Germanium-Based Optical Coatings for Aesthetic Enhancement with Low Radiofrequency Attenuation.

This work focused on developing optical coatings for decorative applications that remain transparent in the radiofrequency range. To achieve this, a combination of dielectric material (silicon-aluminum nitride, SiAlNx) and low-electrical-conductivity semiconductor material (germanium) was utilized. Germanium plays a crucial role in providing absorption in the visible spectrum, facilitating the design of coatings with various aesthetic appearances, while allowing for control over their transmittance. The optical properties of thin germanium layers were thoroughly characterized and leveraged to create multilayer designs with diverse aesthetic features. Different multilayer structures were designed, fabricated, and optically characterized, resulting in coatings with metallic gray, black, or various colors in reflection, while retaining the ability to transmit visible light for illumination and signaling applications. Finally, the radiofrequency attenuation of the developed coatings was measured, revealing negligible attenuation; this is in stark contrast to the metallic coatings used for decorative purposes, which can attenuate by up to 30 dB.

Estadio, perfil biológico y tendencias de incidencia y mortalidad de cáncer de mama en Uruguay: análisis por franjas etarias

Introducción: el cáncer de mama es el tumor maligno más frecuente y la primera causa de muerte por cáncer en mujeres en Uruguay y en el mundo. La evidencia epidemiológica sugiere que el cáncer de mama en diferentes grupos de edades se comportaría como patologías distintas. El objetivo de este trabajo es caracterizar el cáncer de mama en Uruguay para diferentes estratos de edades. Material y método: se analizaron las tendencias temporales de la incidencia de cáncer de mama en mujeres en Uruguay en el período 2002-2019, y de la mortalidad por esta causa en 1990-2020. Para el quinquenio 2015-2019, se analiza además la distribución de estadios al diagnóstico y de perfiles biológicos (luminales, triple negativos y HER2 positivos). Se analizan tres segmentos de edades: mujeres de 20 a 44 años, de 45 a 69 y de 70 y más años. Resultados: las tasas de incidencia para el conjunto de edades se presentaron estables en el período 2002-2019, mientras que la mortalidad presenta una tendencia decreciente en el período 1990-2020. En las mujeres menores de 45 años se encuentra un aumento en la incidencia, con mortalidad que decrece hasta el 2010, seguido de una estabilización de las tasas; en las mujeres de 45 a 69 años la incidencia se mantiene estable y la mortalidad decrece; en las mayores de 70 años, la incidencia decrece mientras la mortalidad se mantiene estable. Más del 70% de los casos se diagnostican en estadios I y II. Los tumores luminales (receptores hormonales positivos, HER2 negativos) son el subtipo más frecuente para todos los grupos, la proporción de tumores con estas características aumenta con la edad, mientras decrece la proporción de HER2 positivo y triple negativo. Conclusión: en las mujeres uruguayas el cáncer de mama presenta características diferenciales para las tres franjas de edades analizadas.

Introduction: Breast cancer is the most common malignant tumor and the leading cause of cancer death in women in Uruguay and worldwide. Epidemiological evidence suggests that breast cancer in different age groups behaves as distinct pathologies. The objective of this work is to characterize breast cancer in Uruguay for different age groups. Method: Temporal trends in the incidence of breast cancer in women in Uruguay are analyzed for the period 2002-2019, along with mortality trends for this cause from 1990 to 2020. For the five-year period 2015-2019, the distribution of stages at diagnosis and biological profiles (Luminal, Triple-negative, and Her2 positive) is also analyzed. Three age segments are analyzed: women aged 20 to 44 years, 45 to 69 years, and 70 years and older. Results: The incidence rates for all age groups remained stable during the period 2002-2019, while mortality showed a decreasing trend in the period 1990-2020. In women under 45, there is an increase in incidence, with mortality decreasing until 2010, followed by a stabilization of rates; in women aged 45 to 69, incidence remains stable and mortality decreases; in those over 70, incidence decreases while mortality remains stable. More than 70% of cases are diagnosed at stages I and II. Luminal tumors (hormone receptor positive, Her2 negative) are the most frequent subtype for all age groups. The proportion of tumors with these characteristics increases with age, while the proportion of Her2 positive and triple-negative tumors decreases. Conclusions: In Uruguayan women, breast cancer presents differential characteristics for the three age groups analyzed.

