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Background: Enrollment of Medicare beneficiaries in medicare advantage (MA) plans has been steadily increasing. Prior research has shown differences in healthcare access and outcomes based on Medicare enrollment status. This study sought to compare utilization of minimally invasive colorectal cancer (CRC) surgery and postoperative outcomes between MA and Fee-for-Service (FFS) beneficiaries. Methods: A retrospective cohort study of beneficiaries  ≥ 65.5 years of age enrolled in FFS and MA plans was performed of patients undergoing a CRC resection from 2016 to 2019. The primary outcome was operative approach, defined as minimally invasive (laparoscopic) or open. Secondary outcomes included robotic assistance, hospital length-of-stay, mortality, discharge disposition, and hospital readmission. Using balancing weights, we performed a tapered analysis to examine outcomes with adjustment for potential confounders. Results: MA beneficiaries were less likely to have lymph node (12.9 vs 14.4%, p< 0.001) or distant metastases (15.5% vs 17.0%, p< 0.001), and less likely to receive chemotherapy (6.2% vs 6.7%, p< 0.001), compared to FFS beneficiaries. MA beneficiaries had a higher risk-adjusted likelihood of undergoing laparoscopic CRC resection (OR 1.12 (1.10–1.15), p< 0.001), and similar rates of robotic assistance (OR 1.00 (0.97–1.03), p= 0.912), compared to FFS beneficiaries. There were no differences in risk-adjusted length-of-stay (βcoefficient 0.03 (− 0.05–0.10), p= 0.461) or mortality at 30-60-and 90-days (OR 0.99 (0.95–1.04), p= 0.787; OR 1.00 (0.96–1.04), p= 0.815; OR 0.98 (0.95–1.02), p= 0.380). MA beneficiaries had a lower likelihood of non-routine disposition (OR 0.77 (0.75–0.78), p< 0.001) and readmission at 30-60-and 90-days (OR 0.76 (0.73–0.80), p< 0.001; OR 0.78 (0.75–0.81), p< 0.001; OR 0.79 (0.76–0.81), p< 0.001). Conclusions: MA beneficiaries had less advanced disease at the time of CRC resection and a greater likelihood of undergoing a laparoscopic procedure. MA enrollment is associated with improved health outcomes for elderly beneficiaries undergoing operative treatment for CRC.

Since there is no current international consensus on the optimal approach for pain management in acute pancreatitis (AP), analgesic practices may vary across different healthcare settings. This study explored global disparities in analgesic use, in particular opioids, during admission and at discharge in hospitalised AP patients. This was a post hoc analysis of the prospective PAINAP database, which included all admissions for AP between April and June 2022 with a 1‐month follow‐up. Demographic details, analgesic use, and clinical outcomes were recorded during admission and at discharge. Odds ratios (ORs) for opioid use during admission and at discharge were identified using multivariable regression analyses. Amongst the 1864 patients (52% males, median age 56 (interquartile range, 41–71)) across three different continents, simple analgesics were predominantly used as the primary analgesic (70%). Opioid use during admission was lowest in European centres (67%). Admission in Asian (OR, 2.53 (95% confidence interval (CI), 1.59–4.04), p< 0.001), and Australian (OR, 5.81 (95% CI, 3.19–10.56), p< 0.001) centres was associated with opioid administration during admission compared with European centres. Increased pain severity, longer pre‐admission pain duration, organ failure, and longer length of admission increased opioid use during admission. At discharge, Asian (OR, 2.01 (95% CI, 1.40–2.88), p< 0.001) and Australian (OR, 1.91 (95% CI, 1.28–2.85), p= 0.002) centres were associated with opioid prescription compared with European centres. Increased pain severity, longer pre‐admission pain duration, acute necrotic collections, and walled‐off necrosis also increased the likelihood of opioid prescription at discharge. There are substantial intercontinental differences in opioid use for AP pain. Accordingly, there is a need for international guidelines on pain management in AP.

