Idiopathic anomalous congenital band causing small intestinal obstruction in a 5-month-old dog

A 5-month-old, intact male, yellow Labrador retriever was presented with a 24-hour history of anorexia and vomiting. Abdominal imaging revealed the presence of a mechanical obstruction in the jejunum and peritoneal effusion. Cytologic evaluation and culture of the effusion prior to surgery identified a suppurative exudate with bacteria consistent with septic peritonitis and suspected to be related to the intestinal lesion. An exploratory laparotomy was performed, and a segment of jejunum was circumferentially severely constricted by an off-white, fibrous band of tissue. Resection and anastomosis of the strangulated segment of jejunum and excision of the constricting band provided resolution of the clinical signs. The dog made a complete recovery. Histologic evaluation revealed the band to be composed of fibrovascular and smooth muscle tissue, consistent with an idiopathic anomalous congenital band. No other gastrointestinal lesions were observed, either grossly at surgery or histologically in the resected segment of intestine. To our knowledge, a similar structure has not been reported in the veterinary literature.Copyright © 2022 Canadian Veterinary Medical Association. All rights reserved.

Effects of Various Mrna-Lnp Vaccine Doses on Neuroinflammation in Balb/C Mice

It has been proven that mRNA vaccines are highly effective against the COVID-19 outbreak, and low prevalence of side effects has been shown. However, there are still many gaps in our understanding of the biology and biosafety of nucleic acids as components of lipid nanoparticles (LNPs) most often used as a system for inctracellular delivery of mRNA-based vaccines. It is known that LNPs cause severe injection site inflammation, have broad biodistribution profiles, and are found in multiple tissues of the body, including the brain, after administration. The role of new medications with such pharmacokinetics in inflammation developing in inaccessible organs is poorly understood. The study was aimed to assess the effects of various doses of mRNA-LNP expressing the reporter protein (0, 5, 10, and 20 microg of mRNA encoding the firefly luciferase) on the expression of neuroinflammation markers (Tnfalpha, Il1beta, Gfap, Aif1) in the prefrontal cortex and hypothalamus of laboratory animals 4, 8, and 30 h after the intramuscular injection of LNP nanoemulsion. It was shown that mRNA-LNP vaccines in a dose of 10-20 microg of mRNA could enhance Aif1 expression in the hypothalamus 8 h after vaccination, however, no such differences were observed after 30 h. It was found that the Gfap, l11beta, Tnfalpha expression levels in the hypothalamus observed at different times in the experimental groups were different. According to the results, mRNA-LNPs administered by the parenteral route can stimulate temporary activation of microglia in certain time intervals in the dose-dependent and site specific manner.Copyright © 2022 Pirogov Russian National Research Medical University. All rights reserved.

Inhaled Sedation with Volatile Anesthetics for Mechanically Ventilated Patients in Intensive Care Units: A Narrative Review.

Inhaled sedation was recently approved in Europe as an alternative to intravenous sedative drugs for intensive care unit (ICU) sedation. The aim of this narrative review was to summarize the available data from the literature published between 2005 and 2023 in terms of the efficacy, safety, and potential clinical benefits of inhaled sedation for ICU mechanically ventilated patients. The results indicated that inhaled sedation reduces the time to extubation and weaning from mechanical ventilation and reduces opioid and muscle relaxant consumption, thereby possibly enhancing recovery. Several researchers have reported its potential cardio-protective, anti-inflammatory or bronchodilator properties, alongside its minimal metabolism by the liver and kidney. The reflection devices used with inhaled sedation may increase the instrumental dead space volume and could lead to hypercapnia if the ventilator settings are not optimal and the end tidal carbon dioxide is not monitored. The risk of air pollution can be prevented by the adequate scavenging of the expired gases. Minimizing atmospheric pollution can be achieved through the judicious use of the inhalation sedation for selected groups of ICU patients, where the benefits are maximized compared to intravenous sedation. Very rarely, inhaled sedation can induce malignant hyperthermia, which prompts urgent diagnosis and treatment by the ICU staff. Overall, there is growing evidence to support the benefits of inhaled sedation as an alternative for intravenous sedation in ICU mechanically ventilated patients. The indication and management of any side effects should be clearly set and protocolized by each ICU. More randomized controlled trials (RCTs) are still required to investigate whether inhaled sedation should be prioritized over the current practice of intravenous sedation.

Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers. © 2022 The Authors

Effect Of Different MAC Values On Bispectral Index In Isoflurane Anaesthesia

Introduction: The bispectral index monitors the unawareness component of balanced anaesthesia and gives us the depth of Anesthesia.It reflects the response of the brain to a variety of hypnotic and inhaled anaesthesia agents. The aim of this study was to see the effect of different MAC values of isoflurane on the bispectral index and hemodynamic variations at different MAC values. Material(s) and Method(s): This prospective study was conducted on 20 patients at tertiary care center for 6 months. After induction of Anesthesia, following parameters were recorded: noninvasive blood pressure measurement, heart rate, oxygen saturation, ETCo2 and BIS values. The BIS was continuously monitored and when the MAC values of isoflurane were 0.5, 0.7, 1, 1.2 and 1.5 corresponding BIS values and all the other haemodynamic parameters were noted. Result(s): In 11 patients out of 20 patients satisfactory BIS of 40-60 was achieved at MAC 0.5. In 16 out of 20 patients satisfactory BIS 40-60 was achieved at 0.7 MAC. In all the 20 patients satisfactory BIS was achieved at 1 MAC.In 2 out of 20 patients we couldn't proceed beyond 1.0 MAC because of the fall in MAP to <65mm of Hg. In 4 out of 20 patients we couldn't proceed beyond 1.2MAC because of the fall in MAP to <65mm of Hg. Conclusion(s): Isoflurane produced satisfactory BIS of 40-60 in 16 patients at 0.7 MAC and in all the 20 patients at 1 MAC.Use of BIS in our study helped in better titration of Isoflurane according to patient's individual needs thereby we avoided light plane of anaesthesia or deep hypnosis and the adverse effects associated with it. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Reducing the carbon footprint from general anaesthesia throughout the North East of England and North Cumbria

In 2019, the North East Anaesthesia Sustainable Healthcare (NEASH) Network was formed. Its aim is to encourage coordinated sustainability efforts. We comprise over 80 anaesthetists with representatives in every Trust in our region. The NHS accounts for 4% of UK carbon emissions. Two per cent of NHS emissions come solely from anaesthetic gases. In late 2020, we began a region-wide project to raise awareness of the environmental impact of general anaesthesia (GA) with the aim of reducing emissions throughout our geographical area. Methods NEASH performed a snapshot audit of 1 full week's GA data in early 2021. Consumed volatile agent, nitrous oxide (N2O) and total intravenous anaesthesia (TIVA) were converted into kilograms of carbon dioxide equivalents (kg CO2e) [1, 2]. Each Trust's emissions were divided by total GA time giving kg CO2e per hour (kg CO2e.h-1), allowing efficiency comparison between sites. We presented our results and the following messages to each Trust. Firstly, stop using desflurane and use N2O only when essential as these agents have the highest global warming potential (GWP). Secondly, we encouraged sevoflurane use as it has the lowest GWP of volatiles (followed by isoflurane);low fresh gas flows are essential. Thirdly, consider TIVA, as its GWP is lower than volatile GA. Although outside the scope of our audit, we reminded colleagues that local or regional anaesthesia have a lower CO2e than GA. In early 2022, we re-audited to assess the impact of our messages. Results The results of 5340 h of GA data are displayed in the table below. Discussion Due to increased operating post-COVID-19 and the inclusion of a hospital that was unable to participate in round 1, round 2 contained 787 more hours of data. Despite this, emissions of CO2e were 12.83 t lower, demonstrating an average hourly emission reduction of 61.1%. This was mainly driven by reduced desflurane and N2O use. Two hospitals in our region have since decommissioned N2O manifolds and two others are undertaking this process. Region-wide procurement data obtained by NEASH showed that three hospitals have ceased ordering desflurane. TIVA use remained broadly the same, which may be due to a lack of availability of equipment. This region-wide project is easily reproducible nationwide and could make significant contributions towards NHS net zero. (Table Presented).

