IgE glycosylation and impact on structure and function: A systematic review.

The impact of human IgE glycosylation on structure, function and disease mechanisms is not fully elucidated, and heterogeneity in different studies renders drawing conclusions challenging. Previous reviews discussed IgE glycosylation focusing on specific topics such as health versus disease, FcεR binding or impact on function. We present the first systematic review of human IgE glycosylation conducted utilizing the PRISMA guidelines. We sought to define the current consensus concerning the roles of glycosylation on structure, biology and disease. Despite diverse analytical methodologies, source, expression systems and the sparsity of data on IgE antibodies from non-allergic individuals, collectively evidence suggests differential glycosylation profiles, particularly in allergic diseases compared with healthy states, and indicates functional impact, and contributions to IgE-mediated hypersensitivities and atopic diseases. Beyond allergic diseases, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism. Glycan sites such as N394 may contribute to stabilizing IgE structure, with alterations in these glycans likely influencing both structure and IgE-FcεR interactions. This systematic review therefore highlights critical IgE glycosylation attributes in health and disease that may be exploitable for therapeutic intervention, and the need for novel analytics to explore pertinent research avenues.

Winter break? The effect of overwintering on immune gene expression in wood frogs.

Among terrestrial ectotherms, hibernation is a common response to extreme cold temperatures and is associated with reduced physiological rates, including immunity. When winter wanes and temperatures increase, so too do vital rates of both ectothermic hosts and their parasites. Due to metabolic scaling, if parasite activity springs back faster than host immune functions then cold seasons and transitions between cold and warm seasons may represent periods of vulnerability for ectothermic hosts. Understanding host regulation of physiological rates at seasonal junctions is a first step toward identifying thermal mismatches between hosts and parasites. Here we show that immune gene expression is responsive to transitions into and out of the cold season in a winter-adapted amphibian, the wood frog (Lithobates sylvaticus), and that frogs experienced parasitism by at least two nematode species throughout the entirety of the cold season. In both splenic and skin tissues, we observed a decrease in immune gene expression going from fall to winter, observed no changes between winter and emergence from hibernation, and observed increases in immune gene expression after hibernation ended. At all timepoints, differentially expressed genes from spleens were more highly enriched for immune system processes than those from ventral skin, especially with respect to terms related to adaptive immune processes. Infection with nematode lungworms was also associated with upregulation of immune processes in the spleen. We suggest that rather than being a period of stagnation, during which physiological processes and infection potential cease, the cold season is immunologically dynamic, requiring coordinated regulation of many biological processes, and that the reemergence period may be an important time during which hosts invest in preparatory immunity.

Crop booms as regime shifts.

A crop boom is a sudden, nonlinear and intense expansion of a new crop. Despite their large impacts, boom-bust dynamics are not well understood; booms are largely unpredictable and difficult to steer once they unfold. Based on the striking resemblances between land regime shifts and crop booms, we apply complex systems theory, highlighting the potential for regime shifts, to provide new insights about crop boom dynamics. We analyse qualitative and quantitative data of rubber and banana plantation expansion in two forest frontier regions of northern Laos. We show that preconditions, including previous booms, explain the occurrence (why) of booms, and triggers like policy and market changes explain their timing (when). Yet, the most important features of booms, their intensity and nonlinearity (how), strongly depended on internal self-reinforcing feedbacks. We identify built-in feedbacks (neighbourhood effects and imitation) and emergent feedbacks (land rush) and show that they were social in nature, multi-scale from plot to region and subject to thresholds. We suggest that these are regular features of booms and propose a definition and causal-mechanistic explanation of crop booms, examining the overlap between booms and regime shifts and the role of frontiers. We then identify opportunities for management interventions before, during and after booms.

Protocols for isolation and characterization of nanoparticle biomolecular corona complexes.

Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC). It is well established that the NP-PC strongly influences the biological fate of various NPs types, including cellular uptake, toxicity, and biodistribution. Thus, for a proper assessment of potential hazards associated with engineered NPs, it is mandatory to study and evaluate the PC that forms around NPs. Herein, we describe protocols in detail for the isolation and characterization of NP-PC complexes and cover the following aspects: 1) isolation protocols for different nanomaterials in a range of exposing media, including magnetic isolation methods for superparamagnetic NPs, 2) NP physico-chemical characterization using advanced and standard techniques available in regular laboratories, and 3) NP- PC characterization of the protein and glycan components.

A Comparative Analysis of Healthcare Quality Perception Among Different Vulnerable Populations with and without Telehealth Utilization: A Cross-Sectional Study from the Health Information National Trends Survey.

OBJECTIVE: The COVID-19 pandemic led to a rapid expansion of telehealth utilization in medicine. However, the quality measures associated with telehealth use remain unclear, particularly among vulnerable populations. This study aims to investigate the impact of telehealth on individuals' perception of overall quality care among vulnerable patient populations. METHODS: This cross-sectional study utilized Health Information National Trends Survey data. The individuals' overall perception of healthcare quality was compared between populations that had at least one telehealth visit and non-telehealth users, who all had the option of utilizing telehealth. This comparison focused on vulnerable populations, considering differences in race and ethnicity (non-Hispanic white vs. non-Hispanic black/Hispanic individuals) and socioeconomic status (high vs. low). Multivariable logistic regressions were employed to ascertain the association between individuals' overall perceptions of quality care with and without telehealth utilization. RESULTS: A total of 2920 participants, representing an unweighted population of 114,608,302, were analyzed. The adjusted odds ratio (AOR) for at least one telehealth visit associated with individuals' overall perception of quality care among the entire survey population was 0.76 with a 95% CI of 0.51-1.13 (p = 0.173). The AOR was 0.83 (95% CI 0.39-1.77, p = 0.618) among the non-White population, and the AOR was 0.71 (95% CI 0.29-1.78, p = 0.462) among individuals with low SES. CONCLUSIONS: Although telehealth utilization has both its limitations and advantages compared to traditional clinical visits, no statistically significant differences in individuals' overall perception of quality care were identified among telehealth and non-telehealth users. These findings were also consistent across various vulnerable populations.

Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.

Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD). We analyzed whole exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes. Older UC patients (age>45) harbored increased myeloid-CHIP mutations compared to younger patients (age≤45) ( p= 0.01). Lymphoid-CHIP was more prevalent in older IBD patients ( p =0.007). Young CD patients were found to have myeloid-CHIP with high-risk features. IBD patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP ( p= 0.05), while anti-TNF therapy was associated with decreased myeloid-CHIP ( p= 0.03). Pathway enrichment analyses indicated overlap between CHIP genes, IBD phenotypes, and inflammatory pathways. Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease and acceleration of their inflammatory disease.

A Strain of Streptococcus mitis Inhibits Biofilm Formation of Caries Pathogens via Abundant Hydrogen Peroxide Production.

Commensal oral streptococci that colonize supragingival biofilms deploy mechanisms to combat competitors within their niche. Here, we determined that Streptococcus mitis more effectively inhibited biofilm formation of Streptococcus mutans within a seven species panel. This phenotype was common amongst all assayed isolates of S. mutans , but was specific to a single strain of S. mitis , ATCC 49456. The growth inhibitory factor was not effectively carried in spent supernatants of S. mitis . However, we documented ATCC 49456 to accumulate 4-5 times more hydrogen peroxide (H 2 O 2 ) than other species tested, and 5-18 times more than other S. mitis strains assayed. The S. mutans biofilm formation inhibitory phenotype was reduced when grown in media containing catalase or with a S. mitis mutant of pyruvate oxidase ( spxB ; pox ), confirming that SpxB-dependent H 2 O 2 production was the main antagonistic factor. Addition of S. mitis within hours after S. mutans inoculation was effective at reducing biofilm biomass, but not for 24 h pre-formed biofilms. Transcriptome analysis revealed responses for both S. mitis and S. mutans , with several S. mutans differentially expressed genes following a gene expression pattern previously described, while others being unique to the interaction with S. mitis . Finally, we show that S. mitis also affected coculture biofilm formation of several other commensal streptococci. Our study shows that strains with abundant H 2 O 2 production are effective at inhibiting initial growth of caries pathogens like S. mutans , but are less effective at disrupting pre-formed biofilms and have the potential to influence the stability of other oral commensal strains.

