Sex differences in the intensity of statin prescriptions at initiation in a primary care setting.

BACKGROUND: Current guidelines for the prevention and management of cardiovascular diseases (CVD) provide similar recommendations for the use of statins in both women and men. In this study, we assessed sex differences in the intensity of statin prescriptions at initiation and in the achievement of treatment targets, among individuals without and with CVD, in a primary care setting. METHODS: Electronic health record data from statin users were extracted from the PHARMO Data Network. Poisson regressions were used to investigate sex differences in statin intensity and in the achievement of treatment targets. Analyses were stratified by age group, disease status and/or CVD risk category. RESULTS: We included 82 714 individuals (46% women) aged 40-99 years old. In both sexes, the proportion of individuals with a dispensed prescription for high-intensity statin at initiation increased between 2011 and 2020. Women were less likely to be prescribed high-intensity statins as compared with men, both in the subgroups without a history of CVD (risk ratio (RR) 0.69 (95% CI: 0.63 to 0.75)) and with CVD (RR 0.77 (95% CI: 0.74 to 0.81)). Women were less likely than men to achieve target levels of low-density lipoprotein cholesterol following statin initiation in the subgroup without CVD (RR 0.98 (95% CI: 0.97 to 1.00)) and with a history of CVD (RR 0.94 (95% CI: 0.89 to 0.98)). CONCLUSION: Compared with men, women were less likely to be prescribed high-intensity statins at initiation and to achieve treatment targets, both in people without and with a history of CVD, and independent of differences in other individual and clinical characteristics.

Protein mimetic 2D FAST rescues alpha synuclein aggregation mediated early and post disease Parkinson's phenotypes.

Abberent protein-protein interactions potentiate many diseases and one example is the toxic, self-assembly of α-Synuclein in the dopaminergic neurons of patients with Parkinson's disease; therefore, a potential therapeutic strategy is the small molecule modulation of α-Synuclein aggregation. In this work, we develop an Oligopyridylamide based 2-dimensional Fragment-Assisted Structure-based Technique to identify antagonists of α-Synuclein aggregation. The technique utilizes a fragment-based screening of an extensive array of non-proteinogenic side chains in Oligopyridylamides, leading to the identification of NS132 as an antagonist of the multiple facets of α-Synuclein aggregation. We further identify a more cell permeable analog (NS163) without sacrificing activity. Oligopyridylamides rescue α-Synuclein aggregation mediated Parkinson's disease phenotypes in dopaminergic neurons in early and post disease Caenorhabditis elegans models. We forsee tremendous potential in our technique to identify lead therapeutics for Parkinson's disease and other diseases as it is expandable to other oligoamide scaffolds and a larger array of side chains.

Worry differentially mediates posttraumatic cognition and posttraumatic stress symptom relationships among veterans seeking treatment associated with military sexual trauma.

Research has established negative posttraumatic cognitions (NPC) affect the development and course of posttraumatic stress symptoms (PTSS) following trauma exposure (L. A. Brown et al., 2019). Previous studies in civilian and combat veteran populations also suggest positive associations among worry, NPC (Beck et al., 2004; Bennett et al., 2009), and PTSS (Fergus & Bardeen, 2017). However, little research has investigated the prevalence of worry in veterans who have experienced military sexual trauma (MST), and no research has examined the role of worry in the relation between NPC and PTSS among veterans seeking treatment associated with MST. This project examined the prevalence of worry in a MST sample and whether worry mediated NPC-PTSS associations. Veterans (N = 91) seeking MST-related treatment presented to a Veterans Affairs Posttraumatic Stress Disorder specialty clinic for assessment and treatment recommendations. Veterans completed questionnaires assessing NPC, worry, and PTSS. Bootstrapped mediation analyses examined NPC-PTSS associations. Veterans reported similar levels of worry as nonveterans seeking treatment associated with generalized anxiety disorder. Mediation analyses showed worry significantly mediated NPC-PTSS relationships for beliefs about the world, self-blame, and coping competence but not for beliefs about the self or global NPC severity. Further, the degree of mediation differed by NPC type. Though a limitation of this study is the use of cross-sectional data, these results inform the use of clinical intervention strategies targeting worry in trauma-focused interventions and necessitate further research on whether trauma-focused interventions ameliorate co-occurring worry among veterans exposed to MST. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Making Ends Meet.

