Salivary Glands and Viral Pathogenesis.

The oral cavity is an epidemiologically relevant route of viral transmission due to the shedding of viruses in saliva. With advancements in salivary diagnostics, an increasing number of viruses have been detected. However, the anatomic source of virus in saliva is still largely unknown. Some viruses have a well-established tropism for the salivary glands (SGs), and recent studies have emphasized the importance of the glands as potential reservoirs for infectious viruses. Viral infections of the SGs have been linked to acute and chronic SG pathology and may be associated with SG dysfunction, with phenotypes similar to those seen in SjÖgren's disease (SjD), an autoimmune condition that affects the salivary and lacrimal glands. Understanding the breadth of viruses that infect the SG and the conserved or distinct host responses to these infections may provide insights into the pathogenesis of virus-mediated SG diseases. There is a need for further research to fully understand the molecular mechanisms by which viruses enter and replicate in the glands, their physiologic impact on SG function, and whether the SGs can serve as a long-term reservoir for infectious viral particles. The purpose of this review is to highlight a group of viruses that infect the salivary gland: hepatitis C virus, hepatitis D virus, severe acute respiratory syndrome coronavirus 2, enteric viruses, human T-cell leukemia virus type I, human immunodeficiency virus, human cytomegalovirus, and BK polyomavirus. We focus on the effects of viral infection on salivary gland (SG) inflammation, function, and its association with SjD.

Unlocking the Hidden Dimensions of Cancer Care: Cross-Cultural Adaptation and Feasibility Study of ESAS-FS, Assessing Spiritual Pain and Financial Distress in a Spanish-speaking Population with Advanced Cancer.

INTRODUCTION: Spiritual pain and financial distress are two important dimensions of cancer care that are often overlooked. Both dimensions can have a significant impact on the quality of life of patients with cancer and their families. METHODS: This study conducted a cross-cultural adaptation, feasibility study, and psychometric properties of the Edmonton Symptom Assessment System-Financial and Spiritual (ESAS-FS) in a Spanish-speaking population with advanced cancer. The ESAS-FS is a patient-reported outcome measure that assesses 12 symptoms, including spiritual pain and financial distress. RESULTS: In the cross-cultural adaptation process, the terms "spiritual pain" and "financial distress" were refined to "sufrimiento espiritual" and "preocupación por asuntos económicos" respectively, with strong professional consensus and high patients' acceptancy (relevant questions 80%, appropriate terms 91%). A cohort of 100 onco-hematologic patients revealed that 70% experienced spiritual pain (mean 2.9/10), while 49% reported financial distress (mean 2.2/10). Symptomatic analyses illustrated significant associations of spiritual pain with various symptoms like fatigue, drowsiness, and depression. Similarly, financial distress correlated notably with drowsiness, depression, and anxiety. Moreover, a distinct correlation was observed between spiritual pain and financial distress. CONCLUSION: The findings of this study suggest that the ESAS-FS is a valuable tool for assessing spiritual pain and financial distress in Spanish-speaking patients with advanced cancer. The tool can be used to identify patients who are experiencing these dimensions of distress and to provide them with appropriate care.

Virtual reality exposure with vibrotactile stimulation for the treatment of fear of flying: A pilot study.

BACKGROUND AND OBJECTIVES: Virtual reality (VR) interventions are becoming more prevalent in treating fear of flying (FoF). Since multisensory stimulation can enhance the sense of presence in a virtual environment, the present study compared virtual reality exposure with and without vibrotactile cues to determine its contribution to the realism of the virtual experience. METHODS: A repeated measures design was used. Thirty-one participants were exposed to two experimental conditions with a minimum of a one-week interval between them: one in which participants were exposed to the virtual environment with vibrotactile cues (smart chair, SC), and another in which participants were exposed to the virtual environment without vibrotactile cues (ordinary chair, OC). The administration order of both conditions was counterbalanced to avoid possible order effects. RESULTS: Participants felt higher levels of sense of presence when using the SC than the OC. However, the addition of vibrotactile stimulation partially influenced experienced anxiety. Some personality traits were also associated with participants' sense of presence and anxiety responses during the exposure. LIMITATIONS: The sample size was smaller than required. Moreover, only self-reported measures were used. Finally, a roller coaster instead of an airplane scenario was used for the exposure, which might not have been suitable enough for provoking anxiety in participants with FoF. CONCLUSIONS: Vibrotactile cues enhanced the sense of presence. However, the addition of vibrotactile stimulation did not have a consistent effect on anxiety experienced during exposure. Therefore, the benefits of incorporating vibrotactile cues in virtual reality environments for exposure therapy are not clear.

