Primary endobronchial melanoma: a case report and clinical management indications.

BACKGROUND: While cutaneous melanomas are well-documented, primary melanoma of the lung (PMML), particularly with endobronchial origin, remains rare and poorly characterized. This case report addresses gaps in understanding by presenting a comprehensive case of a 71-year-old male with primary endobronchial melanoma and conducting a systematic review of PMML cases. CASE PRESENTATION: The patient, a former smoker, presented with dyspnea, cough, and hemoptysis. Imaging revealed left lung atelectasis and a suspicious nodule. Bronchoscopy identified an endobronchial mass, subsequently treated with argon plasma coagulation and resection. Biopsy confirmed melanoma. Extensive examinations ruled out a primary skin lesion. Despite initial treatment, recurrence led to pneumonectomy. Histopathology confirmed melanoma. The patient received treatment with pembrolizumab and ipilimumab, but with poor clinical benefit. CONCLUSIONS: Primary endobronchial melanoma is a rare entity, comprising 0.01% of lung tumors. This case underscores diagnostic challenges and emphasizes histological criteria to distinguish primary from metastatic lesions. The pathogenesis remains unclear, with theories proposing foetal melanocyte migration or squamous metaplasia. Prognosis varies, necessitating radical surgical extirpation. A systematic review revealed diverse outcomes, supporting the need for further research. In conclusion, endobronchial melanoma involves an endoscopic and surgical management, but evolving therapies, such as immunotherapy, may reshape treatment paradigms. This case contributes to our understanding of PMML, guiding future research and clinical management. As therapeutic options evolve, continued research is crucial to refine our understanding and improve outcomes for this rare malignancy.

Prognostic Role of Soluble and Extracellular Vesicle-Associated PD-L1, B7-H3 and B7-H4 in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

The treatment of non-small cell lung cancer (NSCLC) has changed dramatically with the advent of immune checkpoint inhibitors (ICIs). Despite encouraging results, their efficacy remains limited to a subgroup of patients. Circulating immune checkpoints in soluble (s) form and associated with extracellular vesicles (EVs) represent promising markers, especially in ICI-based therapeutic settings. We evaluated the prognostic role of PD-L1 and of two B7 family members (B7-H3, B7-H4), both soluble and EV-associated, in a cohort of advanced NSCLC patients treated with first- (n = 56) or second-line (n = 126) ICIs. In treatment-naïve patients, high baseline concentrations of sPD-L1 (>24.2 pg/mL) were linked to worse survival, whereas high levels of sB7-H3 (>0.5 ng/mL) and sB7-H4 (>63.9 pg/mL) were associated with better outcomes. EV characterization confirmed the presence of EVs positive for PD-L1 and B7-H3, while only a small portion of EVs expressed B7-H4. The comparison between biomarker levels at the baseline and in the first radiological assessment under ICI-based treatment showed a significant decrease in EV-PD-L1 and an increase in EV-B7H3 in patients in the disease response to ICIs. Our study shows that sPD-L1, sB7-H3 and sB7-H4 levels are emerging prognostic markers in patients with advanced NSCLC treated with ICIs and suggests potential EV involvement in the disease response to ICIs.

A High Percentage of CD16+ Monocytes Correlates with the Extent of Bone Erosion in Chronic Lymphocytic Leukemia Patients: The Impact of Leukemic B Cells in Monocyte Differentiation and Osteoclast Maturation.

