Search

Abstract Background Lung ultrasound scoring is a validated tool for assessing lung pathology. However, existing scoring systems typically overlook the size of consolidations, limiting their accuracy in certain clinical scenarios. Case presentation We describe the first application of adding the maximum consolidation depth in centimeters (cm) to the conventional score. This modification (LUS+) was used in an eight-month-old patient with severe respiratory failure undergoing extracorporeal life support (ECLS). Spearman’s correlation analysis revealed a similar correlation in LUS+ compared to conventional lung ultrasound score. Importantly, LUS + showed improvement following cessation of lung rest on day 5, preceding the changes observed in conventional lung ultrasound scores and tidal volume measurements on day 9. Conclusions The integration of consolidation depth, quantified in centimeters, represents a valuable refinement of the conventional lung ultrasound score, enhancing its utility in monitoring pediatric acute respiratory distress patients undergoing ECLS.

BackgroundAs survival rates for lung cancer (LC) patients continue to rise, the adverse impacts of therapies become more relevant. Radiotherapy is known to negatively affect bone health. However, radiotherapy-induced vertebral fractures in lung cancer patients remain an exceedingly rare and underrecognized condition that could be mistaken for bone metastasis.Case presentationWe identified three LC patients (all long-term survivors), aged 67 to 81, who developed thoracic vertebral fractures post-chest radiotherapy, within irradiated fields; two had advanced non-small cell lung cancer (NSCLC) and one had extensive small cell lung cancer (SCLC). Baseline imaging confirmed that the fractures occurred after therapy. The median time from radiotherapy to fracture onset was 19 months (range: 1-30 months), with a median follow-up time from the initial fracture of 39 months (range: 37-61 months). All observed fractures were compressive in nature. These patients shared common characteristics, including advanced age, a history of heavy smoking, and high radiation doses. Additionally, hypermetabolic activity at the fracture sites necessitated MRI to differentiate these fractures from bone metastases. Management involved interventional strategies such as vertebroplasty, kyphoplasty, and rhizotomy, along with general and pharmacological measures to prevent subsequent fractures.ConclusionsDespite their low incidence, radiotherapy-induced vertebral fractures in LC patients are clinically significant and may resemble bone metastases on PET-CT imaging. MRI, alongside risk factors similar to those of osteoporosis, can facilitate prompt identification and differentiation. As survival rates in LC patients improve, the relevance of this adverse effect increases, underscoring the need for implementing bone protective strategies to further enhance patient outcomes and quality of life.

PURPOSECancer constitutes a significant global health challenge, with projections indicating a continued increase in its prevalence in the foreseeable future. This trend is particularly pronounced in Latin America (LATAM), where the cancer burden has increased substantially over the coming decades. Concurrently, nursing, which represents the largest segment of the health care workforce globally, is important for addressing the multifaceted challenges posed by cancer care, particularly in low- and middle-income countries (LMICs). Despite the essential role of nursing in cancer care, several barriers hinder its optimal contribution, particularly in LMICs. These challenges include professional hierarchy, insufficient educational standards, underfunding for research, and limited representation in decision-making processes.METHODSTo address these challenges, collaborative initiatives, such as the INCREASE Proposal, have emerged, aimed at fostering interdisciplinary dialogue and action in oncology nursing within LATAM. Through focused workshops and agile methodologies, the INCREASE Proposal seeks to identify barriers and formulate solutions across key areas including education, research, clinical practice, and policy implementation.RESULTSThe outcomes of the INCREASE Proposal underscore the urgent need for comprehensive strategies to strengthen oncology nursing in the LATAM. These strategies include enhancing education and recognition within health care systems, fostering interdisciplinary collaboration, leveraging advanced technologies, conducting cost-benefit analyses, and promoting research-academic partnerships.CONCLUSIONBy addressing these challenges and implementing the proposed solutions, LATAM can advance toward optimized oncology nursing practice, improving cancer care delivery and outcomes across the region.