Financial toxicity in cancer patients and subsequent risk of repeat acute care utilization.

Background: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization. Methods: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, material, and coping FT burdens). All AC visits, including emergency department (ED) and unplanned hospital admissions, within 1-year follow-up were identified. The association between the severity of FT and the total number of AC visits was tested using Poisson regression models. Results: A total of 18.6% (n = 42) of patients had any AC visit, comprising 64.3% hospital admissions and 35.7% ED visits. Global FT burden was associated with the risk of repeat AC visits within 1-year follow-up (RR = 1.17, 95% CI 1.07-1.29, P < 0.001 for every unit increase), even after adjusting for sociodemographic and disease covariates. When examining subdimensions of FT, the burden of depleted FT coping resources (coping FT) was strongly associated with the risk of repeat AC visits (RR = 1.27, 95% CI 1.15-1.40, P < 0.001) while material FT burden showed a trend toward association (RR = 1.07, 95% CI 0.99-1.15, P = 0.07). Conclusion: In this prospective study of acute oncology care utilization outcomes among adult cancer patients, FT was a predictor of a higher burden of acute care visits. Patients with severely depleted material and also practical and social coping resources were at particular risk for repeated visits. Future studies are needed to identify whether early FT screening and intervention efforts may help to mitigate urgent acute care utilization burdens.

Two rare cancers of the exocrine pancreas: to treat or not to treat like ductal adenocarcinoma?

Pancreatic cancer is an aggressive malignancy with increasing incidence. Pancreatic ductal adenocarcinoma (PDAC) accounts for > 90% of pancreatic cancer diagnoses, while other exocrine tumors are much rarer. In this review, we have focused on two rare cancers of the exocrine pancreas: adenosquamous carcinoma of the pancreas (ASCP) and pancreatic acinar cell carcinoma (PACC). The latest findings regarding their cellular and molecular pathology, clinical characteristics, prognosis, and clinical management are discussed. New genetic and transcriptomic data suggest that ASCP is related to or overlaps with the basal transcriptomic subtype of PDAC. These tumors are highly aggressive and driven by activated KRAS and MYC expression. Clinical outcomes remain poor and effective treatments are limited. PACC has no morphologic or genetic resemblance to PDAC and more favorable outcomes. Early stage PACC patients have improved survival with surgical resection and patients with advanced disease benefit most from platinum- or fluoropyrimidine-containing chemotherapy. Frequency of actionable genetic mutations is high in this disease and case reports suggest good outcomes when matched therapy is given. Dedicated clinical studies examining ASCP and PACC are limited and difficult to accrue. Further research is needed to define optimal clinical management for these rare diseases.

Hispanic Individuals are Underrepresented in Phase III Clinical Trials for Advanced Liver Cancer in the United States.

Background: Hispanic individuals comprise the second-largest subpopulation after non-Hispanic White (NHW) individuals in the United States (US). We compared the relative contribution of Hispanic individuals to the ten most common causes of cancer-related deaths and studied enrollment of Hispanic patients in multinational phase III advanced liver cancer trials with the aim to investigate whether racial subpopulations are adequately represented in liver cancer trials. Methods: Relative cancer incidence rates in Hispanic individuals, NHW individuals, non-Hispanic black (NHB) individuals, and Asian individuals were obtained from both the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results Program and the Center for Disease Control and Prevention (CDC), United States Cancer Statistics (USCS) database. Searching PubMed, Embase, and Web of Science, we identified phase III clinical trials studying advanced liver cancer in the last ten years and collected enrollment for each race and ethnicity. Incidence rates of liver cancer and enrollment rates in phase III trials were compared by race and ethnicity. Results: The cancer type with the relatively highest contribution of Hispanic individuals was liver cancer. From 2015 to 2019, 15.1% of liver cancer cases occurred in Hispanic individuals compared to 12.5% in Asian individuals, 11% in NHB individuals, and 7.5% in NHW individuals. In the last ten years, Hispanic individuals made up 1.6% of patients and NHB individuals 1.3% of patients included in phase III multinational liver cancer trials, compared to 31% NHW individuals and 47% Asian individuals. Conclusion: Hispanic individuals are disproportionately underrepresented in multinational phase III clinical trials for liver cancer despite having the highest relative incidence rates among the four major racial or ethnic groups in the US.

