Predictors of Discordance Between Dry Eye Symptoms and Signs: Insights From the Sjögren's International Collaborative Clinical Alliance.

Purpose: The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology. Methods: We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS). Results: Ten predictors, such as "vitality," "immunomodulating drugs," sensory symptoms," and "ethnicity," remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13). Conclusions: Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.

Assessment and comparison of model estimated and directly observed weather data for prediction of diarrhoea aetiology.

Recent advances in clinical prediction for diarrhoeal aetiology in low- and middle-income countries have revealed that the addition of weather data to clinical data improves predictive performance. However, the optimal source of weather data remains unclear. We aim to compare the use of model estimated satellite- and ground-based observational data with weather station directly observed data for the prediction of aetiology of diarrhoea. We used clinical and etiological data from a large multi-centre study of children with moderate to severe diarrhoea cases to compare their predictive performances. We show that the two sources of weather conditions perform similarly in most locations. We conclude that while model estimated data is a viable, scalable tool for public health interventions and disease prediction, given its ease of access, directly observed weather station data is likely adequate for the prediction of diarrhoeal aetiology in children in low- and middle-income countries.

Characterization of non-coding variants associated with transcription factor binding through ATAC-seq-defined footprint QTLs in liver.

Non-coding variants discovered by genome-wide association studies (GWAS) are enriched in regulatory elements harboring transcription factor (TF) binding motifs, strongly suggesting a connection between disease association and the disruption of cis-regulatory sequences. Occupancy of a TF inside a region of open chromatin can be detected in ATAC-seq where bound TFs block the transposase Tn5, leaving a pattern of relatively depleted Tn5 insertions known as a "footprint". Here, we sought to identify variants associated with TF-binding, or "footprint quantitative trait loci" (fpQTLs) in ATAC-seq data generated from 170 human liver samples. We used computational tools to scan the ATAC-seq reads to quantify TF binding likelihood as "footprint scores" at variants derived from whole genome sequencing generated in the same samples. We tested for association between genotype and footprint score and observed 693 fpQTLs associated with footprint-inferred TF binding (FDR < 5%). Given that Tn5 insertion sites are measured with base-pair resolution, we show that fpQTLs can aid GWAS and QTL fine-mapping by precisely pinpointing TF activity within broad trait-associated loci where the underlying causal variant is unknown. Liver fpQTLs were strongly enriched across ChIP-seq peaks, liver expression QTLs (eQTLs), and liver-related GWAS loci, and their inferred effect on TF binding was concordant with their effect on underlying sequence motifs in 80% of cases. We conclude that fpQTLs can reveal causal GWAS variants, define the role of TF binding site disruption in disease and provide functional insights into non-coding variants, ultimately informing novel treatments for common diseases.

Descemet Endothelial Thickness Comparison Trial II (DETECT II): multicentre, outcome assessor-masked, placebo-controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) to Descemet stripping only (DSO) with adjunctive ripasudil for Fuchs dystrophy.

INTRODUCTION: It remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial II (DETECT II), a multicentre, outcome-masked, randomised, placebo-controlled, clinical trial comparing DMEK to DSO with ripasudil (DSO-R) for this patient population. METHODS AND ANALYSIS: A total of 60 patients with endothelial dysfunction due to symptomatic FECD will be enrolled from seven participating sites in the USA. The patients will be randomly assigned in a 1:1 ratio to one of the following treatment groups: group 1-DMEK plus topical placebo and group 2-DSO plus topical ripasudil 0.4%. The enrolment period is 24 months. The primary outcome is best spectacle-corrected visual acuity at 12 months. Secondary outcomes include peripheral and central endothelial cell density, visual acuity, vision-related quality of life and Pentacam Scheimpflug tomography. Study outcomes will be analysed using mixed effects linear regression. Adverse events, including rebubble procedures, endothelial failure and graft rejection, will be documented and analysed using appropriate statistical methods. DETECT II aims to provide evidence on the comparative effectiveness of DMEK and DSO-R. The results of this trial will contribute to optimising the treatment of FECD, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee has been empanelled by the National Eye Institute. All study protocols will be subject to review and approval by WCG IRB as the single IRB of record. This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request. TRIAL REGISTRATION NUMBER: NCT05275972.

Hyperactive mTORC1/4EBP1 signaling dysregulates proteostasis and accelerates cardiac aging.

