Preoperative Acetaminophen For Microsuspension Laryngoscopy Reduces Postoperative Opioid Use.

OBJECTIVES: The opioid crisis has prompted consideration of analgesic prescriptions. This study explored the value of preoperative acetaminophen for pain control following microsuspension laryngoscopy (MSL) and compared the results with a previous study of pain and opioid use following MSL (Tsang et al.). METHODS: A prospective open-label clinical trial was conducted in patients undergoing MSL. All patients were administered preoperative acetaminophen. Short-form McGill Pain Questionnaire (SF-MPQ), pain visual analogue scale (VAS), and present pain intensity (PPI) scores were collected preoperatively and on postoperative days (PODs) 1, 3, 7, and 14. Statistical analysis identified variables associated with opioid use or increased pain scores, and compared outcomes with Tsang et al. RESULTS: Eighty-nine patients were included (mean age 52.8 ± 17.3 years, 40 males). All patients received preoperative 1 g acetaminophen (77 (86.5%) orally) with no adverse effects. On POD1, opioid usage was 10%. Median [IQR] pain scores were 5 [2-11], 21 [12.3-56.8], and 3 [2-3.3] on SF-MPQ, VAS, and PPI, respectively. Post-Anesthesia Care Unit (PACU) opioid requirements significantly correlated with POD1 opioid consumption (τb = 0.214; p ≤ 0.05), and significant associations with PACU opioid administration were found for total anesthesia time (OR (95%CI) = 1.271 (1.043-1.548), p = 0.017) and total laryngoscope suspension time (OR (95%CI) = 0.791 (0.651-0.962, p = 0.019)). This cohort demonstrated reduced opioid usage on POD1 compared with Tsang et al (23%). CONCLUSIONS: Preoperative acetaminophen is a safe intervention, resulting in decreased postoperative opioid use following MSL. Anesthesia time correlated with need for postoperative opioids. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Measuring the Direct Medical Costs of Hospital-Onset Infections Using an Analogy Costing Framework.

BACKGROUND: The majority of recent estimates on the direct medical cost attributable to hospital-onset infections (HOIs) has focused on device- or procedure-associated HOIs. The attributable costs of HOIs that are not associated with device use or procedures have not been extensively studied. OBJECTIVE: We developed simulation models of attributable cost for 16 HOIs and estimated the total direct medical cost, including nondevice-related HOIs in the USA for 2011 and 2015. DATA AND METHODS: We used total discharge costs associated with HOI-related hospitalization from the National Inpatient Sample and applied an analogy costing methodology to develop simulation models of the costs attributable to HOIs. The mean attributable cost estimate from the simulation analysis was then multiplied by previously published estimates of the number of HOIs for 2011 and 2015 to generate national estimates of direct medical costs. RESULTS: After adjusting all estimates to 2017 US dollars, attributable cost estimates for select nondevice-related infections attributable cost estimates ranged from $7661 for ear, eye, nose, throat, and mouth (EENTM) infections to $27,709 for cardiovascular system infections in 2011; and from $8394 for EENTM to $26,445 for central nervous system infections in 2016 (based on 2015 incidence data). The national direct medical costs for all HOIs were $14.6 billion in 2011 and $12.1 billion in 2016. Nondevice- and nonprocedure-associated HOIs comprise approximately 26-28% of total HOI costs. CONCLUSION: Results suggest that nondevice- and nonprocedure-related HOIs result in considerable costs to the healthcare system.

Baseline Lung Allograft Dysfunction After Bilateral Lung Transplantation Is Associated With an Increased Risk of Death: Results From a Multicenter Cohort Study.