In this narrative medicine essay, a second-year medical student describes how slipping into poverty starting with her father's myocardial infarction has cast a long shadow that persists even in medical school.

Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.

Development of a human liver microphysiological coculture system for higher throughput chemical safety assessment.

Chemicals in the systemic circulation can undergo hepatic xenobiotic metabolism, generate metabolites, and exhibit altered toxicity compared with their parent compounds. This article describes a 2-chamber liver-organ coculture model in a higher-throughput 96-well format for the determination of toxicity on target tissues in the presence of physiologically relevant human liver metabolism. This 2-chamber system is a hydrogel formed within each well consisting of a central well (target tissue) and an outer ring-shaped trough (human liver tissue). The target tissue chamber can be configured to accommodate a three-dimensional (3D) spheroid-shaped microtissue, or a 2-dimensional (2D) cell monolayer. Culture medium and compounds freely diffuse between the 2 chambers. Human-differentiated HepaRG liver cells are used to form the 3D human liver microtissues, which displayed robust protein expression of liver biomarkers (albumin, asialoglycoprotein receptor, Phase I cytochrome P450 [CYP3A4] enzyme, multidrug resistance-associated protein 2 transporter, and glycogen), and exhibited Phase I/II enzyme activities over the course of 17 days. Histological and ultrastructural analyses confirmed that the HepaRG microtissues presented a differentiated hepatocyte phenotype, including abundant mitochondria, endoplasmic reticulum, and bile canaliculi. Liver microtissue zonation characteristics could be easily modulated by maturation in different media supplements. Furthermore, our proof-of-concept study demonstrated the efficacy of this coculture model in evaluating testosterone-mediated androgen receptor responses in the presence of human liver metabolism. This liver-organ coculture system provides a practical, higher-throughput testing platform for metabolism-dependent bioactivity assessment of drugs/chemicals to better recapitulate the biological effects and potential toxicity of human exposures.

Change as a Scientific Enterprise: Practical Suggestions about Using Change Theory.

Change theory has increasingly become an area of scholarship in STEM education. While this area has traditionally been a topic for organizational psychology, business management, communication studies, and higher education, STEM education researchers are increasingly aware of the need to use formal theories to guide change efforts and research. Formal change theory encompasses our current research-based knowledge about how and why change occurs, and therefore, can guide the selection and design of promising interventions. Yet learning about and using theory is challenging because many of us have no formal training in this area and relevant scholarship comes from many different disciplines. Inconsistent terminology creates an additional barrier. Thus, this essay aims to contribute to a common lexicon in STEM higher educational change efforts by clearly distinguishing between formalized change theory, which emerges from research, and a theory of change, which guides the logic of a specific project. We also briefly review the current state of the field regarding the use of formal change theory and provide examples of how change theory has been used in biology education. Lastly, we offer practical guidance for researchers and change agents who wish to more intentionally and effectively use change theory in their work.

Cell Survival Computation via the Generalized Stochastic Microdosimetric Model (GSM2); Part II: Numerical Results.

In the present paper we numerically investigate, using Monte Carlo simulation, the theoretical results predicted by the Generalized Stochastic Microdosimetric Model (GSM2), as shown in the published companion paper. Taking advantage of the particle irradiation data ensemble (PIDE) dataset, we calculated GSM2 biological parameters of human salivary gland (HSG) and V79 cell lines. Further, exploiting the TOPAS-microdosimetric extension, we simulated the microdosimetric spectra of different radiation fields of therapeutic interest generated by four different ions (protons, helium-4, carbon-12 and oxygen-16) each at three different residual ranges. We investigated the properties of the initial damage distributions as well as the cell survival curve predicted by GSM2, focusing especially on the non-Poissonian effects naturally included in the model. GSM2 successfully computed cell survival curves, accurately describing experimental behavior even under challenging LET and dose conditions.