A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion.

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.

Orphan Applicants in Orthopedic Surgery: Where Do Allopathic Applicants Without an Affiliated Residency Program Match?

Background  Orthopedic surgery is one of the most competitive specialties to match into a residency. With a plethora of qualified applicants and the subjective nature of matching into any residency program, it can be difficult to accurately assess the chances of successfully matching into orthopedic surgery and the types of programs an applicant will match into. The purpose of this study is to compare the types of programs that students from medical schools with and without home programs match. Methods This was a five-year retrospective study (2019 to 2023) analyzing 155 United States Doctor of Medicine (M.D.) programs and their orthopedic residency-matched students. Of the 155 programs, 40 were excluded from the study due to the lack of obtainable data. For each medical school, we analyzed several variables: the presence of a home program, the total number of orthopedic residency matches, residency program matches, and residency program affiliation (academic, community, university-affiliated community-based, military). Results Of the 2066 total matched applicants from institutions with home programs, 1508 (73%) matched into academic centers, 315 (15.3%) into university-affiliated community programs, 172 (8.3%) into community programs, and 71 (3.4%) into military programs. In contrast, of the 219 total matched applicants from institutions without home programs (orphan applicants), 144 (67.8%) matched into academic programs, 36 (16.4%) into university-affiliated community programs, 28 (12.8%) into community programs, and 11 (5%) into military programs. Conclusion A greater proportion of students from institutions with home programs matched into academic centers compared to orphan applicants (73% vs. 65.8%). A greater proportion of orphan applicants matched into community programs (12.8% vs. 8.3%).

Does the Chief Executive Officer (CEO)'s Educational Background Have an Impact on the Academic Hospital Leapfrog Safety Grades?

Background This study aims to investigate the potential association of the Chief Executive Officer (CEO)'s educational background on hospital safety metrics, specifically the Leapfrog safety grades. Methods A total of 172 academic and university-affiliated hospitals across the United States were included in the study. Information regarding a CEO's background was obtained through hospital websites, while the Leapfrog safety scores were found through the Leapfrog safety grade website. Hospital sizes were also noted. Results A total of 67 hospitals were led by Doctors of Medicine (MDs), 16 were led by Masters in Business Administration (MBAs), 14 were led by Masters in Healthcare Administration (MHAs), and 62 were led by CEOs with various other degree types. Of the 42 A-rated hospitals included, 17 were led by physicians and 25 by nonphysicians. The average Leapfrog grade point average was similar regardless of the CEO's background, ranging from 2.6 to 3.1. Conclusion The findings suggest that a CEO's educational background has less of an impact on the overall hospital safety performance than what may have previously been hypothesized.

Heart Failure Specialist Care and Long-Term Outcomes for Patients Admitted With Acute Heart Failure.

BACKGROUND: For patients with acute heart failure (HF), specialist HF care during admission improves diagnosis and treatments. OBJECTIVES: The authors aimed to investigate the association of HF specialist care with in-hospital and longer term prognosis. METHODS: The authors used data from the National Heart Failure Audit from January 1, 2018, to December 31, 2022, linked to electronic records for hospitalization and deaths. All-cause mortality was the primary outcome measure and in-hospital mortality the secondary outcome measure. RESULTS: Data for 227,170 patients admitted to hospital with HF (median age: 81 years; IQR: 72-88 years), were analyzed. Approximately 80% of acute HF admissions received support from HF specialists. Thirty-nine percent of patients (n = 70,720) were seen by a multidisciplinary team (HF physicians and HF specialist nurses [HFSNd]), 22% (n = 40,330) were seen by HFSNs alone, and the remaining 39% (n = 71,700) were seen exclusively by specialist HF physicians. At discharge, more patients who received HF specialist care were prescribed medical therapy for HF and had specialized follow-up. Conversely, diuretic agents were prescribed to fewer patients. HF specialist care was independently associated with a higher rate of prescribing HF therapies at discharge and a lower likelihood of receiving diuretic therapy (OR: 0.90 [95% CI: 0.86-0.95]; P < 0.001). HF specialist care was associated with better long-term survival (HR: 0.89 [95% CI: 0.87-0.90]; P < 0.001) and lower in-hospital mortality (OR: 0.92 [95% CI: 0.0.88-0.97]; P < 0.001). CONCLUSIONS: Receiving HF specialist care during admission for HF is associated with a higher rate of implementation of medical therapy, fewer discharges on diuretic therapy, and lower in-hospital and long-term mortality across the left ventricular ejection fraction spectrum, especially for patients with heart failure with reduced ejection fraction.