The mechanistic target of rapamycin complex 1 (mTORC1) has a major impact on aging by regulation of proteostasis. It is well established that mTORC1 signaling is hyperactivated with aging and age-related diseases. Previous studies have shown that partial inhibition of mTOR signaling by rapamycin reverses age-related deteriorations in cardiac function and structure in old mice. However, the downstream signaling pathways involved in this protection against cardiac aging have not been established. mTORC1 phosphorylates 4E-binding protein 1 (4EBP1) to promote the initiation of cap-dependent translation. The objective of this project is to examine the role of the mTORC1/4EBP1 axis in age-related cardiac dysfunction. We used a whole-body 4EBP1 KO mouse model, which mimics a hyperactive mTORC1/4EBP1/eIF4E axis, to investigate the effects of hyperactive mTORC1/4EBP1 axis in cardiac aging. Echocardiographic measurements of middle-aged 4EBP1 KO mice show impaired diastolic function and myocardial performance compared to age-matched WT mice and these parameters are at similar levels as old WT mice, suggesting that 4EBP1 KO mice experience accelerated cardiac aging. Old 4EBP1 KO mice show further decline in systolic and diastolic function compared to middle-aged counterparts and have worse systolic and diastolic function than age-matched WT mice. Gene expression levels of heart failure markers are not different between 4EBP1 KO and WT hearts. However, ribosomal biogenesis and protein ubiquitination are significantly increased in 4EBP1 KO hearts when compared to WT controls, suggesting dysregulated proteostasis in 4EBP1 KO hearts. Together, these results show that a hyperactive mTORC1/4EBP1 axis accelerates cardiac aging, potentially by dysregulating proteostasis.

Spiral volumetric optoacoustic tomography of reduced oxygen saturation in the spinal cord of M83 mouse model of Parkinson's disease.

PURPOSE: Metabolism and bioenergetics in the central nervous system play important roles in the pathophysiology of Parkinson's disease (PD). Here, we employed a multimodal imaging approach to assess oxygenation changes in the spinal cord of the transgenic M83 murine model of PD overexpressing the mutated A53T alpha-synuclein form in comparison with non-transgenic littermates. METHODS: In vivo spiral volumetric optoacoustic tomography (SVOT) was performed to assess oxygen saturation (sO2) in the spinal cords of M83 mice and non-transgenic littermates. Ex vivo high-field T1-weighted (T1w) magnetic resonance imaging (MRI) at 9.4T was used to assess volumetric alterations in the spinal cord. 3D SVOT analysis and deep learning-based automatic segmentation of T1w MRI data for the mouse spinal cord were developed for quantification. Immunostaining for phosphorylated alpha-synuclein (pS129 α-syn), as well as vascular organization (CD31 and GLUT1), was performed after MRI scan. RESULTS: In vivo SVOT imaging revealed a lower sO2SVOT in the spinal cord of M83 mice compared to non-transgenic littermates at sub-100 µm spatial resolution. Ex vivo MRI-assisted by in-house developed deep learning-based automatic segmentation (validated by manual analysis) revealed no volumetric atrophy in the spinal cord of M83 mice compared to non-transgenic littermates at 50 µm spatial resolution. The vascular network was not impaired in the spinal cord of M83 mice in the presence of pS129 α-syn accumulation. CONCLUSION: We developed tools for deep-learning-based analysis for the segmentation of mouse spinal cord structural MRI data, and volumetric analysis of sO2SVOT data. We demonstrated non-invasive high-resolution imaging of reduced sO2SVOT in the absence of volumetric structural changes in the spinal cord of PD M83 mouse model.

Comparing emergency department versus high school-based recruitment for a hypertension research study with adult-youth dyads.

Dyads can be challenging to recruit for research studies, but detailed reporting on strategies employed to recruit adult-adolescent dyads is rare. We describe experiences recruiting adult-youth dyads for a hypertension education intervention comparing recruitment in an emergency department (ED) setting with a school-based community setting. We found more success in recruiting dyads through a school-based model that started with adolescent youth (19 dyads in 7 weeks with < 1 hour recruitment) compared to an ED-based model that started with adults (2 dyads in 17 weeks with 350 hours of recruitment). These findings can benefit future adult-youth dyad recruitment for research studies.

Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation.

