Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

Mn2+-Triggered Swing-Arm Robot Strategy Using Anemone-Like Thi@AuPd@Cu-MOFs as Signaling Probes for the Detection of T-2 Toxin.

Herein, we synthesized anemone-like copper-based metal-organic frameworks (MOFs) loaded with gold-palladium nanoparticles (AuPd@Cu-MOFs) and polyethylenimine-reduced graphene oxide/gold-silver nanosheet composites (PEI-rGO/AuAg NSs) for the first time to construct the sensor and to detect T-2 toxin (T-2) using triple helix molecular switch (THMS) and signal amplification by swing-arm robot. The aptasensor used PEI-rGO/hexagonal AuAg NSs as the electrode modification materials and anemone-like AuPd@Cu-MOFs as the signal materials. The prepared PEI-rGO/hexagonal AuAg NSs had a large specific surface area, excellent electrical conductivity, and good stability, which successfully improved the electrochemical performance of the sensors. The AuPd@Cu-MOFs with high porosity provided a great deal of attachment sites for the signaling molecule thionine (Thi), thereby increasing the signal response. The aptasensor developed in this study demonstrated a remarkable detection limit of 0.054 fg mL-1 under optimized conditions. Furthermore, the successful detection of T-2 in real samples was achieved using the fabricated sensor. The simplicity of the THMS-based method, which entails modifying the aptamer sequence, allows for easy adaptation to different target analytes. Thus, the sensor holds immense potential for applications in quality supervision and food safety.

EI24 promotes cell adaption to ER stress by coordinating IRE1 signaling and calcium homeostasis.

The endoplasmic reticulum (ER) is a subcellular organelle crucial for protein folding and calcium storage. Accumulation of unfolded proteins or calcium depletion causes ER stress. Deficiency of ER stress adaptation leads to apoptosis, which is associated with several human disorders. Here, we reveal that ER transmembrane protein EI24 promotes cell adaptation to ER stress by coordinating the IRE1 branch of the unfolded protein response (UPR) and calcium signaling. Under nonstressed conditions, EI24 binds to the kinase domain of IRE1 to inhibit its activation. Upon ER stress, EI24 disassociates from IRE1 to permit UPR activation, and meanwhile targets IP3R1 to prevent ER calcium depletion, which together promote cell adaptation to ER stress. EI24 knockout causes failure of ER stress adaptation and apoptosis. Thus, EI24 is a novel anti-apoptotic factor implicated in ER stress signaling.

Intramolecular Palladium(II)-Catalyzed Regioselective 6-endo or 6-exo C-H Benzannulation: An Approach for the Diversity-Oriented Synthesis of Quinolinone Derivatives from Pyridones.

Herein, a new intramolecular palladium(II)-catalyzed regioselective 6-endo-trig or 6-exo-trig annulation through direct C-H activation is presented as a method for the diversity-oriented synthesis of highly substituted quinolinones from pyridones. The reaction occurs under mild conditions and exhibits excellent regioselectivity, good functional group tolerance, and broad applications. This innovative approach has been successfully utilized in the synthesis of Glycopentanolone A and an intermediate of (R)-(+)-Tipifarnib.

Collective Information Seeking During a Health Crisis : Predictors of Google Trends During COVID-19.

This article approaches collective health information seeking from computational method by investigating patterns of Google Trends data in the United States during the early stages of the COVID-19 pandemic. We analyzed factors that prompted a community's curiosity, and information that communities were most curious about. The results of our cross-sectional and time-series-based analyses reveal a few salient findings: (1) Republican leaning states searched less frequently, and while states with more cases searched more, partisan lean is a more significant predictor; (2) States with greater level of poverty searched less frequently; (3) Leadership on the national level significantly influenced people's searching behavior; (4) Communities were most interested in "local risk" information as well as quantifiable information. We show in this work that established individual information seeking theoretical predictors (risk) can predict online collective information demand and information seeking subcategories with important contributions from collective conditions (leadership). Health communication practitioners can design health messages and choose media channels more purposefully according to what people are most interested in searching.

