the ensuing 30 minutes, there was progressive narrowing of the QRS. A 12-lead ECG obtained on arrival in the emergency department (ED) 44 minutes later demonstrated a QRS duration of 94 ms. Initially, EMS ECG rhythm strips were unavailable and an isolated benzonatate ingestion was considered less likely as ECG intervals were normal. Benzonatate exposure was later confirmed with a urine benzonatate concentration, which was 8.5 mcg/mL. The patient made a full recovery.Cases of pediatric benzonatate overdose with rapid development of cardiac arrest and full recovery have been previously reported. In this case, evidence of cardiac sodium channel blockade was demonstrated with a prolonged QRS interval on initial ECG rhythm strip analysis. However, unlike previous cases, rapid resolution of QRS prolongation occurred in this case. While transient QRS prolongation may be observed, finding a normal QRS interval should not discount the possibility of benzonatate overdose.

CoreTherm (ProstaLund AB, Lund, Sweden) is an outpatient treatment option in men with lower urinary tract symptoms and catheter-dependent men with chronic urinary retention caused by benign prostatic obstruction (BPO). CoreTherm is high-energy transurethral microwave thermotherapy with feedback technique. Modern treatment with CoreTherm includes transurethral intraprostatic injections of mepivacaine and adrenalineThe aim of this study was to evaluate the short- and long-term retreatment risk in men with large prostates and BPO or chronic urinary retention, all primarily treated with CoreTherm.All men from the same geographical area with prostate volumes ≥ 80 ml treated 1999-2015 with CoreTherm and having BPO or were catheter-dependent due to chronic urinary retention, were included. End of study period was defined as December 31, 2019.We identified and evaluated 570 men treated with CoreTherm, where 12% (71 patients) were surgically retreated during the follow-up. Mean follow-up was 11 years, and maximum follow-up was 20 years. The long-term retreatment rate in our study was 23%. A majority of these could be retreated with CoreTherm or TURP, with only 3% requiring open surgery.We conclude that CoreTherm is a suitable outpatient treatment option in patients with profoundly enlarged prostates, regardless of age, prostate size, and reason for treatment.

An inborn term neonate weighing 2600 g developed meconium aspiration syndrome at birth. Baby had respiratory failure requiring high-frequency oscillatory ventilation support at 15 hours of life. He additionally developed hypotension with left ventricular dysfunction noted on point-of-care echocardiography (POCE), which required dopamine and epinephrine infusions. At 28 hours of life, he was started on inhaled nitric oxide (iNO), followed by milrinone due to hypoxaemic respiratory failure and the POCE revealed severe pulmonary artery hypertension (PAH). As PAH was refractory to iNO and milrinone, vasopressin was added which resulted in rapid improvement in oxygenation and normalisation of pulmonary artery pressures. Baby was weaned off from vasoactive support in the next 120 hours. Vasopressin proved to be the rescue agent in this case of iNO refractory PAH without any side effects during therapy. Baby was successfully extubated on day 18 and was discharged with a normal neurological examination finding.

The present study was designed to investigate the effects of caffeine and adrenaline administration on memory and anxiety in male rats. Rats weighing about 140-200g were used for the study. They were divided into three groups (4 animals per group). Study groups 1; a,b,c,d were healthy rats administered normal saline, 5,10 and 15mg/kg bw caffeine intraperitoneally (i.p.), respectively for 6 weeks. Study groups 2; a,b,c,d administered normal saline, 0.1, 0.2 and 0.31mg/kg bw adrenaline (i.p.), respectively for 6 weeks. Study groups 3; a,b,c,d administered normal saline, 5mg/kg caffeine (i.p.) + 0.1mg/kg adrenaline (i.p.), 10mg/kg Caffeine (i.p.) + 0.2mg/kg Adrenaline (i.p.) and 15mg/kg Caffeine (i.p.) + 0.3mg/kg Adrenaline (i.p.) respectively for 6 weeks. The result showed no significant difference in spatial memory across all animals in study groups 1: b,c,d when compared to control (a). Study groups 2: (b, c) showed increase in spatial memory when compared to control (a). 2(d) showed a significant (p

