Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer.

BACKGROUND: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. PATIENTS AND METHODS: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial. We utilized the GeoMxTM DSP system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was similar between both cohorts, except for SCLC-P, not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple co-existing transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity were not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ³12 months) contained an IFNg-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Pre-existing IFNg-driven immunity and mitochondrial metabolism seem correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

RET Fusion Testing in Patients With NSCLC: The RETING Study.

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion-positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET fusions not identified with RT-PCR were AKAP13(35)-RET(12), KIF5B(24)-RET(9) and KIF5B(24)-RET(11). All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

Innovación continuada en cirugía radioguiada de precisión / Continuous innovation in precision radio-guided surgery

Desde sus inicios, la medicina nuclear se ha enfrentado a cambios tecnológicos que la han obligado a modificar sus modos operativos y a adecuar sus protocolos. En el campo de la cirugía radioguiada (CRG), la incorporación de la imagen gammagráfica preoperatoria y la detección intraoperatoria con la sonda gamma proporcionó un impulso definitivo a la biopsia del ganglio centinela (GC) para convertirse en el procedimiento estándar de aplicación en el melanoma y el cáncer de mama. Las diversas innovaciones tecnológicas y la adaptación consiguiente de protocolos confluyen en lo disruptivo y lo gradual. Como ejemplos evidentes tenemos la introducción de la tomografía por emisión de fotón único/tomografía computarizada (SPECT/TC) en el campo preoperatorio y las sondas Drop-in (Lightpoint Medical Ltd; Crystal photonics, Eurorad) en el intraoperatorio. Otros aspectos innovadores con posible aplicación en la CRG se basan en la utilización de la inteligencia artificial (IA), navegación y teleasistencia (AU)

Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare (AU)

Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial.

BACKGROUND: In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy. METHODS: Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing EGFR/ALK alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population). Assessments included OS, progression-free survival, and objective response rate. Exploratory analyses included efficacy by tumor PD-L1 expression and histology and in patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events (TRAEs), and a treatment-switching adjustment analysis using inverse probability of censoring weighting. RESULTS: With a 47.9-month minimum follow-up for OS, nivolumab plus ipilimumab with chemotherapy continued to prolong OS over chemotherapy in all randomized patients (HR 0.74, 95% CI 0.63 to 0.87; 4-year OS rate: 21% versus 16%), regardless of tumor PD-L1 expression (HR (95% CI): PD-L1<1%, 0.66 (0.50 to 0.86) and ≥1%, 0.74 (0.60 to 0.92)) or histology (squamous, 0.64 (0.48 to 0.84) and non-squamous, 0.80 (0.66 to 0.97)). In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy due to TRAEs (n=61), the 4-year OS rate was 41%. With treatment-switching adjustment for the 36% of patients receiving subsequent immunotherapy in the chemotherapy arm, the estimated HR of nivolumab plus ipilimumab with chemotherapy versus chemotherapy was 0.66 (95% CI 0.55 to 0.80). No new safety signals were observed. CONCLUSIONS: In this 4-year update, patients treated with nivolumab plus ipilimumab with chemotherapy continued to have long-term, durable efficacy benefit over chemotherapy regardless of tumor PD-L1 expression and/or histology. A greater estimated relative OS benefit was observed after adjustment for subsequent immunotherapy use in the chemotherapy arm. These results further support nivolumab plus ipilimumab with chemotherapy as a first-line treatment for patients with metastatic/recurrent NSCLC, including those with tumor PD-L1<1% or squamous histology, populations with high unmet needs.

Sialolipoma of the parotid gland: A rare entity. Case report.

INTRODUCTION AND IMPORTANCE: Lipomatous neoplasms of the parotid gland represent an exceptionally rare and often underdiagnosed category of tumors, accounting for an incidence ranging from 0.6 % to 4.4 % of all neoplasms detected within the parotid gland. Sialolipoma is defined as an uncommon variant of lipoma, characterized by a well-defined proliferation of mature adipocytes with secondary entrapment of salivary gland elements, including serous acini, ducts, and myoepithelial cells. CASE PRESENTATION: The current case pertains to a 17-year-old female who presented with a one-year history of enlargement in the left preauricular region. CLINICAL DISCUSSION: The case we present poses a complex diagnostic challenge due to two distinct characteristics. The diagnostic challenge lies in its remarkably low incidence and the propensity for confusion with pleomorphic adenoma, which is the most common tumor of the parotid gland. It is a benign disease entity characterized by the absence of dysplasia, in marked contrast to pleomorphic adenoma. CONCLUSIONS: The infrequency in the manifestation of these tumor types, coupled with their prolonged asymptomatic course, can pose a diagnostic challenge. Enhancing our knowledge to comprehensively delineate these entities is imperative to effectively address the diagnostic complexities from both clinical and histopathological standpoints.