The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into the plasma membrane and respond to indentation or stretching of the lipid bilayer, thus converting mechanical forces into signals that can be interpreted by cells, in the form of calcium flux and changes in membrane potential. While PIEZO channels participate in diverse physiological processes, from sensing the shear stress of blood flow in the vasculature to detecting touch through mechanoreceptors in the skin, the molecular details that enable these mechanosensors to tune their responses over a vast dynamic range of forces remain largely uncharacterized. To survey the molecular landscape surrounding PIEZO channels at the cell surface, we employed a mass spectrometry-based proteomic approach to capture and identify extracellularly exposed proteins in the vicinity of PIEZO1. This PIEZO1-proximal interactome was enriched in surface proteins localized to cell junctions and signaling hubs within the plasma membrane. Functional screening of these interaction candidates by calcium imaging and electrophysiology in an overexpression system identified the adhesion molecule CADM1/SynCAM that slows the inactivation kinetics of PIEZO1 with little effect on PIEZO2. Conversely, we found that CADM1 knockdown accelerates inactivation of endogenous PIEZO1 in Neuro-2a cells. Systematic deletion of CADM1 domains indicates that the transmembrane region is critical for the observed effects on PIEZO1, suggesting that modulation of inactivation is mediated by interactions in or near the lipid bilayer.

Correction: Flow and clogging of capillary droplets.

Correction for 'Flow and clogging of capillary droplets' by Yuxuan Cheng et al., Soft Matter, 2024, https://doi.org/10.1039/D4SM00752B.

The evolving role of the modern perfusionist: Insights from processed electro-encephalography.

Introduction: Since its origin in the 1920s, electroencephalography (EEG) has become a viable option for anesthesia and perfusion teams to monitor anesthetic delivery, optimizing drug dosage and enhancing patient safety. Patients undergoing cardiopulmonary bypass (CPB) are at particular high risk for excessive or inadequate anesthetic doses. During CPB, traditional physiological indicators such as heart rate and blood pressure can be significantly altered. These abnormalities are compounded by rapid changes in anesthetic concentration from hemodilution, circuit absorption, and altered pharmacokinetics. Method: This narrative highlights the use of processed EEG with spectral analysis for anesthetic management during CPB. Conclusion: We emphasize that neuromonitoring using processed EEG during CPB can assess adequacy of anesthesia delivery and monitor for pathologic conditions that can compromise brain function such as inadequate cerebral blood flow, emboli, and seizures. This information is highly valuable for the clinical team including the perfusionist, who regularly diagnose and manage these pathological conditions.

Beyond Early- and Late-onset Neonatal Sepsis Definitions: What are the Current Causes of Neonatal Sepsis Globally? A Systematic Review and Meta-analysis of the Evidence.

Sepsis remains a leading cause of neonatal mortality, particularly in low- and lower-middle-income countries (LLMIC). In the context of rising antimicrobial resistance, the etiology of neonatal sepsis is evolving, potentially making currently-recommended empirical treatment guidelines less effective. We performed a systematic review and meta-analysis to evaluate the contemporary bacterial pathogens responsible for early-onset sepsis (EOS) and late-onset neonatal sepsis (LOS) to ascertain if historical classifications-that guide empirical therapy recommendations based on assumptions around causative pathogens-may be outdated. We analyzed 48 articles incorporating 757,427 blood and cerebrospinal fluid samples collected from 311,359 neonates across 25 countries, to evaluate 4347 significant bacteria in a random-effects meta-analysis. This revealed gram-negative bacteria were now the predominant cause of both EOS (53%, 2301/4347) and LOS (71%, 2765/3894) globally. In LLMICs, the predominant cause of EOS was Klebsiella spp. (31.7%, 95% CI: 24.1-39.7%) followed by Staphylococcus aureus (17.5%, 95% CI: 8.5 to 28.4%), in marked contrast to the Streptococcus agalactiae burden seen in high-income healthcare settings. Our results reveal clear evidence that the current definitions of EOS and LOS sepsis are outdated, particularly in LLMICs. These outdated definitions may be guiding inappropriate empirical antibiotic prescribing that inadequately covers the causative pathogens responsible for neonatal sepsis globally. Harmonizing sepsis definitions across neonates, children and adults will enable a more acurate comparison of the epidemiology of sepsis in each age group and will enhance knowledge regarding the true morbidity and mortality burden of neonatal sepsis.

Methods to characterize lactate turnover in aging and Alzheimer's disease; The LEAN study.