PURPOSETargeted therapies are indicated for patients with non–small cell lung cancer (NSCLC) and driver tumor mutations. However, real-world studies on the survival benefits of these agents are limited. This study aimed to evaluate the effect of targeted therapies matched to a genomic alteration on the survival of patients with NSCLC.METHODSThis retrospective study included 446 patients with advanced NSCLC who underwent next-generation sequencing between 2016 and 2023 at the Instituto Nacional de Cancerología in Mexico. The primary outcomes were progression-free survival (PFS) and overall survival (OS).RESULTSFor the entire cohort, the PFS and OS were 10.71 months (95% CI, 9.35 to 12.06) and 47.77 months (95% CI, 29.67 to 65.86). PFS was significantly longer in patients with actionable mutations treated with targeted therapies (19.41 months [95% CI, 14.27 to 24.55]; P < .001) than in patients without actionable mutations (6.4 months [95% CI, 4.4 to 8.4]) or not treated with targeted therapies (6.6 months [95% CI, 5.3 to 7.89]). Similarly, OS was significantly longer in patients with actionable mutations treated with targeted therapies (89.69 months [95% CI, 45.54 to 133.84]; P < .001) than in patients without actionable mutations (17.11 months [95% CI, 8.65 to 25.57]) or not treated with targeted therapies (22.3 months [95% CI, 12.48 to 32.1]). Survival gains were driven by significant improvements in PFS and OS in patients with EGFR and ALK mutations.CONCLUSIONThis real-world data analysis demonstrated that targeted therapies improve the survival of patients with NSCLC with actionable mutations, which supports a recommendation for widening access to broad-based genomic testing and targeted therapies.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19) and has been related to more than 7 million deaths globally since 2019. The association of high levels of IL‐6 with severe cases led to the early evaluation of the anti‐IL6 inhibitor tocilizumab as a potential treatment, which unfortunately failed to improve survival in many trials. Moreover, little is known about the development of COVID‐19 sequelae, and biomarkers are needed to understand and anticipate these processes. Because extracellular vesicles (EVs) play an important role in viral infection and immune response, they could potentially serve as predictive and prognostic biomarkers. We isolated EVs from 39 patients with severe COVID‐19, from which 29 received tocilizumab and 10 were considered controls. Blood samples, which were collected at hospitalisation before treatment, at Day 7, and Day 15 during follow‐up, were assessed by immunoblot for longitudinal expression of spike (S) and nucleocapsid (N) proteins. Dynamic expression was calculated and compared with clinicopathological and experimental variables. Expression of EV S was validated by immunogold and imaging flow‐cytometry, revealing an enrichment in CD9+ EVs. As a result, decreasing expression of EV viral proteins was observed in patients treated with tocilizumab. Moreover, higher increase in EV S was observed in patients with lower antibody response, hyperfibrinogenemia, lower respiratory function, higher blood pressure and shorter outcomes. These findings lay the foundation for future studies characterizing the role of EVs in multiorgan assessment and identifying biomarkers in patients with severe COVID‐19 and possible long COVID.

Abstract Background Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs. Main body Here, we validated this model in a prospective cohort of patients receiving ICIs plus chemotherapy and compared it with patients undergoing chemotherapy alone. This multiparametric model showed high sensitivity and specificity at identifying non-responders to ICIs and outperformed tissue PD-L1, being directly correlated with tumor change. Short conclusion These findings indicate that the combination of radiomics and EV PD-L1 dynamics is a minimally invasive and promising biomarker for the stratification of patients to receive ICIs.

Abstract Introduction Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. Methods Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30 μg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. Results Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. Conclusions Among 5- to

Abstract Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 patients with stage III NSCLC undergoing cCRT. Our findings revealed that non-responders exhibited low levels of baseline EV miR-375, miR-200c, and miR-30c. In particular, EV miR-30c showed high predictive value with an area under the curve of 87.2%. Low EV miR-30c and the presence of autophagic-activated CTCs emerged as independent predictive biomarkers for shorter relapse-free survival and overall survival. Furthermore, in experimental models simulating the effects of chemo- and radiotherapy, the administration of miR-30c, either through direct transfection or encapsulation into human EVs, led to the inhibition of autophagy in these cells. This is the first report demonstrating that EV miR-30c inhibits tumor autophagy and its quantification, together with autophagic-activated CTCs, could be used as biomarkers for the stratification and monitoring of patients with NSCLC undergoing cCRT, and they may hold promising potential for guiding subsequent consolidation treatment with immunotherapy or other novel therapies based on autophagy inhibitors.

Abstract Background In Colombia, the best strategy to establish indication for adjuvant chemotherapy in early breast cancer (EBC) remains unknown. This study aimed to identify the cost-utility of Oncotype DX™ (ODX) or Mammaprint™ (MMP) tests to establish the necessity of adjuvant chemotherapy. Methods This study used an adapted decision-analytic model to compare cost and outcomes of care between ODX or MMP tests and routine care without ODX or MMP tests (adjuvant chemotherapy for all patients) over a 5-year time horizon from the perspective of the Colombian National Health System (NHS; payer). Inputs were obtained from national unit cost tariffs, published literature, and clinical trial database. The study population comprised women with hormone-receptor-positive (HR +), HER2-negative, lymph-node-negative (LN0) EBC with high-risk clinical criteria for recurrence. The outcome measures were discounted incremental cost-utility ratio (ICUR; 2021 United States dollar per quality-adjusted life-year [QALY] gained) and net monetary benefit (NMB). Probabilistic (PSA) and deterministic sensitivity analysis (DSA) were performed. Results ODX increases QALYs by 0.05 and MMP by 0.03 with savings of $2374 and $554 compared with the standard strategy, respectively, and were cost-saving in cost-utility plane. NMB for ODX was $2203 and for MMP was $416. Both tests dominate the standard strategy. Sensitivity analysis revealed that with a threshold of 1 gross domestic product per capita, ODX will be cost-effective in 95.5% of the cases compared with 70.2% cases involving MMP.DSA showed that the variable with significant influence was the monthly cost of adjuvant chemotherapy. PSA revealed that ODX was a consistently superior strategy. Conclusions Genomic profiling using ODX or MMP tests to define the need of adjuvant chemotherapy treatment in patients with HR + and HER2 −EBC is a cost-effective strategy that allows Colombian NHS to maintain budget.