Definitive local therapy for T4 prostate cancer associated with improved local control and survival.

OBJECTIVES: To evaluate patients with clinical (c)T4 prostate cancer (PCa), which represent both a heterogenous and understudied population, who often present with locally advanced disease and obstructive symptoms causing significant morbidity and mortality. We analysed whether receiving definitive local therapy influenced symptomatic and oncological outcomes. METHODS: Retrospective analysis of 154 patients with cT4 PCa treated at a single institution in 1996-2020. Systemic therapy with or without local treatment (surgery, radiotherapy [RT], or both). Uni- and multivariate analyses of associations between clinicopathological features (including obstructive symptoms) and receipt of local therapy on overall survival (OS) and disease control were done with Cox regression. RESULTS: The median follow-up time was 5.9 years. Most patients had adenocarcinoma (88%), Gleason score 9-10 (77%), and median baseline prostate-specific antigen (PSA) of 20 ng/mL; most (54%) had metastatic cT4N0-1M1 disease; 24% regionally advanced cT4N1M0, and 22% localised cT4N0M0. Local therapies were RT (n = 44), surgery (n = 28), or both (n = nine). Local therapy was associated with improved OS (hazard ratio [HR] 0.3, P < 0.001), longer freedom from local recurrence (HR 0.39, P = 0.002), less local progression (HR 0.41, P = 0.02), fewer obstructive symptoms with progression (HR 0.31, P = 0.01), and less death from local disease (HR 0.25, P = 0.002). On multivariate, local therapy was associated with improved survival (HR 0.58, P = 0.02), and metastatic disease (HR 2.93, P < 0.001) or high-risk pathology (HR 2.05, P = 0.03) was associated with worse survival. CONCLUSION: Definitive local therapy for cT4 PCa was associated with improved symptomatic outcomes and survival even among men with metastatic disease. Pending prospective evaluation, these findings support definitive treatment with local therapy for cT4 disease in select cases.

Nuevos biomarcadores de cáncer de pulmón basados en miRNA / [New biomarkers of lung cancer based on miRNA]

Objetivo: Determinar si existen diferencias de expresión entre los miRNA de tejido sano y tumoral de adenocarcinoma de pulmón y carcinoma epidermoide de pulmón, con lo que podrían ser usados como biomarcadores. Material y métodos: Se ha extraído y secuenciado el miRNA de tejido tumoral y sano adyacente de muestras de adenocarcinoma y carcinoma epidermoide de dieciséis pacientes intervenidos en el Hospital Regional de Málaga. Esas secuencias se han analizado con un flujo de trabajo bioinformático específico que conlleva varios pasos: 1o) preprocesar las lecturas, 2o) mapearlas sobre el genoma humano de referencia, 3o) determinar la expresión de los miRNA en cada una de las muestras, 4o) calcular su expresión diferencial entre el tejido sano y el tumoral de cada paciente, 5o) realizar un análisis funcional de los miRNA encontrados. Resultados: Hemos analizado los miRNA con expresión diferencial en cada uno de los tipos histológicos estudiados. El análisis del adenocarcinoma y carcinoma epidermoide de pulmón ha dado como resultado un total de 82 y 360 miRNA diferencialmente expresados (miDE), respectivamente. Hemos encontrado 50 miRNA comunes a los dos tipos histológicos, y su análisis funcional indica que están implicados en el crecimiento, desarrollo y movimiento celular, que se produce tanto en la célula normal como en el cáncer. Conclusiones: Los miDE encontrados son una fuente de biomarcadores, al tener una reprogramación específica en cáncer, y ser obtenibles de forma no invasiva. (AU)