Continuous innovation in precision radio-guided surgery.

Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare.

Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer.

BACKGROUND: Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in a phase 1 trial in patients with previously treated small-cell lung cancer. METHODS: In this phase 2 trial, we evaluated the antitumor activity and safety of tarlatamab, administered intravenously every 2 weeks at a dose of 10 mg or 100 mg, in patients with previously treated small-cell lung cancer. The primary end point was objective response (complete or partial response), as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Overall, 220 patients received tarlatamab; patients had previously received a median of two lines of treatment. Among patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months in the 10-mg group and 10.3 months in the 100-mg group. An objective response occurred in 40% (97.5% confidence interval [CI], 29 to 52) of the patients in the 10-mg group and in 32% (97.5% CI, 21 to 44) of those in the 100-mg group. Among patients with an objective response, the duration of response was at least 6 months in 59% (40 of 68 patients). Objective responses at the time of data cutoff were ongoing in 22 of 40 patients (55%) in the 10-mg group and in 16 of 28 patients (57%) in the 100-mg group. The median progression-free survival was 4.9 months (95% CI, 2.9 to 6.7) in the 10-mg group and 3.9 months (95% CI, 2.6 to 4.4) in the 100-mg group; the estimates of overall survival at 9 months were 68% and 66% of patients, respectively. The most common adverse events were cytokine-release syndrome (in 51% of the patients in the 10-mg group and in 61% of those in the 100-mg group), decreased appetite (in 29% and 44%, respectively), and pyrexia (in 35% and 33%). Cytokine-release syndrome occurred primarily during treatment cycle 1, and events in most of the patients were grade 1 or 2 in severity. Grade 3 cytokine-release syndrome occurred less frequently in the 10-mg group (in 1% of the patients) than in the 100-mg group (in 6%). A low percentage of patients (3%) discontinued tarlatamab because of treatment-related adverse events. CONCLUSIONS: Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes in patients with previously treated small-cell lung cancer. No new safety signals were identified. (Funded by Amgen; DeLLphi-301 ClinicalTrials.gov number, NCT05060016.).

Bilateral inguinal hernia repair by laparoscopic totally extraperitoneal (TEP) vs. laparoscopic transabdominal preperitoneal (TAPP).

BACKGROUND: The guidelines recommend laparoscopic repair for bilateral inguinal hernia. However, few studies compare the totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) techniques in bilateral inguinal hernias. This study aimed to compare the outcomes of TEP and TAPP in bilateral inguinal hernia. METHODS: We conducted a retrospective cohort study of patients operated on for bilateral inguinal hernia by TEP and TAPP repair from 2016 to 2020. Intraoperative complications, operative time, acute postoperative pain, hospital stay, postoperative complications, chronic inguinal pain, and recurrence were compared. RESULTS: A total of 155 patients were included in the study. TEP was performed in 71 patients (46%) and TAPP in 84 patients (54%). The mean operative time was longer in the TAPP group than in the TEP group (107 min vs. 82 min, p < 0.001). The conversion rate to open surgery was higher in the TEP group than in the TAPP group (8.5% vs. 0%, p = 0.008). The mean hospital stay was longer in the TAPP group than in the TEP group (p < 0.001). We did not observe significant differences in the proportion of postoperative complications (p = 0.672), postoperative pain at 24 h (p = 0.851), chronic groin pain (p = 0.593), and recurrence (p = 0.471). We did not observe an association between the choice of surgical technique (TEP vs. TAPP) with conversion rate, operative time, hospital stay, postoperative complications, chronic inguinal pain, or hernia recurrence when performing a multivariable analysis adjusted for the male sex, age, BMI, ASA, recurrent hernia repair, surgeon, and hernia size > 3cm. CONCLUSIONS: Bilateral inguinal hernia repair by TEP and TAP presented similar outcomes in our study.

Sex Differences in the Efficacy of Immune Checkpoint Inhibitors in Neoadjuvant Therapy of Non-Small Cell Lung Cancer: A Meta-Analysis.

