Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non-Hodgkin's Lymphoma.

This review focuses on the use of chimeric antigen receptor (CAR)-T cell therapy to treat non-Hodgkin's lymphoma (NHL), a classification of heterogeneous malignant neoplasms of the lymphoid tissue. Despite various conventional and multidrug chemotherapies, the poor prognosis for NHL patients remains and has prompted the utilization of groundbreaking personalized therapies such as CAR-T cells. CAR-T cells are T cells engineered to express a CAR that enables T cells to specifically lyse tumor cells with extracellular expression of a tumor antigen of choice. A CAR is composed of an extracellular antibody fragment or target protein binding domain that is conjugated to activating intracellular signaling motifs common to T cells. In general, CAR-T cell therapies for NHL are designed to recognize cellular markers ubiquitously expressed on B cells such as CD19+, CD20+, and CD22+. Clinical trials using CAR-T cells such as ZUMA-7 and TRANSFORM demonstrated promising results compared to standard of care and ultimately led to FDA approval for the treatment of relapsed/refractory NHL. Despite the success of CAR-T therapy for NHL, challenges include adverse side effects as well as extrinsic and intrinsic mechanisms of tumor resistance that lead to suboptimal outcomes. Overall, CAR-T cell therapies have improved clinical outcomes in NHL patients and generated optimism around their future applications.

Identifying MicroRNAs Suitable for Detection of Breast Cancer: A Systematic Review of Discovery Phases Studies on MicroRNA Expression Profiles.

The analysis of circulating tumor cells and tumor-derived materials, such as circulating tumor DNA, circulating miRNAs (cfmiRNAs), and extracellular vehicles provides crucial information in cancer research. CfmiRNAs, a group of short noncoding regulatory RNAs, have gained attention as diagnostic and prognostic biomarkers. This review focuses on the discovery phases of cfmiRNA studies in breast cancer patients, aiming to identify altered cfmiRNA levels compared to healthy controls. A systematic literature search was conducted, resulting in 16 eligible publications. The studies included a total of 585 breast cancer cases and 496 healthy controls, with diverse sample types and different cfmiRNA assay panels. Several cfmiRNAs, including MIR16, MIR191, MIR484, MIR106a, and MIR193b, showed differential expressions between breast cancer cases and healthy controls. However, the studies had a high risk of bias and lacked standardized protocols. The findings highlight the need for robust study designs, standardized procedures, and larger sample sizes in discovery phase studies. Furthermore, the identified cfmiRNAs can serve as potential candidates for further validation studies in different populations. Improving the design and implementation of cfmiRNA research in liquid biopsies may enhance their clinical diagnostic utility in breast cancer patients.

NK cells from COVID-19 positive patients exhibit enhanced cytotoxic activity upon NKG2A and KIR2DL1 blockade.

SARS CoV-2 has caused a global pandemic leading to significant morbidity and mortality. There is a need to elucidate and further understand the implications of COVID-19 disease on the immune system to develop improved therapeutic strategies. In particular, Natural Killer (NK) cells play an essential role in mediating the innate immune response against viral infections. To better understand the role of innate immunity in COVID-19, we characterized the phenotype of circulating NK cells from 74 COVID-19 patients and 25 controls. Through evaluating the protein expression of activating and inhibitory NK cell surface molecules using dimension reduction analysis and clustering, we identified 4 specific clusters of NK cells specific to disease state (COVID-19 positive or COVID-19 negative) and characterized COVID-19 positive NK cells as: NGK2A+KIR2DL1+NKG2C-. Utilizing blocking antibodies specific for receptors NKG2A and KIR2DL1, we found that both NKG2A and KIR2DL1 blockade markedly enhances the ability of NK cells from COVID-19 positive patients to lyse SARS-Cov-2 infected cells. Overall, this study reveals new insights into NK cell phenotypes during SARS-CoV-2 infection and suggests a therapeutic approach worthy of further investigation to enhance NK cell-mediated responses against the virus.

Mediating Role of Lifestyle Behaviors in the Association between Education and Cancer: Results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. METHODS: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). RESULTS: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). CONCLUSIONS: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. IMPACT: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

Sequential Single-Cell Transcriptional and Protein Marker Profiling Reveals TIGIT as a Marker of CD19 CAR-T Cell Dysfunction in Patients with Non-Hodgkin Lymphoma.