Stirred tanks are often used in industrial applications to store and process liquids and solids. However, these systems have become an increasing challenge to improve and optimize these processes. Computational Fluids Dynamics (CFD) simulation predicts complex phenomena as hydrodynamics system performance. An optimal solution is found using an effective mesh scheme and selecting appropriate boundary conditions. This work aims to validate and describe the distribution velocities inside the tank using a rigorous turbulence model. Stirred tank with a diameter of 27 cm and an oval cone tip using a Rushton impeller (radial impeller) and a 4-blade impeller inclined at 45° (axial impeller) are performed. For both cases, hydrodynamics in the bottom tank is analyzed. In addition, the power and the pumping numbers for each impeller are studied. The overall results show that at the tip of the oval cone, the asymmetry in the mesh is improved, and the divergence in the solution is avoided. Also, the cone designer increased the turbulent kinetic energy, which can enhance the mixture process. A decrease in power impeller is shown when the axial type is applied at low Reynolds numbers; however, when the cone is introduced inside the tank and a radial impeller type is used, the impeller power values are increased. The overall results of CFD simulation are compared to experimental data and provide similar values with an absolute deviation below 4.46 %.

PURPOSEMultidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia.METHODSDemographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care.RESULTSA total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non–small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively.CONCLUSIONUsing an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients.

BackgroundProgrammed death ligand-1 (PD-L1) expression is a predictive biomarker in patients with lung cancer, but its role in malignant pleural mesothelioma (MPM) remains unclear. Evidence suggests that higher PD-L1 expression is correlated with worse survival. CALGB is the main scoring system used to predict the benefit of chemotherapy treatment. This study aimed to determine the prognostic value of PD-L1 expression and its addition to CALGB scoring system in patients with MPM.MethodsIn this retrospective analysis, we evaluated samples with confirmed locally advanced or metastatic MPM. PD-L1 Tumor Proportional Score (TPS) was determined by immunohistochemistry at diagnosis.Results73 patients were included in this study. A cutoff value of 15 was set for a high or low PD-L1 TPS. In total, 71.2% (n=52) and 28.8% (n=21) of individuals harbored low or high PD-L1 expression, respectively. PD-L1High was associated with worse median progression-free Survival (mPFS) [4.9 vs. 10.8 months; HR 2.724, 95% CI (1.44-5.14); p = 0.002] and Overall Survival (OS) [6.0 vs. 20.9 months; HR 6.87, 95% CI (3.4-8.7); p

Abstract Background Most studies evaluating factors associated with the survival of patients with brain metastases (BM) have focused on patients with newly diagnosed BM. This study aimed to identify prognostic factors associated with survival after brain re‐irradiation in order to develop a new prognostic index. Methods This 5‐year retrospective study included patients treated with repeat‐radiotherapy for recurrent BM at the “Instituto Nacional de Cancerología” of Mexico between 2015 and 2019. Significant variables in the multivariate Cox regression analysis were used to create the brain re‐irradiation index (BRI). Survival and group comparisons were performed using the Kaplan–Meier method and the log‐rank test. Results Fifty‐seven patients receiving brain re‐irradiation were identified. Most patients were women (75.4%) with a mean age at BM diagnosis of 51.4 years. Lung and breast cancer were the most prevalent neoplasms (43.9% each). Independent prognostic factors for shorter survival after re‐irradiation were: Age >50 years (hazard ratio [HR]:2.5 [95% confidence interval [CI], 1.1–5.8]; p = 0.026), uncontrolled primary tumor (HR:5.5 [95% CI, 2.2–13.5]; p 20 mm (4.6 [95% CI, 1.7–12.2]; p = 0.002), and an interval

Centrifugal pumps are turbomachines that have wide industrial applications and could perform in different ways such as pump and turbine mode. The maintenance of this equipment is mostly carried out using invasive methods that are expensive, time-consuming, and even complicated. The application of non-invasive methods is sought since they offer the advantage of real-time monitoring without stopping the process, reducing component assembly and disassembly times and providing a faster response. The aim of this work is done an experimental investigation that shows evidence about how the information on the hydraulic variables can be obtained if the electrical variables are monitored for the modes of operation such as pump and turbine. This work is divided into two parts, the first part is based on a statistical analysis to perform a multivariate adjustment through copulas and probability distributions. The second part focuses on the graphical analysis of the power density spectra for the hydraulic variables, the torque, and the defined electrical variables. The amplitude peaks of each variable and which peaks are common between them are determined. A statistically significant fit for Tawn type 2 copula is obtained with the indicator variable of pressure fluctuation and a multivariate transformation of the three-phase network currents. In the spectra analysis, common amplitude peaks are observed between the spectra that indicate the information flow on the phenomena between the hydraulic variables and the electrical variables.

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Abstract Background Programmed death ligand‐1 (PD‐L1) expression predicts immunotherapy utility in nononcogenic addictive lung adenocarcinoma (ADC). However, its reproducibility and reliability may be compromised outside clinical trials. This study aimed to evaluate factors associated with PD‐L1 expression in lung ADC. Methods This observational study assessed 547 tumor samples with advanced lung ADC from January 2016 to December 2020 in a single cancer institution. Tumor samples were stained by at least one approved PD‐L1 clone, SP263 (Ventana) or 22C3 (Dako), and stratified in tumor proportion score (TPS)