Background: A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant recipients. In this multicenter prospective cohort study, we test the association of BLAD with death in bilateral lung transplant recipients, identify clinical risk factors for BLAD, and assess its association with allograft injury on the molecular level. Methods: This multicenter, prospective cohort study included 173 bilateral lung transplant recipients that underwent serial pulmonary function testing and plasma collection for donor-derived cell-free DNA at prespecified time points. BLAD was defined as failure to achieve ≥80% predicted for both forced expiratory volume in 1 s and forced vital capacity after lung transplant, on 2 consecutive measurements at least 3 mo apart. Results: BLAD was associated with increased risk of death (hazard ratio, 1.97; 95% confidence interval [CI], 1.05-3.69; P = 0.03) but not chronic lung allograft dysfunction alone (hazard ratio, 1.60; 95% CI, 0.87-2.95; P = 0.13). Recipient obesity (odds ratio, 1.69; 95% CI, 1.15-2.80; P = 0.04) and donor age (odds ratio, 1.03; 95% CI, 1.02-1.05; P = 0.004) increased the risk of developing BLAD. Patients with BLAD did not demonstrate higher log10(donor-derived cell-free DNA) levels compared with no BLAD (slope [SE]: -0.0095 [0.0007] versus -0.0109 [0.0007]; P = 0.15). Conclusions: BLAD is associated with an increased risk of death following lung transplantation, representing an important posttransplant outcome with valuable prognostic significance; however, early allograft specific injury on the molecular level does not increase the risk of BLAD, supporting further mechanistic insight into disease pathophysiology.

Characterization of CRESS-DNA viruses in human vaginal secretions: An exploratory metagenomic investigation.

The Phylum Cressdnaviricota consists of a large number of circular Rep-encoding single-stranded (CRESS)-DNA viruses. Recently, metagenomic analyzes revealed their ubiquitous distribution in a diverse range of eukaryotes. Data relating to CRESS-DNA viruses in humans remains scarce. Our study investigated the presence and genetic diversity of CRESS-DNA viruses in human vaginal secretions. Vaginal swabs were collected from 28 women between 29 and 43 years old attending a fertility clinic in New York City. An exploratory metagenomic analysis was performed and detection of CRESS-DNA viruses was confirmed through analysis of near full-length sequences of the viral isolates. A phylogenetic tree was based on the REP open reading frame sequences of the CRESS-DNA virus genome. Eleven nearly complete CRESS-DNA viral genomes were identified in 16 (57.1%) women. There were no associations between the presence of these viruses and any demographic or clinical parameters. Phylogenetic analysis indicated that one of the sequences belonged to the genus Gemycircularvirus within the Genomoviridae family, while ten sequences represented previously unclassified species of CRESS-DNA viruses. Novel species of CRESS-DNA viruses are present in the vaginal tract of adult women. Although they be transient commensal agents, the potential clinical implications for their presence at this site cannot be dismissed.

Do phosphorus amendments enhance biodegradation activity in stalled petroleum hydrocarbon-contaminated soil?

Phosphorus (P) fertilizers promote soil petroleum-hydrocarbon (PHC) bioremediation by correcting carbon-to-P ratio imbalances. While these inputs create conditions favorable to microbial growth, areas of a site or an entire site with low degradation rates (i.e., "stalled") occur for unknown reasons. We hypothesized that soil conditions limit P bioavailability, leading to stalls in PHC bioremediation, and adding the correct P amendment restarts microbial activity. Soils were collected and characterized from four cold calcareous PHC-impacted sites in Saskatchewan, Canada, undergoing bioremediation. A generalized linear mixed model identified that regions with lower degradation rates possessed a neutral pH with high magnetic and salinity values. In a subsequent laboratory experiment, the proportion of benzene degraded at greater rates within active (i.e., higher degradation rates) than stalled soils, thereby following model predictions (p-value = 0.19, Kruskal-Wallis). The PHC degradation efficiency of different P amendments was tested by doping stalled soils (n = 3) with one of five treatments: 0 (control), 0 (autoclaved control), or 50 mg phosphate kg-1 soil as sodium diphosphate, triethyl phosphate, or tripolyphosphate. Tripolyphosphate accelerated benzene degradation (75.5 ± 5.4%) in one stalled soil (Outlook 323) and increased degradation non-significantly (43.9 ± 9.4%) in another (Allan 917). Alternatively, the final sample (Davidson 421) possessed the greatest benzene removal with no amendments. This implies that soil P bioavailability may not be the sole cause of decreased microbial activity. Accordingly, combining model outputs with mineralogy and microbiology investigations could enhance PHC biodegradation rates in these cold calcareous soils.

Prevalence Increases as Treatments Improve: An Evolutionary Perspective on the Treatment-Prevalence Paradox in Depression.