Exemplification Effects on Policy Support: Exemplar Familiarity, Narrative Vividness, and Perceptions of Maternal Health Disparities.

This research examined the relationship between exemplar characteristics and concern for maternal health disparities. A two-wave 2 (familiarity) X 2 (vividness) between-subjects experiment tested the effects of exemplar familiarity and vividness on attitudes toward maternal health and maternal health disparities, perceptions of disparate risk, and policy support after exposure to a story about a mother who faced complications during childbirth and again three to five days later. The moderating role of political ideology was also examined. Results revealed positive effects of vividness on attitudes toward maternal mortality in general, attitudes toward maternal health disparities, and support for policies to address them in the short-term. Effects on general attitudes persisted three to five days later. Contrary to predictions, no effects were found for familiarity at Time 1. A familiar exemplar elicited more negative attitudes toward maternal mortality at Time 2. Examination of the moderating role of politics revealed the impact of vividness on general attitudes and policy support was greater among conservative participants, compared to more liberal participants. In addition to extending the applicability of exemplification theory to perceptions of risk toward others and subsequent policy support, this research has practical applications for bringing public attention to racial health disparities.

Magnetoelectric Sensor Operating in d15 Thickness-Shear Mode for High-Frequency Current Detection.

For the application of high-frequency current detection in power systems, such as very fast transient current, lightning current, partial discharge pulse current, etc., current sensors with a quick response are indispensable. Here, we propose a high-frequency magnetoelectric current sensor, which consists of a PZT piezoelectric ceramic and Metglas amorphous alloy. The proposed sensor is designed to work under d15 thickness-shear mode, with the resonant frequency around 1.029 MHz. Furthermore, the proposed sensor is fabricated as a high-frequency magnetoelectric current sensor. A comparative experiment is carried out between the tunnel magnetoresistance sensor and the magnetoelectric sensor, in the aspect of high-frequency current detection up to 3 MHz. Our experimental results demonstrate that the d15 thickness-shear mode magnetoelectric sensor has great potential for high-frequency current detection in smart grids.

A Nomogram Based on Nutrition-Related Indicators and Computed Tomography Imaging Features for Predicting Preoperative Lymph Node Metastasis in Curatively Resected Esophagogastric Junction Adenocarcinoma.

BACKGROUNDS: Preoperative noninvasive tools to predict pretreatment lymph node metastasis (PLNM) status accurately for esophagogastric junction adenocarcinoma (EJA) are few. Thus, the authors aimed to construct a nomogram for predicting PLNM in curatively resected EJA. METHODS: This study enrolled 638 EJA patients who received curative surgery resection and divided them randomly (7:3) into training and validation groups. For nomogram construction, 26 candidate parameters involving 21 preoperative clinical laboratory blood nutrition-related indicators, computed tomography (CT)-reported tumor size, CT-reported PLNM, gender, age, and body mass index were screened. RESULTS: In the training group, Lasso regression included nine nutrition-related blood indicators in the PLNM-prediction nomogram. The PLNM prediction nomogram yielded an area under the receiver operating characteristic (ROC) curve of 0.741 (95 % confidence interval [CI], 0.697-0.781), which was better than that of the CT-reported PLNM (0.635; 95% CI 0.588-0.680; p < 0.0001). Application of the nomogram in the validation cohort still gave good discrimination (0.725 [95% CI 0.658-0.785] vs 0.634 [95% CI 0.563-0.700]; p = 0.0042). Good calibration and a net benefit were observed in both groups. CONCLUSIONS: This study presented a nomogram incorporating preoperative nutrition-related blood indicators and CT imaging features that might be used as a convenient tool to facilitate the preoperative individualized prediction of PLNM for patients with curatively resected EJA.

Effectiveness of virtual reality intervention on reducing the pain, anxiety and fear of needle-related procedures in paediatric patients: A systematic review and meta-analysis.