Objective: Determine if there are differences in expression between the miRNAs of healthy and tumor tissue of lung adenocarcinoma and squamous cell carcinoma of the lung, with which they could be used as biomarkers. Material and methods: miRNA has been extracted and sequenced from tumor and adjacent healthy tissue from samples of adenocarcinoma and squamous cell carcinoma from sixteen patients operated at the Regional Hospital of Malaga. These sequences have been analyzed with a specific bioinformatic workflow that involves several steps: 1st) preprocessing the reads, 2nd) mapping them onto the reference human genome, 3rd) determining the expression of the miRNAs in each of the samples, 4th) calculate its differential expression between the healthy and tumor tissue of each patient, 5th) perform a functional analysis of the miRNAs found. Results: We have analyzed the miRNAs with differential expression in each of the histological types studied. Analysis of adenocarcinoma and squamous cell carcinoma of the lung has resulted in a total of 82 and 360 differentially expressed miRNAs (miDE), respectively. We have found 50 miRNAs common to the two histological types, and their functional analysis indicates that they are involved in cell growth, development and movement, which occurs both in normal cells and in cancer. Conclusions: The miDEs found are a source of biomarkers, as they have a specific reprogramming in cancer, and are obtainable non-invasively. (AU)

Radiological Structured Report Integrated with Quantitative Imaging Biomarkers and Qualitative Scoring Systems.

The benefits of structured reporting (SR) in radiology are well-known and have been widely described. However, there are limitations that must be overcome. Radiologists may be reluctant to change the conventional way of reporting. Error rates could potentially increase if SR is used improperly. Interruption of the visual search pattern by keeping the eyes focused on the report rather than the images may increase reporting time. Templates that include unnecessary or irrelevant information may undermine the consistency of the report. Last, the lack of support for multiple languages may hamper the adaptation of the report to the target audience. This work aims to mitigate these limitations with a web-based structured reporting system based on templates. By including field validators and logical rules, the system avoids reporting mistakes and allows to automatically calculate values and radiological qualitative scores. The system can manage quantitative information from imaging biomarkers, combining this with qualitative radiological information usually present in the structured report. It manages SR templates as plugins (IHE MRRT compliant and compatible with RSNA's Radreport templates), ensures a seamless integration with PACS/RIS systems, and adapts the report to the target audience by means of natural language extracts generated in multiple languages. We describe a use case of SR template for prostate cancer including PI-RADS 2.1 scoring system and imaging biomarkers. For the time being, the system comprises 24 SR templates and provides service in 37 hospitals and healthcare institutions, endorsing the success of this contribution to mitigate some of the limitations of the SR.

Stereotactic ablative radiation therapy for renal cell carcinoma with inferior vena cava tumor thrombus.

BACKGROUND: Inferior vena cava tumor thrombus (IVC-TT) is a rare yet deadly sequel of renal cell carcinoma (RCC) with limited treatment options. The standard treatment is extirpative surgery, which has high rates of morbidity and mortality. As a result, many patients are unfit or unwilling to undergo surgery and face poor prognosis. This stresses the need for alternative options for local disease control. Our study aims to assess the feasibility and oncological outcomes of stereotactic ablative radiation (SAbR) for IVC-TT. METHODS: A retrospective study reviewing six leading international institutions' experience in treating RCC with IVC-TT with SAbR. Primary end point was overall survival using Kaplan-Meier. RESULTS: Fifteen patients were included in the cohort. Over 50% of patients had high level IVC-TT (level III or IV), 66.7% had metastatic disease. Most eschewed surgery due to high surgical risk (7/15) or recurrent thrombus (3/15). All patients received SAbR to the IVC-TT with a median biologically equivalent dose (BED10) of 72 Gy (range: 37.5-100.8) delivered in a median of 5 fractions (range 1-5). Median overall survival was 34 months. Radiographic response was observed in 58% of patients. Symptom palliation was recorded in all patients receiving SAbR for this indication. Only grade 1 to 2 adverse events were noted. CONCLUSIONS: SAbR for IVC-TT appears feasible and safe. In patients who are not candidates for surgery, SAbR may palliate symptoms and improve outcomes. SAbR may be considered as part of a multimodal treatment approach for patients with RCC IVC-TT.

HCV Infection Alters Salivary Gland Histology and Saliva Composition.

