Is biochemical pregnancy loss associated with embryo or endometrium? A retrospective cohort study in frozen single embryo transfer of own and donated oocytes.

STUDY QUESTION: Does the use of preimplantation genetic testing for aneuploidies (PGT-A), personalized embryo transfer with endometrial receptivity assay (pET-ERA), or the use of donated oocytes modify the incidence of biochemical pregnancy loss (BPL) in frozen single embryo transfer (FSET)? SUMMARY ANSWER: Following FSET, BPL incidence does not differ between own and donated oocytes, and the use of PGT-A with euploid embryo transfer or pET-ERA results in a similar incidence of BPL compared to cycles without embryo or endometrial analysis. WHAT IS KNOWN ALREADY: BPL occurs frequently after IVF, and many factors have been associated with its incidence. The etiology of BPL is not well known, but the most probable cause seems to be either a low-quality embryo or impaired endometrial maintenance. The impact of techniques diagnosing embryonic ploidy or endometrial receptivity on BPL incidence and the BPL incidence between own and donated oocytes have not been analyzed. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study analyzing the incidence of BPL over 3741 cycles of FSET derived from own (2399 cycles) and donated (1342 cycles) oocytes between January 2013 and January 2022 in 1736 of which PGT-A, pET-ERA, or both were applied. PARTICIPANTS/MATERIALS, SETTING, METHODS: We defined BPL as a pregnancy diagnosed only by serum ß-hCG > 10 UI/l followed by a decrease that does not result in a clinical pregnancy. Clinical pregnancy was defined as the presence of gestational sac on transvaginal ultrasound. We compared BPL rates among patients undergoing 2399 FSETs from own oocytes, which comprised 1310 cycles of embryos analyzed by PGT-A, 950 cycles of untested embryos, 30 cycles of untested embryos with pET-ERA, and a subgroup of 109 cycles analyzed by both PGT-A and pET-ERA. We also included a total of 1342 FSET cycles from donated oocytes comprising 132, 1055, 140, and 15 cycles in the same groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In FSET from own oocytes, the overall BPL rate per embryo transfer was 8.2% (95% CI [7.09-9.33]). In untested embryo transfers, the BPL rate was 7.5% [5.91-9.37]. In the PGT-A group, the BPL rate was 8.8% [7.32-10.47]. In the pET-ERA group, the rate was 6.7% [0.82-22.07]. In the PGT-A+ERA group, the rate was 6.5% [2.65-12.90]. No significant differences were found (P = 0.626). A multivariate analysis considering clinically meaningful variables that were significantly different among groups, taking the untested embryos/endometrium group as a reference, showed comparable incidences among groups. For PGT-A, the adjusted odds ratio (AdjOR) was 1.154 [0.768-1.735] (P = 0.49) and for PGT-A+ERA 0.885 [0.330-2.375] (P = 0.808). Because of a low number of registered cases in the pET-ERA group, and to prevent statistical errors and convergence issues, this group was excluded from further analysis. In FSET of donated oocytes, the overall BPL rate per embryo transfer was 4.9% [3.76-6.14]. In the PGT-A group, the BPL rate was 6.8% [3.16-12.55]. In the pET-ERA group, the rate was 5.0% [2.03-10.03]. In untested embryo transfers, the rate was 4.7% [3.46-6.10]. No cases occurred in the PGT-A+ERA group, and no significant differences were found (P = 0.578). The multivariate analysis showed comparable incidences among groups. For PGT-A the AdjOR was 1.669 [0.702-3.972] (P = 0.247) and for pET-ERA 1.189 [0.433-3.265] (P = 0.737). The PGT-A+ERA group was eliminated from the model to prevent statistical errors and convergence issues because no BPL cases were registered in this group. In the multivariate analysis, when the sources of oocytes were compared, own versus donated, no significant differences were found in the incidence of BPL. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective cohort study with potential biases. In addition, we were unable to control differences among groups due to modifications in medical or laboratory protocols during this long time period, which may modify the relationships being addressed. Factors previously associated with BPL, such as immunological conditions other than thyroid autoimmunity, were not considered in this study. Limited sample sizes of some groups may limit the statistical power for finding differences that can be present in the general population. WIDER IMPLICATIONS OF THE FINDINGS: BPL may be related to a mechanism not associated with the chromosomal constitution of the embryo or the transcriptome of the endometrium. More studies are needed to explore the factors associated with this reproductive issue. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was available for this study. None of the authors have a conflict of interest to declare with regard to this study. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov (NCT04549909).