AIMS: To evaluate the effectiveness of virtual reality (VR) intervention in the management of pain, anxiety and fear in paediatric patients undergoing needle-related procedures. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: A librarian-designed search of the Cochrane Library, PubMed, Web of Science, EMBASE, CINAHL, CBM, CNKI, and Wanfang databases was conducted to identify research articles in English or Chinese on RCTs up to February 28, 2022. REVIEW METHODS: Two researchers independently screened eligible articles. The Cochrane Handbook for Systematic Reviews was used to assess the risk of bias in the included studies. A fixed- or random-effects meta-analysis model was used to determine the pooled mean difference based on the results of the heterogeneity test. RESULTS: A total of 2269 articles were initially screened. The meta-analysis included data from 27 studies representing 2224 participants. Compared with the non-VR group, the VR intervention group significantly reduced pain, anxiety, and fear in paediatric patients who underwent puncture-related procedures. Subgroup analysis showed that VR has advantages over conventional and other distraction methods. CONCLUSION: Paediatric patients undergoing needle-related procedures would benefit from VR interventions for pain, anxiety and fear management. IMPACT: VR intervention has the potential to reduce pain, anxiety and fear in paediatric patients undergoing puncture-related procedures. Future clinical interventions could incorporate VR into puncture procedures as an effective method to reduce negative emotions in children eligible for VR distractions. PATIENT OR PUBLIC CONTRIBUTION: Our paper is a systematic review and meta-analysis and such details don't apply to our work.

AgPdNFs and AuNOs@GO nanocomposites for T-2 toxin detection by catalytic hairpin assembly.

T-2 toxin is the most potent and toxic mycotoxin, produced by various Fusarium species that can potentially affect human health, and widely exists in field crops and stored grain. In this work, an electrochemical aptasensor with nonenzymatic signal amplification strategy for the detection of T-2 toxin is presented, using noble metal nanocomposites and catalytic hairpin assembly as signal amplification strategy. Silver palladium nanoflowers and gold octahedron nanoparticles@graphene oxide nanocomposites are used for synergistic amplification of electrical signals. Simultaneously, the catalytic hairpin assembly strategy based on artificial molecular technology was introduced to further amplify the signal. Under optimal conditions, T-2 toxin was measured within a linear concentration range 1 × 10-2 ~ 1 × 104 pg·mL-1 with an extremely low detection limit of 6.71 fg·mL-1. The aptasensor exhibited high sensitivity, good selectivity, satisfactory stability, and excellent reproducibility. Moreover, this method had high accuracy in detecting T-2 toxin in beer sample. The encouraging results show the potential application in foodstuff analysis. A dual signal amplification electrochemical biosensor for the detection of T-2 toxins was constructed, through the signal amplification of noble metal nanomaterials and CHA strategy.

Molecular Recognition-Triggered Aptazyme Sensor Using a Co-MOF@MCA Hybrid Nanostructure as Signal Labels for Adenosine Triphosphate Detection in Food Samples.

Developing rapid detection technology for adenosine triphosphate (ATP) is crucial in quality supervision and food safety. Herein, an electrochemical aptasensor based on an aptazyme-catalyzed signal amplification strategy is constructed for ATP detection using polyethyleneimine-functionalized molybdenum disulfide (PEI-MoS2)/Au@PtPd nanobipyramids (MoS2/Au@PtPd NBPs) as a modification material. Additionally, a novel kind of nitrogen-rich covalent organic framework (COF) is prepared using melamine and cyanuric acid (MCA). We synthesize MCA and the Co-based metal organic framework (Co-MOF) as the signal label. Due to the fact that π-π stacking interactions of Co-MOF@MCA can expand the load efficiency and surface concentration of the signal label, the signal response is an order of magnitude higher than that of Co-MOF or MCA as the signal label. Target ATP changes the conformation of the aptazyme, and it becomes activated. With the assistance of metal ions, the signal label is circularly cleaved, causing an amplification of the signal. Among them, MoS2/Au@PtPd NBPs have a large specific surface area and good electrical conductivity and can carry substantial DNA strands and amplify the redox signal of methylene blue (MB). Under optimal conditions, the aptasensor can detect ATP from 10 pM to 100 µM with a low limit of detection of 7.37 × 10-10 µM. Therefore, the novel aptasensor has extensive application prospects in quality supervision and food safety.

Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment.

Nicotinamide adenine dinucleotide (NAD) is the core of cellular energy metabolism. NAMPT, Sirtuins, PARP, CD38, and other molecules in this classic metabolic pathway affect many key cellular functions and are closely related to the occurrence and development of many diseases. In recent years, several studies have found that these molecules can regulate cell energy metabolism, promote the release of related cytokines, induce the expression of neoantigens, change the tumor immune microenvironment (TIME), and then play an anticancer role. Drugs targeting these molecules are under development or approved for clinical use. Although there are some side effects and drug resistance, the discovery of novel drugs, the development of combination therapies, and the application of new technologies provide solutions to these challenges and improve efficacy. This review presents the mechanisms of action of NAD pathway-related molecules in tumor immunity, advances in drug research, combination therapies, and some new technology-related therapies.

Antireflux surgery leads to durable improvement in laryngopharyngeal reflux symptoms.

BACKGROUND: Laryngopharyngeal reflux (LPR) symptoms are often present in patients with Gastroesophageal reflux disease (GERD). Whereas antireflux surgery (ARS) provides predictably excellent results in patients with typical GERD, those with atypical symptoms have variable outcomes. The goal of this study was to characterize the response of LPR symptoms to antireflux surgery. METHODS: Patients who underwent ARS between January 2009 and May 2020 were prospectively identified from a single institutional database. Patient-reported information on LPR symptoms was collected at standardized time points (preoperative and 2 weeks, 8 weeks, and 1 year postoperatively) using a validated Reflux Symptom Index (RSI) questionnaire. Patients were grouped by preoperative RSI score: ≤ 13 (normal) and > 13 (abnormal). Baseline characteristics were compared between groups using chi-square test or t-test. A mixed effects model was used to evaluate improvement in RSI scores. RESULTS: One hundred and seventy-six patients fulfilled inclusion criteria (mean age 57.8 years, 70% female, mean BMI 29.4). Patients with a preoperative RSI ≤ 13 (n = 61) and RSI > 13 (n = 115) were similar in age, BMI, primary reason for evaluation, DeMeester score, presence of esophagitis, and hiatal hernia (p > 0.05). The RSI > 13 group had more female patients (80 vs 52%, p = < 0.001), higher mean GERD-HRQL score, lower rates of PPI use, and normal esophageal motility. The RSI of all patients improved from a mean preoperative value of 19.2 to 7.8 (2 weeks), 6.1 (8 weeks), and 10.9 (1 year). Those with the highest preoperative scores (RSI > 30) had the best response to ARS. When analyzing individual symptoms, the most likely to improve included heartburn, hoarseness, and choking. CONCLUSIONS: In our study population, patients with LPR symptoms achieved a rapid and durable response to antireflux surgery. Those with higher preoperative RSI scores experienced the greatest improvement. Our data suggest that antireflux surgery is a viable treatment option for this patient population.

Virulence Characterization of Puccinia graminis f. sp. avenae and Resistance of Oat Cultivars in China.