BACKGROUND: There is evidence that chronic exercise can benefit the brain, but the effects vary markedly between studies. One potential mechanism for exercise-related benefit is the increase in systemic lactate concentration that is well-characterized to occur during exercise. Lactate is known to cross the blood brain barrier and can be used readily as a fuel for neurons. This may be particularly important in Alzheimer's Disease, which is characterized by cerebral hypometabolism. However, little is known about how whole-body lactate metabolism differs between older adults and individuals with cognitive impairment. This information is critical when considering potential differences in responses to exercise in various cognitive diagnosis groups. METHODS: Here we describe the use of a "lactate clamp" procedure to adjust blood lactate levels to approximate those achieved during exercise, but while at rest. This trial will compare lactate oxidation between cognitively healthy older adults and cognitively impaired participants. We will further evaluate the effect of acute lactate infusion on cognitive performance. DISCUSSION: The findings of the study described here, the Lactate for Energy and Neurocognition trial (clinicaltrials.gov # NCT05207397) will add to our understanding of systemic lactate mechanics in cognitively healthy older adults and individuals with Alzheimer's Disease. These findings will be applicable to ongoing exercise trials and to future studies aimed at modulating systemic bioenergetic function in aging and Alzheimer's Disease.

Flow and clogging of capillary droplets.

Capillary droplets form due to surface tension when two immiscible fluids are mixed. We describe the motion of gravity-driven capillary droplets flowing through narrow constrictions and obstacle arrays in both simulations and experiments. Our new capillary deformable particle model recapitulates the shape and velocity of single oil droplets in water as they pass through narrow constrictions in microfluidic chambers. Using this experimentally validated model, we simulate the flow and clogging of single capillary droplets in narrow channels and obstacle arrays and find several important results. First, the capillary droplet speed profile is nonmonotonic as the droplet exits the narrow orifice, and we can tune the droplet properties so that the speed overshoots the terminal speed far from the constriction. Second, in obstacle arrays, we find that extremely deformable droplets can wrap around obstacles, which leads to decreased average droplet speed in the continuous flow regime and increased probability for clogging in the regime where permanent clogs form. Third, the wrapping mechanism causes the clogging probability in obstacle arrays to become nonmonotonic with surface tension Γ. At large Γ, the droplets are nearly rigid and the clogging probability is large since the droplets can not squeeze through the gaps between obstacles. With decreasing Γ, the clogging probability decreases as the droplets become more deformable. However, in the small-Γ limit, the clogging probability increases since the droplets are extremely deformable and wrap around the obstacles. The results from these studies are important for developing a predictive understanding of capillary droplet flows through complex and confined geometries.

Antimicrobial susceptibility profiles of invasive bacterial infections among children from low- and middle-income countries in the Western Pacific Region (WPRO) - a systematic review and meta-analysis.

Background: Antimicrobial resistance increasingly impacts paediatric mortality, particularly in resource-constrained settings. We aimed to evaluate the susceptibility profiles of bacteria causing infections in children from the Western Pacific region. Methods: We conducted a systematic review and meta-analysis of bacteria responsible for common infections in children. We included studies published from January 2011 to December 2023 (PROSPERO CRD42021248722). Pooled susceptibilities were evaluated against empiric antibiotics recommended to treat common clinical syndromes. Findings: Fifty-one papers met inclusion criteria, incorporating 18,330 bacterial isolates. Of available published data, only six countries from the region were represented. Escherichia coli revealed a pooled susceptibility to ampicillin of 17% (95% CI 12-23%, n = 3292), gentamicin 63% (95% CI 59-67%, n = 3956), and third-generation cephalosporins 59% (95% CI 49-69%, n = 3585). Susceptibility of Klebsiella spp. to gentamicin was 71% (95% CI 61-80%, n = 2323), third-generation cephalosporins 35% (95% CI 22-49%, n = 2076), and carbapenems 89% (95% CI 78-97%, n = 2080). Pooled susceptibility of Staphylococcus aureus to flucloxacillin was 72% (95% CI 58-83%, n = 1666), and susceptibility of Streptococcus pneumoniae meningitis isolates to ampicillin was 26% (95% CI 11-44%, n = 375), and 63% (95% CI 40-84%, n = 246) to third-generation cephalosporins. Interpretation: The burden of antimicrobial resistance among bacteria responsible for common infections in children across the Western Pacific region is significant, and the currently recommended World Health Organization antibiotics to treat these infections may be inefficacious. Strategies to improve the availability of high-quality data to understand the burden of antimicrobial resistance in the region are necessary. Funding: The study was supported by an Australian GovernmentNational Health and Medical Research Council Investigator Grant. This research was funded in part by the Wellcome Trust [220211/Z/20/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Cytokine-mediated CAR T therapy resistance in AML.