Forecasting methods are important decision support tools in geo-distributed sensor networks. However, challenges such as the multivariate nature of data, the existence of multiple nodes, and the presence of spatio-temporal autocorrelation increase the complexity of the task. Existing forecasting methods are unable to address these challenges in a combined manner, resulting in a suboptimal model accuracy. In this article, we propose GAP-LSTM, a novel geo-distributed forecasting method that leverages the synergic interaction of graph convolution, attention-based long short-term memory (LSTM), 2-D-convolution, and latent memory states to effectively exploit spatio-temporal autocorrelation in multivariate data generated by multiple nodes, resulting in improved modeling capabilities. Our extensive evaluation, involving real-world datasets on traffic, energy, and pollution domains, showcases the ability of our method to outperform state-of-the-art forecasting methods. An ablation study confirms that all method components provide a positive contribution to the accuracy of the extracted forecasts. The method also provides an interpretable visualization that complements forecasts with additional insights for domain experts.

Background: Gaming can serve as an educational tool to allow trainees to practice surgical decision-making in a low-stakes environment. LapBot is a novel free interactive mobile game application that uses artificial intelligence (AI) to provide players with feedback on safe dissection during laparoscopic cholecystectomy (LC). This study aims to provide validity evidence for this mobile game. Methods: Trainees and surgeons participated by downloading and playing LapBot on their smartphone. Players were presented with intraoperative LC scenes and required to locate their preferred location of dissection of the hepatocystic triangle. They received immediate accuracy scores and personalized feedback using an AI algorithm (“GoNoGoNet”) that identifies safe/dangerous zones of dissection. Player scores were assessed globally and across training experience using non-parametric ANOVA. Three-month questionnaires were administered to assess the educational value of LapBot. Results: A total of 903 participants from 64 countries played LapBot. As game difficulty increased, average scores (p&lt; 0.0001) and confidence levels (p&lt; 0.0001) decreased significantly. Scores were significantly positively correlated with players’ case volume (p= 0.0002) and training level (p= 0.0003). Most agreed that LapBot should be incorporated as an adjunct into training programs (64.1%), as it improved their ability to reflect critically on feedback they receive during LC (47.5%) or while watching others perform LC (57.5%). Conclusions: Serious games, such as LapBot, can be effective educational tools for deliberate practice and surgical coaching by promoting learner engagement and experiential learning. Our study demonstrates that players’ scores were correlated to their level of expertise, and that after playing the game, most players perceived a significant educational value.

Background: Paraesophageal hernia repairs (PEHRs) have high rates of radiographic recurrence, with some patients requiring repeat operation. This study characterizes patients who underwent PEHR to identify the factors associated with postoperative symptom improvement and radiographic recurrence. We furthermore use propensity score matching to compare patients undergoing initial and reoperative PEHR to identify the factors predictive of recurrence or need for reoperation. Methods: After IRB approval, patients who underwent PEHR at a tertiary care center between January 2018 and December 2022 were identified. Patient characteristics, preoperative imaging, operative findings, and postoperative outcomes were recorded. A computational generalization of inverse propensity score weight was then used to construct populations of initial and redo PEHR patients with similar covariate distributions. Results: A total of 244 patients underwent PEHR (78.7% female, mean age 65.4 ± 12.3 years). Most repairs were performed with crural closure (81.4%) and fundoplication (71.7%) with 14.2% utilizing mesh. Postoperatively, 76.5% of patients had subjective symptom improvement and of 157 patients with postoperative imaging, 52.9% had evidence of radiographic recurrence at a mean follow-up of 10.4 ± 13.6 months. Only 4.9% of patients required a redo operation. Hernia type, crural closure, fundoplication, and mesh usage were not predictors of radiographic recurrence or symptom improvement (P> 0.05). Propensity weight score analysis of 50 redo PEHRs compared to a matched cohort of 194 initial operations revealed lower rates of postoperative symptom improvement (P&lt; 0.05) but no differences in need for revision, complication rates, ED visits, or readmissions. Conclusions: Most PEHR patients have symptomatic improvement with minimal complications and reoperations despite frequent radiographic recurrence. Hernia type, crural closure, fundoplication, and mesh usage were not significantly associated with recurrence or symptom improvement. Compared to initial PEHR, reoperative PEHRs had lower rates of symptom improvement but similar rates of recurrence, complications, and need for reoperation.