De-escalating axillary management after neoadjuvant chemotherapy in breast cancer: The ratio of positive sentinel lymph nodes matters.

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) patients diminishes sequelae without compromising cancer outcomes. Surgical management of the axilla is challenging after neoadjuvant treatment. We aimed to identify the factors associated with residual axillary disease amenable to lymphadenectomy in patients with positive sentinel lymph node biopsy (SLNB). METHODS: We conducted a retrospective observational study in Hospital 12 de Octubre (Spain). We included BC patients with positive SLNB who underwent axillary dissection after neoadjuvant chemotherapy. Univariate and multivariate logistic regression models were performed to identify independent predictors of residual axillary disease. We estimated the ratio of positive nodes in SLNB and assessed the diagnostic validity of this ratio in relation to residual axillary disease. RESULTS: We included 103 patients in the study. Residual axillary disease was identified in 54 patients (52.4%). Clinically node positive status at diagnosis (OR = 18.3, 95%CI: 4.0-83.6) and a ratio of positive nodes in SLNB ≥0.5 (OR = 6.5, 95%CI 41.7-23.7) were associated with residual axillary disease. The sensitivity and negative predictive value of a ratio of positive nodes in SLNB ≥0.5 were 87% (95%CI 75.1%-94.6%) and 75% (95%CI 55.1%-89.3%), respectively. CONCLUSIONS: In our study, for patients with positive SLNB after neoadjuvant chemotherapy, stage N+ at diagnosis and a ratio of positive nodes in SLNB ≥0.5 were independent risk factors of positive residual axillary disease. This ratio is a feasible measure with a good diagnostic validity for residual axillary disease and could be used as a guiding factor in the surgical management of these patients.

Gemcitabine combination therapies induce apoptosis in uterine carcinosarcoma patient-derived organoids.

Uterine carcinosarcoma (UCS) is a rare but aggressive endometrial cancer. Survival outcomes for women diagnosed with UCS remain poor with lower survival than those of endometrioid or high-grade serous uterine cancers. The histopathological hallmark of carcinosarcoma is the presence of both sarcomatous and carcinomatous elements. The survival rates for UCS have not improved for over 40 years; therefore, there is a profound need to identify new treatments. To investigate novel chemotherapy treatment combinations for UCS, we generated a UCS patient-derived organoid (PDO) cell line from a patient that received neoadjuvant treatment with paclitaxel and carboplatin. The PDO cell line (UCS1) was grown in three-dimensional domes. The PDO domes were treated with six individual chemotherapies or nine combinations of those six drugs. Cell death in response to chemotherapy was assessed. We found that the six monotherapies had minimal effectiveness at inducing cell death after 48 h of treatment. The combination of paclitaxel and carboplatin (which is the standard-of-care chemotherapy treatment for UCS) led to a small increase in apoptosis compared with the monotherapies. Importantly, when either carboplatin or paclitaxel was combined with gemcitabine, there was an appreciable increase in cell death. In conclusion, for the UCS1 patient-derived tumor cells, gemcitabine combinations were more effective than carboplatin/paclitaxel. Our data support the use of PDOs to predict responses to second-line chemotherapy.