Hepatitis C virus (HCV) infection is the most common blood-borne chronic infection in the United States. Chronic lymphocytic sialadenitis and sicca syndrome have been reported in chronic HCV infection. Up to 55% of these patients may have xerostomia; the mechanisms of the xerostomia and salivary gland (SG) hypofunction remain controversial. The objectives of this project are to establish if xerostomia associates with SG and HCV infection and to characterize the structural changes in SG and saliva composition. Eighteen HCV-infected patients with xerostomia were evaluated for SG dysfunction; 6 of these patients (patients 1-6) were further evaluated for SG histopathological changes and changes in saliva composition. The techniques used include clinical and laboratory assessment, SG ultrasonography, histological evaluation, sialochemical and proteomics analysis, and RNA in situ hybridization. All the HCV patients had low saliva flow, chronic sialadenitis, and SG fibrosis and lacked Sjögren syndrome (SS) characteristic autoantibodies. Further evaluation of a subgroup of 6 HCV patients (patients 1-6) demonstrated diffuse lymphocytic infiltrates that are predominantly CD8+ T cells with a significant increase in the number of inflammatory cells. Alcian Blue/periodic acid-Schiff staining showed significant changes in the ratio and intensity of the acinar secretory units of the HCV patients' minor SG. The submandibular glands showed significant ultrasonographic abnormalities in the parenchyma relative to the parotid glands. Significant changes were also observed in the concentration of sodium and mucin 5b. Although no significant correlation was observed between the lymphocytic infiltrates and the years of HCV chronic infection, a positive correlation was observed between HCV RNA-positive epithelial cells and the years of HCV infection. Consistent with the low saliva flow and xerostomia, patients showed changes in several markers of SG acinar and ductal function. Changes in the composition of the saliva suggest that HCV infection can cause xerostomia by mechanisms distinct from SS.

Differences in Time Burden across Local Therapy Strategies for Early-stage Breast Cancer.

"Time burden" (time required during treatment) is relevant when choosing a local therapy option for early-stage breast cancer but has not been rigorously studied. We compared the time burden for three common local therapies for breast cancer: (1) lumpectomy plus whole-breast irradiation (Lump+WBI), (2) mastectomy without radiation or reconstruction (Mast alone), and (3) mastectomy without radiation but with reconstruction (Mast+Recon). METHODS: Using the MarketScan database, we identified 35,406 breast cancer patients treated from 2000 to 2011 with these local therapies. We quantified the total time burden as the sum of inpatient days (inpatient-days), outpatient days excluding radiation fractions (outpatient-days), and radiation fractions (radiation-days) in the first two years postdiagnosis. Multivariable regression evaluated the effect of local therapy on inpatient-days and outpatient-days adjusted for patient and treatment covariates. RESULTS: Adjusted mean number of inpatient-days was 1.0 for Lump+WBI, 2.0 for Mast alone, and 3.1 for Mast+Recon (P < 0.001). Adjusted mean number of outpatient-days was 42.9 for Lump+WBI, 42.2 for Mast alone, and 45.8 for Mast+Recon (P < 0.001). The mean number of radiation-days for Lump+WBI was 32.4. Compared with Mast+Recon (48.9 days), total adjusted time burden was 4.7 days shorter for Mast alone (44.2 days) and 27.4 days longer for Lump+WBI (76.3 days). However, use of a 15 fraction WBI regimen would reduce the time burden differential between Lump+WBI and Mast+Recon to just 10.0 days. CONCLUSIONS: Although Mast+Recon confers the highest inpatient and outpatient time burden, Lump+WBI carries the highest total time burden. Increased use of hypofractionation will reduce the total time burden for Lump+WBI.

On the evolution of the exclusion zone produced by hydrophilic surfaces: A contracted description.

After exciting scientific debates about its nature, the development of the exclusion zone, a region near hydrophilic surfaces from which charged colloidal particles are strongly expelled, has been finally traced back to the diffusiophoresis produced by unbalanced ion gradients. This was done by numerically solving the coupled Poisson equation for electrostatics, the two stationary Stokes equations for low Reynolds numbers in incompressible fluids, and the Nernst-Planck equation for mass transport. Recently, it has also been claimed that the leading mechanism behind the diffusiophoretic phenomenon is electrophoresis [Esplandiu et al., Soft Matter 16, 3717 (2020)]. In this paper, we analyze the evolution of the exclusion zone based on a one-component interaction model at the Langevin equation level, which leads to simple analytical expressions instead of the complex numerical scheme of previous works, yet being consistent with it. We manage to reproduce the evolution of the exclusion zone width and the mean-square displacements of colloidal particles we measure near Nafion, a perfluorinated polymer membrane material, along with all characteristic time regimes, in a unified way. Our findings are also strongly supported by complementary experiments using two parallel planar conductors kept at a fixed voltage, mimicking the hydrophilic surfaces, and some computer simulations.