Significant skeletal alterations are present in Chronic Lymphocytic Leukemia (CLL) patients; bone erosion, particularly evident in the long bone shaft, appeared increased in the progressive disease stage. Moreover, the partial colonization of the bone with reactive bone marrow we documented via PET-FDG imaging suggests that neoplastic cell overgrowth contributes to bone derangement. Indeed, cytokines released by leukemic B cells impair osteoblast differentiation and enhance osteoclast formation in vitro. CD16, Fcγ-RIIIa, has been previously indicated as a marker of osteoclast precursors. We demonstrate, here, that the percentage of circulating monocytes, CD16+, is significantly higher in CLL patients than in normal controls and directly correlated with the extent of bone erosion. When we assessed if healthy monocytes, treated with a CLL-conditioned medium, modulated RANK, RANKL and CD16, we observed that all these molecules were up-regulated and CD16 to a greater extent. Altogether, these findings suggest that leukemic cells facilitate osteoclast differentiation. Interestingly, the evidence that monocytes, polarized toward the M2 phenotype, were characterized by high CD16 expression and showed a striking propensity to differentiate toward osteoclasts may provide further explanations for the enhanced levels of bone erosion detected, in agreement with the high number of immunosuppressive-M2 cells present in these patients.

Baseline values and environmental assessment for metal(loid)s in soils under a tropical rainy climate in a Colombian region.

The baseline values for metal(loid)s in soils are known as a tool for the evaluation, prevention, and monitoring of the environmental quality of the soil. The main aim is to propose baseline values for metal(loid)s through the analysis of the concentrations in soils within natural areas; additionally, this study attempts to assess the environmental quality of soils in agricultural areas. The study was developed in the Piedemonte Llanero from Colombia a region with more than 5000 mm year-1 of pluviometry. A total of 90 soil samples were collected in agricultural and natural areas. Chemical analysis was conducted by acid digestion following the method EPA 3050B and determined the metal(loid)s (Al, As, Fe, Cd, Cr, Cu, Mg, Mn, Ni, Pb, and Zn) through ICP-OES. This is the first time that baseline values are proposed for a region in Colombia. The values proposed (expressed in mg kg-1) are Cd (0.3), As (2.8), Cu (9.9), Ni (10.2), Pb (11.3), Cr (21.1), Zn (28.2), Mn (83.8), Mg (348), Fe (22,775), and Al (28,975). These values are comparatively lower than those reported for other regions in Latin America and the rest of the world. Also, agricultural soils are not contaminated. The possible explanation is as a consequence of the intense washing caused by the intense rainfall of the place. The results also demonstrated that the soils in this region are not contaminated. Finally, these advances will allow public and private organizations to establish criteria for the environmental and sustainable management of soils, especially on agricultural activities.

Diffuse Pruritic Papular and Nodular Skin Eruption in a Febrile Farmer: A Quiz.

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Lysyl-Oxidase Dependent Extracellular Matrix Stiffness in Hodgkin Lymphomas: Mechanical and Topographical Evidence.

PURPOSE: The biochemical composition and architecture of the extracellular matrix (ECM) is known to condition development and invasiveness of neoplasms. To clarify this point, we analyzed ECM stiffness, collagen cross-linking and anisotropy in lymph nodes (LN) of Hodgkin lymphomas (HL), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL), compared with non-neoplastic LN (LDN). METHODS AND RESULTS: We found increased elastic (Young's) modulus in HL and advanced FL (grade 3A) over LDN, FL grade 1-2 and DLBCL. Digital imaging evidenced larger stromal areas in HL, where increased collagen cross-linking was found; in turn, architectural modifications were documented in FL3A by scanning electron microscopy and enhanced anisotropy by polarized light microscopy. Interestingly, HL expressed high levels of lysyl oxidase (LOX), an enzyme responsible for collagen cross-linking. Using gelatin scaffolds fabricated with a low elastic modulus, comparable to that of non-neoplastic tissues, we demonstrated that HL LN-derived mesenchymal stromal cells and HL cells increased the Young's modulus of the extracellular microenvironment through the expression of LOX. Indeed, LOX inhibition by ß-aminopropionitrile prevented the gelatin stiffness increase. CONCLUSIONS: These data indicate that different mechanical, topographical and/or architectural modifications of ECM are detectable in human lymphomas and are related to their histotype and grading.

Potential application of cryobiopsy for histo-molecular characterization of mediastinal lymph nodes in patients with thoracic malignancies: a case presentation series and implications for future developments.