Reflexiones sobre la aplicación de la "Ley Trans” en la atención sanitaria / Reflections on the application of the “trans law” in health care

En este artículo se reflexiona sobre la reciente ley aprobada por el Congreso de los Diputados conocida como Ley 4/2023 para la igualdad real y efectiva de las personas trans y para la garantía de los derechos de las personas LGTBI (BOE-A-2023-5366, 2023). Se analizan inicialmente los artículos que más polémica han causado en el ámbito social, que son los relativos a la rectificación registral (Art. 43-51), y posteriormente los que hacen referencia directa o indirectamente a aspectos sanitarios; 1) el que prohíbe de métodos, programas o las llamadas terapias de conversión (Art. 17), 2) los que definen cómo debe ser en términos generales la atención sanitaria (Art. 56-59), y 3) finalmente el único artículo que menciona a los menores (Art 70). Se comenta que el término utilizado de persona trans, al englobar un amplio abanico de diversidades sexuales, variantes y expresiones de género, incluye tanto a personas que necesitan una atención médica como a otras que no. Se plantea que la rectificación registral acorde con esta ley 2023 al no precisar ningún requisito para su inscripción, ofrece menos garantías que la legislación ya existente de marzo 2007. Se considera que las directrices de la nueva ley se están traduciendo en una toma de decisiones por parte del usuario sin disponer de una valoración o diagnóstico por el equipo de profesionales que atienden el caso. Se destaca que la ley no incluye ninguna referencia a la atención por salud mental. Y en conjunto, se concluye que el texto aprobado, en el ámbito sanitario, puede mermar la calidad de la asistencia integral, sobre todo en menores, o personas con identidades complejas, dudosas, o con comorbilidades, que pueden generar discrepancia entre el criterio del profesional y la opinión del usuario.(AU)

Metabolically defined body size and body shape phenotypes and risk of postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of C-peptide-a marker for insulin secretion-were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C-peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI < 25 kg/m2 , or WC < 80 cm, or WHR < 0.8) and overweight or obese (OW/OB; BMI ≥ 25 kg/m2 , or WC ≥ 80 cm, or WHR ≥ 0.8) status for each of the three anthropometric measures separately: (1) MHNW, (2) MHOW/OB, (3) MUNW, and (4) MUOW/OB. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14-2.19) and WC (OR = 1.51, 95% CI = 1.09-2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94-1.77) definition. Conversely, women with the MHOW/OB and MUNW were not at statistically significant elevated risk of postmenopausal breast cancer risk compared to MHNW women. CONCLUSION: These findings suggest that being overweight or obese and metabolically unhealthy raises risk of postmenopausal breast cancer while overweight or obese women with normal insulin levels are not at higher risk. Additional research should consider the combined utility of anthropometric measures with metabolic parameters in predicting breast cancer risk.

Associations between food portion sizes, insulin resistance, VO2 max and metabolic syndrome in European adolescents: The HELENA study.

BACKGROUND AND AIMS: This study aims to examine the associations of food portion size (PS) with markers of insulin resistance (IR) and clustered of metabolic risk score in European adolescents. METHODS: A total of 495 adolescents (53.5% females) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study were included. The association between PS from food groups and homeostasis model assessment of insulin resistance (HOMA-IR) index, VO2 max, and metabolic risk score was assessed by multilinear regression analysis adjusting for several confounders. Analysis of covariance (ANCOVA) was used to determine the mean differences of food PS from food groups by HOMA-IR cutoff categories by using maternal education as a covariable. RESULTS: Larger PS from vegetables in both gender and milk, yoghurt, and milk beverages in males were associated with higher VO2 max, while larger PS from margarines and vegetable oils were associated with lower VO2 max (p < 0.05). Males who consumed larger PS from fish and fish products; meat substitutes, nuts, and pulses; cakes, pies, and biscuits; and sugar, honey, jams, and chocolate have a higher metabolic risk score (p < 0.05). Males with lower HOMA-IR cutoff values consumed larger PS from vegetables, milk, yoghurt, and milk beverages (p < 0.05). Females with lower HOMA-IR cutoff values consumed larger PS from breakfast cereals, while those with higher HOMA-IR cutoff values consumed larger PS from butter and animal fats (p = 0.018). CONCLUSION: The results show that larger PS from dairy products, cereals, and high energy dense foods are a significant determinant of IR and VO2 max, and larger PS from food with higher content of sugar were associated with higher metabolic risk score.