Introdução: O câncer de mama é o tumor maligno mais comum e a principal causa de morte por câncer em mulheres no Uruguai e no mundo. Evidências epidemiológicas sugerem que o câncer de mama se comportaria como patologias distintas em diferentes faixas etárias. O objetivo deste trabalho é caracterizar o câncer de mama no Uruguai para diferentes faixas etárias. Materiais e Métodos: São analisadas as tendências temporais da incidência de câncer de mama em mulheres no Uruguai no período 2002-2019 e a mortalidade por esta causa no período 1990-2020. Para o quinquénio 2015-2019 são também analisadas a distribuição dos estádios ao diagnóstico e os perfis biológicos (Luminal, Triplo negativo e Her2 positivo). São analisados três segmentos etários: mulheres dos 20 aos 44 anos, dos 45 aos 69 anos e dos 70 anos ou mais. Resultados: As taxas de incidência para todas as idades permaneceram estáveis no período 2002-2019 enquanto a mortalidade apresentou tendência decrescente no período 1990-2020. Nas mulheres com menos de 45 anos verifica-se um aumento da incidência, com uma redução da mortalidade até 2010, seguida de uma estabilização das taxas; nas mulheres de 45 a 69 anos, a incidência permanece estável e a mortalidade diminui; nas pessoas com mais de 70 anos, a incidência diminui enquanto a mortalidade permanece estável. Mais de 70% dos casos são diagnosticados nos estágios I e II. Os tumores luminais (receptor hormonal positivo, Her2 negativo) são o subtipo mais comum para todos os grupos sem do que a proporção de tumores com essas características aumenta com a idade, enquanto a proporção de (Her2 positivo e triplo negativo) diminui. Conclusão: Nas mulheres uruguaias, o câncer de mama apresenta características diferenciadas para as três faixas etárias analisadas.

Short-Chain Fatty Acid Production by Gut Microbiota Predicts Treatment Response in Multiple Myeloma.

PURPOSE: The gut microbiota plays important roles in health and disease. We questioned whether the gut microbiota and related metabolites are altered in monoclonal gammopathies and evaluated their potential role in multiple myeloma and its response to treatment. EXPERIMENTAL DESIGN: We used 16S rRNA sequencing to characterize and compare the gut microbiota of patients with monoclonal gammopathy of undetermined significance (n = 11), smoldering multiple myeloma (n = 9), newly diagnosed multiple myeloma (n = 11), relapsed/refractory multiple myeloma (n = 6), or with complete remission (n = 9). Short-chain fatty acids (SCFA) were quantified in serum and tested in cell lines. Relevant metabolites were validated in a second cohort of 62 patients. RESULTS: Significant differences in alpha- and beta diversity were present across the groups and both were lower in patients with relapse/refractory disease and higher in patients with complete remission after treatment. Differences were found in the abundance of several microbiota taxa across disease progression and in response to treatment. Bacteria involved in SCFA production, including Prevotella, Blautia, Weissella, and Agathobacter, were more represented in the premalignant or complete remission samples, and patients with higher levels of Agathobacter showed better overall survival. Serum levels of butyrate and propionate decreased across disease progression and butyrate was positively associated with a better response. Both metabolites had antiproliferative effects in multiple myeloma cell lines. CONCLUSIONS: We demonstrate that SCFAs metabolites and the gut microbiota associated with their production might have beneficial effects in disease evolution and response to treatment, underscoring its therapeutic potential and value as a predictor.

Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.

Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with Minimal Residual Disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA/GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (CI95% 0.21-0.81; p=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (-0.04-0.14; p<0.001) when adding uHLC IP recovery. Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after one year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment.

Management of Pediatric Humeral Supracondylar Fractures in a Referral Center From a Developing Country: A Comparison With American Academy of Orthopaedic Surgeons (AAOS) Guidelines.