The impact of hospital experience in bariatric surgery on short-term outcomes after minimally invasive esophagectomy: a nationwide analysis.

BACKGROUND: Minimally invasive esophagectomy (MIE) is a technically challenging procedure with a substantial learning curve. Composite volume of upper gastrointestinal (upper GI) procedures for cancer has been previously linked to postoperative outcomes. This study aimed to investigate an association between hospital experience in bariatric surgery and short-term outcomes in MIE. METHOD: Data on esophagectomy patients between 2016 and 2020 were collected from the Dutch Upper Gastrointestinal Cancer Audit, a mandatory nationwide registry. Hospitals were categorized as bariatric or non-bariatric. Multivariable logistic regression investigated short-term postoperative outcomes, adjusting for case mix. RESULTS: Of 3371 patients undergoing esophagectomy in sixteen hospitals, 2450 (72.7%) underwent MIE. Bariatric hospitals (N = 6) accounted for 1057 (43.1%) MIE. Annual volume of bariatric procedures was median 523 and esophagectomies 42. In non-bariatric hospitals, volume of esophagectomies was median 52 (P = 0.145). Overall postoperative complication rate was lower in bariatric hospitals (59.2% vs. 65.9%, P < 0.001). Bariatric hospitals were associated with a reduced risk of overall complications (aOR 0.76 [95% CI 0.62-0.92]), length of hospital (aOR 0.79 [95% CI 0.65-0.95]), and ICU stay (aOR 0.81 [95% CI 0.67-0.98]) after MIE. Surgical radicality (R0) did not differ. Lymph node yield (≥ 15) was lower in bariatric hospitals (90.0% vs. 94.7%, P < 0.001). Over the years, several short-term outcomes improved in bariatric hospitals compared to non-bariatric hospitals. CONCLUSION: In this nationwide analysis, there was an association between bariatric hospitals and improved short-term outcomes after MIE. Characteristics of bariatric hospitals that could explain this phenomenon and whether this translates to other upper GI procedures may be warranted to identify.

Variation in litter occupancy and dust bathing patterns among layer strains following periods of litter restriction.

Producers are moving toward cage-free systems to house laying hens. These include aviary styles with multilevel wire enclosures and litter areas on the floor. In aviaries with doors hens can be confined within the tiered enclosure, which can be done to promote oviposition in nests and prevent hens from laying eggs in litter. However, there are multiple genetic strains of laying hen used in the egg industry, and some show different temporal patterns for key behaviors that could affect when they want to be on litter. For example, though dust bathing by laying hens is typically considered to peak in early afternoon, there may be variation in timing of motivation to dust bathe among strains. Differences in hens' temporal patterns, coupled with aviary configurations or management practices, may restricts birds' ability to perform important behaviors, such as dust bathing (DB), when they would most prefer to do them. Our objective was to determine if there were strain differences in the temporal pattern of DB. We examined the timing of DB in 4 strains of laying hen (Hy-Line Brown [HB], Bovans Brown [BB], DeKalb White [DW], and Hy-Line W36 [W36]) housed in aviaries using 144 hens of each strain per aviary unit (4 units/strain). We recorded the number of hens DB and on litter using instantaneous scan sampling every 5 min using video collected at 26 and 28 wk of age beginning at 11:35 (when litter access began each day) to 20:00 (lights off). Brown strains acclimated to litter access more slowly than white strains. Hens of all strains DB most often soon after gaining access to litter, and more white hens (DW and W36) DB simultaneously and in the presence of more conspecifics. Further examination of diurnal rhythm of behaviors, such as dust bathing, under unconstrained conditions by a range of genetic strains of laying hens is needed to design management practices and aviary styles that best meet hens' needs.

Microdosimetry of a 62-MeV clinical proton beam with five detectors.