Hierarchical Classification from Relational Frame Theory: A Review

Hierarchical classification is of tremendous interest to both basic and applied research. This review explores hierarchical classification empirical studies from Relational Frame Theory (RFT). We identified 11 empirical articles that met inclusion criteria (demonstrated hierarchical responding in children or adults with an RFT theoretical approach). The objective of this qualitative systematic review is to offer both researchers and practitioners a solid and comprehensive view of types of protocols used from an RFT approach in establishing and analyzing hierarchical classification. Limitations and possible future research is discussed (AU)

In children and adolescents with temporomandibular disorder assembled with juvenile idiopathic arthritis - no association were found between pain and TMJ deformities using CBCT.

BACKGROUND: Children and adolescents with juvenile idiopathic arthritis (JIA) may suffer from temporomandibular disorder (TMD). Due to this, imaging diagnosis is crucial in JIA with non-symptomatic TM joint (TMJ) involvement. The aim of the study was to examine the association between clinical TMD signs/symptoms and cone-beam computed tomography (CBCT) findings of TMJ structural deformities in children and adolescents with JIA. METHODS: This cross-sectional study is part of a longitudinal prospective multi-centre study performed from 2015-2020, including 228 children and adolescents aged 4-16 years diagnosed with JIA, according to the International League of Associations for Rheumatology (ILAR). For this sub-study, we included the Bergen cohort of 72 patients (32 female, median age 13.1 years, median duration of JIA 4.5 years). Clinical TMD signs/symptoms were registered as pain on palpation, pain on jaw movement, and combined pain of those two. The severity of TMJ deformity was classified as sound (no deformity), mild, or moderate/severe according to the radiographic findings of CBCT. RESULTS: Of 72 patients, 21 (29.2%) had pain on palpation at and around the lateral pole, while 41 (56.9%) had TMJ pain upon jaw movement and 26 (36.1%) had pain from both. Of 141 TMJs, 18.4% had mild and 14.2% had moderate/severe structural deformities visible on CBCT. CBCT findings were not significantly associated with either the pain on palpation or the pain on jaw movement. A significant difference was found between structural deformities in CBCT and the combined pain outcome (pain at both palpation and movement) for both TMJs for the persistent oligoarticular subtype (p = 0.031). CONCLUSIONS: There was no association between painful TMD and CBCT imaging features of the TMJ in patients with JIA, but the oligoarticular subtype of JIA, there was a significant difference associated with TMJ pain and structural CBCT deformities.

Search for Lepton Number and Flavor Violation in K

Searches for the lepton number violating K^{+}→π^{-}µ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}µ^{-}e^{+} and π^{0}→µ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}µ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}µ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→µ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

Mortalidad en pacientes con hemorragia intracerebral asociada a anticoagulación oral. Eficacia de un protocolo de reversión y seguimiento clínico (proyecto HIC-ACO) / Mortality in patients with intracerebral haemorrhage associated with oral anticoagulation. Efficacy of a reversal protocol and clinical follow-up (ICH-OAC project)