Acute myeloid leukemia (AML) is a rapidly progressive malignancy without effective therapies for refractory disease. So far, chimeric antigen receptor (CAR) T cell therapy in AML has not recapitulated the efficacy seen in B cell malignancies. Here we report a pilot study of autologous anti-CD123 CAR T cells in 12 adults with relapsed or refractory AML. CAR T cells targeting CD123+ cells were successfully manufactured in 90.4% of runs. Cytokine release syndrome was observed in 10 of 12 infused individuals (83.3%, 90% confidence interval 0.5-0.97). Three individuals achieved clinical response (25%, 90% confidence interval 0.07-0.53). We found that myeloid-supporting cytokines are secreted during cell therapy and support AML blast survival via kinase signaling, leading to CAR T cell exhaustion. The prosurvival effect of therapy-induced cytokines presents a unique resistance mechanism in AML that is distinct from any observed in B cell malignancies. Our findings suggest that autologous CART manufacturing is feasible in AML, but treatment is associated with high rates of cytokine release syndrome and relatively poor clinical efficacy. Combining CAR T cell therapies with cytokine signaling inhibitors could enhance immunotherapy efficacy in AML and achieve improved outcomes (ClinicalTrials.gov identifier: NCT03766126 ).

Unacylated Ghrelin Protects Against Age-Related Loss of Muscle Mass and Contractile Dysfunction in Skeletal Muscle.

Sarcopenia, the progressive loss of muscle mass and function, universally affects older adults and is closely associated with frailty and reduced quality of life. Despite the inevitable consequences of sarcopenia and its relevance to healthspan, no pharmacological therapies are currently available. Ghrelin is a gut-released hormone that increases appetite and body weight through acylation. Acylated ghrelin activates its receptor, growth hormone secretagogue receptor 1a (GHSR1a), in the brain by binding to it. Studies have demonstrated that acyl and unacylated ghrelin (UnAG) both have protective effects against acute pathological conditions independent of receptor activation. Here, we investigated the long-term effects of UnAG in age-associated muscle atrophy and contractile dysfunction in mice. Four-month-old and 18-month-old mice were subjected to either UnAG or control treatment for 10 months. UnAG did not affect food consumption or body weight. Gastrocnemius and quadriceps muscle weights were reduced by 20%-30% with age, which was partially protected against by UnAG. Specific force, force per cross-sectional area, measured in isolated extensor digitorum longus muscle was diminished by 30% in old mice; however, UnAG prevented the loss of specific force. UnAG also protected from decreases in mitochondrial respiration and increases in hydrogen peroxide generation of skeletal muscle of old mice. Results of bulk mRNA-seq analysis and our contractile function data show that UnAG reversed neuromuscular junction impairment that occurs with age. Collectively, our data revealed the direct role of UnAG in mitigating sarcopenia in mice, independent of food consumption or body weight, implicating UnAG treatment as a potential therapy against sarcopenia.

Cause-Specific Mortality among Infants in a Randomized Controlled Trial of Azithromycin Compared to Placebo for Prevention of Mortality.

Although community randomized trials have found a reduction in all-cause child mortality in communities receiving mass azithromycin distribution compared with placebo, individually randomized trials have not found similar protective effects. If a direct effect of azithromycin for prevention of child mortality exists, it is likely due to reduction in infectious mortality. Here, we assessed cause-specific mortality in a large randomized controlled trial of azithromycin administered during well-infant visits in Burkina Faso for prevention of mortality. Among 32,877 enrolled infants, the most common causes of death by 6 months of age were malaria, acute respiratory infections, and diarrheal disease. We found no evidence of a difference in the distribution of cause of death by randomized treatment assignment (P = 0.42) or in any infectious-specific cause of death. The results of this analysis are consistent with no direct effect of azithromycin on infant mortality when administered during well-infant visits.

Falls as a mental health risk among Korean-American residents in subsidized senior housing: mediating effect of fall-related self-efficacy.