Sensitivity of Psychosocial Distress Screening to Identify Cancer Patients at Risk for Financial Hardship During Care Delivery.

PURPOSE: Patients with cancer frequently encounter financial hardship, yet systematic strategies to identify at-risk patients are not established in care delivery. We assessed sensitivity of distress-based screening to identify patients with cancer-related financial hardship and associated care delivery outcomes. METHODS: A survey of 225 patients at a large cancer center assessed cancer-related financial hardship (0-10 Likert scale; highest quintile scores ≥ 5 defined severe hardship). Responses were linked to electronic medical records identifying patients' distress screening scores 6 months presurvey (0-10 scale) and outcomes of missed cancer care visits and bad debt charges (unrecovered patient charges) within 6 months postsurvey. A positive screen for distress was defined as score ≥ 4. We analyzed screening test characteristics for identifying severe financial hardship within 6 months and associations between financial hardship and outcomes using logistic models. RESULTS: Although patients with positive distress screens were more likely to report financial hardship (odds ratio [OR], 1.21; 1.08-1.37; P < .001), a positive distress screen was only 48% sensitive and 70% specific for identifying severe financial hardship. Patients with worse financial hardship scores were more likely to miss oncology care visits within 6 months (for every additional point in financial hardship score from 0 to 10, OR, 1.28; 1.12-1.47; P < .001). Of patients with severe hardship, 72% missed oncology visits versus 35% without severe hardship (P = .006). Patients with worse hardship were more likely to incur any bad debt charges within 6 months (OR, 1.32; 1.13-1.54; P < .001). CONCLUSION: Systematic financial hardship screening is needed to help mitigate adverse care delivery outcomes. Existing distress-based screening lacks sensitivity.

Definition and validation of SNOMED CT subsets using the expression constraint language.

BACKGROUND: SNOMED CT Expression Constraint Language (ECL) is a declarative language developed by SNOMED International for the definition of SNOMED CT Expression Constraints (ECs). ECs are executable expressions that define intensional subsets of clinical meanings by stating constraints over the logic definition of concepts. The execution of an EC on some SNOMED CT substrate yields the intended subset, and it requires an execution engine able to receive an EC as input, execute it, and return the matching concepts. An important issue regarding subsets of clinical concepts is their use in terminology binding between clinical information models and terminologies for defining the set of valid values of codified data. OBJECTIVE: To define and implement methods for the simplification, semantic validation and execution of ECs over a graph-oriented SNOMED CT database, and to provide a method for the visual representation of subsets in order to explore, understand and validate its content, as well as to develop an EC execution platform, called SNQuery, which makes use of these methods. METHODS: Since SNOMED CT is a directed and acyclic graph, we have used a graph-oriented database to represent the content of SNOMED CT, where the schema and instances are represented as graphs and the data manipulation is expressed by graph-oriented operations. For the execution of ECs over the graph database, it is performed a translation process in which ECs are translated into a set of Cypher Query Language queries. We have defined some EC simplification methods that leverage the logic structure underlying SNOMED CT. The purpose of these methods is to reduce the complexity of ECs and, in turn, its execution time, as well as to validate them from a SNOMED CT Concept Model and logical definition points of view. We also have developed a graphic representation based on the circle packing geometrical concept, which allows validating subsets, as well as pre-defined refsets and the terminology itself. RESULTS: We have developed SNQuery, a platform for the definition of intensional subsets of SNOMED CT concepts by means of the execution of ECs over a graph-oriented SNOMED CT database. Additionally, we have incorporated methods for the simplification and semantic validation of ECs, as well as for the visualization of subsets as a mechanism to understand and validate them. SNQuery has been evaluated in terms of EC execution times. CONCLUSION: In this paper, we provide methods to simplify, semantically validate and execute ECs over a graph-oriented database. We also offer a method to visualize the intensional subsets obtained by executing ECs to explore, understand and validate them, as well as refsets and the terminology itself. The definition of intensional subsets is useful to bind content between clinical information models and clinical terminologies, which is a necessary step to achieve semantic interoperability between EHR systems.