(1) Background: Liver kinase B1 (LKB1) is a tumor suppressor gene involved in cell growth and metabolism. However, its alterations are not routinely assessed for guiding therapy in clinical practice. We assessed LKB1 expression by immunohistochemistry as a potential biomarker. (2) Methods: This bicentric retrospective cohort study analyzed data from patients with advanced NSCLC who initiated platinum-based chemotherapy or epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI) between January 2016 and December 2020. Kaplan–Meier and Cox regression models were used for survival curves and multivariate analysis. (3) Results: 110 patients were evaluated, and the clinical stage IV predominated the lung adenocarcinoma histology. LKB1 loss was observed in 66.3% of cases. LKB1 loss was associated with non-smokers, the absence of wood smoke exposure and an EGFR wild-type status. The median progression-free survival (PFS) and overall survival (OS) in the population were 11.1 and 26.8 months, respectively, in the loss group, compared with cases exhibiting a positive expression. After an adjustment by age, smoking status, Eastern Cooperative Oncology Group Performance Score (ECOG-PS), EGFR status and type of administered therapy, LKB1 loss was significantly associated with worse PFS and OS. (4) Conclusion: Patients with an LKB1 loss had worse clinical outcomes. This study warrants prospective assessments to confirm the prognostic role of the LKB1 expression in advanced NSCLC.

BackgroundDifferent prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD).AimThe aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT.MethodsOut of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively.ResultsMinor PED was independently associated with a better iORR [78.8% vs. 50%, OR 3.71 (95% CI 1.26–10.99); p = 0.018] to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED [6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7–4.4); p < 0.001] independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS [18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4–3.3); p = 0.001].ConclusionHigher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.

The identification of Epidermal Growth Factor Receptor (EGFR) mutations in lung adenocarcinoma has facilitated the development of personalized medicine based on oncogenic drivers. EGFR-Tyrosine Kinase Inhibitors (TKIs) are part of the targeted therapy; they impede the phosphorylation of the intracellular tyrosine kinase component of EGFR and consequently block signal transduction pathways. These drugs inhibit the proliferation and survival of tumor cells, leading to long-term progression-free survival and overall survival. Diarrhea is one of the most frequent adverse events associated with EGFR-TKIs, affecting at least 18% of patients and reaching up to 95% in some cases. Diarrhea should be managed carefully given its association with important complications, treatment interruptions, and dose reductions. Moreover, nutritional status and quality of life (QoL) can deteriorate due to severe diarrhea. Changes in diet, such as increment of fiber, supplementation with glutamine, and use of probiotics, may contribute to a decrease in the incidence of diarrhea. Improving the control of diarrhea can provide a significant benefit to the QoL of patients.

Abstract Background Immune-checkpoint inhibitors (ICIs) changed the therapeutic landscape of patients with lung cancer. However, only a subset of them derived clinical benefit and evidenced the need to identify reliable predictive biomarkers. Liquid biopsy is the non-invasive and repeatable analysis of biological material in body fluids and a promising tool for cancer biomarkers discovery. In particular, there is growing evidence that extracellular vesicles (EVs) play an important role in tumor progression and in tumor-immune interactions. Thus, we evaluated whether extracellular vesicle PD-L1 expression could be used as a biomarker for prediction of durable treatment response and survival in patients with non-small cell lung cancer (NSCLC) undergoing treatment with ICIs. Methods Dynamic changes in EV PD-L1 were analyzed in plasma samples collected before and at 9 ± 1 weeks during treatment in a retrospective and a prospective independent cohorts of 33 and 39 patients, respectively. Results As a result, an increase in EV PD-L1 was observed in non-responders in comparison to responders and was an independent biomarker for shorter progression-free survival and overall survival. To the contrary, tissue PD-L1 expression, the commonly used biomarker, was not predictive neither for durable response nor survival. Conclusion These findings indicate that EV PD-L1 dynamics could be used to stratify patients with advanced NSCLC who would experience durable benefit from ICIs.

The combustion of ammonia (NH3) has sparked a renewed interest in the scientific community because it is a carbon-free fuel that does not contribute to global warming. Nevertheless, some of its disadvantages include the fact that (i) it has lower laminar flame speeds when compared to hydrocarbons, and (ii) that it is prone to the formation of nitride oxides (NOx) through the fuel route. As an alternative to address the first issue, it has been proposed to mix ammonia with hydrogen, but at the expense of even higher NOx emissions. Such emissions, however, can be reduced by operating at restrictive equivalence ratios near stoichiometry, which reduces oxygen availability in the reactions for NOx formation. This is a drawback because lean combustion, a technique that has been proven to reduce emissions for most fuels, is usually avoided in NH3 combustion. Therefore, with the goal of reducing NOx, this paper presents a numerical study using perfectly stirred reactors to investigate the potential use of both lean equivalence ratios and hydrogen enrichment in the MILD combustion of NH3. Some features of the MILD regime, such as low temperature increases due to reaction and the possibility of sustaining reactions under low oxygen concentrations, could be beneficial to ammonia combustion. Simulations were carried out in open-source software Cantera. According to the results, reaction can be sustained at lean equivalence ratios like 0.6 with a 50% hydrogen enrichment, and emissions of less than 100 ppm NO at 15% O2 on a dry basis can be obtained. In conclusion, MILD is a promising strategy for the clean burning of ammonia.