Cannabidiol (CBD), one of the main Cannabis sativabioactive compounds, is utilized in the treatment of major epileptic syndromes. Its efficacy can be attributed to a multimodal mechanism of action that includes, as potential targets, several types of ion channels. In the brain, CBD reduces the firing frequency in rat hippocampal neurons, partly prolonging the duration of action potentials, suggesting a potential blockade of voltage-operated K+channels. We postulate that this effect might involve the inhibition of the large-conductance voltage- and Ca2+-operated K+channel (BK channel), which plays a role in the neuronal action potential’s repolarization. Thus, we assessed the impact of CBD on the BK channel activity, heterologously expressed in HEK293 cells. Our findings, using the patch-clamp technique, revealed that CBD inhibits BK channel currents in a concentration-dependent manner with an IC50of 280 nM. The inhibition is through a direct interaction, reducing both the unitary conductance and voltage-dependent activation of the channel. Additionally, the cannabinoid significantly delays channel activation kinetics, indicating stabilization of the closed state. These effects could explain the changes induced by CBD in action potential shape and duration, and they may contribute to the observed anticonvulsant activity of this cannabinoid.

AbstractTo present evidence of the validity and reliability of the Brief MTL-BR Battery, a screening tool for language assessment for people with aphasia (PWA). The sample consisted of 138 participants, including 96 neurologically healthy adults and 42 individuals with aphasia. Construct validity was investigated through convergent validity. To examine convergent validity, correlations between the Brief MTL-BR and the Montreal Toulouse Language Assessment Battery - MTL-BR tasks were used. Criterion validity was determined using Holm-Bonferroni to compare people with aphasia and healthy adults. Reliability was determined through inter-rater (Interclass Correlation Coefficients), the test-retest method (Interclass Correlation Coefficients), and internal consistency (Cronbach’s Alpha). The Brief MTL-BR demonstrated satisfactory construct validity, with correlation coefficients ranging from substantial to very strong (0.553 to 0.862). The assessment of criterion validity demonstrated significant differences between neurologically healthy adults and people with aphasia on all tasks examined. Reliability assessments revealed excellent inter-rater agreement (0.972 to 1). All tasks in the Brief MTL-BR Battery displayed Cronbach’s alpha values above 0.88. Significant correlations between tasks and retest scores were identified ranging from good to excellent (0.752 to 0.967). The present findings support the reliability and validity of the Brief MTL-BR Battery.

Purpose: Hadrons, i.e. particles that are heavier than electrons, are playing an increasingly important role in radiation oncology. Due to the high investment costs for the necessary infrastructure, this option is only available in specialized centers. Methods: This article describes some of the physical properties that make hadrons attractive for external beam radiation therapy (EBRT), but also some of the challenges that need to be considered. Results: The importance of linear energy transfer for biological effects is discussed. Conclusions: In addition to the use of charged particles, the importance of neutrons for radiotherapy is also highlighted, in particular the properties of boron neutron capture therapy (BNCT), which open up completely new possibilities for the further development of EBRT.

Context: Cushing syndrome (CS) is associated with different hematological abnormalities. Nevertheless, conflicting data about erythropoiesis in CS have been reported. Furthermore, it is unclear whether CS sex and subtype-specific alterations in red blood cells (RBC) parameters are present. Objective: To investigate sex and subtype-specific changes in RBC in patients with CS at initial diagnosis and after remission. Design: Retrospective, monocentric study including 210 patients with CS (women, n = 162) matched 1:1 for sex and age to patients with pituitary microadenomas or adrenal incidentalomas (both hormonally inactive). RBC parameters were evaluated at initial diagnosis and after remission. Results: Women with CS had higher hematocrit (median 42.2 vs39.7%), hemoglobin (14.1 vs13.4 g/dl) and mean corpuscular volume (MCV) (91.2 vs87.9 fl) compared to the controls (all p&lt; 0.0001). Women with Cushing disease (CD) showed higher hematocrit, RBC and hemoglobin levels than those with ectopic Cushing (ECS) (all p&lt; 0.005). Men with CS had lower hematocrit (42.9 vs44.7%), RBC count (4.8 vs5.1n*106/µl) and hemoglobin (14.2 vs15.4 g/dl), but higher MCV (90.8 vs87.5 fl) than controls (all p&lt; 0.05). In men with CS, no subtype-specific differences were identified. Three months after remission hemoglobin decreased in both sexes. Conclusion: CS is characterized by sexual and subtype-specific differences in RBC parameters. Compared to controls, women with CS showed higher hematocrit/hemoglobin levels, whereas men had lower hematocrit/hemoglobin, which further decreased directly after remission. Therefore, anemia should be considered as complication of CS in men. In women, differences in RBC parameters may help to differentiate CD from ECS.

