Evaluation of traditional targeted axillary dissection eligibility criteria for node-positive breast cancer after neoadjuvant chemotherapy in a prospective multicenter registry.

INTRODUCTION: Targeted axillary dissection (TAD) is performed after neoadjuvant systemic therapy (NST) to decrease the rate of non-therapeutic axillary dissection (ALND) for patients with node-positive breast cancer. In order to ensure the oncologic safety of TAD, eligibility criteria resulting in a low false negative rate (FNR) have been proposed. The purpose of this study was to evaluate the utility of the traditional criteria. METHODS: Data was collected from a prospective multicenter registry. In order to ascertain FNRs, pathologic findings in the sentinel lymph nodes (LN)s, malignant clipped LN, and axillary contents were determined. The FNRs within TAD eligibility criterion groups were compared. RESULTS: A total of 110 patients underwent TAD and ALND, and were therefore eligible for analysis. TAD retained a low FNR in advanced clinical T-N stage compared with earlier disease (T stage: 95% CI 0.00-11.93, p = 0.42; N stage: 95% CI 0.00-8.76, p = 0.31). Presentation with ≥4 abnormal LNs on axillary ultrasound did not predict a high TAD FNR (95% CI 0.00-5.37, p = 0.16). No significant differences were noted in TAD FNR when single was compared with dual tracer (blue dye vs dual tracer 95% CI 0.72-52.49, p = 0.13; radiotracer vs dual tracer 0.04-20.11, p = 0.51). Excision of the clipped LN and only one SLN was as accurate as excision of the clipped LN and ≥2 SLNs (95% CI 0.00-10.61, p = 0.38). CONCLUSIONS: TAD retained a low FNR among patients traditionally considered ineligible for this technique. However, excision of the clipped LN and at least one SLN remained essential to a low FNR.

Behavior of immunoglobulin G antibodies for SARS-COV-2 in Mexican pediatric patients with comorbidities: a prospective comparative cohort study.

Background: More than two years after the pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) there is a great lack of information. The presence of immunoglobulin G (IgG) have been related with disease severity. Patients with comorbidities could develop more severe infection; however, the evaluation of the humoral response in pediatric population are needed especially in patients with comorbidities. Our aim was to describe the behavior of IgG in pediatric patients and to know if there is a difference between patients with comorbidities. Methods: A prospective comparative cohort study was carried out in a single center from June 2020 to January 2021, with a follow-up of 6 months. The study included all the subjects with confirmatory test for SARS-CoV-2 from 1 month to 17 years 11 months, the follow-up of the disease's evolution and measurement of IgG antibodies was collected. We obtained the clinical data, and comorbidities like arterial hypertension, diabetes, obesity, and cancer, the initial symptoms were recorded as well as the evolution regarding the severity of COVID-19 and the need for hospitalization, intensive care unit or mechanical ventilation. The follow up was carried out through medical consultation with an appointment every month that included direct interrogation, examination, and peripheral blood collection for the IgG quantification. The antibodies detection was done through peripheral blood and chemiluminescence microparticle immunoassay. Results: A total of 237 patients with positive polymerase chain reaction (PCR) for SARS-COV-2 were included, of which 147 presented IgG antibodies (62%), 112 (76%) without comorbidity and 35 (24%) with comorbidities, by the sixth month only 2.7% continue with positive antibody measurements. Patients with comorbidities reach higher IgG levels than patients without comorbidities the basal titters were: 5.17 for patients without comorbidities vs. 6.96 for the group with comorbidities (P<0.001). Conclusions: We found an association between the presence of comorbidities and high levels of IgG units in pediatric patients with COVID-19. Additionally, patients with more severe course of the disease have higher levels of IgG and by the third month less than 35% have immunity.

Deep Isoflurane Anesthesia Is Associated with Alterations in Ion Homeostasis and Specific Na+/K+-ATPase Impairment in the Rat Brain.