Purpose Identifying actionable oncogenic mutations have changed the therapeutic landscape in different types of tumors. This study investigated the utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) assay, in clinical practice in a developing country. Methods In this retrospective cohort study, CGP was performed on clinical samples from patients with different solid tumors recruited between December 2016 and November 2020, using hybrid capture-based genomic profiling, at the individual treating physicians’ request in the clinical care for therapy decisions. Kaplan–Meier survival curves were estimated to characterize the time-to-event variables. Results Patients median age was 61 years (range: 14–87 years), and 64.7% were female. The most common histological diagnosis was lung primary tumors, with 90 patients corresponding to 52.9% of the samples (95% CI 45.4-60.4%). Actionable mutations with FDA-approved medications for specific alterations correspondent to tumoral histology were identified in 58 cases (46.4%), whereas other alterations were detected in 47 different samples (37.6%). The median overall survival was 15.5 months (95% CI 11.7 months-NR). Patients who were subjected to genomic evaluation at diagnosis reached a median overall survival of 18.3 months (95% CI 14.9 months-NR) compared to 14.1 months (95% CI 11.1 months-NR) in patients who obtained genomic evaluation after tumor progression and during standard treatment ( P = .7). Conclusion CGP of different types of tumors identifies clinically relevant genomic alterations that have benefited from targeted therapy and improve cancer care in a developing country to guide personalized treatment to beneficial outcomes of cancer patients.

Lung cancer (LC) is one of the most common causes of death worldwide. The identification of oncogene-addicted driving mutations suitable for targeted therapy has improved clinical outcomes in advanced diseases. Clinical trials, on the other hand, rarely involve vulnerable groups such as pregnant women. We report a 37-year-old woman with advanced non-small cell lung cancer (NSCLC) harboring an exon 19 deletion of EGFR treated with afatinib. After the initial treatment, the patient achieved a complete response and had an unplanned pregnancy. Targeted therapy was withheld during the first trimester and resumed with osimertinib in the second trimester in which the patient developed oligohydramnios and intrauterine growth restriction (IUGR) of the baby. Osimertinib was delayed at two different times during the third trimester with complete resolution of the oligohydramnios. The baby was born at 37.3 weeks of gestation (WOG) with no signs of congenital disorders. After delivery, the mother restarted osimertinib and maintained a complete response. This case suggests that osimertinib could be an acceptable option for tumor control during pregnancy in EGFR-mutant NSCLC. This information do not replace current recommendations for avoiding pregnancy and promoting contraceptive usage in patients receiving any cancer therapy.

Abstract Lung cancer (LC) and pulmonary tuberculosis (TB) are the deadliest neoplastic and bacterial infectious diseases worldwide, respectively. Clinicians and pathologists have long discussed the co-existence of LC and TB, and several epidemiologic studies have presented evidence indicating that TB could be associated with the development of LC, particularly adenocarcinoma. Nonetheless, this data remains controversial, and the mechanism which could underlie the association remains largely unexplored. Some bioinformatic studies have shown that human cancer biopsies have a very high frequency of bacterial DNA integration; since Mycobacterium Tuberculosis (MTb) is an intracellular pathogen, it could play an active role in the cellular transformation. Our group performed an exploratory study in a cohort of 88 LC patients treated at the Instituto Nacional de Cancelorogía (INCan) of Mexico City to evaluate the presence of MTb DNA in LC tissue specimens. For the first time, our results show the presence of the MTb IS6110 transposon in 40.9% (n = 36/88) of patients with lung adenocarcinomas. Additionally, through in-situ PCR we identified the presence of IS6110 in the nuclei of tumor cells. Furthermore, shotgun sequencing from two samples identified traces of MTb genomes present in tumor tissue, suggesting that similar Mtb strains could be infecting both patients.

PURPOSECOVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments.METHODSThis was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group.RESULTSThere were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine.CONCLUSIONTo our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.

Summary: Background: Global brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers. Methods: This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort). Findings: A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex. Interpretation: Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region. Funding: This work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOS ACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and is usually not diagnosed until an advanced-stage disease is present. Chemotherapy is the recommended treatment; however, it is known that chemotherapy alone has a low cure rate, harmful side effects, and a lack of sensitivity. Therefore, alternatives to improve the patient's experience and outcomes with immunotherapy are being used as first-line treatment in patients with NSCLC. Patients may develop primary or acquired resistance against immunotherapy, and the mechanisms of resistance are not yet fully understood. Currently, several new approaches are being developed to overcome immunotherapy resistance in NSCLC. Herein, we briefly discuss pathways driving resistance to immunotherapy and new alternatives that are being developed to overcome resistance.

Next-generation medicine encompasses different concepts related to healthcare models and technological developments. In Latin America and the Caribbean, healthcare systems are quite different between countries, and cancer control is known to be insufficient and inefficient considering socioeconomically discrepancies. Despite advancements in knowledge about the biology of different oncological diseases, the disease remains a challenge in terms of diagnosis, treatment, and prognosis for clinicians and researchers. With the development of molecular biology, better diagnosis methods, and therapeutic tools in the last years, artificial intelligence (AI) has become important, because it could improve different clinical scenarios: predicting clinically relevant parameters, cancer diagnosis, cancer research, and accelerating the growth of personalized medicine. The incorporation of AI represents an important challenge in terms of diagnosis, treatment, and prognosis for clinicians and researchers in cancer care. Therefore, some studies about AI in Latin America and the Caribbean are being conducted with the aim to improve the performance of AI in those countries. This review introduces AI in cancer care in Latin America and the Caribbean, and the advantages and promising results that it has shown in this socio-demographic context.