Objective: We aimed at defining the most effective routine immunoassay- or liquid chromatography-tandem mass spectrometry (LC–MS/MS)-determined steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in a PCOS-like population before genotyping. Methods: Seventy PCOS-like patients in reproductive age with immunoassay-determined follicular 17OH-progesterone (17OHP) ≥ 2.00 ng/mL underwent CYP21A2gene analysis and 1–24ACTH test. Serum steroids were measured by immunoassays at baseline and 60 min after ACTH stimulation; basal steroid profile was measured by LC–MS/MS. Results: Genotyping revealed 23 21-NCAH, 15 single allele heterozygous CYP21A2mutations (21-HTZ) and 32 PCOS patients displaying similar clinical and metabolic features. Immunoassays revealed higher baseline 17OHP and testosterone, and after ACTH stimulation, higher 17OHP (17OHP60) and lower cortisol, whereas LC–MS/MS revealed higher 17OHP (17OHPLC-MS/MS), progesterone and 21-deoxycortisol and lower corticosterone in 21-NCAH compared with both 21-HTZ and PCOS patients. Steroid thresholds best discriminating 21-NCAH from 21-HTZ and PCOS were estimated, and their diagnostic accuracy in identifying 21-NCAH from PCOS was established by ROC analysis. The highest accuracy was observed for 21-deoxycortisol ≥ 0.087 ng/mL, showing 100% sensitivity, while the combination of 17OHPLC-MS/MS≥ 1.79 ng/mL and corticosterone ≤ 8.76 ng/mL, as well as the combination of ACTH-stimulated 17OHP ≥ 6.77 ng/mL and cortisol ≤ 240 ng/mL by immunoassay, showed 100% specificity. Conclusions: LC–MS/MS measurement of basal follicular 21-deoxycortisol, 17OHP and corticosterone seems the most convenient method for diagnosing 21-NCAH in a population of PCOS with a positive first level screening, providing high accuracy and reducing the need for ACTH stimulation test.

In this study, we present the preliminary imaging results obtained with a gamma module called BeNEdiCTE, specifically designed for boron neutron capture therapy (BNCT). The primary objective of the BNCT-SPECT system is to quantitatively assess and pinpoint the 10B contribution to the dose administered to a patient during BNCT treatment by detecting the 478-keV gamma rays emitted from the 10B(n, $\alpha $ )7Li reactions. Starting from a feasibility study of a collimator suitable for a BNCT-SPECT system, we end up presenting the first images obtained by reconstructing vials containing boron powder thanks to the aid of an artificial neural network (ANN). However, the extremely high-intensity neutron flux of $10{^{{9}}}$ n/cm2/s and the presence of mixed radiation fields in the irradiation room pose significant challenges to this task. To overcome these challenges, the implementation of an appropriate collimator becomes essential. Thanks to Monte Carlo simulations, we designed a lead pinhole collimator, with a twofold focus on enhancing spatial resolution (achieving <1 cm) and maximizing geometric efficiency (GE) (attaining $\gt 10{^{-}6 }$ ).

DNA double-strand breaks (DSBs) contribute to genome instability, a key feature of cancer. DSBs are mainly repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ). We investigated the role of an isoform of the multifunctional cyclin-dependent kinase 9, CDK9-55, in DNA repair, by generating CDK9-55-knockout HeLa clones (through CRISPR-Cas9), which showed potential HR dysfunction. A phosphoproteomic screening in these clones treated with camptothecin revealed that CDC23 (cell division cycle 23), a component of the E3-ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), is a new substrate of CDK9-55, with S588 being its putative phosphorylation site. Mutated non-phosphorylatable CDC23(S588A) affected the repair pathway choice by impairing HR and favouring error-prone NHEJ. This CDK9 role should be considered when designing CDK-inhibitor-based cancer therapies.