Does a Custom Electronic Health Record Alert System Improve Physician Compliance With National Quality Measures for Palliative Bone Metastasis Radiotherapy?

PURPOSE: In an effort to promote cost-conscious, high-quality, and patient-centered care in the palliative radiation of painful bone metastases, the National Quality Forum (NQF) formed measure 1822 in 2012, which recommends the use of one of the four dose-fractionation schemes (30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction). We investigated whether a custom electronic health record (EHR) alert system improved quality measure compliance among 88 physicians at a large academic center and institutional network. METHODS: In March 2018, a multiphase alert system was embedded in a custom web-based EHR. Prior to a course of palliative bone radiation, the alert system notified the user of NQF 1822 recommendations and, once prescription was completed, either affirmed compliance or advised a change in treatment schedule. Rates of compliance were evaluated before and after implementation of alert system. RESULTS: Of 2,399 treatment courses, 86.5% were compliant with NQF 1822 recommendations. There was no difference in rates of NQF 1822 compliance before or after implementation of the custom EHR alert (86.0% before March 2018 v 86.9% during and after March 2018, P = .551). CONCLUSION: There was no change in rates of compliance following implementation of a custom EHR alert system designed to make treatment recommendations based on national quality measure guidelines. To be of most benefit, future palliative bone metastasis decision aids should leverage peer review, target a clear practice deficiency, center upon high-quality practice guidelines, and allow flexibility to reflect the diversity of clinical scenarios.

Perineurioma versus meningioma. A multi-institutional immunohistochemical and ultrastructural studY.

The differential diagnosis between perineurioma (PN) and meningioma (MEN) can be difficult by histology and immunohistochemistry (IHC) because the perineurium and arachnoid have the same embryological origin. However, there are no comparative studies determining conclusive parameters for the differential diagnosis. The aim of this study is to compare IHC of PN and MEN and their ultra-structural characteristics to elucidate which are the useful data that allow differentiate both entities. Thirty-five MEN were analyzed, and 15 PN, (11 skin and soft tissues and four oral cavity). IHC for epithelial membrane antigen (EMA), Claudin-1, GLUT-1, somatostatin-2 receptor (SSTR-2), and progesterone receptor (RP) was performed. Ultrastructural studies were performed on 8 MEN and 15 PN. Only in PN Claudin-1 was positive in 9/11 (90%) cases and GLUT-1 in 7/11 (63%) cases. In MEN, the progesterone receptor was expressed in 21/35 (60%) cases and no case expressed Claudin-1 and GLUT-1; EMA was expressed in all MEN cases and 93% of PN. SSTR-2 was expressed weakly in six cases of MEN (17%), and it was not considered useful for differential diagnosis. On ultrastructure, PN showed thin and parallel processes, some caveolae, and lacked cell junctions. The cellular processes were surrounded by a collagenous stroma in 94% of the cases. MEN were characterized by curved cytoplasmic cell processes showing desmosomes in 75% of cases. Ultrastructural findings aid in the differential diagnosis between PN and MEN, especially if molecular studies are not available.

Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial.

Infantile colic is a prevalent condition characterised by excessive crying with no effective treatment available. We aimed to evaluate the efficacy of Bifidobacterium breve CECT7263 and a combination of this and Lactobacillus fermentum CECT5716 versus simethicone in reducing the daily time spent crying in colicky infants. A multicentre randomised, open-label, parallel, controlled trial of 28 days was performed in 150 infants who were diagnosed with colic according to the Rome III criteria and who randomly received simethicone (80 mg/day; Simethicone group), B. breve CECT7263 (2×108 cfu/day, Bb group), or a combination of L. fermentum CECT5716 and B. breve CECT7263 (1×108 cfu/day per strain, Bb+Lf group). The main outcomes were minutes of crying per day and the percentage of reduction in daily crying from baseline. Data were analysed per intention to treat. All treatments significantly decreased the daily crying time at the end of the intervention (P-time <0.001). However, the infants in the Bb group had significantly decreased crying time from the first week of the study (P<0.05), whereas the Bb+Lf group and the simethicone group had significantly decreased crying time from the second week (P<0.05). The percentage of reduction in the minutes of crying from baseline in the Bb group was significantly higher than that in the Simethicone group every week of the intervention (-40.3 vs -27.6% at 1-week; -59.2 vs -43.2% at 2-weeks; -64.5 vs -53.5% at 3-week and -68.5 vs -59.5% at 4-weeks, P<0.05). Additionally, in the Bb group, infants had better night sleep, and parents reported a more positive mood at the end of the intervention. All the products used in the study were safe and well tolerated. In conclusion, the breastmilk-isolated probiotic strain B. breve CECT7263 is a safe and effective treatment for infantile colic, presenting an earlier and more robust effect than the reference prescribed drug, simethicone.