Abstract Background Malignant Pleural Mesothelioma (MPM) is a rare but aggressive neoplasia that usually presents at advanced stages. Even though some advances have been achieved in the management of patients with MPM, this malignancy continuous to impose a deleterious prognosis for affected patients (12–18 months as median survival, and 5–10% 5-year survival rate), accordingly, the recognition of biomarkers that allow us to select the most appropriate therapy are necessary. Methods Immunohistochemistry semi-quantitative analysis was performed to evaluate four different biomarkers (ERCC1, RRM1, RRM2, and hENT-1) with the intent to explore if any of them was useful to predict response to treatment with continuous infusion gemcitabine plus cisplatin. Tissue biopsies from patients with locally advanced or metastatic MPM were analyzed to quantitatively asses the aforementioned biomarkers. Every included patient received treatment with low-dose gemcitabine (250 mg/m2) in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks as first-line therapy. Results From the 70 eligible patients, the mean and standard deviation (SD) for ERCC1, RRM1, RRM2 and hENT-1 were 286,178.3 (± 219, 019.8); 104,647.1 (± 65, 773.4); 4536.5 (± 5, 521.3); and 2458.7 (± 4, 983.4), respectively. Patients with high expression of RRM1 had an increased median PFS compared with those with lower expression (9.5 vs 4.8 months, p =

Abstract EGFR tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients is inevitable. Identification of resistance mechanisms and corresponding targeting strategies can lead to more successful later-line treatment in many patients. Using spectrometry-based proteomics, we identified increased fibroblast growth factor receptor 1 (FGFR1) expression and Akt activation across erlotinib, gefitinib, and osimertinib EGFR-TKI-resistant cell line models. We show that while combined EGFR-TKI and FGFR inhibition showed some efficacy, simultaneous inhibition of FGFR and Akt or PI3K induced superior synergistic growth inhibition of FGFR1-overexpressing EGFR-TKI-resistant NSCLC cells. This effect was confirmed in vivo. Only dual FGFR and Akt inhibition completely blocked the resistance-mediating signaling pathways downstream of Akt. Further, increased FGFR1 expression was associated with significantly lower PFS in EGFR-TKI-treated NSCLC patients, and increased FGFR1 were demonstrated in a few post- vs. pre-EGFR-TKI treatment clinical biopsies. The superior therapeutic benefit of combining FGFR and Akt inhibitors provide the rationale for clinical trials of this strategy.

Abstract Background Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. Methods This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. Results A total of 135 patients were included. Median age at diagnosis was 53 years old (19–84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0–1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka‐Koga system, overall survival (OS) at five‐years was 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1–7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3–12.7]; p = 0.016) were significantly associated with increased risk of death. Conclusions Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control.

We present the case of a 73-year-old male patient with a history of tobacco use who presented with a central nervous system mass that was confirmed to be a lung adenocarcinoma metastasis. High PD-L1 expression as well as negativity to other targetable drivers led to initiation of pembrolizumab monotherapy and ablative stereotactic radiation therapy on oligo­residual disease, achieving a complete response after 2 years of therapy. Following discontinuation of systemic treatment, the patient developed widespread desquamative plaques. A skin biopsy revealed subepidermal blistering and eosinophilic infiltration in conjunction with C3 and IgG depositions on the basement membrane, detected by immunofluorescence. A diagnosis of bullous pemphigoid was obtained, and systemic corticosteroids were administered with lesion progression. Infliximab was also administered without meaningful clinical improvement. Metronomic cyclophosphamide achieved a complete resolution of skin lesions and up to this day the patient continues with tumor control and is free of dermatological findings. In conclusion, bullous pemphigoid is a very rare dermatological adverse effect related with pembrolizumab treatment. Only two cases, including this one, have been reported, especially with this medication for the treatment of non-small cell lung cancer. With more reported cases, management strategies can be optimized even in the steroid refractory setting.

ObjectivesTo compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non-small cell lung cancer (NSCLC), one non-Hispanic White (NHW), and the other Latin-American.MethodsA multicenter retrospective study was performed, including 80 Hispanic and 45 NHW LA stage III NSCLC patients treated with cCRT followed by durvalumab. Both cohorts were analyzed in terms of main outcomes (OS, PFS, and safety) and compared between them and with the PACIFIC trial population outcomes. The efficacy-effectiveness gap was assessed using an efficacy-effectiveness (EE) factor that was calculated by dividing each cohort median overall survival by the corresponding reference OS from the PACIFIC trial. In both cohorts, results of PD-L1 testing were recorded, and the main outcomes were compared according to PD-1 expression levels (≥50%, 1–49%, and