Introducción: La hemorragia intracerebral espontánea asociada a anticoagulantes orales (HIC-ACO) presenta una elevada mortalidad. La aparición de nuevos fármacos anticoagulantes y protocolos de reversión aumenta el interés por esta entidad. Objetivos: El objetivo principal es determinar la tasa de mortalidad en pacientes con HIC-ACO (precoz, hospitalaria, global) en nuestra área sanitaria y analizar las principales variables relacionadas. El objetivo secundario es determinar la eficacia de las terapias de reversión de la anticoagulación (TRA), reflejada por la expansión radiológica del hematoma y el pronóstico funcional. Pacientes y métodos: Estudio prospectivo observacional que introdujo un protocolo dirigido al manejo de pacientes con HIC-ACO. Incluyó medidas generales y neuromonitorización, administración individualizada de TRA, tomografía craneal y seguimiento durante seis meses. Se recogieron los fármacos prescritos en el área durante este período, mortalidad y pronóstico funcional. Se diseñó un estudio bivariante y regresión logística para investigar variables relacionadas con la mortalidad. Resultados: Se incluyó a 49 pacientes durante tres años; de ellos, un 71,4% recibió TRA. La mortalidad fue del 16,3% (primeras 24 horas), el 53,1% (ingreso) y el 61,2% (180 días). Se observó una menor supervivencia entre pacientes con puntuaciones basales mayores en la National Institutes of Healt Stroke Scale (NIHSS) (p < 0,0001), valor de creatinina (p = 0,02), índice internacional normalizado (p = 0,048), volumen hemorrágico (p = 0,008), hidrocefalia (p = 0,015) y toma de acenocumarol (p = 0,030). Los pacientes que no recibieron TRA tuvieron una mayor mortalidad precoz (p = 0,003). La única variable relacionada con la mortalidad global de forma independiente fue la puntuación en la NIHSS basal (odds ratio = 1,282; intervalo de confianza al 95%: 1,023-1,608; p = 0,031)...(AU)

Introduction: Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity. Objectives: The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis. Patients and methods: A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables. Results: Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031)...(AU)

Cervical Recurrence from an Intraparotid Kimura Disease.

INTRODUCTION: Kimura disease is a rare, benign, chronic, lymphoproliferative disorder of unknown etiology that affects the skin and lymph nodes and mostly observed in males of Asia. CASE REPORT: We report a 55-year-old man who presented neck and intraparotid lymphadenopathy. Surgical removal of the growth confirmed the histological diagnosis of Kimura disease. DISCUSSION: Kimura disease is endemic in the Far East (China and Japan) but exceptional in Europe; < 200 cases have been reported in the literature, with less than 40 involving a parotid region. The histological characteristics of Kimura disease are lymphocyte follicular hyperplasia, eosinophilic tissue infiltration, fibrocollagenous deposition and vascular proliferation. Main treatment is surgical, but recurrence is frequent. CONCLUSION: Kimura disease is a rare condition, but should be considered in the case of cervical mass associated with hypereosinophilia and/or strongly elevated IgE levels, especially in Far Eastern patients.

[Mortality in patients with intracerebral haemorrhage associated with oral anticoagulation. Efficacy of a reversal protocol and clinical follow-up (ICH-OAC project)]. / Mortalidad en pacientes con hemorragia intracerebral asociada a anticoagulación oral. Eficacia de un protocolo de reversión y seguimiento clínico (proyecto HIC-ACO).

INTRODUCTION: Spontaneous intracerebral haemorrhage associated with oral anticoagulants (ICH-OAC) has a high mortality rate. The emergence of new anticoagulant drugs and reversal protocols increases interest in this entity. OBJECTIVES: The main objective is to determine the mortality rate in patients with ICH-OAC (early, in-hospital, global) in our health area and to analyse the main variables related to it. The secondary objective is to determine the efficacy of anticoagulation reversal therapies (ART) as reflected by radiological expansion of the haematoma and the functional prognosis. PATIENTS AND METHODS: A prospective observational study that introduced a protocol aimed at the management of patients with ICH-OAC. It included general measures and neuromonitoring, individualised administration of ART, cranial tomography and a six-month follow-up. Data on the drugs prescribed in the area during this period, mortality and functional prognosis were collected. A bivariate and logistic regression study was designed to investigate mortality-related variables. RESULTS: Forty-nine patients were included over three years; of these, 71.4% received ART. Mortality was 16.3% (first 24 hours), 53.1% (admission) and 61.2% (180 days). Lower survival was observed among patients with higher baseline scores on the National Institutes of Health Stroke Scale (NIHSS) (p < 0.0001), creatinine value (p = 0.02), International Normalised Index (p = 0.048), bleeding volume (p = 0.008), hydrocephalus (p = 0.015) and acenocoumarol intake (p = 0.030). Patients who did not receive ART had a greater rate of early mortality (p = 0.003). The only variable independently related to overall mortality was the baseline NIHSS score (odds ratio = 1.282; 95% confidence interval: 1.023-1.608; p = 0.031). CONCLUSIONS: ICH-OAC has a high mortality rate, related to the use of acenocoumarol and regardless of the initial clinical situation. A lower rate of early mortality was found among patients who received ART.