Introduction Supracondylar fractures are the predominant type of pediatric elbow fractures. The usual mechanism of injury is falling over the hand with the elbow extended and the hand open. The management of these fractures encompasses a range of treatment options, and their goal is to recover the anatomy and achieve a stable contact area between them. There are some controversies on the management of these injuries mainly focused on those that present some degree of displacement. A review and analysis of the current treatment at our institution and a comparison with the guidelines suggested by the American Academy of Orthopaedic Surgeons (AAOS) for the treatment of these fractures in the pediatric population were performed. Materials and methods This was an observational, analytical, retrospective study of consecutive pediatric patients with displaced supracondylar humeral fracture treated at Hospital de Trauma "Manuel Giagni" in Asunción, Paraguay, from January 2016 to December 2021. Demographic and clinical data were assessed, and patients were clinically and radiologically followed for at least 12 months. The management of supracondylar humeral fractures at our hospital was compared with the guidelines suggested by the American Academy of Orthopaedic Surgeons (AAOS) by analyzing whether these guidelines were applied in each case. The mechanism of injury was divided into three groups, initial X-rays were measured, extension-type fractures were categorized into three groups, and the type of treatment was divided into two groups: non-operative and operative. Furthermore, trauma-related preoperative complications and postoperative complications were reported. Outpatient follow-up was performed for at least 12 months in all cases. Results Of the 843 patients analyzed, 71.5% were male, with a mean age of 5.6 years. It was observed that 57.5% of injuries were caused by falls on the same level. The most frequent type of injury was Gartland type III, accounting for 55% of the cases, and associated injuries were found in 4% of the cases. With regard to the type of treatment, 91.8% of patients were treated with closed reduction and percutaneous pin fixation. Complications on admission were found in 12% of the cases and late complications in 12% of the cases. Most patients (82%) had excellent Mayo Elbow Performance Score. Conclusion Supracondylar fractures were more frequent in males and in schoolchildren. Garland type III fractures were the most common type of injury. The treatment of choice was predominantly closed reduction and percutaneous pin fixation. The Mayo Elbow Performance Score was excellent in most patients. Our service, a referral center of a public hospital in a developing country, complies with the guidelines recommended by the AAOS.

Clinical Outcomes of Patients with Multiple Myeloma after Daratumumab Failure.

Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line. A total of 38.2% had received a previous autologous stem cell transplantation (ASCT), and 61.7% had received both an immunomodulatory drug (IMID) and a proteasome inhibitor (PI). The median overall survival (OS) was 21 months for the global cohort but it decreased to 14 months for triple-class refractory patients and 5 months for penta-refractory patients. Most of the patients (83.9%) received treatment after daratumumab progression, in many cases with second generation IMID or PI, but seven patients were treated with anti-BCMA therapy and three patients received CART therapy within a clinical trial. In conclusion, patients R/R to daratumumab represent an unmet clinical need with poor prognosis and in need of incorporation of new treatments.

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain.

Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.

Radiomics analysis of bone marrow biopsy locations in [18F]FDG PET/CT images for measurable residual disease assessment in multiple myeloma.

The combination of visual assessment of whole body [18F]FDG PET images and evaluation of bone marrow samples by Multiparameter Flow Cytometry (MFC) or Next-Generation Sequencing (NGS) is currently the most common clinical practice for the detection of Measurable Residual Disease (MRD) in Multiple Myeloma (MM) patients. In this study, radiomic features extracted from the bone marrow biopsy locations are analyzed and compared to those extracted from the whole bone marrow in order to study the representativeness of these biopsy locations in the image-based MRD assessment. Whole body [18F]FDG PET of 39 patients with newly diagnosed MM were included in the database, and visually evaluated by experts in nuclear medicine. A methodology for the segmentation of biopsy sites from PET images, including sternum and posterior iliac crest, and their subsequent quantification is proposed. First, starting from the bone marrow segmentation, a segmentation of the biopsy sites is performed. Then, segmentations are quantified extracting SUV metrics and radiomic features from the [18F]FDG PET images and are evaluated by Mann-Whitney U-tests as valuable features differentiating PET+/PET- and MFC+ /MFC- groups. Moreover, correlation between whole bone marrow and biopsy sites is studied by Spearman ρ rank. Classification performance of the radiomics features is evaluated applying seven machine learning algorithms. Statistical analyses reveal that some images features are significant in PET+/PET- differentiation, such as SUVmax, Gray Level Non-Uniformity or Entropy, especially with a balanced database where 16 of the features show a p value < 0.001. Correlation analyses between whole bone marrow and biopsy sites results in significant and acceptable coefficients, with 11 of the variables reaching a correlation coefficient greater than 0.7, with a maximum of 0.853. Machine learning algorithms demonstrate high performances in PET+/PET- classification reaching a maximum AUC of 0.974, but not for MFC+/MFC- classification. The results demonstrate the representativeness of sample sites as well as the effectiveness of extracted features (SUV metrics and radiomic features) from the [18F]FDG PET images in MRD assessment in MM patients.