Chimeric antigen receptor T-cell (CAR-T cell) therapy directed at CD19 produces durable remissions in the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL). Nonetheless, many patients receiving CD19 CAR-T cells fail to respond for unknown reasons. To reveal changes in 4-1BB-based CD19 CAR-T cells and identify biomarkers of response, we used single-cell RNA sequencing and protein surface marker profiling of patient CAR-T cells pre- and postinfusion into patients with NHL. At the transcriptional and protein levels, we note the evolution of CAR-T cells toward a nonproliferative, highly differentiated, and exhausted state, with an enriched exhaustion profile in CAR-T cells of patients with poor response marked by TIGIT expression. Utilizing in vitro and in vivo studies, we demonstrate that TIGIT blockade alone improves the antitumor function of CAR-T cells. Altogether, we provide evidence of CAR-T cell dysfunction marked by TIGIT expression driving a poor response in patients with NHL. SIGNIFICANCE: This is the first study investigating the mechanisms linked to CAR-T patient responses based on the sequential analysis of manufactured and infused CAR-T cells using single-cell RNA and protein expression data. Furthermore, our findings are the first to demonstrate an improvement of CAR-T cell efficacy with TIGIT inhibition alone. This article is highlighted in the In This Issue feature, p. 1825.

Usefulness of 99mTc-Pertechnetate SPECT-CT in Thyroid Tissue Volumetry: Phantom Studies and a Clinical Case Series.

BACKGROUND: An accurate measurement of the target volume is of primary importance in theragnostics of hyperthyroidism. OBJECTIVE: Our purpose was to evaluate the accuracy of a threshold-based isocontour extraction procedure for thyroid tissue volumetry from SPECT-CT. METHODS: Cylindrical vials with a fixed volume of 99mTcO4 at different activities were inserted into a neck phantom in two different thickness settings. Images were acquired by orienting the phantom in different positions, i.e., 40 planar images and 40 SPECT-CT. The fixed values of the isocontouring threshold for SPECT and SPECT-CT were calculated by means of linear and spline regression models. Mean, Median, Standard Deviation, Standard Error, Mean Absolute Percentage Error and Root Mean-Square Error were computed. Any difference between the planar method, SPECT and SPECT-CT and the effective volume was evaluated by means of ANOVA and posthoc tests. Moreover, planar and SPECT-CT acquisitions were performed in 8 patients with hyperthyroidism, considering relevant percentage differences greater than > 20% from the CT gold standard. RESULTS: Concerning phantom studies, the planar method shows higher values of each parameter than the other two methods. SPECT-CT shows lower variability. However, no significant differences were observed between SPECT and SPECT-CT measurements. In patients, relevant differences were found in 7 out of 9 lesions with the planar method, in 6 lesions with SPECT, but in only one with SPECT-CT. CONCLUSION: Our study confirms the superiority of SPECT in volume measurement if compared with the planar method. A more accurate measurement can be obtained from SPECT-CT.

Systems thinking in COVID-19 recovery is urgently needed to deliver sustainable development for women and girls.

In low-income and middle-income countries, such as those in sub-Saharan Africa and Latin America, the COVID-19 pandemic has had substantial implications for women's wellbeing. Policy responses to the COVID-19 pandemic have highlighted the gendered aspect of pandemics; however, addressing the gendered implications of the COVID-19 pandemic comprehensively and effectively requires a planetary health perspective that embraces systems thinking to inequalities. This Viewpoint is based on collective reflections from research done by the authors on COVID-19 responses by international and regional organisations, and national governments, in Latin America and sub-Saharan Africa between June, 2020, and June, 2021. A range of international and regional actors have made important policy recommendations to address the gendered implications of the COVID-19 pandemic on women's health and wellbeing since the start of the pandemic. However, national-level policy responses to the COVID-19 pandemic have been partial and inconsistent with regards to gender in both sub-Saharan Africa and Latin America, largely failing to recognise the multiple drivers of gendered health inequalities. This Viewpoint proposes that addressing the effects of the COVID-19 pandemic on women in low-income and middle-income countries should adopt a systems thinking approach and be informed by the question of who is affected as opposed to who is infected. In adopting the systems thinking approach, responses will be more able to recognise and address the direct gendered effects of the pandemic and those that emerge indirectly through a combination of long-standing structural inequalities and gendered responses to the pandemic.

[The wave train of COVID-19 infections]. / COVID-19: il treno di onde dei contagi.