Inhaled Sedation in Patients with COVID-19-Related Acute Respiratory Distress Syndrome: An International Retrospective Study.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic and the shortage of intravenous sedatives has led to renewed interest in inhaled sedation for patients with acute respiratory distress syndrome (ARDS). We hypothesized that inhaled sedation would be associated with improved clinical outcomes in COVID-19 ARDS patients. METHODS: Retrospective international study including mechanically ventilated patients with COVID-19 ARDS who required sedation and were admitted to 10 European and US intensive care units. The primary endpoint of ventilator-free days through day 28 was analyzed using zero-inflated negative binomial regression, before and after adjustment for site, clinically relevant covariates determined according to the univariate results, and propensity score matching. RESULTS: A total of 196 patients were enrolled, 78 of whom died within 28 days. The number of ventilator-free days through day 28 did not differ significantly between the patients who received inhaled sedation for at least 24 h (n = 111) and those who received intravenous sedation only (n = 85), with medians of 0 (interquartile range [IQR] 0-8) and 0 (IQR 0-17), respectively (odds ratio for having zero ventilator-free days through day 28, 1.63, 95% confidence interval [CI], 0.91-2.92, p = 0.10). The incidence rate ratio for the number of ventilator-free days through day 28 if not 0 was 1.13 (95% CI, 0.84-1.52, p = 0.40). Similar results were found after multivariable adjustment and propensity matching. CONCLUSION: The use of inhaled sedation in COVID-19 ARDS was not associated with the number of ventilator-free days through day 28.

Role of Dexmedetomidine in Perioperative Management of Pheochromocytoma

The prevalence of Pheochromocytoma in pat ient with hypertension is 0.1 -0.6%. These types of tumours are known for unpredictable perioperative course and hemodynamic instability. Various different drugs and anaesthesia techniques can be used to tackle these situations. Dexmedetomidine is emerged as newer agent with better hemodynamic stability, reducing requirement of other anaesthesia drugs, blunting of sympathoadrenal response in resection of Pheochromocytoma. We report four cases operated between January 2021 to June 2021.Preoperative preparation was done with α and β blockade. Dexmedetomidine was used during induction as 1 mcg/kg over 10 mins followed by 0.7mcg/kg/hr intraoperatively. Combination of Dexmedetomidine, Fentanyl, NTG, Isoflurane and Epidural analgesia was used. IF needed boluses of Esmolol and Labetalol were used during tumor manipulation. All the patients had an uneventful perioperative course. Dexmedetomidine with pre-operative α and β blockade reduce the need of other drugs intraoperatively and can be used as anaesthetic adjunct to maintain steady hemodynamic.

Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice.

With the widespread use of volatile anesthetic agents in the prolonged sedation for COVID-19 pneumonia and ARDS, there is an urgent need to investigate the effects and treatments of lengthy low-concentration inhaled anesthetics exposure on cognitive function in adults. Previous studies showed that general anesthetics dose- and exposure length-dependently induced neuroinflammatory response and cognitive decline in neonatal and aging animals. The anti-diabetes drug metformin has anti-neuroinflammation effects by modulating microglial polarization and inhibiting astrocyte activation. In this study, we demonstrated that the inhalation of 1.3% isoflurane (a sub-minimal alveolar concentration, sub-MAC) for 6 h impaired recognition of novel objects from Day 1 to Day3 in adult mice. Prolonged sub-MAC isoflurane exposure also triggered typically reactive microglia and A1-like astrocytes in the hippocampus of adult mice on Day 3 after anesthesia. In addition, prolonged isoflurane inhalation switched microglia into a proinflammatory M1 phenotype characterized by elevated CD68 and iNOS as well as decreased arginase-1 and IL-10. Metformin pretreatment before anesthesia enhanced cognitive performance in the novel object test. The positive cellular modifications promoted by metformin pretreatment included the inhibition of reactive microglia and A1-like astrocytes and the polarization of microglia into M2 phenotype in the hippocampus of adult mice. In conclusion, prolonged sub-MAC isoflurane exposure triggered significant hippocampal neuroinflammation and cognitive decline in adult mice which can be alleviated by metformin pretreatment via inhibiting reactive microglia and A1-like astrocytes and promoting microglia polarization toward anti-inflammatory phenotype in the hippocampus.