Depression is an eminently treatable disorder that responds to psychotherapy or medications; the efficacy of each has been established in hundreds of controlled trials. Nonetheless, the prevalence of depression has increased in recent years despite the existence of efficacious treatments-a phenomenon known as the treatment-prevalence paradox. We consider several possible explanations for this paradox, which range from a misunderstanding of the very nature of depression, inflated efficacy of the established treatments, and a lack of access to efficacious delivery of treatments. We find support for each of these possible explanations but especially the notion that large segments of the population lack access to efficacious treatments that are implemented as intended. We conclude by describing the potential of using lay therapists and digital technologies to overcome this lack of access and to reach historically underserved populations and simultaneously guarantee the quality of the interventions delivered.

Human Cardiac ß-Myosin Powerstroke Energetics: Thin Filament, Pi Displacement and Mutation Effects.

The powerstroke of human cardiac ß-myosin is an important stage of the cross-bridge cycle that generates force for muscle contraction. However, the starting structure of this process has never been resolved, and the relative timing of the powerstroke and inorganic phosphate (Pi) release is still controversial. In this study, we generated an atomistic model of myosin on the thin filament and utilized metadynamics simulations to predict the absent starting structure of the powerstroke. We demonstrated that the displacement of Pi from the active site during the powerstroke is likely necessary, reducing the energy barrier of the conformation change. The effects of the presence of the thin filament, the hypertrophic cardiomyopathy (HCM) mutation R712L, and the binding of Mavacamten on the powerstroke process were also investigated.

Recurrent choroid plexus carcinoma treated with CyberKnife radiosurgery: illustrative case.

BACKGROUND: Choroid plexus carcinomas (CPCs) are rare malignant brain tumors primarily affecting children younger than 2 years old. These tumors originate from the choroid plexus epithelium and are a subtype of choroid plexus tumors, which account for 1%-4% of pediatric brain tumors. Although CPCs often show a notably high recurrence rate after surgery, the standard treatment approach remains gross-total resection (GTR) of the tumor, given the lack of clinical data supporting the effectiveness of adjunct treatment options such as radiotherapy or chemotherapy. OBSERVATIONS: A 16-year-old female with a history of a recurrent cranial CPC resistant to surgery and radiotherapy was treated with CyberKnife stereotactic radiosurgery (SRS), following resection. The procedures successfully maintained local disease control for 41 months; however, there was a subsequent recurrence, ultimately leading to the death of the patient. LESSONS: CPC treatment remains challenging. SRS can be used as a viable adjunct to surgery, which remains the gold standard, although it can also be considered for nonsurgical candidates or when GTR cannot be achieved. Nevertheless, it is crucial to conduct additional research to explore diverse approaches for radiosurgery, including its role as the primary treatment modality versus its combination with surgery, radiotherapy, or chemotherapy. https://thejns.org/doi/10.3171/CASE23748.

Enhancing monolignol ferulate conjugate levels in poplar lignin via OsFMT1.

BACKGROUND: The phenolic polymer lignin is one of the primary chemical constituents of the plant secondary cell wall. Due to the inherent plasticity of lignin biosynthesis, several phenolic monomers have been shown to be incorporated into the polymer, as long as the monomer can undergo radicalization so it can participate in coupling reactions. In this study, we significantly enhance the level of incorporation of monolignol ferulate conjugates into the lignin polymer to improve the digestibility of lignocellulosic biomass. RESULTS: Overexpression of a rice Feruloyl-CoA Monolignol Transferase (FMT), OsFMT1, in hybrid poplar (Populus alba x grandidentata) produced transgenic trees clearly displaying increased cell wall-bound ester-linked ferulate, p-hydroxybenzoate, and p-coumarate, all of which are in the lignin cell wall fraction, as shown by NMR and DFRC. We also demonstrate the use of a novel UV-Vis spectroscopic technique to rapidly screen plants for the presence of both ferulate and p-hydroxybenzoate esters. Lastly we show, via saccharification assays, that the OsFMT1 transgenic p oplars have significantly improved processing efficiency compared to wild-type and Angelica sinensis-FMT-expressing poplars. CONCLUSIONS: The findings demonstrate that OsFMT1 has a broad substrate specificity and a higher catalytic efficiency compared to the previously published FMT from Angelica sinensis (AsFMT). Importantly, enhanced wood processability makes OsFMT1 a promising gene to optimize the composition of lignocellulosic biomass.

Biomarker Testing Disparities in Metastatic Colorectal Cancer.