The present work studies the epidemic curve of COVID-19 in Italy between September 2020 and mid-June 2021 in terms of poussées, that is successive waves. There is obviously only one pandemic, although the virus has spread in the form of several variants, but the daily incidence trend can also be read in terms of overlapping of events that are different from each other or, in any case, induced by various phenomena. It can be hypothesized that in this way a succession of various waves was generated, which are modelled here using appropriate adaptation curves used in the study of epidemic data. Each curve corresponds approximately to the situation that would have occurred if no element had intervened to prevent the decrease of infections after the relative peak, while their overlap is considered to describe the subsequent increases. This interpolation has no predictive purpose, being purely descriptive over the time window under consideration. The discrepancies between the superposition of the modelling curves and the real epidemic curve are therefore also highlighted, especially in the transition periods between the various poussées. Finally, the analysis carried out allows to match the trend of the epidemic in the period considered with, on one hand, the series of events and, on the other, with the containment measures adopted which may have determined the succession of increases and decreases in the incidence of infections.

Angiogenic Potential in Biological Hydrogels.

Hydrogels are three-dimensional (3D) materials able to absorb and retain water in large amounts while maintaining their structural stability. Due to their considerable biocompatibility and similarity with the body's tissues, hydrogels are one of the most promising groups of biomaterials. The main application of these hydrogels is in regenerative medicine, in which they allow the formation of an environment suitable for cell differentiation and growth. Deriving from these hydrogels, it is, therefore, possible to obtain bioactive materials that can regenerate tissues. Because vessels guarantee the right amount of oxygen and nutrients but also assure the elimination of waste products, angiogenesis is one of the processes at the base of the regeneration of a tissue. On the other hand, it is a very complex mechanism and the parameters to consider are several. Indeed, the factors and the cells involved in this process are numerous and, for this reason, it has been a challenge to recreate a biomaterial able to adequately sustain the angiogenic process. However, in this review the focal point is the application of natural hydrogels in angiogenesis enhancing and their potential to guide this process.

Management strategies for newly diagnosed immune thrombocytopenia in Italian AIEOP Centres: do we overtreat? Data from a multicentre, prospective cohort study.

BACKGROUND: The aim of the present study was to assess management strategies for immune thrombocytopenia (ITP) among Italian paediatric haematologists, and to compare these with those of recent international guidelines. Predictors of early remission or disease chronicity were also evaluated. MATERIALS AND METHODS: During a period of 1 year, 205 children (age: 1 month-18 years) with newly diagnosed ITP were prospectively enrolled by 16 centres belonging to the Italian Association of Paediatric Haematology and Oncology (AIEOP). We collected the subjects demographic data, history, clinical symptoms, platelet count and treatment at presentation and at subsequent visits. RESULTS: Of the 205 patients, 47 (23%) were initially managed with a wait-and-see approach. Compared to these patients, children administered platelet-enhancing therapies were significantly younger (median age: 4.75 vs 7.96 years; p<0.001) and had lower platelet counts. At the 3-month follow-up, 92/202 patients (46%) had persistent ITP. Recovery within 3 months was predicted by younger median age (5.3 vs 7.8 years; p<0.001), and recent viral infection (p<0.001) . At 1 year, 56 patients had chronic ITP, which was associated with older median age (7.54 vs 5.35 years; p<0.001), and a family history of autoimmunity (p<0.05; relative risk: 1.81; 95% confidence interval: 1.09-2.98). In total, 357 pharmacological treatments were recorded (216 intravenous immunoglobulins, 80 steroids). Response to intravenous immunoglobulins did not have an effect on remission rate at 12 months. DISCUSSION: Pediatric hematologists in Italian Centre treat over three-quarters of patients with newly diagnosed ITP, despite recent international guidelines. Almost 80% of patients with mild clinical symptoms received pharmacological treatment at diagnosis, which was significantly associated with younger age. Chronicity at 12 months was not affected by different therapeutic approaches at diagnosis or response to therapy.

[Rt or RDt, that is the question!] / Rt or RDt, that is the question!