BACKGROUND: The management of non-small cell lung cancer (NSCLC) has become increasingly complex due to the evolution of personalized medicine approaches. Such approaches are characterized by the necessity of adequate tumor samples; hence, improved biopsy techniques are needed. Transbronchial lung cryobiopsy is a novel endoscopic procedure designed to collect peripheral pulmonary tissue, and it is currently employed in interstitial lung diseases. The use of this technique in oncology might result in improved mediastinum staging and molecular characterizations; however, available data involving the use of a cryoprobe on mediastinal lymph nodes are still limited. CASE PRESENTATION: Here we present a series of five consecutive patients who underwent endoscopic assessment of mediastinal lymph nodes for oncologic reasons. All patients were subjected both to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA) and cryobiopsy of mediastinal lymph nodes during the same procedure, and no complications were observed. In three of the reported cases, both cryobiopsy and cell block from EBUS TBNA were positive, while in one case cryobiopsy was not diagnostic and EBUS TBNA was negative; moreover, one case showed discordance between the procedures, as cryobiopsy was negative and cell block obtained from multiple stations was diagnostic for small cell lung cancer. In one case involving a patient treated for lymphoma, cryobiopsy provided more complete histologic characterization, and in another case involving a patient affected by NSCLC cryobiopsy provided more material for molecular analyses. CONCLUSION: This case presentation series suggests that cryobiopsy, which has been generally used on peripheral lung lesions so far, is a feasible and safe approach for diagnosis and staging of mediastinal lymph nodal involvement, especially when station 7 is involved. Compared to EBUS TBNA, cryobiopsy might provide more adequate histological samples, with a possible impact on molecular characterizations and, therefore, therapeutic decisions. However, the learning curve of the procedure has not to be understated and optimal protocols for implementing this technique are needed. In our opinion, further studies designed to integrate the routine use of cryobiopsy in current practice for solid and eventually hematologic tumors with mediastinal lymph node involvement are warranted.

Laparoscopic lymph node biopsy for lymphoma with a novel use of indocyanine green fluorescence in a 66-year-old male patient.

INTRODUCTION: Indocyanine green (ICG) near-infrared fluorescence is primarily employed in detecting Intraoperative sentinel lymph node (SLN) mapping or to evaluate the extent of radical lymphadenectomy mainly in colo-rectal and gastric cancer. To date there are no reports indicating the use of this dye to detect pathologic lymphatic tissue when a lymph node biopsy for suspected lymphoproliferative disease is performed. PRESENTATION OF CASE: A 66-year-old male patient was admitted to the hospital for severe pain of left renal colic type. A computed tomography (CT) scan and a positron emission tomography (PET) showed a left hydroureteronephrosis due to ureter compression by paraortic solid tissue of lymphomatous aspect with a standardized uptake value (SUV) of 15. Multiple lymphadenopathies on paracaval, para-aortic and common iliac sites were present as well. DISCUSSION: A laparoscopic lymph node biopsy (LLB) was planned for diagnostic purposes. After induction of anesthesia a ICG solution was injected Intradermally at both inguinal regions. At laparoscopy a complete visualization of the pathologic lymphnodes was achieved, enabling incisional biopsies of the lymphomatous mass. Histopathological examination showed an extranodal localization of an aggressive B-cell non-Hodgkin lymphoma. CONCLUSION: ICG-fluorescence seems to offer a simple and safe method for pathologic lymph node detection. LLB in the suspicion of intra abdominal lymphoma can largely take advantage by this novel opportunity not yet tested to date. More studies with large case series are needed to confirm the efficacy of ICG-fluorescence for detecting pathologic lymph nodes.

Concomitant Prostate Cancer and Hodgkin Lymphoma: A Differential Diagnosis Guided by a Combined 68Ga-PSMA-11 and 18F-FDG PET/CT Approach.