Introduction: Susceptibility to decompression sickness (DCS) is characterised by a wide inter-individual variability whose origins are still poorly understood. This hampers reliable prediction of DCS by decompression algorithms. We previously selectively bred rats with a 3-fold greater resistance to DCS than standard rats. Based on its previously reported relation with decompression outcomes, we assessed whether modification in vascular function is associated with resistance to DCS. Methods: The arterial pressure response to intravenous administration of acetylcholine (ACh, 5 µg.kg-1) and adrenaline (5 and 10 µg.kg-1) was compared in anaesthetised DCS-resistant rats (seven females, seven males) and standard Wistar rats (seven females, 10 males) aged 14-15 weeks. None of these rats had previously undergone hyperbaric exposure. Results: There was a non-significant tendency for a lower diastolic (DBP) and mean blood pressure (MBP) in DCS-resistant rats. After ACh administration, MBP was significantly lower in resistant rats, for both males (P = 0.007) and females (P = 0.034). After administration of adrenaline 10 µg.kg-1, DCS-resistant rats exhibited lower maximal DBP (P = 0.016) and MBP (P = 0.038). Systolic and pulse blood pressure changes did not differ between groups in any of the experiments. Conclusions: Resistance to DCS in rats is associated to a trend towards a lower vascular tone but not blood pressure reactivity. Whether these differences are a component of the susceptibility to DCS remains to be confirmed.

To systematically evaluate the clinical efficacy of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) alone or in combination with other agents for preventing pancreatitis after endoscopic retrograde cholangiopanography.We carried out a literature search of random controlled trials (RCTs) on preventing post-operative pancreatitis by administration of the anti-inflammatory drugs, indomethacin and diclofenac, following endoscopic retrograde cholangiopancreatography (ERCP). The databases searched for relevant publications up to July 7, 2021, included PubMed, Cochrane Library, and Embase. We screened the literature according to inclusion criteria and analyzed the extracted data. The overall population and high-risk patient groups were analyzed, with the main outcome being the incidence of PEP.The search identified 32 RCTs that included 15019 patients with post-ERCP pancreatitis and 9 different interventions. The results of the overall population network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs significantly reduced the incidence of PEP compared with placebo. However, compared with placebo, there was no statistically significant difference between the two interventions (NSAIDs + standard hydration and high-dose NSAIDs). In addition, NSAIDs + sublingual nitrates were associated with a lower incidence of PEP compared to that observed with NSAIDs alone. Probability ranking results showed that NSAIDs + sublingual nitrate had the best effect, followed by NSAIDs + standard hydration, NSAIDs + melatonin, NSAIDs + aggressive hydration, NSAIDs + somatostatin, NSAIDs alone, NSAIDs + epinephrine, high-dose NSAIDs, and placebo. In the high-risk subgroup, the results of the network meta-analysis showed that NSAIDs alone, high-dose NSAIDs, and a combination of NSAIDs showed no statistically significant difference in their ability to reduce the incidence of PEP compared with placebo. Probability ranking results showed that NSAIDs + hydration had the best effect, followed by NSAIDs + sublingual nitroglycerin and NSAIDs + aggressive hydration.Of the nine interventions, NSAIDs + sublingual nitrates had considerably better efficacy than the other drugs for reducing the incidence of PEP in the overall population. In high-risk patients, NSAIDs + standard hydration may be the best preventive treatment; however, more randomized, controlled trials are needed to validate our results.Name of the registry: PROSPERO-International prospective register of systematic reviews. Unique identifying number or registration ID: CRD42021282205.