The article compares two of the most followed indices in the monitoring of COVID-19 epidemic cases: the Rt and the RDt indices. The first was disseminated by the Italian National Institute of Health (ISS) and the second, which is more usable due to the lower difficulty of calculation and the availability of data, was adopted by various regional and local institutions.The rationale for the Rt index refers to that for the R0 index, the basic reproduction number, which is used by infectivologists as a measure of contagiousness of a given infectious agent in a completely susceptible population. The RDt index, on the other hand, is borrowed from the techniques of time series analysis for the trend of an event measurement that develops as a function of time. The RDt index does not take into account the time of infection, but the date of the diagnosis of positivity and for this reason it is defined as diagnostic replication index, as it aims to describe the intensity of the development of frequency for cases recognized as positive in the population.The comparison between different possible applications of the methods and the use of different types of monitoring data was limited to four areas for which complete individual data were available in March and April 2020. The main problems in the use of Rt, which is based on the date of symptoms onset, arise from the lack of completeness of this information due both to the difficulty in the recording and to the absence in asymptomatic subjects.The general trend of RDt, at least at an intermediate lag of 6 or 7 days, is very similar to that of Rt, as confirmed by the very high value of the correlation index between the two indices. The maximum correlation between Rt and RDt is reached at lag 7 with a value of R exceeding 0.97 (R2=0.944).The two indices, albeit formally distinct, are both valid; they show specific aspects of the phenomenon, but provide basically similar information to the public health decision-maker. Their distinction lies not so much in the method of calculation, rather in the use of different information, i.e., the beginning of symptoms and the swabs outcome.Therefore, it is not appropriate to make a judgment of preference for one of the two indices, but only to invite people to understand their different potentials so that they can choose the one they consider the most appropriate for the purpose they want to use it for.

DNA methylation, colon cancer and Mediterranean diet: results from the EPIC-Italy cohort.

The biological mechanisms through which adherence to Mediterranean Diet (MD) protects against colon cancer (CC) are poorly understood. Evidence suggests that chronic inflammation may be implicated in the pathway. Both diet and CC are related to epigenetic regulation. We performed a nested case-control study on 161 pairs from the Italian component of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, in which we looked for the methylation signals in DNA extracted from leucocytes associated with both CC and MD in 995 CpGs located in 48 inflammation genes. The DNA methylation signals detected in this analysis were validated in a subgroup of 47 case-control pairs and further replicated (where validated) in 95 new pairs by means of pyrosequencing. Among the CpG sites selected a-priori in inflammation-related genes, seven CpG sites were found to be associated with CC status and with MD, in line with its protective effect. Only two CpG sites (cg17968347-SERPINE1 and cg20674490-RUNX3) were validated using bisulphite pyrosequencing and, after replication, we found that DNA methylation of cg20674490-RUNX3 may be a potential molecular mediator explaining the protective effect of MD on CC onset. The use of a 'meet-in-the-middle' approach to identify the overlap between exposure and predictive markers of disease is innovative in studies on the relationship between diet and cancer, in which exposure assessment is difficult and the mechanisms through which the nutrients exert their protective effect is largely unknown.

Marginal Time-Dependent Causal Effects in Mediation Analysis With Survival Data.

The main aim of mediation analysis is to study the direct and indirect effects of an exposure on an outcome. To date, the literature on mediation analysis with multiple mediators has mainly focused on continuous and dichotomous outcomes. However, the development of methods for multiple mediation analysis of survival outcomes is still limited. Here we extend to survival outcomes a method for multiple mediation analysis based on the computation of appropriate weights. The approach considered has the advantages of not requiring specific models for mediators, allowing nonindependent mediators of any nature, and not relying on the assumption of rare outcomes. Simulation studies show good performance of the proposed estimator in terms of bias and coverage probability. The method is further applied to an example from a published study on prostate cancer mortality aimed at understanding the extent to which the effect of DNA methyltransferase 3b (DNMT3b) genotype on mortality was explained by DNA methylation and tumor aggressiveness. This approach can be used to quantify the marginal time-dependent direct and indirect effects carried by multiple indirect pathways, and software code is provided to facilitate its application.

New insights on occupational exposure and bladder cancer risk: a pooled analysis of two Italian case-control studies.

PURPOSE: The main risk factor for bladder cancer (BC) is cigarette smoking, but also occupational exposure to carcinogens is relevant, causing about 4-10% of BC. We aimed at investigating the association between BC risk, occupations held in the past and exposure to occupational carcinogens, also assessing whether these associations were influenced by tumour grade. METHODS: We pooled data from two Italian case-control studies on male BC, analyzing 893 cases and 978 controls. Occupations were classified using the International Standard Classification of Occupations and exposure to carcinogens was assigned using a validated Job Exposure Matrix. Logistic regression approach was used as well as a semi-Bayesian model, based on a priori information on exposure. RESULTS: A significantly increased BC risk was found for chemical engineering technicians, postmen, and lathe operators, but only, for the latter, the association remained significant after Bayesian control for type I error. Among carcinogens, cadmium and trichloroethylene were associated with BC. When analyzing data by grade, exposure to these carcinogens was associated with low-grade BC only. CONCLUSIONS: Our results suggest that monitoring workplaces to prevent exposure to carcinogenic agents is still an important task, which should be still given adequate importance in public health.