Non-small cell lung cancer (NSCLC) is one of the world's leading causes of morbidity and mortality. ICIs alone or combined with chemotherapy have become the standard first-line treatment of metastatic NSCLC. The impressive results obtained have stimulated our interest in applying these therapies in early disease stage treatments, as neoadjuvant immunotherapy has shown promising results. Among many of the factors that may influence responses, the role played by sex is attracting increased interest and needs to be addressed. Here, we aim to first review the state of the art regarding neoadjuvant ICIs, whether they are administered in monotherapy or in combination with chemotherapy at stages IB-IIIA, particularly at stage IIIA, before analyzing whether sex may influence responses. To this end, a meta-analysis of publicly available data comparing male and female major pathological responses (MPR) and pathological complete responses (pCR) was performed. In our meta-analysis, MPR was found to be significantly higher in females than in males, with an odds ratio (OR) of 1.82 (95% CI 1.13-2.93; p = 0.01), while pCR showed a trend to be more favorable in females than in males, but the OR of 1.62 was not statistically significant (95% CI 0.97-2.75; p = 0.08). Overall, our results showed that sex should be systematically considered in future clinical trials settings in order to establish the optimal treatment sequence.

SEOM-GECP Clinical guidelines for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) (2022)

SEOM-GECP Clinical guidelines for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) (2022) (AU)

Immunogenicity of COVID-19 vaccines in lung cancer patients.

OBJECTIVE: Patients with lung cancer are at increased risk of SARS-CoV-2 infection and severe complications from COVID-19, but information on the efficacy of anti-SARS-CoV-2 vaccine in these patients is scarce. We aimed at evaluating the safety and immunogenicity of COVID-19 vaccines in this population. PATIENTS AND METHODS: The prospective, nationwide SOLID substudy, enrolled adults with lung cancer who were fully vaccinated against COVID-19. Serum anti-SARS-CoV-2 IgG antibody levels were quantitatively assessed two weeks and six months after receipt of the last dose using a chemiluminescent microparticle immunoassay. Multivariate odds ratios for the association between demographic and clinical factors and seronegativity after vaccination were estimated. RESULTS: 1973 lung cancer patients were enrolled. Most patients had stage IV disease (66%) and were receiving active cancer treatment (82.7%). No significant differences were found in the probability of being seronegative for anti-SARS-CoV-2 IgG antibodies after full vaccination between patients who were receiving active cancer treatment and those who were not (p = 0.396). The administration of immunotherapy or oral targeted therapy and immunization with mRNA-1273 COVID-19 vaccine were factors independently associated with increased odds of being seropositive after vaccination. From all patients, 1405 received the second dose of vaccine and high levels of antibody titers were observed in 93.6% of patients two weeks after second dose. At six months, multivariate logistic regression analysis showed that performance status ≥ 2 was independently associated with a higher probability of being seronegative after full vaccination with an OR 4.15. On the other hand, received chemotherapy or oral target therapy and vaccination with mRNA-1273 were a factor independently associated with lower odds of being seronegative after full vaccination with an OR 0.52, 0.37 and 0.34, respectively. CONCLUSIONS: Lung cancer patients can safely achieve a strong immune response against SARS-CoV-2 after full vaccination, regardless of the cancer treatment received. TRIAL REGISTRATION: NCT04407143.

SEOM-GECP Clinical guidelines for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) (2022).

Small-cell lung cancer (SCLC) is a highly aggressive malignancy comprising approximately 15% of lung cancers. Only one-third of patients are diagnosed at limited-stage (LS). Surgical resection can be curative in early stages, followed by platinum-etoposide adjuvant therapy, although only a minority of patients with SCLC qualify for surgery. Concurrent chemo-radiotherapy is the standard of care for LS-SCLC that is not surgically resectable, followed by prophylactic cranial irradiation (PCI) for patients without progression. For extensive-stage (ES)-SCLC, a combination of platinum and etoposide has historically been a mainstay of treatment. Recently, the efficacy of programmed death-ligand 1 inhibitors combined with chemotherapy has become the new front-line standard of care for ES-SCLC. Emerging knowledge regarding SCLC biology, including genomic characterization and molecular subtyping, and new treatment approaches will potentially lead to advances in SCLC patient care.

Sex differences in the diagnosis, treatment and prognosis of cancer: the rationale for an individualised approach

Background Precision medicine in oncology aims to identify the most beneficial interventions based on a patient’s individual features and disease. However, disparities exist when providing cancer care to patients based on an individual’s sex. Objective To discuss how sex differences impact the epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment, with a focus on data from Spain. Results Genetic and environmental factors (social or economic inequalities, power imbalances, and discrimination) that contribute to these differences adversely affect cancer patient health outcomes. Increased health professional awareness of sex differences is essential to the success of translational research and clinical oncological care. Conclusions The Sociedad Española de Oncología Médica created a Task Force group to raise oncologists’ awareness and to implement measures to address sex differences in cancer patient management in Spain. This is a necessary and fundamental step towards optimizing precision medicine that will benefit all individuals equally and equitably (AU)

[COVID-19 in maternal, perinatal and neonatal mortality in four locations in Bogotá. Descriptive study.] / COVID-19 en la mortalidad materna, perinatal y neonatal de cuatro localidades de Bogotá. Estudio descriptivo.