Importance: Among patients with metastatic colorectal cancer (mCRC), data are limited on disparate biomarker testing and its association with clinical outcomes on a national scale. Objective: To evaluate the socioeconomic and demographic inequities in microsatellite instability (MSI) and KRAS biomarker testing among patients with mCRC and to explore the association of testing with overall survival (OS). Design, Setting, and Participants: This cohort study, conducted between November 2022 and March 2024, included patients who were diagnosed with mCRC between January 1, 2010, and December 31, 2017. The study obtained data from the National Cancer Database, a hospital-based cancer registry in the US. Patients with mCRC and available information on biomarker testing were included. Patients were classified based on whether they completed or did not complete MSI or KRAS tests. Exposure: Demographic and socioeconomic factors, such as age, race, ethnicity, educational level in area of residence, median household income, insurance type, area of residence, facility type, and facility location were evaluated. Main Outcomes and Measures: The main outcomes were MSI and KRAS testing between the date of diagnosis and the date of first-course therapy. Univariable and multivariable logistic regressions were used to identify the relevant factors in MSI and KRAS testing. The OS outcomes were also evaluated. Results: Among the 41 061 patients included (22 362 males [54.5%]; mean [SD] age, 62.3 [10.1] years; 17.3% identified as Black individuals, 78.0% as White individuals, 4.7% as individuals of other race, with 6.5% Hispanic or 93.5% non-Hispanic ethnicity), 28.8% underwent KRAS testing and 43.7% received MSI testing. A significant proportion of patients had Medicare insurance (43.6%), received treatment at a comprehensive community cancer program (40.5%), and lived in an area with lower educational level (51.3%). Factors associated with a lower likelihood of MSI testing included age of 70 to 79 years (relative risk [RR], 0.70; 95% CI, 0.66-0.74; P < .001), treatment at a community cancer program (RR, 0.74; 95% CI, 0.70-0.79; P < .001), rural residency (RR, 0.80; 95% CI, 0.69-0.92; P < .001), lower educational level in area of residence (RR, 0.84; 95% CI, 0.79-0.89; P < .001), and treatment at East South Central facilities (RR, 0.67; 95% CI, 0.61-0.73; P < .001). Similar patterns were observed for KRAS testing. Survival analysis showed modest OS improvement in patients with MSI testing (hazard ratio, 0.93; 95% CI, 0.91-0.96; P < .001). The median (IQR) follow-up time for the survival analysis was 13.96 (3.71-29.34) months. Conclusions and Relevance: This cohort study of patients with mCRC found that older age, community-setting treatment, lower educational level in area of residence, and treatment at East South Central facilities were associated with a reduced likelihood of MSI and KRAS testing. Highlighting the sociodemographic-based disparities in biomarker testing can inform the development of strategies that promote equity in cancer care and improve outcomes for underserved populations.

Outcomes of Near-Total and Subtotal Resection of Sporadic Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate tumor control and facial nerve outcomes after gross-total (GTR), near-total (NTR), and subtotal resection (STR) of sporadic vestibular schwannomas (VS). DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched in August 2021 through inception following PRISMA guidelines. REVIEW METHODS: English language articles reporting tumor control and facial nerve outcomes of adults (≥18 years) with NTR and STR of VS were evaluated. Study characteristics, demographics data, tumor characteristics, type of surgical intervention, and outcome measures on tumor control and facial nerve function were collected. Pooled relative risk (RR) estimates for tumor recurrence and facial nerve outcomes were calculated and stratified by extent of resection. RESULTS: From an initial search of 2504 articles, 48 studies were included in the analysis. When comparing 1108 patients who underwent NTR to 3349 patients with GTR, the pooled RR of recurrence in the NTR cohort was 2.94 (95% confidence interval [CI] 1.65-5.24, P = .0002). When comparing 1016 patients who underwent STR to 6171 patients with GTR, the pooled RR of recurrence in the STR cohort was 11.50 (95% CI 6.64-19.92, P < .0001). Estimates for risk of tumor regrowth for less-than-complete resection are presented. There was no elevated risk of adverse facial nerve outcome (defined as House-Brackmann grade III and above) in each category of extent of resection compared to GTR. CONCLUSION: Extent of resection predicts risk of tumor recurrence/regrowth following microsurgical resection. Favorable facial nerve outcome should be weighed against the increased risk of regrowth and the potential need for further treatment.