Oat stem rust, caused by Puccinia graminis f. sp. avenae, is one of the most devastating diseases of oat. The most cost-effective and environmentally friendly strategy to control this disease is the use of resistant cultivars. However, P. graminis f. sp. avenae can overcome the resistance of cultivars by rapidly changing its virulence. Thus, information on the virulence of P. graminis f. sp. avenae populations and resistance of cultivars is critical to control the disease. The current study was conducted to monitor the virulence composition and dynamics of the P. graminis f. sp. avenae population in China and to evaluate resistance of oat cultivars. Oat leaves naturally infected by P. graminis f. sp. avenae were collected in 2018 and 2019, and 159 isolates were derived from single uredinia. The isolates were tested on 12 international differential lines, and eight races, TJJ, TBD, TJB, TJD, TJL, TJN, TGD, and TKN, were identified for the first time in China. The predominant race was TJD, virulent against Pg1, Pg2, Pg3, Pg4, Pg8, Pg9, and Pg15, accounting for 35.8 and 37.8% in 2018 and 2019, respectively. The sub-predominant races were TJN (30.2% in 2018, 28.3% in 2019) and TKN (20.8% in 2018, 12.3% in 2019). All isolates were virulent to Pg1, Pg2, Pg3, and Pg4, and avirulent to Pg6 and Pg16. The three predominant races (TJD, TJN, and TKN) were used to evaluate resistance in 30 Chinese oat cultivars at the seedling and adult plant stages. Five cultivars, Bayan 1, Baiyan 2, Baiyan 3, Baiyan 5, and Baiyan 9, were highly resistant to the three races at both seedling and adult plant stages. The results of the virulences and frequencies of P. graminis f. sp. avenae races and the resistant cultivars will be useful in elucidating the pathogen migration and evolution and for breeding oat cultivars with stem rust resistance.

Evidence-Based Message Strategies to Increase Public Support for State Investment in Early Childhood Education: Results from a Longitudinal Panel Experiment.

Policy Points  Investments in early childhood education can have long-lasting influence on health and well-being at later stages of the life course.  Widespread public support and strategies to counter opposition will be critical to the future political feasibility of enhancing early childhood policies and programs.  Simple advocacy messages emphasizing the need for affordable, accessible, high-quality childcare for all can increase public support for state investments in these policies.  Policy narratives (short stories with a setting, characters, and a plot that unfolds over time and offers a policy solution to a social problem) that describe structural barriers to childcare and policy solutions to address these barriers may be particularly effective to persuade individuals inclined to oppose such policies to become supportive.  Inoculation messages (messages designed to prepare audiences for encountering and building resistance to opposing messages) may protect favorable childcare policy attitudes in the face of oppositional messaging. CONTEXT: Early childhood education (ECE) programs enhance the health and social well-being of children and families. This preregistered, randomized, controlled study tested the effectiveness of communication strategies to increase public support for state investments in affordable, accessible, and high-quality childcare for all. METHODS: At time 1 (August-September 2019), we randomly assigned members of an online research panel (n  =  4,363) to read one of four messages promoting state investment in childcare policies and programs, or to a no-exposure control group. Messages included an argument-based message ("simple pro-policy"), a message preparing audiences for encountering and building resistance to opposing messages ("inoculation"), a story illustrating the structural nature of the problem and solution ("narrative"), and both inoculation and narrative messages ("combined"). At time 2 (two weeks later) a subset of respondents (n  =  1,436) read an oppositional anti-policy message and, in two conditions, another narrative or inoculation message. Ordinary least squares regression compared groups' levels of support for state investment in childcare policies and programs. FINDINGS: As hypothesized, respondents who read the narrative message had higher support for state investment in childcare policies than those who read the inoculation message or those in the no-exposure control group at time 1. Among respondents who were initially opposed to such investments, those who read the narrative had greater support than respondents who read the simple pro-policy message. Those who received the inoculation message at time 2 were more resistant to the anti-policy message than respondents who did not receive such a message, but effects from exposures to strategic messages at time 1 did not persist at follow-up. CONCLUSIONS: Results offer guidance for policy advocates seeking to increase public support for early childhood policies and programs and could inform broader efforts to promote high-value policies with potential to improve population health.

The Early Diagnostic Value of Serum Interleukin-8 in Esophagogastric Junction Adenocarcinoma.