OBJECTIVE: The multiple effects of the COVID-19 pandemic are beginning to be seen from the alteration of vital statistics figures. This is summarized in changes in the usual causes of death and excess attributable mortality, which can finally be seen in structural changes in the populations of the countries. For this reason, this research was created with the objective of determining the impact of the COVID-19 pandemic on maternal, perinatal and neonatal mortality in four locations in Bogotá D.C. (Colombia). METHODS: A retrospective longitudinal investigation was carried out in which 217,419 mortality data were analyzed in the towns of Kennedy, Fontibón, Bosa and Puente Aranda in the city of Bogotá - Colombia that occurred between the years 2018 to 2021, of which maternal (54), perinatal (1,370) and neonatal (483) deaths in order to identify a history of SARS-CoV-2 infection that could be related to the excess mortality associated with COVID-19. The data were collected from the open records of vital statistics of the National Statistics Department (DANE), where they were analyzed from frequency measures or central tendency and dispersion according to the types of variables. The specific mortality indicators related to maternal, perinatal and neonatal death events were calculated. RESULTS: A decrease in perinatal and neonatal mortality was evidenced since 2020, which was associated with the progressive decrease in pregnancies in those same years; Additionally, a considerable increase in maternal deaths was observed for 2021 compared to the other years analyzed. The proportion of maternal deaths in 2020 and 2021 by 10% and 17%, respectively, were attributed to COVID-19. CONCLUSIONS: It is observed that the trend of maternal mortality is related to the increase in mortality from COVID-19, maternal deaths associated with COVID-19 occurred specifically in the zonal planning units that registered more than 160 cases of COVID-19 for the year 2021.

OBJETIVO: Los múltiples efectos de la pandemia por la COVID-19 se empiezan a ver a partir de la alteración de las cifras de estadísticas vitales. Esto se resume en cambios en las causas de muertes habituales y el exceso de mortalidad atribuible, lo que finalmente se puede ver en modificaciones estructurales de las poblaciones de los países. Por esta razón se crea esta investigación que tuvo como objetivo determinar el impacto de la pandemia de COVID-19 sobre la mortalidad materna, perinatal y neonatal en cuatro localidades de Bogotá D.C. (Colombia). METODOS: Se realizó una investigación de tipo longitudinal retrospectiva en el que se analizaron 217.419 datos de mortalidades las localidades de Kennedy, Fontibón, Bosa y Puente Aranda de la ciudad de Bogotá - Colombia ocurridas entre los años 2018 a 2021, de los cuales se determinaron las muertes maternas (54), perinatales (1.370) y neonatales (483) a fin de identificar antecedente de infección por SARS-CoV-2 que pudiera estar relacionada con el exceso de mortalidad asociada a la COVID-19. Los datos fueron recopilados de los registros abiertos de estadísticas vitales del Departamento Nacional de Estadística (DANE), en donde fueron analizados a partir de medidas de frecuencias o tendencia central y dispersión de acuerdo con los tipos de variables. Se calcularon los indicadores de mortalidad específicos relacionados con los eventos de muerte materna, perinatal y neonatal. RESULTADOS: Se evidenció una disminución en la mortalidad perinatal y neonatal desde el año 2020, la cual estuvo asociada a la disminución progresiva de embarazos en esos mismos años; de forma adicional se observó un aumento considerable de las muertes maternas para 2021 con respecto a los demás años analizados. La proporción de las muertes maternas en 2020 y 2021 en un 10% y 17%, respectivamente, se atribuyeron a la COVID-19. CONCLUSIONES: Se observa que la tendencia de la mortalidad materna está relacionada con el aumento de la mortalidad por la COVID-19, las muertes maternas asociadas a COVID-19 se presentaron específicamente en las unidades de planeación zonal que registraron más de 160 casos de COVID-19 para el año 2021.