Here we report the case of concomitant favorable-risk prostate cancer and Hodgkin Lymphoma in a 38-year old male. 68Ga-Prostate Specific Membrane Antigen-11 Positron Emission Tomography/Computed Tomography (68Ga-PSMA-11 PET/CT) was performed for staging purposes, showing the focal PSMA prostatic uptake as well as the presence of enlarged low-PSMA expressing mediastinal lymphadenopathies, thus raising the suspicion of another malignancy. A subsequent 18F-Fluorodeoxyglucose (18F-FDG) PET/CT demonstrated a high FDG-avidity by mediastinal lymphadenopathies as opposed to the low prostate cancer FDG uptake. Of note, both tumor entities were clearly detected by the two scans. However, different ranges in terms of Maximum Standardized Uptake Value (SUVmax) uptake allowed the discrimination between the two tumor entities. At the subsequent mediastinal lymph nodal biopsy, the coexistence of Hodgkin lymphoma was documented. The present case suggests that even if specific for prostate cancer, 68Ga-PSMA-11 PET/CT may raise the suspicion of other concurrent malignancies thanks to its non-receptor bounding mechanism. Further, it shows that in certain cases, the combination of 18F-FDG and 68Ga-PSMA PET/CT imaging may non-invasively guide the clinical management, optimizing the diagnostic process and the subsequent therapeutic interventions.

A Model Based on Clusters of Similar Color and NIR to Estimate Oil Content of Single Olives.

Lipid extraction using the traditional, destructive Soxhlet method is not able to measure oil content (OC) on a single olive. As the color and near infrared spectrum are key parameters to build an oil estimation model (EM), this study grouped olives with similar color and NIR for building EM of oil content obtained by Soxhlet from a cluster of similar olives. The objective was to estimate OC of individual olives, based on clusters of similar color and NIR in two seasons. This study was performed with Arbequina olives in 2016 and 2017. The descriptor of the cluster consisted of the three color channels of c1c2c3 color model plus 11 reflectance points between 1710 and 1735 nm of each olive, normalized with the Z-score index. Clusters of similar color and NIR spectrum were formed with the k-means++ algorithm, leaving a sufficient number of olives to perform the Soxhlet analysis of OC, as reference value of EM. The training of EM was based on Support Vector Machine. The test was performed with Leave One-Out Cross Validation in different training-testing combinations. The best EM predicted the OC with 6 and 13% deviation with respect to the real value when one season was tested with itself and with another season, respectively. The use of clustering in EM is discussed.

New record of Arcella gandalfi (Amoebozoa: Arcellinida) from Colombia.

The reports of testate amoebae species in Colombia are limited to a few studies in lentic and peat bog systems; however, the diversity in lotic systems has been poorly investigated. Zooplankton sampling was performed in lotic environments of the Piedemonte Llanero in Colombia. Ten individuals of the species Arcella gandalfi were identified to document the first record of A. gandalfi from the Piedemonte Llanero in Colombia, expanding its distribution from Brazil to Colombia. This finding corroborates the status of A. gandalfi as a flagship species from the South America continent.

Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer.

INTRODUCTION: Breast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk. PATIENTS AND METHODS: Thirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups. RESULTS: Estrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform ß was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer. CONCLUSION: The decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation.

Performance Assessment of Thermal Infrared Cameras of Different Resolutions to Estimate Tree Water Status from Two Cherry Cultivars: An Alternative to Midday Stem Water Potential and Stomatal Conductance.

The midday stem water potential (Ψs) and stomatal conductance (gs) have been traditionally used to monitor the water status of cherry trees (Prunus avium L.). Due to the complexity of direct measurement, the use of infrared thermography has been proposed as an alternative. This study compares Ψs and gs against crop water stress indexes (CWSI) calculated from thermal infrared (TIR) data from high-resolution (HR) and low-resolution (LR) cameras for two cherry tree cultivars: 'Regina' and 'Sweetheart'. For this purpose, a water stress-recovery cycle experiment was carried out at the post-harvest period in a commercial drip-irrigated cherry tree orchard under three irrigation treatments based on Ψs levels. The water status of trees was measured weekly using Ψs, gs, and compared to CWSIs, computed from both thermal cameras. Results showed that the accuracy in the estimation of CWSIs was not statistically significant when comparing both cameras for the representation of Ψs and gs in both cultivars. The performance of all evaluated physiological indicators presented similar trends for both cultivars, and the averaged differences between CWSI's from both cameras were 11 ± 0.27%. However, these CWSI's were not able to detect differences among irrigation treatments as compared to Ψs and gs.