BACKGROUND: Esophagogastric junction adenocarcinoma (EJA) is one of the most common malignant tumors of digestive tract with high mortality worldwide. Given a lack of early diagnosis biomarkers, the prognosis of EJA is poor. Non-invasive biomarkers for early-stage EJA are urgently required. OBJECTIVE: We aimed at evaluating the early diagnostic value of serum interleukin-8 (IL-8) level in EJA patients. METHODS: The IL-8 mRNA expression data were analyzed based on the stomach cardia adenocarcinoma samples of The Cancer Genome Atlas (TCGA) database. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of serum IL-8 in 95 EJA patients and 95 normal controls enrolled from 2 different cancer hospitals. The diagnostic accuracy of serum IL-8 was evaluated by applying Mann-Whitney U test and receiver operating characteristic (ROC) curve. RESULTS: The mRNA expression levels and serum levels of IL-8 in EJA group were significantly higher than those in the normal group (all P < 0.001). The areas under the ROC curve (AUC) were 0.661 (95% CI, 0.583-0.740) and 0.745 (95% CI, 0.606-0.885), with the sensitivities of 43.2% (95% CI, 33.2%-53.7%) and 66.7% (95% CI, 46.0%-82.8%) and the specificities of 87.4% (95% CI, 78.6%-93.1%) in EJA group and early-EJA group, respectively, when the optimal cutoff value was 109.086 pg/mL. The clinical data analysis showed there were significant correlations between patient genders, depth of invasion, lymph node metastasis, TNM stage and the serum level of IL-8 (all P < 0.05). CONCLUSIONS: Serum IL-8 represents a potential diagnostic biomarker to identify early-stage EJA.

Prevalence of High-Grade Anal Dysplasia and Anal Cancer in Veterans Living With HIV and CD4/CD8 Ratio as a Marker For Increased Risk: A Regional Retrospective Cohort Study.

BACKGROUND: The Department of Veterans Affairs cares for the largest population of patients with HIV of any healthcare system in the United States. Screening for anal dysplasia/cancer is recommended for all veterans with HIV. Exams are invasive, burdensome, and resource intensive. We currently lack markers of disease to tailor screening. OBJECTIVE: The purpose of this study was to establish the prevalence of advanced anal disease (high-grade dysplasia and anal cancer) and to determine whether CD4/CD8 ratio correlates with risk. DESIGN: This was a retrospective regional cohort study of veterans with HIV. SETTINGS: The study was conducted at eight medical centers between 2001 and 2019. PATIENTS: Patients with advanced disease were compared with patients with nonadvanced anal pathology. MAIN OUTCOME MEASURES: Logistic regression modeling was used to estimate adjusted odds of disease as a function of CD4/CD8. Lowest (nadir) CD4/CD8 and nearest CD4/CD8 ratio in each cohort were evaluated. RESULTS: A total of 2267 veterans were included. Fifteen percent had anal pathology (112 with advanced disease (37 cancer and 75 high-grade), 222 with nonadvanced disease). Nadir and nearest ratio were lower in patients with advanced disease versus nonadvanced (0.24 vs 0.45 (p < 0.001) and 0.50 vs 0.88 (p < 0.001)). In adjusted models, a 1-unit increase in nadir or nearest ratio conferred decreased risk of advanced disease (OR = 0.19 (95% CI, 0.07-0.53); p < 0.001; OR = 0.22 (95% CI, 0.12-0.43); p < 0.001). Using a minimum sensitivity analysis, a cutoff nadir ratio of 0.42 or nearest ratio of 0.76 could be used to risk stratify. LIMITATIONS: This was a retrospective analysis with a low screening rate. CONCLUSIONS: In a regional cohort of veterans with HIV, 15% were formally assessed for anal dysplasia. Advanced anal disease was present in 33% of those screened, 5% of the HIV-positive population. A strong predictor of advanced disease in this cohort is the CD4/CD8 ratio, which is a promising marker to stratify screening practices. Risk stratification using CD4/CD8 has the potential to decrease burdensome invasive examinations for low-risk patients and to intensify examinations for those at high risk. See Video Abstract at http://links.lww.com/DCR/B528. PREVALENCIA DE DISPLASIA ANAL DE ALTO GRADO Y CNCER ANAL EN VETERANOS QUE VIVEN CON EL VIH Y LA RELACIN CD / CD COMO MARCADOR DE MAYOR RIESGO UN ESTUDIO DE COHORTE REGIONAL RETROSPECTIVE: ANTECEDENTES:El Departamento de Asuntos de Veteranos atiende a la población más grande de pacientes con el virus de inmunodeficiencia humana (VIH) de cualquier sistema de salud en los Estados Unidos. Se recomienda la detección de displasia / cáncer anal para todos los veteranos con VIH. Los exámenes son invasivos, onerosos y requieren muchos recursos. Actualmente carecemos de marcadores de enfermedad para adaptar la detección.OBJETIVO:Establecer la prevalencia de enfermedad anal avanzada (displasia de alto grado y cáncer anal) y determinar si la relación CD4 / CD8 se correlaciona con el riesgo.DISEÑO:Estudio de cohorte regional retrospectivo de veteranos con VIH.AJUSTE:Ocho centros médicos entre 2001-2019.PACIENTES:Se comparó a pacientes con enfermedad avanzada con pacientes con patología anal no avanzada.PRINCIPALES MEDIDAS DE RESULTADO:Se utilizó un modelo de regresión logística para estimar las probabilidades ajustadas de enfermedad en función de CD4 / CD8. Se evaluó la relación CD4 / CD8 más baja (nadir) y la relación CD4 / CD8 más cercana en cada cohorte.RESULTADOS:Se incluyeron un total de 2267 veteranos. El 15% tenía patología anal (112 enfermedad avanzada (37 cáncer, 75 de alto grado), 222 enfermedad no avanzada). El nadir y el cociente más cercano fueron menores en los pacientes con enfermedad avanzada frente a los no avanzados (0,24 frente a 0,45 (p <0,001) y 0,50 frente a 0,88 (p <0,001)), respectivamente. En modelos ajustados, el aumento de una unidad en el nadir o el cociente más cercano confirió una disminución del riesgo de enfermedad avanzada (OR 0,19 (IC del 95%: 0,07, 0,53, p <0,001)) y (OR 0,22 (IC del 95%: 0,12, 0,43, p <0,001))), respectivamente. Utilizando un análisis de sensibilidad mínima, se podría utilizar un cociente del nadir de corte de 0,42 o el cociente más cercano de 0,76 para estratificar el riesgo.LIMITACIONES:Análisis retrospectivo con una tasa de detección baja.CONCLUSIONES:En una cohorte regional de veteranos con VIH, el 15% fueron evaluados formalmente por displasia anal. La enfermedad anal avanzada estuvo presente en el 33% de los examinados, el 5% de la población VIH +. Un fuerte predictor de enfermedad avanzada en esta cohorte es la relación CD4 / CD8, que es un marcador prometedor para estratificar las prácticas de detección. La estratificación del riesgo usando CD4 / CD8 tiene el potencial de disminuir los exámenes invasivos onerosos para los pacientes de bajo riesgo e intensificar los exámenes para los de alto riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B528.