PURPOSE In the midst of a global pandemic, evidence suggests that similar to other severe respiratory viral infections, patients with cancer are at higher risk of becoming infected by COVID-19 and have a poorer prognosis. METHODS We have modeled the mortality and the intensive care unit (ICU) requirement for the care of patients with cancer infected with COVID-19 in Latin America. A dynamic multistate Markov model was constructed. Transition probabilities were estimated on the basis of published reports for cumulative probability of complications. Basic reproductive number (R0) values were modeled with R using the EpiEstim package. Estimations of days of ICU requirement and absolute mortality were calculated by imputing number of cumulative cases in the Markov model. RESULTS Estimated median time of ICU requirement was 12.7 days, median time to mortality was 16.3 days after infection, and median time to severe event was 8.1 days. Peak ICU occupancy for patients with cancer was calculated at 16 days after infection. Deterministic sensitivity analysis revealed an interval for mortality between 18.5% and 30.4%. With the actual incidence tendency, Latin America would be expected to lose approximately 111,725 patients with cancer to SARS-CoV-2 (range, 87,116-143,154 patients) by the 60th day since the start of the outbreak. Losses calculated vary between < 1% to 17.6% of all patients with cancer in the region. CONCLUSION Cancer-related cases and deaths attributable to SARS-CoV-2 will put a great strain on health care systems in Latin America. Early implementation of interventions on the basis of data given by disease modeling could mitigate both infections and deaths among patients with cancer.

Background The intestinal microbiota is an important factor in modulating immune‐mediated tumor cell destruction. Alterations in the microbiome composition have been linked to reduced efficacy of immune checkpoint inhibitor (ICI) therapies. Therefore, antibiotic treatment (ATB), which modifies the diversity of the gut bacteria populations, could lead to a reduced efficacy of ICI treatments. Methods This was a retrospective cohort study. Patients with advanced non‐small cell lung cancer (NSCLC) treated with anti‐programmed cell death ligand‐1 (PD‐L1) alone, or in combination in three different countries in Latin America were included. After identification, patients were placed into three groups: Non‐ATB exposed (no‐ATB), exposed within 30 days of the first dose of ICI (pre‐ICI ATB) and patients receiving ATB concomitantly with ICI (ICI‐ATB). Progression‐free survival (PFS), overall survival (OS) and response rates to treatment with ICI were assessed. Results A total of 140 patients were included, of which 32 patients (23%) received ATB treatment. The most common ATB types were fluoroquinolones and B‐lactams. No differences in survival according to antibiotic type were identified. Median OS in patients not exposed to ATB was 40.6 months (95% CI: 32–67.7), compared with 20.3 months (95% CI: 12.1‐non‐reached [NR]) for patients with pre‐ICI ATB treatment and 24.7 months (95% CI: 13‐NR) for patients treated with ATB concomitantly with ICI. There were no significant differences in terms of PFS, or response rates across all treatment groups. Conclusions Antibiotic treatment was associated with reduced OS in Hispanic patients with NSCLC treated with ICIs.

Abstract Objective CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non‐Small Cell Lung Cancer (NSCLC) has not been completely understood. Materials and Methods In this retrospective study, CD47 expression was immunohistochemically examined in tumor biopsies from 169 NSCLC patients. The association of CD47 levels (H‐score) with clinicopathological characteristics and survival outcomes was evaluated. Results CD47 protein was detected in 84% of patients with a median expression of 80% (0‐100). Tumor CD47 levels above 1% and 50% were found in 84% and 65.7% of patients, respectively. While, median CD47 staining index was 160 (0‐300). Patients were divided into two groups according to CD47 expression (high or low), using a cutoff value of 150. High CD47 expression was associated with wood smoke exposure (71.1% vs 28.9%, P = .013) and presence of EGFR (+) mutations (66.7% vs 33.3%, P = .04). Survival analysis carried out in the whole population did not show any association of CD47 expression and survival outcome. However, in patients with EGFR (+) mutations, CD47 expression was associated with higher progression‐free survival (PFS) (12.2 vs. 4.4 months, P = .032). When the survival analysis was performed according to CD47 levels (cut off value: 150), both, PFS and overall survival (OS) were shortened in patients with a high expression of CD47 (10.7 vs. NR, P = .156) and (29.2 vs. NR months P = .023), respectively. Conclusions CD47 overexpression is not a prognostic factor for PFS and OS in NSCLC patients. However, the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS. Coexpression of these markers represents a potential biomarker and characterizes a therapeutic niche for lung cancer.

Abstract Background Previous studies have identified that patients with EGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT)‐related outcomes has not been fully assessed. We studied the impact of common non‐small cell lung cancer (NSCLC) genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases. Methods From 2009–2015, 153 patients with an available genotyping status were treated with whole‐brain irradiation (WBI) before receiving systemic therapy. Primary outcome was ORR; secondary outcomes included intracranial progression‐free survival (IPFS) and overall survival (OS). Results Overall, ORR was 47.1%. ORR to RT varied significantly according to molecular status: EGFR (64.5%) ALK (54.5%) KRAS (20%) and WT (35.4%) (P = 0.001). EGFR mutation was the only independently associated factor for response to WBI (RR 3.52 [95% CI 1.6–7.7]; P = 0.002). Median IPFS was 10.8 months [95% CI 8.2–13.5] overall; however, IPFS also varied significantly according to molecular status: EGFR (18.2 months), ALK (18.4 months), KRAS (6.0 months) and WT (8.7 months) (P

Due to the widespread use of immune checkpoint inhibitors and the growing research efforts in this area, immune-mediated toxicity is well recognized. Nonetheless, few severe cases of oral or upper gastrointestinal tract mucosal involvement have been documented. Early recognition and prompt treatment are key to the adequate management of these patients. We present a male 93-year-old patient with an advanced head and neck tumor treated with nivolumab who developed severe oral ulcers. After discontinuation of nivolumab, he received initial steroid treatment without any significant improvement. Histopathologic analysis of the lesions revealed a pattern similar to graft versus host disease. Extrapolating the results of colchicine mouth washing in patients with active oral ulcers and Behçet’s disease, this strategy was implemented with concomitant metronomic cyclophosphamide, achieving complete ulcer resolution. Metagenomic oral bacterial sequencing during instauration of the lesions and highest extension revealed a significant decrease in microbiomic diversity and expansion of Haemophilus parainfluenzae similar to patients with active Behçet’s disease. In conclusion, oral ulcers associated with immune checkpoint inhibitors correspond to a difficult-to-treat entity that could physiopathologically be related to both graft versus host disease and Behçet’s disease.