In proton therapy, most treatment planning systems (TPS) use a fixed relative biological effectiveness (RBE) of 1.1 all along the depth-dose profile. Innovative TPS are now investigated considering the variability of RBE with radiation quality. New TPS need an experimental verification in the quality assurance (QA) routine in clinics, but RBE data are usually obtained with radiobiological measurements that are time consuming and not suitable for daily QA. Microdosimetry is a useful tool based on physical measurements which can monitor the radiation quality. Several microdosimeters are available in different research institutions, which could potentially be used for the QA in TPS. In this study, the response functions of five detectors in the same 62-MeV proton Spread Out Bragg Peak is compared in terms of spectral distributions and their average values and microdosimetric RBE. Their different response function has been commented and must be considered in the clinical practice.

Microdosimetric analysis of the radiation quality of two different proton beams in the distal edge of the depth-dose profile.

Proton-therapy exploits the advantageous depth-dose profile of protons to induce the highest damage to tumoral cells in the last millimetres of their range in sharp Bragg Peak. To cover the whole tumoral volume, beams of different energies are combined to create the Spread Out Bragg Peak (SOBP). In passive modulated beams, the energy spread is created with modulators in which the highest energy beam is degraded through different thicknesses of calibrated plastic materials. The highest energy is chosen depending on the deepest point that needs to be treated. This study aims to investigate differences in the radiation quality in the distal edge of SOBP beams with different initial energy and modulation techniques based on microdosimetric measurements with mini Tissue-Equivalent Proportional Counters. The beams investigated are the 62 MeV proton SOBP of the clinical facility of CATANA and the 148 MeV proton SOBP of the research beam line of the proton-therapy centre of Trento.

Long-Term Survival Associated with Direct Oral Feeding Following Minimally Invasive Esophagectomy: Results from a Randomized Controlled Trial (NUTRIENT II).

Advancements in perioperative care have improved postoperative morbidity and recovery after esophagectomy. The direct start of oral intake can also enhance short-term outcomes following minimally invasive Ivor Lewis esophagectomy (MIE-IL). Subsequently, short-term outcomes may affect long-term survival. This planned sub-study of the NUTRIENT II trial, a multicenter randomized controlled trial, investigated the long-term survival of direct versus delayed oral feeding following MIE-IL. The outcomes included 3- and 5-year overall survival (OS) and disease-free survival (DFS), and the influence of complications and caloric intake on OS. After excluding cases of 90-day mortality, 145 participants were analyzed. Of these, 63 patients (43.4%) received direct oral feeding. At 3 years, OS was significantly better in the direct oral feeding group (p = 0.027), but not at 5 years (p = 0.115). Moreover, 5-year DFS was significantly better in the direct oral feeding group (p = 0.047) and a trend towards improved DFS was shown at 3 years (p = 0.079). Postoperative complications and caloric intake on day 5 did not impact OS. The results of this study show a tendency of improved 3-year OS and 5-year DFS, suggesting a potential long-term survival benefit in patients receiving direct oral feeding after esophagectomy. However, the findings should be further explored in larger future trials.

Psychometrics of the patient-reported outcomes measurement information system measures in hemophilia: the applicability of the pediatric item banks.

Background: The use of patient-reported outcomes measures (PROMs) is important in hemophilia care, as it facilitates communication between patients and clinicians and promotes patient-centered care. Currently, a variety of PROMs with insufficient psychometric properties are used. Patient-reported outcomes measurement information system (PROMIS) measures, including Computer Adaptive Tests, were designed to measure generically and more efficiently and, therefore, are an alternative for the existing PROMs. Objectives: To assess the feasibility, measurement properties, and outcomes of 8 PROMIS pediatric measures for boys with hemophilia. Methods: In this multicenter study, boys with hemophilia completed 8 PROMIS measures and 2 legacy instruments. Feasibility was determined by the number of completed items and floor or ceiling effects (percentage of participants that achieved the lowest or highest possible score). Reliability was assessed as the percentage of scores with a SE ≤ 4.5. Construct validity was evaluated by comparing the PROMIS measures with the legacy instruments. Mean PROMIS T-scores were calculated and compared with the Dutch general population. Results: In total, 77 boys with hemophilia participated. Reliability was good for almost all PROMIS measures and legacy instruments. The total number of completed items varied from 49 to 90 for the PROMIS pediatric measures, while the legacy instruments contained 117 to 130 items. Floor and ceiling effects were observed in both the PROMIS measures (0-39.5%) and legacy instruments (0-66.7%), but were higher for the legacy instruments. Conclusions: The PROMIS pediatric measures are feasible to use for boys with hemophilia. With the use of the PROMIS measures in clinical care and research, a step toward worldwide standardization of PROM administration can be taken.