Healthcare Resource Utilization in Inguinal Hernia Repair: A Three-Year Cost Evaluation of Truven Health Marketscan Research Databases.

BACKGROUND: Inguinal hernia repair is the most commonly performed elective operation in the United States, with over 800,000 cases annually. While clinical outcomes comparing laparoscopic versus open techniques have been well documented, there is little data comparing costs associated with these techniques. This study evaluates the cost of healthcare resources during the 90-d postoperative period following inguinal hernia repair. METHODS: We analyzed data from the Truven Health MarketScan Research Databases. Adult patients with an ICD-9 or CPT code for inguinal hernia repair from 2012 to 2014 were included. Patients with continuous enrollment for 6 mo prior to surgery and 6 mo after surgery were analyzed. Related healthcare service costs (readmission and/or ER visit and/or outpatient visit) were calculated by clinical classification software and generalized linear modeling was used to compare healthcare utilization between groups. RESULTS: 124,582 cases were identified (open = 84,535; lap = 40,047). Index surgery cost was 41% higher in laparoscopic cases. The cost for readmission was close to $25,000 and similar between both groups, but the laparoscopic group were 12% less likely to be readmitted for surgical complications within 90-d when compared to the open group. Cost of bilateral laparoscopic repair is less than that of serial unilateral open repairs. CONCLUSION: Laparoscopic inguinal hernia repair carries a higher index surgery cost than open repair. However, open repair has an increased rate of readmission. To maximize value, efforts should be directed at minimizing readmissions and improving identification of bilateral hernias at the time of initial presentation.