TITLE: Mortalidad en pacientes con hemorragia intracerebral asociada a anticoagulación oral. Eficacia de un protocolo de reversión y seguimiento clínico (proyecto HIC-ACO).Introducción. La hemorragia intracerebral espontánea asociada a anticoagulantes orales (HIC-ACO) presenta una elevada mortalidad. La aparición de nuevos fármacos anticoagulantes y protocolos de reversión aumenta el interés por esta entidad. Objetivos. El objetivo principal es determinar la tasa de mortalidad en pacientes con HIC-ACO (precoz, hospitalaria, global) en nuestra área sanitaria y analizar las principales variables relacionadas. El objetivo secundario es determinar la eficacia de las terapias de reversión de la anticoagulación (TRA), reflejada por la expansión radiológica del hematoma y el pronóstico funcional. Pacientes y métodos. Estudio prospectivo observacional que introdujo un protocolo dirigido al manejo de pacientes con HIC-ACO. Incluyó medidas generales y neuromonitorización, administración individualizada de TRA, tomografía craneal y seguimiento durante seis meses. Se recogieron los fármacos prescritos en el área durante este período, mortalidad y pronóstico funcional. Se diseñó un estudio bivariante y regresión logística para investigar variables relacionadas con la mortalidad. Resultados. Se incluyó a 49 pacientes durante tres años; de ellos, un 71,4% recibió TRA. La mortalidad fue del 16,3% (primeras 24 horas), el 53,1% (ingreso) y el 61,2% (180 días). Se observó una menor supervivencia entre pacientes con puntuaciones basales mayores en la National Institutes of Healt Stroke Scale (NIHSS) (p lower than 0,0001), valor de creatinina (p = 0,02), índice internacional normalizado (p = 0,048), volumen hemorrágico (p = 0,008), hidrocefalia (p = 0,015) y toma de acenocumarol (p = 0,030). Los pacientes que no recibieron TRA tuvieron una mayor mortalidad precoz (p = 0,003). La única variable relacionada con la mortalidad global de forma independiente fue la puntuación en la NIHSS basal (odds ratio = 1,282; intervalo de confianza al 95%: 1,023-1,608; p = 0,031). Conclusiones. La HIC-ACO presenta una elevada mortalidad, relacionada con la toma de acenocumarol y de forma independiente con la situación clínica inicial. Se comprobó una menor tasa de mortalidad precoz entre pacientes que recibieron TRA.

Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer.

BACKGROUND: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. PATIENTS AND METHODS: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. RESULTS: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations. CONCLUSIONS: SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.

Radon alpha track counting on solid state nuclear track detector by an ImageJ-based software macro.

Radon (222Rn) is a radioactive gas emanating from geological materials. Inhalation of this gas is closely related to an increase in the probability of lung cancer if the levels are high. The usual methodology for the quantification of radon by passive methods is the use of etched solid-state nuclear track detectors, frequently in combination with optical microscopes or image scanning for image acquisition and software-based image processing for track counting. Currently available commercial instrumentation, as the Radosys microscopy system, is quite expensive, so the development of alternative methodologies is desirable. In this work, a simple, fast and low-cost image acquisition system for the determination of tracks in chemically etched CR-39 solid-state nuclear track detectors to quantify 222Rn alpha tracks has been proposed. The image of the detector surface is obtained by a conventional light stereoscopic microscope, transmitted by a CCD camera into the computer, and analyzed by the ImageJ open-source software. This methodology was employed to analyze 45 samples collected in dwellings and caves located in the region of Extremadura (Southwest Spain). Results show a good correlation coefficient of r2 = 0.98 between the reference and purposed methodology and excellent repeatability, demonstrating that the system enables routine counting tracks for radon measurement as an alternative to the Radosys microscopy instrument.