Aspectos éticos del uso de identificadores biométricos / Bioethical aspects of the use of biometric identifiers / Aspectos éticos do uso de identificadores biométricos

La biometría ha tenido una rápida expansión como tecnología, siendo cada vez más accesible para el público general, prestando utilidad a los gobiernos y a la sociedad en el manejo de la seguridad ciudadana. Se aplica para la verificación o la identificación de la identidad de un individuo y, desde un punto de vista puramente técnico, constituye un problema de reconocimiento de patrones. En Chile, el marco legal acerca del manejo de datos personales no incluye específicamente a la biometría. A la fecha, se encuentra en trámite un nuevo proyecto de ley que considera tanto los datos biométricos como los perfiles biológicos. En otros países, los informes de las últimas dos décadas, que analizan el uso de biometría, plantean como principal foco de preocupación, desde el punto de vista ético, el derecho a la privacidad de los individuos, entregándose orientaciones prácticas acerca de la aplicación apropiada de estas tecnologías. Finalmente, desde un breve análisis de la biopolítica, se contextualiza el papel que cumple la biometría y los requerimientos éticos básicos para su desarrollo en dicho marco.

Biometrics has had a rapid expansion as a technology, being increasingly accessible to the public, and lending utility to governments and society in the management of citizen security. It is applied either for verification or for identification of an individual's identity and technically constitutes a problem of pattern recognition. In Chile, the existing legal framework regarding the handling of personal data does not include specific biometrics in its regulation. A new bill that considers both biometric data and Biological profiles is in process. In addition, we revised the international reports of the last two decades that analyze the use of biometrics. The primary focus of concern of these documents, from the ethical point of view, is the right to privacy of individuals, giving practical guidance and discussion regarding the elements necessary for the application of these novel technologies in an appropriate ethically manner. Finally, we contextualize from a brief analysis of biopolitics the role of biometrics and the basic ethical requirements for its development in that framework.

A biometria teve uma rápida expansão como tecnologia, sendo cada vez mais acessível para o público geral, sendo de utilidade para os governos e à sociedade no manejo da segurança cidadã. Ela pode ser aplicada para a verificação ou estabelecimento da identidade de um indivíduo e, desde um ponto de vista puramente técnico, constitui um problema de reconhecimento de padrões. No Chile, o contexto legal acerca do manejo de dados pessoais não inclui especificamente a biometria. Atualmente, encontra-se tramitando um novo projeto de lei que considera tanto os dados biométricos como os perfis biológicos. Em outros países, os informes das últimas duas décadas que analisam o uso da biometria, propõem como principal foco de preocupação, do ponto de vista ético, o direito à privacidade dos indivíduos, entregando-se orientações práticas acerca da aplicação apropriada destas tecnologias. Finalmente, desde uma breve análise da bio-política, contextualiza-se o papel que cumpre a biometria e os requerimentos éticos básicos para seu desenvolvimento em tal contexto legal.

Assessment of urban environmental quality through the measurement of lead in bryophytes: case study in a medium-sized city.