Association of leptin receptor expression in placenta and peripheral blood mononuclear cell with maternal weight in birth outcomes.

INTRODUCTION: The pregnancy period represents the most intense period of growth and development. Pre-pregnancy weight influences weight gain during pregnancy. Leptin is a hormone mainly derived from white adipose tissue, during pregnancy leptin is also produced by the placenta. It has been suggested that the effects of placental leptin on the mother may contribute to endocrine-mediated alterations in energy balance; a dysregulation in leptin levels or its receptors may lead to poor birth outcomes. Therefore, the main goal of the present study was to analyze the differences in birth outcomes by maternal weight with the expression level of leptin receptor in maternal peripheral blood mononuclear cell (PBMC) and placental tissue. METHODS: Women with full-term gestation and its offspring were enrolled. Total RNA from maternal PBMC and placenta was obtained to perform the analysis of expression of the leptin receptor (LEPR) gene trough real-time PCR technique. Data were analyzed using one-way ANOVA or Mann-Whitney u test when applicable. Pearson correlation coefficient was used to determine the relationship between continuous variables (Stata v.13); p ≤ 0.05 was considered statistically significant. RESULTS: No statistically significant differences were found between LEPR expression level and the BMI studied groups in maternal PBMC and placental tissue. Interaction between gestational weight gain (GWG) and LEPR in maternal PBMC explain in a 32% the variability of the newborn weight. CONCLUSIONS: LEPR expression level in maternal PBMC correlates with newborn measurements independent from sex. GWG can affect fetal development by increasing fetal birth weight.

[Reconstruction of medial collateral ligament: Description of a new augmentation technique with allograft and interference biocomposite screws]. / Reconstrucción de ligamento colateral medial: descripción de una nueva técnica de aumentación con aloinjerto y tornillos biocompuestos interferenciales.

INTRODUCTION: Medial Collateral Ligament (LCM) instability is associated with multi-ligamentary lesions. There are several procedures for the reconstruction of MCL, we present a percutaneous technique of augmentation. Our goal is to describe a new technique of reconstruction of the LCM by grafting and fixing with biocomposite screws. MATERIAL AND METHODS: We present the technique in a total of 21 consecutive patients with MCL injury operated in the period of December 2011 to October 2014. Reconstruction of MCL was performed with long, tibial or long hallux tendon allografts in 18 patients and only one patient was used autograft. Eighteen of the 20 patients had associated lesions: 5 with medial meniscus injury, 8 with anterior cruciate ligament injury, (ACL), 8 with condral injury and 1 with lateral meniscus injury. CONCLUSION: The surgical technique presented is simple to perform, without damage to other structures and with a strong fixation.

INTRODUCCIÓN: La inestabilidad del ligamento colateral medial (LCM) se asocia con lesiones multiligamentarias. Existen varios procedimientos para la reconstrucción del LCM, presentamos una técnica percutánea de aumentación. Nuestro objetivo es describir una nueva técnica de reconstrucción del LCM mediante injerto y fijación con tornillos biocompuestos. MATERIAL Y MÉTODOS: Presentamos la técnica en un total de 21 pacientes consecutivos con lesión del LCM operados en el período de Diciembre de 2011 a Octubre de 2014. La reconstrucción del LCM se realizó con aloinjertos del tendón del peroneo largo, tibial posterior o flexor largo del Hallux en 18 pacientes y solamente en un paciente se utilizó autoinjerto. De los 20 pacientes, 18 presentaron lesiones asociadas: cinco con lesión de menisco medial, ocho con lesión del ligamento cruzado anterior, (LCA), ocho con lesión condral y uno con lesión del menisco lateral. CONCLUSIÓN: La técnica quirúrgica presentada es sencilla de realizar, sin daño a otras estructuras y con una fijación resistente.