NTS, NTSR1 and ERs in the Pituitary-Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment.

The neuropeptide neurotensin (NTS) is involved in regulating the reproductive axis and is expressed at each level of this axis (hypothalamus-pituitary-gonads). This dependence on estrogen levels has been widely demonstrated in the hypothalamus and pituitary. We focused on confirming the relationship of NTS with estrogens and the gonadal axis, using a particularly important environmental estrogenic molecule, bisphenol-A (BPA). Based on the experimental models or in vitro cell studies, it has been shown that BPA can negatively affect reproductive function. We studied for the first time the action of an exogenous estrogenic substance on the expression of NTS and estrogen receptors in the pituitary-gonadal axis during prolonged in vivo exposure. The exposure to BPA at 0.5 and 2 mg/kg body weight per day during gestation and lactation was monitored through indirect immunohistochemical procedures applied to the pituitary and ovary sections. Our results demonstrate that BPA induces alterations in the reproductive axis of the offspring, mainly after the first postnatal week. The rat pups exposed to BPA exhibited accelerated sexual maturation to puberty. There was no effect on the number of rats born per litter, although the fewer primordial follicles suggest a shorter fertile life.

Cell Count Differentials by Cytomorphology and Next-Generation Flow Cytometry in Bone Marrow Aspirate: An Evidence-Based Approach.

Despite a lack of evidence, a bone marrow aspirate differential of 500 cells is commonly used in the clinical setting. We aimed to test the performance of 200-cell counts for daily hematological workup. In total, 660 consecutive samples were analyzed recording differentials at 200 and 500 cells. Additionally, immunophenotype results and preanalytical issues were also evaluated. Clinical and statistical differences between both cutoffs and both methods were checked. An independent control group of 122 patients was included. All comparisons between both cutoffs and both methods for all relevant types of cells did not show statistically significant differences. No significant diagnostic discrepancies were demonstrated in the contingency table analysis. This is a real-life study, and some limitations may be pointed out, such as a different sample sizes according to the type of cell in the immunophenotype analysis, the lack of standardization of some preanalytical events, and the relatively small sample size of the control group. The comparisons of differentials by morphology on 200 and 500 cells, as well as by morphology (both cutoffs) and by immunophenotype, are equivalent from the clinical and statistical point of view. The preanalytical issues play a critical role in the assessment of bone marrow aspirate samples.

Big Data and Machine Learning to Improve European Grapevine Moth (Lobesia botrana) Predictions.

Machine Learning (ML) techniques can be used to convert Big Data into valuable information for agri-environmental applications, such as predictive pest modeling. Lobesia botrana (Denis & Schiffermüller) 1775 (Lepidoptera: Tortricidae) is one of the main pests of grapevine, causing high productivity losses in some vineyards worldwide. This work focuses on the optimization of the Touzeau model, a classical correlation model between temperature and L. botrana development using data-driven models. Data collected from field observations were combined with 30 GB of registered weather data updated every 30 min to train the ML models and make predictions on this pest's flights, as well as to assess the accuracy of both Touzeau and ML models. The results obtained highlight a much higher F1 score of the ML models in comparison with the Touzeau model. The best-performing model was an artificial neural network of four layers, which considered several variables together and not only the temperature, taking advantage of the ability of ML models to find relationships in nonlinear systems. Despite the room for improvement of artificial intelligence-based models, the process and results presented herein highlight the benefits of ML applied to agricultural pest management strategies.