The use of bryophytes as an indicator of environmental quality has been addressed on numerous occasions and in different places of the world under a variety of conditions. However, in Latin America their use is still limited. In the study described here, the presence and distribution of the bioaccumulation of lead in bryophytes has been evaluated in both contaminated and uncontaminated sites in Villavicencio (Colombia) and its surroundings. Villavicencio is a medium-sized city that is similar in size to many other cities in Latin America. A total of 52 samples of bryophytes were collected, of which 43 belong to points distributed in urban areas of the city (residential, commercial, highway), and the remaining nine are from uncontaminated areas (reference) taken in the surroundings of the city. The samples were treated with acid (nitric and hydrochloric) and subsequently measured by atomic absorption spectrometry. It was found that Pb concentrations in the commercial sector are between 1 and 6 times higher than in the residential and highway sectors. Spatial distribution maps of lead over the sampled territory were created using Arc-GIS 10.1. It is noteworthy that the values obtained are higher than those found in European cities.

El compostaje, una alternativa para el aprovechamiento de residuos orgánicos en las centrales de abastecimiento / Composting, an alternative for the use of organic residues In the supply centers / Compostagem, uma alternativa para o uso de resíduos orgânicos no suprimento central

Resumen La pérdida de alimentos a lo largo de la cadena de suministro se ha convertido en un tema de gran interés en el mundo, debido a que afecta la seguridad alimentaria de la sociedad. Uno de estos eslabones de la cadena de distribución de alimentos son las centrales de abasto local, donde diariamente se pierden importantes cantidades de alimentos especialmente por carencia de protocolos de poscosecha. El objetivo del presente estudio consistió en analizar la pérdida de alimentos en la central de abastos del municipio de Acacias, Colombia y evaluar el sistema de compostaje como alternativa de gestión ambiental. Se realizó mediante el método de cuarteo la estimación de la cantidad y tipo de residuos desperdiciados, que posteriormente se sometieron al proceso de compostaje donde se evaluó la calidad del producto. En conclusión, los residuos orgánicos son un problema ambiental que requiere de alternativas como el compostaje, que permite reducir la cantidad y aprovechar el contenido nutricional de la fracción orgánica, generando subproductos con alto valor agregado.

Abstract The loss of food along the supply chain has become a topic of great interest in the world, because this affect to the food security of society. One of these stages in the food distribution chain are the local supply centers, where important quantities of food are often lost, especially due to the lack of post-harvest protocols. The objective of this study was to analyze the loss of food in the supply center of the municipalities of Acacias, Colombia and evaluate the composting system as an alternative for environmental management. It was carried out by means of the quartering method the estimation of the quantity and type of residues lost, and subsequently, the composting process, where the quality of the product is evaluated. In conclusion, organic residues is an environmental problem that requires alternatives such as composting, which allows to reduce the amount and take advantage of the nutritional content of organic matter, generating by-products with high added value.

Resumo A perdida de alimentos ao longo da cadeia de fornecimento converteu-se em um tema de grande interesse no mundo, como isto afeta a segurança alimentar da sociedade. Um destes elos da cadeia de distribuição de alimentos são as centrais de abastecimento locais, onde diariamente se perdem importantes quantidades de alimentos especialmente por carência de protocolos de pós-colheita. O objetivo do presente estudo consistiu em analisar a perdida de alimentos na central de abastecimento do município de Acacias, Colômbia e avaliar o sistema de compostagem como alternativa de gerenciamento ambiental. Realizou-se mediante o método de cuarteo a estimativa da quantidade e tipo de resíduos perdidos, que posteriormente se submeteram ao processo de compostagem onde se avaliou a qualidade do produto. Em conclusão, os resíduos orgânicos são um problema ambiental que requer de alternativas como o compostagem, que permite reduzir a quantidade e aproveitar o conteúdo nutricional da fração orgânica, gerando subprodutos com alto valor agregado.

Correlation between B7-H4 and Survival of Non-Small-Cell Lung Cancer Patients Treated with Nivolumab.