Leptothrix ochracea genomes reveal potential for mixotrophic growth on Fe(II) and organic carbon.

Leptothrix ochracea creates distinctive iron-mineralized mats that carpet streams and wetlands. Easily recognized by its iron-mineralized sheaths, L. ochracea was one of the first microorganisms described in the 1800s. Yet it has never been isolated and does not have a complete genome sequence available, so key questions about its physiology remain unresolved. It is debated whether iron oxidation can be used for energy or growth and if L. ochracea is an autotroph, heterotroph, or mixotroph. To address these issues, we sampled L. ochracea-rich mats from three of its typical environments (a stream, wetlands, and a drainage channel) and reconstructed nine high-quality genomes of L. ochracea from metagenomes. These genomes contain iron oxidase genes cyc2 and mtoA, showing that L. ochracea has the potential to conserve energy from iron oxidation. Sox genes confer potential to oxidize sulfur for energy. There are genes for both carbon fixation (RuBisCO) and utilization of sugars and organic acids (acetate, lactate, and formate). In silico stoichiometric metabolic models further demonstrated the potential for growth using sugars and organic acids. Metatranscriptomes showed a high expression of genes for iron oxidation; aerobic respiration; and utilization of lactate, acetate, and sugars, as well as RuBisCO, supporting mixotrophic growth in the environment. In summary, our results suggest that L. ochracea has substantial metabolic flexibility. It is adapted to iron-rich, organic carbon-containing wetland niches, where it can thrive as a mixotrophic iron oxidizer by utilizing both iron oxidation and organics for energy generation and both inorganic and organic carbon for cell and sheath production. IMPORTANCE: Winogradsky's observations of L. ochracea led him to propose autotrophic iron oxidation as a new microbial metabolism, following his work on autotrophic sulfur-oxidizers. While much culture-based research has ensued, isolation proved elusive, so most work on L. ochracea has been based in the environment and in microcosms. Meanwhile, the autotrophic Gallionella became the model for freshwater microbial iron oxidation, while heterotrophic and mixotrophic iron oxidation is not well-studied. Ecological studies have shown that Leptothrix overtakes Gallionella when dissolved organic carbon content increases, demonstrating distinct niches. This study presents the first near-complete genomes of L. ochracea, which share some features with autotrophic iron oxidizers, while also incorporating heterotrophic metabolisms. These genome, metabolic modeling, and transcriptome results give us a detailed metabolic picture of how the organism may combine lithoautotrophy with organoheterotrophy to promote Fe oxidation and C cycling and drive many biogeochemical processes resulting from microbial growth and iron oxyhydroxide formation in wetlands.

Radionuclide Solid:liquid partitioning in an aged, reducing-grout wasteform recovered from a disposal facility.