Adherence to a Mediterranean diet and long-term changes in weight and waist circumference in the EPIC-Italy cohort.

Excessive calorie intake and physical inactivity are considered key determinants of the rapid worldwide increase in obesity prevalence, however the relationship between diet and weight gain is complex. We investigated associations between adherence to a Mediterranean diet and long-term changes in weight and waist circumference in volunteers recruited to the Italian section of the prospective European Prospective Investigation into Cancer and Nutrition (EPIC). We investigated 32,119 cohort members who provided anthropometric measures at recruitment and updated information on recall a mean of 12 years later. Adherence to a Mediterranean diet was assessed using the Italian Mediterranean Index (score range 0-11). Associations between index score and weight and waist changes were assessed by multivariate linear regression models. Risks of developing overweight/obesity and abdominal obesity were investigated by multivariate logistic models. Increasing Italian Mediterranean Index score (indicating better adherence) was associated with lower 5-year weight change in volunteers of normal weight at baseline (ß -0.12, 95% CI -0.16 to -0.08 for 1 tertile increase in score), but not in those overweight/obese at baseline (P interaction between Index score and BMI 0.0001). High adherence was also associated with reduced risk of becoming overweight/obese (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile); smaller 5-year change in waist circumference (ß -0.09, 95% CI -0.14 to -0.03 for 1 tertile increase in score); and lower risk of abdominal obesity (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile). Adherence to a traditional Italian Mediterranean diet may help prevent weight gain and abdominal obesity.

Current practice of iron prophylaxis in preterm and low birth weight neonates: A survey among Italian Neonatal Units.

BACKGROUND: Preterm babies are at high risk of iron deficiency. METHODS: We investigated current practices regarding iron prophylaxis in preterm and low birth weight newborns among Local Neonatal Units (LNUs, n = 74) and Neonatal Intensive Care Units (NICUs, n = 20) of three Italian Regions (Piemonte, Marche and Lazio). RESULTS: Birth weight is considered an indicative parameter in only 64% of LNUs and 71% of NICUs, with a significant difference between LNUs in the three regions (86%, 20% and 62%, respectively; p < 0.001). Iron is recommended to infants with a birth weight between 2000 and 2500 g in only 25% of LNUs and 21% of NICUs, and to late-preterm (gestational age between 34 and 37 weeks) in a minority of Units (26% of LNUs, 7% of NICUs). CONCLUSIONS: Our pilot survey documents a great variability and the urgent need to standardize practices according to literature recommendations.

Transient elastography for non-invasive evaluation of post-transplant liver graft fibrosis in children.

As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.

Nonsuppressing normal thymus on chemical-shift MR imaging and anterior mediastinal lymphoma: differentiation with diffusion-weighted MR imaging by using the apparent diffusion coefficient.

OBJECTIVES: To prospectively evaluate usefulness of the apparent diffusion coefficient (ADC) in differentiating anterior mediastinal lymphoma from nonsuppressing normal thymus on chemical-shift MR, and to look at the relationship between patient age and ADC. METHODS: Seventy-three young subjects (25 men, 48 women; age range, 9-29 years), who underwent chemical-shift MR and diffusion-weighted MR were divided into a normal thymus group (group A, 40 subjects), and a lymphoma group (group B, 33 patients). For group A, all subjects had normal thymus with no suppression on opposed-phase chemical-shift MR. Two readers measured the signal intensity index (SII) and ADC. Differences in SII and ADC between groups were tested using t-test. ADC was correlated with age using Pearson correlation coefficient. RESULTS: Mean SII±standard deviation was 2.7±1.8% for group A and 2.2±2.4% for group B, with no significant difference between groups (P=.270). Mean ADC was 2.48±0.38x10-3mm2/s for group A and 1.24±0.23x10-3mm2/s for group B. A significant difference between groups was found (P<.001), with no overlap in range. Lastly, significant correlation was found between age and ADC (r=0.935, P<.001) in group A. CONCLUSIONS: ADC of diffusion-weighted MR is a noninvasive and accurate parameter for differentiating lymphoma from nonsuppressing thymus on chemical-shift MR in young subjects. KEY POINTS: • SII cannot differentiate mediastinal lymphoma from nonsuppressing normal thymus at visual assessment • ADC is useful for distinguishing nonsuppressing normal thymus from mediastinal lymphoma • ADC is more accurate than transverse-diameter and surface-area in this discrimination • ADC of normal thymus is age dependent and increases with increasing age.