Dealing with acute cholecystitis in high-risk, critically ill, and unfit-for-surgery patients is frequent during daily practice and requires complex management. Several procedures exist to postpone and/or prevent surgical intervention in those patients who temporarily or definitively cannot undergo surgery. After a systematic review of the literature, an expert panel from the Italian Society of Emergency Surgery and Trauma (SICUT) discussed the different issues and statements in subsequent rounds. The final version of the statements was discussed during the annual meeting in Rome (September 2022). The present paper presents the definitive conclusions of the discussion. Fifteen statements based on the literature evidence were provided. The statements gave precise indications regarding the decisional process and the management of patients who cannot temporarily or definitively undergo cholecystectomy for acute cholecystitis. Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients should be multidisciplinary. The different gallbladder drainage methods must be tailored according to each patient and based on the expertise of the hospital. Percutaneous gallbladder drainage is recommended as the first choice as a bridge to surgery or in severely physiologically deranged patients. Endoscopic gallbladder drainage (cholecystoduodenostomy and cholecystogastrostomy) is suggested as a second-line alternative especially as a definitive procedure for those patients not amenable to surgical management. Trans-papillary gallbladder drainage is the last option to be reserved only to those unfit for other techniques. Delayed laparoscopic cholecystectomy in patients with percutaneous gallbladder drainage is suggested in all those patients recovering from the conditions that previously discouraged surgical intervention after at least 6 weeks from the gallbladder drainage.

Introduction:TNFα-inducible matrix metalloproteinases play a critical role in the process of airway remodeling in respiratory inflammatory disease including asthma. The cationic host defense peptide LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood. Here, we examined the effect of LL-37 on TNFα-mediated responses in human bronchial epithelial cells (HBECs). Methods:We used a slow off-rate modified aptamer-based proteomics approach to define the HBEC proteome altered in response to TNFα. Abundance of selected protein candidates and signaling intermediates was examined using immunoassays, ELISA and Western blots, and mRNA abundance was examined by qRT-PCR. Results:Proteomics analysis revealed that 124 proteins were significantly altered, 12 proteins were enhanced by ≥2-fold compared to unstimulated cells, in response to TNFα. MMP9 was the topmost increased protein in response to TNFα, enhanced by ∼10-fold, and MMP13 was increased by ∼3-fold, compared to unstimulated cells. Furthermore, we demonstrated that LL-37 significantly suppressed TNFα-mediated MMP9 and MMP13 in HBEC. Mechanistic data revealed that TNFα-mediated MMP9 and MMP13 production is controlled by SRC kinase and that LL-37 enhances related upstream negative regulators, namely, phospho-AKT (T308) and TNFα-mediated TNFAIP3 or A20. Conclusions:The findings of this study suggest that LL-37 may play a role in intervening in the process of airway remodeling in chronic inflammatory respiratory disease such as asthma.

Background: Surgery generates a vast amount of data from each procedure. Particularly video data provides significant value for surgical research, clinical outcome assessment, quality control, and education. The data lifecycle is influenced by various factors, including data structure, acquisition, storage, and sharing; data use and exploration, and finally data governance, which encompasses all ethical and legal regulations associated with the data. There is a universal need among stakeholders in surgical data science to establish standardized frameworks that address all aspects of this lifecycle to ensure data quality and purpose. Methods: Working groups were formed, among 48 representatives from academia and industry, including clinicians, computer scientists and industry representatives. These working groups focused on: Data Use, Data Structure, Data Exploration, and Data Governance. After working group and panel discussions, a modified Delphi process was conducted. Results: The resulting Delphi consensus provides conceptualized and structured recommendations for each domain related to surgical video data. We identified the key stakeholders within the data lifecycle and formulated comprehensive, easily understandable, and widely applicable guidelines for data utilization. Standardization of data structure should encompass format and quality, data sources, documentation, metadata, and account for biases within the data. To foster scientific data exploration, datasets should reflect diversity and remain adaptable to future applications. Data governance must be transparent to all stakeholders, addressing legal and ethical considerations surrounding the data. Conclusion: This consensus presents essential recommendations around the generation of standardized and diverse surgical video databanks, accounting for multiple stakeholders involved in data generation and use throughout its lifecycle. Following the SAGES annotation framework, we lay the foundation for standardization of data use, structure, and exploration. A detailed exploration of requirements for adequate data governance will follow.