Comparison of isoflurane and propofol sedation in critically ill COVID-19 patients-a retrospective chart review.

PURPOSE: In this retrospective study, we compared inhaled sedation with isoflurane to intravenous propofol in invasively ventilated COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome). METHODS: Charts of all 20 patients with COVID-19 ARDS admitted to the ICU of a German University Hospital during the first wave of the pandemic between 22/03/2020 and 21/04/2020 were reviewed. Among screened 333 days, isoflurane was used in 97 days, while in 187 days, propofol was used for 12 h or more. The effect and dose of these two sedatives were compared. Mixed sedation days were excluded. RESULTS: Patients' age (median [interquartile range]) was 64 (60-68) years. They were invasively ventilated for 36 [21-50] days. End-tidal isoflurane concentrations were high (0.96 ± 0.41 Vol %); multiple linear regression yielded the ratio (isoflurane infusion rate)/(minute ventilation) as the single best predictor. Infusion rates were decreased under ECMO (3.5 ± 1.4 versus 7.1 ± 3.2 ml∙h-1; p < 0.001). In five patients, the maximum recommended dose of propofol of 4 mg∙hour-1∙kg-1ABW was exceeded on several days. On isoflurane compared to propofol days, neuro-muscular blocking agents (NMBAs) were used less frequently (11% versus 21%; p < 0.05), as were co-sedatives (7% versus 31%, p < 0.001); daily opioid doses were lower (720 [720-960] versus 1080 [720-1620] mg morphine equivalents, p < 0.001); and RASS scores indicated deeper levels of sedation (- 4.0 [- 4.0 to - 3.0] versus - 3.0 [- 3.6 to - 2.5]; p < 0.01). CONCLUSION: Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients.

Standard Sedation and Sedation With Isoflurane in Mechanically Ventilated Patients With Coronavirus Disease 2019.

OBJECTIVES: To describe sedative and analgesic drug utilization in a cohort of critically ill patients with coronavirus disease 2019 and compare standard sedation with an alternative approach using inhaled isoflurane. DESIGN: This was a retrospective cohort study designed to compare doses of sedatives between ICU patients receiving standard IV sedation and patients receiving mixed sedation including inhaled isoflurane. Data were obtained from electronic medical records. SETTING: ICU at large academic medical center where mechanical ventilation was delivered with Draeger Apollo (Draeger Medical, Telford, PA) anesthesia machines. PATIENTS: Consecutive adult patients (≥ 18 yr) with confirmed coronavirus disease 2019 admitted to ICU between April 2, 2020, and May 4, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five mechanically ventilated patients were included in the study, with a mean (sd) age of 59.4 (12.8) years. Twenty-three patients (65.7%) were men. Seventeen patients (48.6%) received standard IV sedation, whereas 18 (51.4%) also received isoflurane. The mean duration of mechanical ventilation (sd) was 23.3 (11.6) days in the standard sedation group and 23.8 (12.5) days in the isoflurane group. Mean (sd) duration of isoflurane exposure was 5.61 (2.99) days, representing 29.1% of total sedation time (sd, 20.4). Cumulative opioid exposure did not differ between the standard sedation and isoflurane sedation groups (mean morphine milligram equivalent 6668 [sd, 1,346] vs 6678 [sd, 2,000] mg). However, the initiation of isoflurane in patients was associated with decreased utilization of propofol (mean daily amount 3,656 [sd, 1,635] before vs 950 [sd, 1,804] mg during isoflurane) and hydromorphone (mean daily amount 48 [sd, 30] before vs 23 [sd, 27] mg). CONCLUSIONS: In the subjects that received isoflurane, its use was associated with significant decreases in propofol and hydromorphone infusions.