Medición de impedancias in-vivo durante la cirugía de implante coclear como predictor de la posición de los electrodos dentro de la cóclea / Impedance measures during in-vivo cochlear implantation predict array positioning / Medição das impedâncias in-vivo durante a cirurgia de implante coclear como preditor da posição dos eletrodos no interior da cóclea

INTRODUCCIÓN: Los implantes cocleares son dispositivos protésicos neuronales utilizados para el tratamiento de las hipoacusias neurosensoriales severas a profundas. La activación de electrodos estimula las células del ganglio espiral y las vías nerviosas. Una estimulación más discreta de subpoblaciones neuronales se puede obtener cuando los electrodos están más cerca de las células ganglionares en la pared del modiolo. La distancia del electrodo al modiolo podría ser una de las múltiples variables que influyen en el resultado del paciente con un implante coclear. Actualmente no hay un protocolo establecido para medir esta distancia. Mediante diversas técnicas de imágenes se puede determinar la posición de la guía de electrodos dentro de la cóclea. La tomografía computada cone beam ha sido validada como una herramienta útil para evaluar la posición de los electrodos luego de la implantación. Tykocinski et al. describieron un modelo de la interfase electrodo-electrolito del implante coclear como una resistencia y un condensador en paralelo, y la resistencia del tejido circundante como una resistencia en serie. Realizando un registro detallado de la forma de la curva de voltaje, los datos pueden usarse para calcular la impedancia clínica o total, la resistencia de acceso, la impedancia de polarización y sus subcomponentes: Resistencia de polarización y capacitancia de polarización. El objetivo de este estudio es determinar si la distancia electrodo modiolar de cada uno de los electrodos podría predecirse a partir de mediciones de impedancia...

INTRODUCTION: Cochlear implants are neuronal prosthetic devices used for the treatment of severe to profound sensorineural hearing loss. The activation of electrodes stimulates spiral ganglion cells and nerve pathways. A more discrete stimulation of neuronal subpopulations can be obtained when the electrodes are closer to the ganglion cells in the modiolus wall. The distance from the electrode to the modiolus could be one of the multiple variables that influence the outcome of the patient with a cochlear implant. Currently there is no established protocol to measure this distance. By means of various imaging techniques, the position of the electrode guide inside the cochlea can be determined. Cone beam computed tomography has been validated as a useful tool to evaluate the position of the electrodes after implantation. Tykocinski et al., described a model of the electrode-electrolyte interface of the cochlear implant as a resistance and a capacitor in parallel, and the resistance of the surrounding tissue as a series resistance. By making a detailed record of the shape of the voltage curve, the data can be used to calculate the clinical or total impedance, the access resistance, the polarization impedance and its subcomponents: polarization resistance and polarization capacitance. The objective of this study is to determine if the electrode distance modiolar of each of the electrodes could be predicted from impedance measurements…

INTRODUCÃO: Os implantes cocleares são dispositivos protéticos neuronais utilizados no tratamento da perda auditiva neurossensorial severa a profunda. A ativação de eletrodos estimula as células ganglionares espirais e as vias nervosas. Uma estimulação mais discreta de subpopulações neuronais pode ser obtida quando os eletrodos estão mais próximos das células ganglionares na parede do modíolo. A distância do eletrodo ao modíolo pode ser uma das múltiplas variáveis que influenciam o resultado do paciente com implante coclear. Atualmente não há protocolo estabelecido para medir essa distância. Por meio de várias técnicas de imagem, a posição do guia do eletrodo dentro da cóclea pode ser determinada. A tomografia computadorizada por feixe cônico foi validada como uma ferramenta útil para avaliar a posição dos eletrodos após o implante. Tykocinski et al. Descreveu um modelo da interface eletrodo-eletrólito do implante coclear como uma resistência e um capacitor em paralelo, e a resistência do tecido circundante como uma resistência em série. Realizando um registo detalhado da forma da curva de tensão, os dados podem ser usados para calcular a impedância clínico ou total, a resistência de acesso, a impedância de polarização e seus subcomponentes: resistência de polarização e capacitância de polarização. O objetivo deste estudo é determinar se a distância modiolar do eletrodo de cada um dos eletrodos poderia ser prevista a partir de medidas de impedância...

Diet and endometrial cancer: a focus on the role of fruit and vegetable intake, Mediterranean diet and dietary inflammatory index in the endometrial cancer risk.

BACKGROUND: Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation. METHODS: In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk. RESULTS: Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26). CONCLUSIONS: These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.