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP).

INTRODUCTION: Belantamab mafodotin (BM) is a new anti-BCMA antibody-drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). METHODS: We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Thirty-three patients were included with a median of 70 years of age (range, 46-79 years). Median time from diagnosis was 71 months (range, 10-858 months). Median prior lines was 5 (range, 3-8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1-16 doses), with a median follow-up of 11 months (6-15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92-5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10-0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107-740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient's decision (3%). CONCLUSIONS: BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.

Fe3O4-Nanoparticle-Doped Epoxy Resin as a Detachable Adhesive by Electromagnetic Heating for GFRP Single-Lap Joints.

An adhesive based on a Fe3O4-nanoparticle (MNP)-doped epoxy resin was proposed for the development of detachable adhesive joints with GFRP substrates. The analysis of cryofractures showed that the increasing MNP content promotes a higher presence of larger aggregates and a lower sedimentation of nanoparticles due to the higher viscosity of the mixture. In this regard, the inclusion of expandable microspheres (MS) induces a more uniform dispersion of MNPs, reducing their sedimentation. The capability of the proposed adhesives for electromagnetic (EM) heating was also evaluated, with increases in temperature of around 100 °C at 750 A, enough to reach the Tg of the polymer required to facilitate the adhesive detachment, which is around 80 °C. Finally, the lap shear strength (LSS) of 14 and 20 wt.% MNP samples was evaluated in a single-lap shear joint with simultaneous EM heating. The LSS values were reduced by 60-80% at 750 A, thus promoting successful adhesive joint detachment under EM heating.

Cancer incidence and mortality in Uruguay: 2013-2017.

Background: Uruguay has the highest cancer incidence and mortality rates in Latin America. The National Cancer Registry of Uruguay, which has been in operation since 1992, provides epidemiological information on incidence and mortality at the country level. Objective: The objective of this article is to update the incidence and mortality figures by reporting the information for the period 2013-2017. Methods: All incident cases of invasive neoplasias except non melanoma of the skin and all cancer deaths occurred in from 2013 to 2017 were analyzed. Age standardized rates were calculated by the direct method, using the world standard population. Complementary, incidence (2002-2017) and mortality (1990-2017) trends were studied for the leading sites. Results: Among females, the most common cancers are breast, colon and rectum, lung, cervix and thyroid. The most frequent cancers in males are prostate, lung, colon and rectum, bladder and kidney. Lung, prostate and colorectal cancer are the leading causes of cancer death in males while breast cancer is the first cause of cancer death among females. Conclusions: Although cancer mortality has declined monotonously since 1990, cancer control is a challenge for Uruguay, wherein breast, lung and prostate cancer have very high incidence while the country must still make an effort to reduce other cancers that are very common in economically less favored countries.

Antecedentes: Uruguay tiene las mayores tasas de incidencia y mortalidad por cáncer en América Latina. El Registro Nacional de Cáncer de Uruguay, que ha estado en funcionamiento desde 1992 provee información epidemiológica sobre incidencia y mortalidad de todo el país. Objetivo: El objetivo de este artículo es actualizar las cifras de incidencia y mortalidad reportando la información para el período 2013-2017. Métodos: Se analizaron todos los casos incidentes de neoplasias invasivas excluyendo el cáncer de piel no melanoma y todas las muertes por cáncer del período 2013-2017. Se calcularon las tasas estandarizadas por edad según el método directo, utilizando como estándar la población mundial. En forma complementaria, se estudiaron las tendencias de incidencia (2002-2017) y de mortalidad (1990-2017) para los sitios más frecuentes. Resultados: Entre las mujeres, los cánceres más frecuentes son mama, colorrecto, pulmón, cérvix y tiroides. Los cánceres más frecuentes en hombres son próstata, pulmón colorrecto, vejiga y riñón. Los cánceres de pulmón, próstata y colorrecto ocupan los primeros lugares en las muertes por cáncer en hombres, mientras que en mujeres el cáncer de mama ocupa el primer lugar. Conclusiones: Si bien la mortalidad por cáncer ha disminuído de manera monótona desde 1990, el control del cáncer es un desafío para Uruguay dónde los cánceres de mama, pulmón y próstata tienen una incidencia muy alta, a la vez que aún se debe hacer un esfuerzo para reducir otros cánceres que son muy comunes en los países económicamente menos favorecidos.