Reliable predictors of benefit from immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are still limited. We aimed to evaluate the association between the expression of selected molecules involved in immune response and clinical outcomes in NSCLC patients receiving nivolumab. In our study, the outcomes of 46 NSCLC patients treated with nivolumab in second or subsequent lines (Nivolumab Cohort) were compared with the expression of PD-L1, PD-L2, PD-1, B7-H3, and B7-H4 assessed by immunohistochemistry (IHC). Samples from 17 patients (37.0%) in the Nivolumab Cohort were positive for B7-H4 expression. At univariate analyses, only B7-H4 expression was associated with significantly decreased progression-free survival (PFS; 1.7 vs. 2.0 months; p = 0.026) and with a disadvantage in terms of overall survival (OS) close to statistical significance (4.4 vs. 9.8 months; p = 0.064). At multivariate analyses, B7-H4 expression was significantly associated with decreased PFS (hazard ratio (HR) = 2.28; p = 0.021) and OS (HR = 2.38; p = 0.022). Subsequently, B7-H4 expression was compared with clinical outcomes of 27 NSCLC patients receiving platinum-based chemotherapy (Chemotherapy Cohort), but no significant association was observed. Our results suggest a negative predictive role of B7-H4 in a population of NSCLC treated with immune checkpoint inhibitors, which deserves further research.

Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma.

We report a case of an elderly woman presenting with a huge cervical mass invading the tracheal lumen. Diagnosed as invasive poorly differentiated thyroid cancer, after an endotracheal biopsy, stenting and radiotherapy, it was judged eligible for total thyroidectomy, but surgery was delayed due to pulmonary thromboembolism. The patient was therefore treated with lenvatinib with a neoadjuvant intent until hemodynamic stability was obtained. Thyroidectomy and radioiodine therapy were then performed and the postdose scan revealed an area of modest uptake in the anterior part of the neck. The patient is now in a good clinical status and she continues her follow-up program without any adjuvant therapy.

Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer.

Women treated for breast cancer (BC) are at risk of developing secondary tumors, such as lung cancer (LC). Since rare germline variants have been linked to multiple cancer development, we hypothesized that BC survivors might be prone to develop LC as a result of harboring rare variants. Sixty patients with LC with previous BC (the study population; SP) and 53 women with either BC or LC and no secondary cancer (control population; CP) were enrolled. Whole exome sequencing was performed in both tumors and unaffected tissues from 28/60 SP patients, and in germline DNA from 32/53 CP. Candidate genes were validated in the remaining individuals from both populations. We found two main mutational signature profiles: S1 (C>T) in all BCs and 16/28 LCs, and S2 (C>A) which is strongly associated with smoking, in 12/28 LCs. The burden test over rare germline variants in S1-LC vs CP identified 248 genes. Validation confirmed GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk.

Land-use-dependent spatial variation and exposure risk of heavy metals in road-deposited sediment in Villavicencio, Colombia.

Urbanization-induced land-use changes cause several environmental problems, especially in developing countries due to a lack of sufficient urban planning. This study was performed in a medium-size city of Villavicencio, Colombia. Copper, lead, nickel, zinc, chromium, manganese, and cadmium in road-deposited sediment (RDS) from different land uses were determined. Multiple geo- and statistical approaches of geographic information system mapping, Pearson correlation, Kruskal-Wallis H, hierarchical cluster analysis (HCA), and principal component analyze (PCA) were employed to assess the influence of land use on the metals' spatial distribution. The enrichment of given metals in RDS was evaluated by geo-accumulation (Igeo) and pollution load (PLI) indexes. The exposure human health risk was assessed by hazard index (HI). Results show that the average contents of the given metals decreased in the order of commercial > residential > highway > government institutions and public parks areas. Commercial areas thereafter always have the highest metals enrichment (Igeo) and pollution level (PLI). HI assessment indicates that child has a higher health risk than adult due to the exposure to metals in RDS. HCA analysis reveals that surface roughness had a more direct influence than land-use type on metals' distribution. Kruskal-Wallis H test further suggests land-use type had a significant influence on certain metals' spatial variation. Two potential (group) sources of geochemical and vehicular sources, along with leaded petrol and paintings, were inferred to be the main contributors to metals in RDS by PCA analysis.