The Saltstone Disposal Facility on the Savannah River Site in South Carolina disposes of Low-Level Waste in a reducing-grout waste form. Reducing grout is presently being evaluated as a subsurface disposal waste form at several other locations in the United States, as well as in Europe and Asia. The objective of this study was to collect core samples directly from the Saltstone Disposal Facility and measure desorption distribution coefficients (Kd; radionuclide concentration ratio of saltstone:liquid; (Bq/kg)/Bq/L)) and desorption apparent solubility values (ksp; radionuclide aqueous concentration (moles/L)). An important attribute of this study was that these tests were conducted with actual aged, grout waste form materials, not small-volume simulants prepared in a laboratory. The reducing grout is comprised of blast furnace slag, Class F fly ash, ordinary portland cement, and a radioactive salt waste solution generated during nuclear processing. The grout sample used in this study underwent hydrolyzation in the disposal facility for 30 months prior to measuring radionuclide leaching. Leaching experiments were conducted either in an inert (no oxygen) atmosphere to simulate conditions within the saltstone monolith prior to aging (becoming oxidized) or they were exposed to atmosphere conditions to simulate conditions of an aged saltstone. Importantly, these experiments were designed not to be diffusion limited, that is, the saltstone was ground finely and the suspensions were under constant agitation during the equilibration period. Under oxidized conditions, measured Tc Kd values were 10 mL/g, which was appreciably greater than the historical best-estimate value of 0.8 mL/g. This difference is likely the result of a fraction of the Tc remaining in the less soluble Tc(IV) form, even after extensive oxidation during the experiment. Under oxidized and reducing conditions, the measured Ba and Sr (both divalent alkaline earth metals) Kd value were more than an order of magnitude greater than historical best-estimate values of 100 mL/g. The unexpectedly high Ba and Sr Kd values were attributed to these radionuclides having sufficient time to age (form strong bonds) in the sulfur-rich saltstone sample. Apparent ksp values under reducing conditions were 10-9 mol/L Tc and 10-13 mol/L Pu, consistent with values measured with surrogate materials. Measured apparent Ba, Sr, and Th ksp values were significantly greater than historical best-estimates. The implications of the generally greater Kd values and lower ksp values in these measurements is that these cementitious waste forms have greater radionuclide retention than was previously estimated based on laboratory studies using surrogate materials. This work represents the first leaching study performed with an actual aged, reducing-grout sample and as such provides an important comparison to studies conducted with surrogate materials, and provides high pedigree data for other programs around the world evaluating reducing grouts as a wasteform for subsurface nuclear waste disposal.

Reducing intravenous contrast utilization for CT: A health-system wide intervention with sustained impact.

OBJECTIVE: To determine the volume of intravenous iodinated contrast media utilized for CT before, during, and after the global iohexol shortage over a total of 17 months at a multisite health system. METHODS: This retrospective study included all patients who underwent CT at a large health system with 12 sites. Standardized contrast doses for 13 CT examinations were implemented 5/23/22. Mean contrast utilization per CT encounter was compared between 3 periods (pre-intervention 1/1/22-5/22/22; intervention 5/23/22-9/11/22; post-intervention 9/12/23-6/30/23). Contrast doses and CT encounter data were extracted from the enterprise data warehouse. Categorical variables were compared with a chi-squared test and continuous variables were compared with a two-tailed t-test. Multivariable linear regression assessed significance, with coefficients noted to determine magnitude and direction of effect. RESULTS: Pre-intervention, there were 152,009 examinations (87,722 with contrast, 57.7%), during the intervention 120,031 examinations (63,217 with contrast, 52.7%), and post-intervention 341,862 examinations (194,231 with contrast, 56.8%). Pre-intervention, mean contrast dose was 89.3 mL per exam, which decreased to 78.0 mL following standardization (Δ of -12.7%) (p<0.001). This decrease continued throughout the intervention and persisted in the post-intervention period (80.4 mL; Δ -10.0%, p<0.001). On multivariable analysis, patient weight, sex, and performing site were all associated with variations in contrast dose. Most but not all sites (9/12) sustained the decreased contrast media dose in the post-intervention period. DISCUSSION: Implementing standardized contrast media dosing for commonly performed CT examinations led to a rapid decrease in contrast media utilization which persisted over 1 year.

Which individual components of a colorectal surgery enhanced recovery program are associated with improved surgical outcomes?