"What's Your Thinking behind That?" Exploring Why Biology Instructors Use Classroom Discourse.

Instructor discourse, defined as verbal interactions with students in the classroom, can play an important role in student learning. Instructors who use dialogic discourse invite students to develop their own ideas, and both students and the instructor share ideas in back-and-forth exchanges. This type of discourse is well-suited to facilitate deep learning for students but is rare in undergraduate biology classrooms. Understanding the reasoning that underlies the use of dialogic discourse can inform teaching professional development for instructors who are learning to use discourse to support student learning. Through classroom video recordings to identify dialogic discourse and stimulated recall interviews to elicit instructor reasoning, we investigated why undergraduate biology instructors used dialogic discourse in active-learning lessons. Using inductive and deductive qualitative analysis of interview transcripts, we identified and characterized seven reasons that instructors used dialogic discourse, including three aligned with a theoretical framework of student cognitive engagement and four that emerged from our data set. In addition to aiming to prompt generative cognitive engagement in 34% of instances of dialogic discourse, instructors used dialogic discourse to prompt activity, supply information, provide feedback, decipher student thinking, leverage student thinking, and cue students to make connections. Reasoning varied across different types of dialogic discourse. These findings provide valuable insights that can inform research, teaching professional development, and individual instructors' reflections.

RALGAPA1 Deletion in Belgian Shepherd Dogs with Cerebellar Ataxia.

Several genetically distinct forms of cerebellar ataxia exist in Belgian shepherd dogs. We investigated a litter in which two puppies developed cerebellar ataxia. The clinical signs stabilized at around six weeks of age, but remained visible into adulthood. Combined linkage and homozygosity mapping delineated a 5.5 Mb critical interval. The comparison of whole-genome sequence data of one affected dog to 929 control genomes revealed a private homozygous ~4.8 kb deletion in the critical interval, Chr8:14,468,376_14,473,136del4761. The deletion comprises exon 35 of the RALGAPA1 gene, XM_038544497.1:c.6080-2893_6944+1003del. It is predicted to introduce a premature stop codon into the transcript, truncating ~23% of the wild-type open reading frame of the encoded Ral GTPase-activating protein catalytic subunit α 1, XP_038400425.1:(p.Val2027Glnfs*7). Genotypes at the deletion showed the expected co-segregation with the phenotype in the family. Genotyping additional ataxic Belgian shepherd dogs revealed three additional homozygous mutant dogs from a single litter, which had been euthanized at five weeks of age due to their severe clinical phenotype. Histopathology revealed cytoplasmic accumulation of granular material within cerebellar Purkinje cells. Genotyping a cohort of almost 900 Belgian shepherd dogs showed the expected genotype-phenotype association and a carrier frequency of 5% in the population. Human patients with loss-of-function variants in RALGAPA1 develop psychomotor disability and early-onset epilepsy. The available clinical and histopathological data, together with current knowledge about RALGAPA1 variants and their functional impact in other species, suggest the RALGAPA1 deletion is the likely causative defect for the observed phenotype in the affected dogs.

Bringing Trauma Education to the Frontier: Overcoming Distance Barriers Utilizing a Virtual Platform.