Human papillomavirus genotyping using next generation sequencing (NGS) in cervical lesions: Genotypes by histologic grade and their relative proportion in multiple infections.

Sensitive and specific genotyping of human papillomaviruses (HPVs) is critical for the surveillance and monitoring of the vaccine effectiveness. Here, HPV genotypes were identified in 137 cervical samples with different histology (79 ≤CIN1 and 58 CIN3+) using Nested-PCR followed by Next-Generation sequencing (NGS) and relative proportions for each genotype in multiple infections were computed. All samples had been previously genotyped by PCR-Reverse Blotting Hybridization (PCR-RBH) thus allowing for a concordance analysis between both techniques. Multiple infections were present in 85% of ≤CIN1 cases compared to only 41% in CIN3+ cases (p<0.001). Among ≤CIN1 cases a towering genotypic diversity was observed, considering both low (LR-) and high risk (HR-) HPV genotypes; while among CIN3+, diversity was lower, HR-HPVs prevailing in most cases, especially HPV16. Furthermore, the predominance of HR-HPV genotypes in the proportions identified in each sample was higher in CIN3+ cases [(HPV16 (62.5%), followed by HPV31 and HPV58 (8.3% each)], than in ≤CIN1 cases [(HPV16 (17.7%), followed by HPV52 (14.7%) and HPV31 (10.3%)]. Agreement between PCR-RBH and NGS was higher than 90% for all genotypes (with an overall Kappa of 0.7), even though NGS identified eighty-nine positive results for HPV genotypes that had not been detected by PCR-RBH, evidencing its greater sensitivity. These results suggest that a reduction in genotypic diversity and/or an increase in the relative proportion of HR-HPVs in multiple infections can be considered as a biomarker for the potential risk of malignant progression.

Bone marrow segmentation and radiomics analysis of [18F]FDG PET/CT images for measurable residual disease assessment in multiple myeloma.

BACKGROUND AND OBJECTIVES: The last few years have been crucial in defining the most appropriate way to quantitatively assess [18F]FDG PET images in Multiple Myeloma (MM) patients to detect persistent tumor burden. The visual evaluation of images complements the assessment of Measurable Residual Disease (MRD) in bone marrow samples by multiparameter flow cytometry (MFC) or next-generation sequencing (NGS). The aim of this study was to quantify MRD by analyzing quantitative and texture [18F]FDG PET features. METHODS: Whole body [18F]FDG PET of 39 patients with newly diagnosed MM were included in the database, and visually evaluated by experts in nuclear medicine. A segmentation methodology of the skeleton from CT images and an additional manual segmentation tool were proposed, implemented in a software solution including a graphical user interface. Both the compact bone and the spinal canal were removed from the segmentation to obtain only the bone marrow mask. SUV metrics, GLCM, GLRLM, and NGTDM parameters were extracted from the PET images and evaluated by Mann-Whitney U-tests and Spearman ρ rank correlation as valuable features differentiating PET+/PET- and MFC+/MFC- groups. Seven machine learning algorithms were applied for evaluating the classification performance of the extracted features. RESULTS: Quantitative analysis for PET+/PET- differentiating demonstrated to be significant for most of the variables assessed with Mann-Whitney U-test such as Variance, Energy, and Entropy (p-value = 0.001). Moreover, the quantitative analysis with a balanced database evaluated by Mann-Whitney U-test revealed in even better results with 19 features with p-values < 0.001. On the other hand, radiomics analysis for MFC+/MFC- differentiating demonstrated the necessity of combining MFC evaluation with [18F]FDG PET assessment in the MRD diagnosis. Machine learning algorithms using the image features for the PET+/PET- classification demonstrated high performance metrics but decreasing for the MFC+/MFC- classification. CONCLUSIONS: A proof-of-concept for the extraction and evaluation of bone marrow radiomics features of [18F]FDG PET images was proposed and implemented. The validation showed the possible use of these features for the image-based assessment of MRD.