The purpose of this study was to determine the effects of a multidrug injectate containing morphine, ropivacaine, epinephrine, and ketorolac, commonly referred to as the "Orthococktail," on cartilage tissue viability and metabolic responses using an established in vitro model.With institutional review board approval and informed patient consent, tissues normally discarded after total knee arthroplasty (TKA) were recovered. Full-thickness cartilage explants (n = 72, Outerbridge grade 1 to 3) were created and bisected. Paired explant halves were treated with either 1 mL Orthococktail or 1 mL of saline and cultured for 8 hours at 37°C, with 0.5 mL of the treatment being removed and replaced with tissue culture media every hour. Explants were cultured for 6 days, and media were changed and collected on days 3 and 6. After day 6, tissues were processed for cell viability, weighed, and processed for histologic grading. Outcome measures were compared for significant differences between treated and untreated samples.There were no significant differences in cartilage viability between control and Orthococktail-treated samples across a spectrum of cartilage pathologies. Orthococktail treatment consistently resulted in a significant decrease in the release of PGE2, MCP-1, MMP-7, and MMP-8 on day 3 of culture and PGE2, MMP-3, MMP-7, and MMP-8 on day 6 of culture, compared with saline controls.The results of the present study indicate that an Orthococktail injection composed of morphine, ropivacaine, epinephrine, and ketorolac is associated with a transient decrease in degradative and inflammatory mediators produced by more severely affected articular cartilage and may mitigate perioperative joint pain such that postoperative narcotic drug use could be reduced.The Orthococktail solution used in this study may be a safe intraoperative, intra-articular injection option for patients undergoing joint arthroplasty and other joint preservation surgical procedures.

Wide awake local anesthetic no tourniquet (WALANT) is gaining popularity amongst hand surgeons. Digital adrenaline use has been shown to be safe in multiple studies and the misconception forbidding it is receding. Phentolamine has been shown to safely reverse the effects of adrenaline should the feared complication of digital ischemia occur. A survey was circulated to 40 specialist practitioners who regularly perform hand procedures at a major tertiary plastic and hand surgery unit. Knowledge and understanding of WALANT, onset and duration of adrenaline effects and reversal was assessed. Whilst the majority of respondents (80%) recognized digital adrenaline use as safe, only 65% were aware of the delay until adrenaline takes full effect. Similarly, only 25% of respondents were aware of the duration of effect of adrenaline. Half of respondents were aware that phentolamine is the established reversal agent for adrenaline with only 20% knowing the correct dose. Given the lack of clinician knowledge surrounding adrenaline and its reversal, we feel that to safely undertake WALANT surgery at our Unit a WALANT protocol must be implemented. Drawing on the successes in the airline industry, a variety of safety frameworks have been established to deliver targeted education for prevention and eventual management of predictable risks. We plan to develop a checklist style protocol targeting the knowledge gaps raised in the survey. This will educate and equip all practitioners working with adrenaline with the knowledge to safely manage complications should they occur. LEVEL OF EVIDENCE: Level 5 (UK Oxford Centre for Evidence based Medicine (CEBM) Levels of Evidence).

Restrictive blood transfusion is recommended by major guidelines for perioperative management, but requires objective assessment at 7-10 g/dl haemoglobin (Hb). A scoring system that considers the physiological needs of the heart may simply the practice and reduce transfusion.Patients (14-65 years of age) undergoing non-cardiac surgery were randomised at a 1:1 ratio to a control group versus a Perioperative Transfusion Trigger Score (POTTS) group. POTTS (maximum of 10) was calculated as 6 plus the following: adrenaline infusion rate (0 for no infusion, 1 for ≤0.05 μg·kgA total of 864 patients (mean age 44.4 years, 244 men and 620 women) were enrolled from December 2017 to January 2021 (433 in the control and 431 in the POTTS group). Baseline Hb was 9.2 ± 1.8 and 9.2 ± 1.7 g/dl in the control and POTTS groups, respectively. In the ITT analysis, the proportion of the patients receiving allogeneic RBCs was 43.9% (190/433) in the control group versus 36.9% (159/431) in the POTTS group (p = 0.036). Lower rate of allogeneic RBCs transfusion in the POTTS group was also evident in the per-protocol analysis (42.8% vs. 35.5%, p = 0.030). Transfusion volume was 4.0 (2.0, 6.0) and 3.5 (2.0, 5.5) units (200 ml/unit) in the control and POTTS groups, respectively (p = 0.25). The rate of severe postoperative complications (Clavien-Dindo grade IIIa and higher) was 3.9% in the control group versus 1.2% in the POTTS group (p = 0.010).Transfusion of allogeneic RBCs based on the POTTS was safe and reduced the transfusion requirement in patients undergoing non-cardiac surgery.