BACKGROUND: Enhanced recovery programs improve surgical outcomes. However, the association of adherence to individual components and outcomes in a comprehensive enhanced recovery program remains unclear. METHODS: We performed a retrospective study of all elective colorectal surgery patients at our institution from 2019 to 2022 (n = 1,175). Data were acquired from our institution's enhanced recovery program dashboard and American College of Surgeons National Surgical Quality Improvement Program database. Traditional analyses and machine-learning classification trees were used to identify enhanced recovery program components associated with length of stay, readmissions, and complication rates. RESULTS: The average length of stay was 5.0 days, readmission rate was 12.3%, and complication rate was 32.6%. On linear regression analysis, adherence to preoperative education, regional analgesia, pre- and postoperative multimodal analgesia, no nasogastric tube, early mobilization, early regular diet, early discontinuation of maintenance intravenous fluids, postoperative venous thromboembolism prophylaxis, and early Foley catheter removal were associated with an decrease in length of stay by 0.7-7.1 days (P < .05). Patients who adhered to no prolonged fasting had a 4.1% decrease in readmission rate (P = .04). Patients who adhered to no nasogastric tube, early mobilization, early regular diet, postoperative multimodal analgesia, and discontinuation of maintenance intravenous fluids had decreases in complication rates ranging from 7.0 to 28.2% (P < .001). Machine learning demonstrated that no nasogastric tube and discontinuation of maintenance intravenous fluids were significant predictors of shorter length of stay and no nasogastric tube and early mobilization were significant predictors of reduced complication rates. CONCLUSIONS: Although multiple components were associated outcomes, no nasogastric tube, early mobilization, early regular diet, postoperative multimodal analgesia, and early discontinuation of maintenance intravenous fluids were associated with more than 1 outcome. Focusing on these components may make enhanced recovery program implementation more feasible for resource-limited hospitals.

Efficacy and safety of intraoperative controlled hypotension: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Intraoperative controlled hypotension improves surgical field visibility by reducing blood loss (efficacy) but poses potential risks linked to organ hypoperfusion (safety). The use of controlled hypotension persists despite increasing evidence of associations between intraoperative inadvertent hypotension and adverse outcomes. Therefore, we tested the hypothesis that the focus and results of intraoperative controlled hypertension research differ across anaesthesia and surgery investigators because of differing priorities. METHODS: We systematically reviewed randomised trials comparing controlled hypotension with usual care with trials categorised by investigators' affiliation. RESULTS: We identified 48 eligible trials, of which 37 were conducted by anaesthesia investigators and 11 by surgery investigators. For the primary outcome, 54% of the anaesthesia-led trials focused on safety, whereas all (100%) surgery-led trials focused on efficacy (P=0.004). Compared with usual care, mean arterial pressure in controlled hypotension was 23% (95% confidence interval [CI] 17-29%) lower in anaesthesia trials and 30% (95% CI 14-37%) lower in surgery trials; estimated blood loss was 44% (95% CI 30-55%) less in anaesthesia trials and 38% (95% CI 30-49%) less in surgery trials. Overall, blood loss was reduced by 43% (95% CI 32-53%), and trial sequential analysis supported an efficacy conclusion. Mean arterial pressure and estimated blood loss reductions were associated (R2=0.41, P=0.002). All trials were underpowered for safety outcomes, and none adequately evaluated myocardial or renal injury. CONCLUSIONS: Anaesthesia researchers prioritised safety outcomes, whereas surgery researchers emphasised efficacy in controlled hypotension trials. Controlled hypotension significantly reduces blood loss. In contrast, safety outcomes were poorly studied. Given increasing observational evidence linking inadvertent hypotension to myocardial and renal injury, the safety of controlled hypotension remains to be addressed. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023450397).

Modulation of gut microbiota composition and predicted metabolic capacity after nutritional programming with a plant-rich diet in Atlantic salmon (Salmo salar): insights across developmental stages.