COVID-19 en la mortalidad materna, perinatal y neonatal de cuatro localidades de Bogotá. Estudio descriptivo / COVID-19 in maternal, perinatal and neonatal mortality in four locations in Bogotá. Descriptive study

Fundamentos: Los múltiples efectos de la pandemia por la COVID-19 se empiezan a ver a partir de la alteración de las cifrasde estadísticas vitales. Esto se resume en cambios en las causas de muertes habituales y el exceso de mortalidad atribuible, lo quefinalmente se puede ver en modificaciones estructurales de las poblaciones de los países. Por esta razón se crea esta investigaciónque tuvo como objetivo determinar el impacto de la pandemia de COVID-19 sobre la mortalidad materna, perinatal y neonatal encuatro localidades de Bogotá D.C. (Colombia).Métodos: Se realizó una investigación de tipo longitudinal retrospectiva en el que se analizaron 217.419 datos de mortalidades laslocalidades de Kennedy, Fontibón, Bosa y Puente Aranda de la ciudad de Bogotá - Colombia ocurridas entre los años 2018 a 2021, de loscuales se determinaron las muertes maternas (54), perinatales (1.370) y neonatales (483) a fin de identificar antecedente de infecciónpor SARS-CoV-2 que pudiera estar relacionada con el exceso de mortalidad asociada a la COVID-19. Los datos fueron recopilados delos registros abiertos de estadísticas vitales del Departamento Nacional de Estadística (DANE), en donde fueron analizados a partirde medidas de frecuencias o tendencia central y dispersión de acuerdo con los tipos de variables. Se calcularon los indicadores demortalidad específicos relacionados con los eventos de muerte materna, perinatal y neonatal.Resultados: Se evidenció una disminución en la mortalidad perinatal y neonatal desde el año 2020, la cual estuvo asociada a ladisminución progresiva de embarazos en esos mismos años; de forma adicional se observó un aumento considerable de las muertesmaternas para 2021 con respecto a los demás años analizados. La proporción de las muertes maternas en 2020 y 2021 en un 10% y17%, respectivamente, se atribuyeron a la COVID-19.Conclusiones: Se observa que la tendencia de la mortalidad materna está relacionada con el aumento de la mortalidad...(AU)

Background: The multiple effects of the COVID-19 pandemic are beginning to be seen from the alteration of vital statisticsfigures. This is summarized in changes in the usual causes of death and excess attributable mortality, which can finally be seen instructural changes in the populations of the countries. For this reason, this research was created with the objective of determining theimpact of the COVID-19 pandemic on maternal, perinatal and neonatal mortality in four locations in Bogotá D.C. (Colombia).Methods: A retrospective longitudinal investigation was carried out in which 217,419 mortality data were analyzed in the towns ofKennedy, Fontibón, Bosa and Puente Aranda in the city of Bogotá - Colombia that occurred between the years 2018 to 2021, of whichmaternal (54), perinatal (1,370) and neonatal (483) deaths in order to identify a history of SARS-CoV-2 infection that could be related tothe excess mortality associated with COVID-19. The data were collected from the open records of vital statistics of the National StatisticsDepartment (DANE), where they were analyzed from frequency measures or central tendency and dispersion according to the types ofvariables. The specific mortality indicators related to maternal, perinatal and neonatal death events were calculated.Results: A decrease in perinatal and neonatal mortality was evidenced since 2020, which was associated with the progressive de-crease in pregnancies in those same years; Additionally, a considerable increase in maternal deaths was observed for 2021 compared tothe other years analyzed. The proportion of maternal deaths in 2020 and 2021 by 10% and 17%, respectively, were attributed to COVID-19.Conclusions: It is observed that the trend of maternal mortality is related to the increase in mortality from COVID-19, maternaldeaths associated with COVID-19 occurred specifically in the zonal planning units that registered more than 160 cases of COVID-19for the year 2021.(AU)

FAMetA: a mass isotopologue-based tool for the comprehensive analysis of fatty acid metabolism.

The use of stable isotope tracers and mass spectrometry (MS) is the gold standard method for the analysis of fatty acid (FA) metabolism. Yet, current state-of-the-art tools provide limited and difficult-to-interpret information about FA biosynthetic routes. Here we present FAMetA, an R package and a web-based application (www.fameta.es) that uses 13C mass isotopologue profiles to estimate FA import, de novo lipogenesis, elongation and desaturation in a user-friendly platform. The FAMetA workflow covers the required functionalities needed for MS data analyses. To illustrate its utility, different in vitro and in vivo experimental settings are used in which FA metabolism is modified. Thanks to the comprehensive characterization of FA biosynthesis and the easy-to-interpret graphical representations compared to previous tools, FAMetA discloses unnoticed insights into how cells reprogram their FA metabolism and, when combined with FASN, SCD1 and FADS2 inhibitors, it enables the identification of new FAs by the metabolic reconstruction of their synthesis route.