BACKGROUND: The American College of Surgeons and state regulations mandate that trauma facilities offer trauma-specific continuing education throughout the region they serve. These requirements come with unique challenges when serving a rural and sparsely populated state. A novel approach to providing education was necessitated by the coronavirus disease 2019 pandemic, travel distance, and limited local specialists. OBJECTIVE: The purpose of this article is to describe the development of a virtual educational program used to improve access to quality trauma education and decrease barriers to obtaining continuing education hours inherent in the region. METHODS: This article describes the development and implementation of the Virtual Trauma Education program, which provided one free continuing education hour per month from October 2020 to October 2021. The program reached more than 2,000 viewers and established a method to provide continuous monthly educational offerings throughout the region. RESULTS: After the Virtual Trauma Education program implementation, monthly educational attendance increased from an average of 55 to 190. Viewership data indicate that trauma education across our region is far more robust, available, and accessible using a virtual platform. With more than 2,000 views from October 2020 to October 2021, Virtual Trauma Education offerings have spread far beyond regional borders, reaching 25 states and 169 communities. CONCLUSION: Virtual Trauma Education delivers easily accessible trauma education and is a program that has proven its sustainability.

Methylene blue as treatment for vasoplegic shock in severe metformin overdose: A case report.

Introduction: Severe metformin overdose can result in life-threatening conditions such as metabolic acidosis with hyperlactatemia and vasoplegic shock. Current treatment guidelines recommend hemodialysis and supportive care. However, this case report presents the use of methylene blue as an additional treatment for severe metformin overdose-induced vasoplegic shock, which is not commonly described in the literature or guidelines. Case report: A 55-year-old woman presented to the emergency department after ingesting 82.5 g of metformin, resulting in severe metabolic acidosis with hyperlactatemia and refractory vasoplegic shock. Despite continuous hemodialysis and high levels of noradrenalin and vasopressin, the shock persisted. Methylene blue was administered, leading to an immediate and persistent reduction in the noradrenalin dose and rapid shock resolution. Discussion: This case illustrates the potential use of methylene blue in the treatment of severe metformin overdose. The mechanism for metformin-induced vasoplegia is likely mediated by nitric oxide (NO). Methylene blue has been used to treat NO-mediated vasoplegia in other conditions, such as sepsis and poisoning with beta-blockers and calcium channel blockers, but it is rarely described in metformin toxicity. Methylene blue has a rapid onset of action, with only a few mild side effects. This case report emphasizes the need for clinicians to consider methylene blue as a potential treatment option in cases of refractory vasoplegic shock due to severe metformin overdose.

Exploring the Modulatory Effect of High-Fat Nutrition on Lipopolysaccharide-Induced Acute Lung Injury in Vagotomized Rats and the Role of the Vagus Nerve.

During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by a high-fat nutrition via the release of acetylcholine. This binds to α7 nicotinic acetylcholine receptors (α7nAChR) and inhibits α7nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an α7nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an α7nAChR-antagonist and cervical vagotomy with an α7nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group (p > 0.999). There was a trend in aggravation of LIS after cervical vagotomy (p = 0.051), even after an α7nAChR-agonist (p = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury (p = 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-α and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham (p = 0.012) and selective vagotomy (p = 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy.

Treatment implications of augmented renal clearance in a critically ill COVID-19 patient: A case report.

Augmented renal clearance (ARC) is a pathophysiological phenomenon that can occur in critically ill patients, leading to enhanced renal function. It is defined as a creatinine clearance of >130 mL/min/1.73 m2 . ARC can lead to subtherapeutic levels of renally cleared drugs and subsequent treatment failure. In COVID-19, it has only been described in the literature in a few cases. We present the case of a 38-year-old critically ill patient with COVID-19 who developed ARC with an initial clearance of 226 mL/min/1.73 m2 , persisting for 30 days. He required high doses of sedatives and neuromuscular blocking agents, as well as increased doses of vancomycin and dalteparin, to reach adequate serum levels. This case emphasizes the importance for clinicians to consider ARC in the dosing of all renally cleared drugs, including antibiotics, low molecular weight heparins, and sedatives, to prevent subtherapeutic drug levels and treatment failure.