To promote sustainable aquaculture, the formulation of Atlantic salmon (Salmo salar) feeds has changed in recent decades, focusing on replacing standard marine-based ingredients with plant-based alternatives, increasingly demonstrating successful outcomes in terms of fish performance. However, little is known about how these plant-based diets may impact the gut microbiota at first feeding and onwards. Nutritional programming (NP) is one strategy applied for exposing fish to a plant-based (V) diet at an early stage in life to promote full utilisation of plant-based ingredients and prevent potential adverse impacts of exposure to a plant-rich diet later in life. We investigated the impact of NP on gut microbiota by introducing fish to plant ingredients (V fish) during first feeding for a brief period of two weeks (stimulus phase) and compared those to fish fed a marine-based diet (M fish). Results demonstrated that V fish not only maintained growth performance at 16 (intermediate phase) and 22 (challenge phase) weeks post first feeding (wpff) when compared to M fish but also modulated gut microbiota. PERMANOVA general effects revealed gut microbiota dissimilarity by fish group (V vs. M fish) and phases (stimulus vs. intermediate vs. challenge). However, no interaction effect of both groups and phases was demonstrated, suggesting a sustained impact of V diet (nutritional history) on fish across time points/phases. Moreover, the V diet exerted a significant cumulative modulatory effect on the Atlantic salmon gut microbiota at 16 wpff that was not demonstrated at two wpff, although both fish groups were fed the M diet at 16 wpff. The nutritional history/dietary regime is the main NP influencing factor, whereas environmental and host factors significantly impacted microbiota composition in M fish. Microbial metabolic reactions of amino acid metabolism were higher in M fish when compared to V fish at two wpff suggesting microbiota played a role in digesting the essential amino acids of M feed. The excessive mucin O-degradation revealed in V fish at two wpff was mitigated in later life stages after NP, suggesting physiological adaptability and tolerance to V diet. Future studies are required to explore more fully how the microbiota functionally contributes to the NP.

Postoperative Infection Following Hip Arthroscopy in Patients Receiving Preoperative Intra-articular Injections: A Systematic Review and Meta-Analysis.

Intra-articular injections prior to hip arthroscopy are often used to diagnose and conservatively manage hip pathologies, such as femoroacetabular impingement, labral tears, and chondral lesions. As a diagnostic tool, the relief of hip pain following an intra-articular injection helps pinpoint the primary source of pain and assists surgeons in recommending arthroscopic intervention for underlying intra-articular pathologies. However, when injections are not sufficiently spaced apart in time prior to hip arthroscopy, there is an elevated risk of postoperative infection. This systematic review aims to assess whether preoperative intra-articular injections prior to hip arthroscopy are associated with an increased risk of postoperative infection and to determine the safety timeframe for administering such injections prior to the procedure. A comprehensive search was conducted in the PubMed, Embase, and Cochrane Library databases to identify studies examining the relationship between preoperative intra-articular injections and postoperative infection following hip arthroscopy. A meta-analysis was conducted to compare the risk of infection between patients who received injections prior to hip arthroscopy at varying intervals and those who did not receive any preoperative injections. Five studies were included (four level III and one level IV), which consisted of 58,576 patients (58.4% female). Injections administered anytime prior to hip arthroscopy posed a significantly higher risk of infection compared to no history of prior injections (risk ratio: 1.45, 95% confidence interval: 1.14-1.85, P = 0.003). However, upon subanalysis, the risk of infection was significantly higher among patients who received injections within three months prior to hip arthroscopy compared to those who did not receive injections (risk ratio: 1.55, 95% confidence interval: 1.19-2.01, P = 0.001). Additionally, no significant difference in infection risk was observed when injections were administered more than three months before hip arthroscopy compared to no injections (risk ratio: 1.05, 95% confidence interval: 0.56-1.99, P = 0.87). The findings suggest that patients undergoing hip arthroscopy who have previously received intra-articular injections may face a statistically higher risk of postoperative infection, particularly when the injection is administered within three months prior to hip arthroscopy. Consequently, surgeons should exercise caution and avoid administering intra-articular injections to patients scheduled for hip arthroscopy within the subsequent three months to mitigate the increased risk of infection.