The most frequent genetic alteration of familial isolated growth hormone producing pituitary neuroendocrine tumors is a germline mutation of the aryl hydrocarbon receptor-interacting protein (AIP)gene. Various AIPmutations are already known; however, an AIPmutation in exon 6 (c.811_812del; p.Arg271Glyfs*16) has not been reported yet. Here, we report a German family with two identical twins who were both affected by acromegaly and carried the above-mentioned novel AIPmutation. The father was found to be an unaffected carrier, while the paternal aunt most likely suffered from acromegaly as well and died from metastatic colorectal cancer. Apart from reporting a novel AIPmutation, this study does not only highlight the different clinical and histological features of the AIPmutated growth hormone producing pituitary neuroendocrine tumors but also confirms the poor responsiveness of dopamine agonists in AIPmutated acromegaly. Furthermore, it highlights the increased mortality risk of comorbidities typically associated with acromegaly.

Background: Communication is key to success in bariatric surgery. This study aims to understand how outcomes after bariatric surgery differ between patients with a non-English primary language and those with English as their primary language. Methods: This retrospective, observational cohort study of bariatric surgery patients age ≥ 18 years utilized the Michigan, Maryland, and New Jersey State Inpatient Databases and State Ambulatory Surgery and Services Databases, 2016 to 2018. Patients were classified by primary spoken language: English and non-English. Primary outcome was complications. Secondary outcomes included length of stay (LOS) and cost, with cost calculated using cost-to-charge ratios provided by Healthcare Cost and Utilization Project and reported in 2019 United States dollars. Multivariable regression models (logistic, Poisson, and quantile) were used to examine associations between primary language and outcomes. Given the uneven distribution of race by primary language, interaction terms were used to examine conditional effects of race. Results: Among 69,749 bariatric surgery patients, 2811 (4.2%) spoke a non-English primary language. Covariates, notably race distribution, and unadjusted outcomes differed significantly by primary language. However, after adjustment, non-English primary language was not associated with significantly increased odds of complications (odds ratio 1.24, p= 0.389), significantly different LOS (− 0.02 days, p= 0.677), nor significantly different mean healthcare costs (− $265, p= 0.309). There were no significant conditional effects of race seen among outcomes. Conclusions: Though non-English primary language was associated with a significantly different distribution of observable characteristics (including race, income quartile, and insurance type), after adjustment, non-English primary language was not associated with significant differential risk of adverse outcomes after bariatric surgery, and there were no significant conditional effects of race. As such, this study suggests that disparities in bariatric surgery by primary spoken language more likely related to access to care, or the pre- and post-hospital care continuum, rather than index hospitalization after surgery. Graphical abstract:

Olive cultivars present unique chemical properties due to the different ripening conditions and the dielectric factor of the extracted extra virgin olive oil (EVOO) is one of the most acceptable parameters for their evaluation. This study aims at discriminating olive oil samples using their chemical and dielectric properties. Three cultivars of olives: Oily, Yellowand Fishemi, at three ripening stages of unripe, semi-ripe and ripe, harvested using two different machines were tested. The quality characteristics of olive oil include the value of acidity, peroxide, sterol compounds, fatty acid composition and total phenol of the extracted olive oil were measured. The EVOO’s dielectric parameters were measured using a laboratory developed low-frequency device. The measures were done in the range from 0.1 to 10 MHz. The obtained parameters consisted of gain and phase shift voltages that were analyzed by principal component analysis, linear discriminant analysis, decision trees, support vector machine and artificial neural network. Out-of sample validation indicated the artificial neural network had the best performance with correlation coefficient of 0.9479, mean absolute error of 4.762 and root mean square error of 6.6652.The results revealed that the sensor measure followed by a machine learning approach have potential for the industrial application for discriminating the EVOO on the basis of the cultivar and ripening stage of the processed olive.