Both gastric electrical stimulation and pyloric surgery offer long-term symptom improvement in patients with gastroparesis.

BACKGROUND: Gastroparesis (GP) is hallmarked by nausea, vomiting, and early satiety. While dietary and medical therapy are the mainstay of treatment, surgery has been used to palliate symptoms. Two established first-line surgical options are gastric electrostimulation (GES) and pyloric procedures (PP) including pyloroplasty or pyloromyotomy. We sought to compare these modalities' improvement in Gastroparesis cardinal symptom index (GCSI) subscores and potential predictors of therapy failure. METHODS: All patients undergoing surgery at a single institution were prospectively identified and separated by surgery: GES, PP, or combined GESPP. GCSI was collected preoperatively, at 6 weeks and 1 year. Postoperative GCSI score over 2.5 or receipt of another gastroparesis operation were considered treatment failures. Groups were compared using Pearson's chi-squared and Kruskal-Wallis one-way ANOVA. RESULTS: Eighty-two patients were included: 18 GES, 51 PP, and 13 GESPP. Mean age was 44, BMI was 26.7, and 80% were female. Preoperative GCSI was 3.7. The PP group was older with more postsurgical gastroparesis. More patients with diabetes underwent GESPP. Preoperative symptom scores and gastric emptying were similar among all groups. All surgical therapies resulted in a significantly improved GCSI and nausea/vomiting subscore at 6 weeks and 1 year. Bloating improved initially, but relapsed in the GES and GESPP group. Satiety improved initially, but relapsed in the PP group. Fifty-nine (72%) had surgical success. Ten underwent additional surgery (7 crossed into the GESPP group, 3 underwent gastric resection). Treatment failures had higher preoperative GCSI, bloating, and satiety scores. Treatment failures and successes had similar preoperative gastric emptying. CONCLUSIONS: Both gastric electrical stimulation and pyloric surgery are successful gastroparesis treatments, with durable improvement in nausea and vomiting. Choice of operation should be guided by patient characteristics and discussion of surgical risks and benefits. Combination GESPP does not appear to confer an advantage over GES or PP alone.

Phone follow-up after inguinal hernia repair.

BACKGROUND: Typically, in-person follow-up in clinic is utilized after outpatient inguinal hernia repair. Studies have shown that phone follow-up may be successfully used for the detection of postoperative hernia recurrences. However, no studies have evaluated the detection rates of other postoperative complications, such as emergency department visits and readmissions, with the utilization of phone follow-up after inguinal hernia repair. The objective of our study was to investigate the safety of a phone follow-up care pathway following elective, outpatient inguinal hernia repair. METHODS: In this retrospective cohort study, adult patients who underwent elective, outpatient inguinal hernia repair between 2013 and 2019 at a large academic health system in the Midwest United States were identified from the electronic health record. Patients were categorized by type of postoperative follow-up: in-person or phone follow-up. Baseline demographics, operative, and postoperative data were compared between follow-up groups. Multivariable logistic regression was performed to investigate predictors of having any related emergency department (ED) visit/readmission/reoperation within 90 days. RESULTS: We included 2009 patients who underwent elective inguinal hernia repair during the study period. 321 patients had in-person follow-up only, while 1,688 patients had phone follow-up. There was a higher rate of laparoscopic repair in the phone follow-up group (85.4% vs. 53.0% for in-person follow-up). There were no differences in rates of related 90-day ED visits, readmissions, and reoperations between the phone and in-person follow-up groups. On multivariable logistic regression, receipt of phone follow-up was not a predictor of having 90-day ED visits, readmissions, or reoperations (OR 1.30, 95% CI [0.83, 2.05]). CONCLUSIONS: Patients who underwent phone follow-up had similarly low rates of adverse outcomes to those with in-person follow-up. Phone follow-up protocols may be implemented as an alternative for patients and provide a means to decrease healthcare utilization following inguinal hernia repair.