Context The Arg16 variant in the β2-receptor gene is associated with increased risk of severe hypoglycemia in subjects with type 1 diabetes mellitus. Objective We hypothesized that the Arg16 variant is associated with decreased metabolic and symptomatic responses to recurrent hypoglycemia. Methods Twenty-five healthy male subjects selected according to ADRB2 genotype and being homozygous for either Arg16 (AA; n = 13) or Gly16 (GG; n = 12) participated in 2 consecutive trial days with 3 periods of hypoglycemia (H1-H3) induced by a hyperinsulinemic hypoglycemic clamp. The main outcome measure was mean glucose infusion rate (GIR) during H1-H3. Results During H1-H3, there was no difference between AA or GG subjects in GIR, counter-regulatory hormones (glucagon, epinephrine, cortisol, growth hormone), or substrate levels of lactate, glycerol, and free fatty acids (FFAs), and no differences in symptom response score or cognitive performance (trail making test, Stroop test). At H3, lactate response was reduced in both genotype groups, but AA subjects had decreased response (mean ± standard error of the mean of area under the curve) of glycerol (–13.1 ± 3.8 μmol L–1 hours; P = .0052), FFA (–30.2 ± 11.1 μmol L–1 hours; P = .021), and β-hydroxybutyrate (–0.008 ± 0.003 mmol L–1 hour; P = .027), while in GG subjects alanine response was increased (negative response values) (–53.9 ± 20.6 μmol L–1 hour; P = .024). Conclusion There was no difference in GIR between genotype groups, but secondary outcomes suggest a downregulation of the lipolytic and β-hydroxybutyrate responses to recurrent hypoglycemia in AA subjects, in contrast to the responses in GG subjects.

Erector spinae plane blocks (ESPB) and pectointercostal fascial (PIFB) plane blocks are novel interfascial blocks for which local anesthetic (LA) doses and concentrations necessary to achieve safe and effective analgesia are unknown. The goal of this prospective observational study was to provide the timing (TErector spinae plane blocks or PIFBs (18 patients per block; total, 36 patients) were performed with 2 mg⋅kgFor ESPB, the mean (standard deviation [SD]) total bupivacaine CTotal and free bupivacaine CRéSUMé: OBJECTIF: Les blocs des muscles érecteurs du rachis (ESP) et les blocs des plans fasciaux pecto-intercostaux (PIFB) sont de nouveaux blocs interfasciaux pour lesquels les doses et les concentrations d’anesthésique local (AL) nécessaires à obtenir une analgésie sécuritaire et efficace sont inconnues. L’objectif de cette étude observationnelle prospective était de déterminer le moment d’administration (T

Explore the prevalence of childhood anaphylaxis and clinical presentation of anaphylaxis in children across two regional emergency departments over a 7-year period.Retrospective audit of all children (0-18 years) presenting to emergency from 1 January 2010 to 31 December 2016 with anaphylaxis, defined by Australasian Society of Clinical Immunology and Allergy definitions and doctor diagnosis.Seven hundred and twenty-four patients were identified with allergic diagnosis, 60% were diagnosed with non-anaphylaxis allergic reactions or unspecified urticaria and 40% with anaphylaxis (n = 286). Annual prevalence of anaphylaxis remained stable over the study period (M = 30.9/10 000 cases, range: 20.8-48.3/10 000). Gender distribution was equal, median age was 9.48 years (interquartile range = 4-15). Most (71%) arrived by private transport. 23% had a prior history of anaphylaxis. Food triggers (44%) were the most common cause of anaphylaxis. Insect bites/stings triggers occurred in 21%. Patients were promptly assessed (average wait time = 13 min), 16% received prior adrenaline injections. Adrenaline was administered in 26% and 20% were admitted to hospital. On discharge, 29% had a follow-up plan, 9% received an allergy clinic referral, 6% anaphylaxis action plan, 26% adrenaline autoinjector prescriptions and allergy testing performed in 6%.We found a relatively low prevalence of overall childhood anaphylaxis in a regional area. The two most common causes of anaphylaxis in this population (food and bites/stings) recorded increased prevalence providing an opportunity for further study. Significant gaps in evidence-based care of anaphylaxis were noted, demonstrating the need for improved recognition and treatment guideline implementation in regional areas.