OBJECTIVES: The study examined the mediating role of fall-related self-efficacy in the association between falls and mental health among older Korean Americans living in subsidized senior housing in the greater Los Angeles area. We focused on serious fall incidents (i.e. multiple falls or any fall with a fracture) and used symptoms of depression and anxiety as indicators of mental health. METHOD: Survey data from 315 participants (M age = 79.4 years) were used to examine the direct effects of serious fall incidents on mental health symptoms, as well as indirect effects through fall-related self-efficacy. RESULTS: The mediating effect of fall-related self-efficacy was found to be significant in both models for depressive symptoms (B [SE] = 0.15 [0.07], bias-corrected 95% CI = [0.03, 0.31]) and anxiety symptoms (B [SE] = 0.11 [0.05], bias-corrected 95% CI = [0.02, 0.23]). CONCLUSION: The mental health impact of serious fall incidents was shaped by older individuals' perceived concerns about falls and confidence in performance. The findings highlight the importance of addressing fall-related psychological responses in preventing falls and promoting mental health among senior housing residents.

The Impact of Code Bundling on Medicare Volume and Reimbursements Within Endoscopic Sinus Surgery.

In 2018, Medicare introduced new codes to the Endoscopic Sinus Surgery (FESS) and balloon sinus dilation (BSD) families of Current Procedural Terminology (CPT) codes. Using the Medicare Part B National Summary Data File from 2010 to 2022, an interrupted time-series analysis examined trends in volume and reimbursements before and after 2018. Prior to 2018, volume and reimbursements for FESS grew at a mean rate of 2.5% ± 2.2% per year and 6.9% ± 6.6% per year, respectively, before reimbursements decreased significantly in 2018 by -13.9% (P = .014), leading to a stabilization of volume (growth of 0.72%, P = .602). Volume and reimbursements for BSD saw rapid growth from 2011 to 2015 which plateaued prior to the introduction of bundled codes and did not appear to change significantly in 2018 (-0.6%, P = .306 and 11.9%, P = .392, respectively). In addition to concurrent devaluation of FESS and BSD codes, bundling appears to have further contributed to falling reimbursements in rhinology.

Predictors of length of postoperative stay following endoscopic skull base surgery with intraoperative CSF leak.

OBJECTIVE: Establishing benchmarks for length of stay (LOS) may inform strategies to improve resource efficiency, decrease costs, and advance care quality. In this study, the authors characterize postoperative LOS in endoscopic skull base surgery (ESBS) and elucidate prolonging factors. METHODS: A retrospective chart review was conducted at a tertiary academic center including consecutive adult patients who underwent intradural ESBS with intraoperative CSF leak during primary repair between July 2018 and March 2024. LOS, calculated as the time between the end of anesthesia until discharge from the hospital, comprised the primary outcome. Categorical and continuous independent study variables were assessed for univariate LOS association via the Mann-Whitney U-test and Kendall's tau-b correlation, respectively, and those with significant associations were included as multiple linear regression inputs. RESULTS: One hundred sixty-three patients were included, with a median LOS of 4.0 (interquartile range [IQR] 2.8-5.8) days. LOS was significantly prolonged in high-flow (n = 82) compared with low-flow (n = 81) CSF leak cohorts (median 4.5 [IQR 3.9-6.5] vs 2.9 [IQR 2.1-4.7] days, p = 0.002). Defects involving the anterior cranial fossa (n = 16, median 4.6 [IQR 3.3-7.5)] days), suprasellar region (n = 94, median 4.4 [IQR 3.2-6.4] days), sella (n = 138, median 3.9 [IQR 2.8-5.8] days), or posterior cranial fossa (n = 17, median 4.5 [IQR 3.9-6.5] days) had variable LOSs. On multiple linear regression, after controlling for numerous patient, surgical, and postoperative factors, lesion diameter (B = 0.16, 95% CI 0.048-0.26), bone defect area (B = 0.008, 95% CI 0.001-0.014), anesthesia time (B = 0.015, 95% CI 0.004-0.026), bed rest length (B = 2.34, 95% CI 1.12-3.56), postoperative CSF leak (B = 11.06, 95% CI 4.11-18.01), postoperative meningitis (B = 11.79, 95% CI 4.83-18.74), postoperative stroke/hemorrhage (B = 25.25, 95% CI 18.43-32.06), and postoperative pneumonia (B = 5.59, 95% CI 0.79-10.38) independently predicted overall prolonged LOS. CONCLUSIONS: With healthcare utilization receiving increased attention, mitigating factors that extend LOS are important. Extent of surgery and certain postoperative complications may constitute key factors prolonging LOS following intradural ESBS with intraoperative CSF leak.