The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies.

The increase in the number of therapeutic alternatives for both newly diagnosed and relapsed/refractory multiple myeloma (RRMM) patients has widened the clinical scenario, leading to a level of complexity that no algorithm has been able to cover up to date. At present, this complexity increases due to the wide variety of clinical situations found in MM patients before they reach the status of relapsed/refractory disease. These different backgrounds may include primary refractoriness, early relapse after completion of first-line therapy with latest-generation agents, or very late relapse after chemotherapy or autologous transplantation. It is also important to bear in mind that many patient profiles are not fully represented in the main randomized clinical trials (RCT), and this further complicates treatment decision-making. In RRMM patients, the choice of previously unused drugs and the number and duration of previous therapeutic regimens until progression has a greater impact on treatment efficacy than the adverse biological characteristics of MM itself. In addition to proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and corticosteroids, a new generation of drugs such as XPO inhibitors, BCL-2 inhibitors, new alkylators and, above all, immunotherapy based on conjugated anti-BCMA antibodies and CAR-T cells, have been developed to fight RRMM. This comprehensive review addresses the fundamentals and controversies regarding RRMM, and discusses the main aspects of management and treatment. The basis for the clinical management of RRMM (complexity of clinical scenarios, key factors to consider before choosing an appropriate treatment, or when to treat), the arsenal of new drugs with no cross resistance with previously administered standard first line regimens (main phase 3 clinical trials), the future outlook including the usefulness of abandoned resources, together with the controversies surrounding the clinical management of RRMM patients will be reviewed in detail.

Predictive Value of Genetic Risk Scores in the Development of Colorectal Adenomas.

INTRODUCTION: Unlike colorectal cancer (CRC), few studies have explored the predictive value of genetic risk scores (GRS) in the development of colorectal adenomas (CRA), either alone or in combination with other demographic and clinical factors. METHODS: In this study, genomic DNA from 613 Spanish Caucasian patients with CRA and 829 polyp-free individuals was genotyped for 88 single-nucleotide polymorphisms (SNPs) associated with CRC risk using the MassArray™ (Sequenom) platform. After applying a multivariate logistic regression model, five SNPs were selected to calculate the GRS. Regression models adjusted by sex, age, family history of CRC, chronic use of NSAIDs, low-dose ASA, and consumption of tobacco were built in order to study the association between GRS and CRA risk. We evaluated the discriminatory capacity using the area under the receiver operating characteristic curve (AUC). The interactions between demographic information and GRS were also analyzed. RESULTS: Significant associations between high GRS values and risk of CRA for analyzed models were observed. In particular, patients with higher GRS values had 2.3-2.6-fold increase in risk of CRA compared to patients with middle values. Combining sex and age with the GRS significantly increased the discriminatory accuracy of the univariate model with GRS alone. The best model achieved an AUC value of 0.665 (95% CI: 0.63-0.69). The GRS showed a different behavior depending on sex and age. CONCLUSION: Our findings showed that, besides sex and age, GRS is an important risk factor for development of CRA and may be useful for CRC risk stratification and adaptation of screening programs.

The Current Role of the Heavy/Light Chain Assay in the Diagnosis, Prognosis and Monitoring of Multiple Myeloma: An Evidence-Based Approach.

Despite tremendous progress being made in recent years, multiple myeloma (MM) remains a challenging disease. The laboratory plays a critical role in the overall management of patients. The diagnosis, prognosis, clinical monitoring and evaluation of the response are key moments in the clinical care process. Conventional laboratory methods have been and continue to be the basis of laboratory testing in monoclonal gammopathies, along with the serum free light chain test. However, more accurate methods are needed to achieve new and more stringent clinical goals. The heavy/light chain assay is a relatively new test which can overcome some of the limitations of the conventional methods for the evaluation of intact immunoglobulin MM patients. Here, we report an update of the evidence accumulated in recent years on this method regarding its use in MM.