Stereotactic radiosurgery for facial nerve hemangioma: Case report and systematic review.

BACKGROUND: Facial nerve hemangiomas (FNHs) are rare tumors that primarily occur near the geniculate ganglion in the temporal bone. Despite their rarity, they can cause significant facial nerve dysfunction. The optimal management approach for FNHs remains uncertain, with surgery being the mainstay but subject to debate regarding the extent of resection and preservation of the facial nerve. METHODS: Systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We queried the PubMed/Medline (accessed on 5 March 2024) electronic database using combinations of the following search terms and words text: "geniculate ganglion hemangioma", "ganglional hemangioma", "hemangioma of the facial nerve", "facial hemangioma", and "intratemporal hemangioma". RESULTS: We identified a total of 30 literatures (321 patients). The most common site involved for the facial nerve hemangioma was the geniculate ganglion area followed by internal auditory canal, tympanic segment, labyrinthine segment and mastoid involvement. All patients were treated with conservative management or surgery. We report a 48-year-old female patient with HB grade 2 facial palsy and hemifacial spasm underwent SRS using Cyberknife technology. The treatment targeted the FNH in the left internal acoustic canal near the geniculate ganglion. Six months post-treatment, clinical improvement was evident, and lesion control was confirmed in a follow-up brain MRI. CONCLUSION: The rarity of FNHs contributes to the lack of consensus on optimal management. This illustrative case demonstrates the feasibility of SRS as a standalone treatment for FNHs.

Strangulated Indirect Inguinal Hernia-Containing Bladder: A Case Report.

Inguinal hernias involving the bladder are exceedingly rare and pose a diagnostic challenge. Identifying bladder involvement within an inguinal hernia is imperative to avoid iatrogenic bladder injuries and subsequent complications. Here we discuss a case of inguinal bladder herniation and bladder visualization using methylene blue dye intraoperatively. We present a case of a 45-year-old male who presented with a six-hour history of dysuria and a painful non-reducible right-sided groin mass that had previously been reducible for 17 years. Computed tomography demonstrated an irreducible indirect inguinal hernia-containing bladder. Open Lichtenstein repair was performed, and intraoperative methylene blue-dyed saline successfully identified the herniated bladder, preventing iatrogenic bladder injury. This case report demonstrates the importance of preoperative imaging and intraoperative visualization for the prevention of complications in a rare occurrence of a strangulated indirect inguinal hernia-containing bladder.

Neratinib, a pan ERBB/HER inhibitor, restores sensitivity of PTEN-null, BRAFV600E melanoma to BRAF/MEK inhibition.

Introduction: Approximately 50% of melanomas harbor an activating BRAFV600E mutation. Standard of care involves a combination of inhibitors targeting mutant BRAF and MEK1/2, the substrate for BRAF in the MAPK pathway. PTEN loss-of-function mutations occur in ~40% of BRAFV600E melanomas, resulting in increased PI3K/AKT activity that enhances resistance to BRAF/MEK combination inhibitor therapy. Methods: To compare the response of PTEN null to PTEN wild-type cells in an isogenic background, CRISPR/Cas9 was used to knock out PTEN in a melanoma cell line that harbors a BRAFV600E mutation. RNA sequencing, functional kinome analysis, and drug synergy screening were employed in the context of BRAF/MEK inhibition. Results: RNA sequencing and functional kinome analysis revealed that the loss of PTEN led to an induction of FOXD3 and an increase in expression of the FOXD3 target gene, ERBB3/HER3. Inhibition of BRAF and MEK1/2 in PTEN null, BRAFV600E cells dramatically induced the expression of ERBB3/HER3 relative to wild-type cells. A synergy screen of epigenetic modifiers and kinase inhibitors in combination with BRAFi/MEKi revealed that the pan ERBB/HER inhibitor, neratinib, could reverse the resistance observed in PTEN null, BRAFV600E cells. Conclusions: The findings indicate that PTEN null BRAFV600E melanoma exhibits increased reliance on ERBB/HER signaling when treated with clinically approved BRAFi/MEKi combinations. Future studies are warranted to test neratinib reversal of BRAFi/MEKi resistance in patient melanomas expressing ERBB3/HER3 in combination with its dimerization partner ERBB2/HER2.