Background: The KRAS exon 2 p. G12C mutation in patients with lung adenocarcinoma has been increasing in relevance due to the development and effectiveness of new treatment medications. Studies around different populations indicate that regional variability between ethnic groups and ancestries could play an essential role in developing this molecular alteration within lung cancer. Methods: In a prospective and retrospective cohort study on samples from lung adenocarcinoma from 1000 patients from different administrative regions in Colombia were tested for the KRAS p.G12C mutation. An analysis of STR populations markers was conducted to identify substructure contributions to mutation prevalence. Results: Included were 979 patients with a national mean frequency for the KRAS exon 2 p.G12C mutation of 7.97% (95%CI 6.27–9.66%). Variation between regions was also identified with Antioquia reaching a positivity value of 12.7% (95%CI 9.1–16.3%) in contrast to other regions such as Bogota DC (Capital region) with 5.4% (2.7–8.2%) and Bolivar with 2.4% (95%CI 0–7.2%) (p-value = 0.00262). Furthermore, Short tandem repeat population substructures were found for eight markers that strongly yielded association with KRAS exon 2 p.G12C frequency reaching an adjusted R2 of 0.945 and a p-value of < 0.0001. Conclusions: Widespread identification of KRAS exon 2 p.G12C mutations, especially in cases where NGS is not easily achieved is feasible at a population based level that can characterize regional and national patterns of mutation status. Furthermore, this type of mutation prevalence follows a population substructure pattern that can be easily determined by population and ancestral markers such as STR.

Primary melanocytic tumors of the CNS are extremely rare conditions, encompassing different disease processes including meningeal melanoma and meningeal melanocytosis. Its incidence range between 3-5%, with approximately 0.005 cases per 100,000 people. Tumor biological behavior is commonly aggressive, with poor prognosis and very low survivability, and a high recurrence rate, even after disease remission with multimodal treatments. Specific genetic alterations involving gene transcription, alternative splicing, RNA translation, and cell proliferation are usually seen, affecting genes like BRAF, TERT, GNAQ, SF3B1, and EIF1AX. Here we present an interesting case of a 59-year-old male presenting with neurologic symptoms and a further confirmed diagnosis of primary meningeal melanoma. Multiple therapy lines were used, including radiosurgery, immunotherapy, and chemotherapy. The patient developed two relapses and an evolving genetic makeup that confirmed the disease’s clonal origin. We also provide a review of the literature on the genetic basis of primary melanocytic tumors of the CNS.

Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, and therapeutic management has advanced to identify various critical oncogenic mutations that promote lung cancer tumorigenesis. Subsequent studies have developed targeted therapies against these oncogenes in the hope of personalized treatment based on the tumor’s molecular genomics. This review presents a comprehensive review of the biology, new therapeutic interventions, and resistance patterns of two well-defined subgroups, tumors with KRAS and MET alterations. We also discuss the status of molecular testing practices for these two key oncogenic drivers, considering the progressive introduction of next-generation sequencing (NGS) and RNA sequencing in regular clinical practice.

The group contribution concept is used and a simple and general method is proposed for estimating phase change properties of ionic liquids. The proposal includes some especial characteristics, such as: (i) the model considers the well-known relation between the melting temperature, the heat of melting, and the entropy of melting; (ii) the model considers that a given group has a contribution value if the group occurs in the cation and another different value if it occurs in the anion; and (iii) the correlation process considers experimental data of melting temperature and heat of melting. Despite its simplicity, the proposed model provides deviations that are similar to other more sophisticated, multiparametric models. The literature analysis and our own results indicate that there are still some unknown facts that determine phase transitions and that models have not been able to include and quantify. All this indicates that the goal of having the most general and accurate model for predicting the melting temperature and melting enthalpy of ionic liquids is still far away. However, the present proposal represents a new attempt for contributing to this interesting puzzle of getting good and reasonable estimates for the melting properties which could help in choosing the appropriate ionic liquid for an existing or new application.

Background To compare survival outcomes of patients with advanced or metastatic non‐small cell lung cancer (NSCLC) who received immunotherapy as first‐, second‐ or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. Methods A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first‐, second‐, third‐ or fourth‐line of immunotherapy was conducted. A matched comparison with a historical cohort of first‐line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. Results Median age was 64 years (range 34–90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first‐line was given to 39 patients (13.7%), second‐line to 140 (48.8%), and as third‐line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67–14 months) and progression‐free survival (PFS) of 4.27 months (95% CI 3.97–5.0). Factors associated with increased survival included treatment with immunotherapy as first‐line (P