BACKGROUND: Maintenance of ion homeostasis is essential for normal brain function. Inhalational anesthetics are known to act on various receptors, but their effects on ion homeostatic systems, such as sodium/potassium-adenosine triphosphatase (Na+/K+-ATPase), remain largely unexplored. Based on reports demonstrating global network activity and wakefulness modulation by interstitial ions, the hypothesis was that deep isoflurane anesthesia affects ion homeostasis and the key mechanism for clearing extracellular potassium, Na+/K+-ATPase. METHODS: Using ion-selective microelectrodes, this study assessed isoflurane-induced extracellular ion dynamics in cortical slices of male and female Wistar rats in the absence of synaptic activity, in the presence of two-pore-domain potassium channel antagonists, during seizures, and during spreading depolarizations. The specific isoflurane effects on Na+/K+-ATPase function were measured using a coupled enzyme assay and studied the relevance of the findings in vivo and in silico. RESULTS: Isoflurane concentrations clinically relevant for burst suppression anesthesia increased baseline extracellular potassium (mean ± SD, 3.0 ± 0.0 vs. 3.9 ± 0.5 mM; P < 0.001; n = 39) and lowered extracellular sodium (153.4 ± 0.8 vs. 145.2 ± 6.0 mM; P < 0.001; n = 28). Similar changes in extracellular potassium and extracellular sodium and a substantial drop in extracellular calcium (1.5 ± 0.0 vs. 1.2 ± 0.1 mM; P = 0.001; n = 16) during inhibition of synaptic activity and two-pore-domain potassium suggested a different underlying mechanism. After seizure-like events and spreading depolarization, isoflurane greatly slowed extracellular potassium clearance (63.4 ± 18.2 vs. 196.2 ± 82.4 s; P < 0.001; n = 14). Na+/K+-ATPase activity was markedly reduced after isoflurane exposure (greater than 25%), affecting specifically the α2/3 activity fraction. In vivo, isoflurane-induced burst suppression resulted in impaired extracellular potassium clearance and interstitial potassium accumulation. A computational biophysical model reproduced the observed effects on extracellular potassium and displayed intensified bursting when Na+/K+-ATPase activity was reduced by 35%. Finally, Na+/K+-ATPase inhibition with ouabain induced burst-like activity during light anesthesia in vivo. CONCLUSIONS: The results demonstrate cortical ion homeostasis perturbation and specific Na+/K+-ATPase impairment during deep isoflurane anesthesia. Slowed potassium clearance and extracellular accumulation might modulate cortical excitability during burst suppression generation, while prolonged Na+/K+-ATPase impairment could contribute to neuronal dysfunction after deep anesthesia.

Fármacovigilancia de la carbamazepina en el Policlínico Marta Abreu. Santa Clara, 2022

Fundamento: en la práctica, el término estupefaciente se aplica a las especialidades farmacéuticas que contienen principios activos que actúan sobre el sistema nervioso central modificándolo y a las fórmulas magistrales con los mismos principios activos. Objetivo: caracterizar clínica y epidemiológicamente los pacientes que consumen carbamazepina en un área de salud del municipio de Santa Clara. Métodos: estudio descriptivo, transversal, en pacientes que consumen carbamazepina, pertenecientes al Policlínico Docente Marta Abreu, en el período del 1 de enero de 2021 al 1 de abril de 2022. Se incluyeron 209 pacientes y se midieron las siguientes variables: edad, sexo, número de pacientes según diagnósticos, número de pacientes según nuevos protocolos y tiempo de consumo del tratamiento. Resultados: predominó el grupo de edades de 51 a 60 con 43 pacientes (20,5 %), dentro de este grupo el sexo femenino (11,0 % del total); el diagnóstico predominante fue la epilepsia generalizada (93 pacientes). Predominó el sexo femenino, con 59 pacientes, y en ellas se encontró la mayor cantidad de expedientes vencidos, con un total de 16. Según nuevos protocolos, prevalecieron los pacientes con diagnóstico de neuralgia trigeminal, glosofaríngeo o facial (7 pacientes). En cuanto al tiempo de consumo predominaron los pacientes con igual diagnóstico a los anteriores y trastorno del comportamiento debido a enfermedad médica, ambos grupos con tratamientos de hasta tres años. Conclusiones: es importante el conocimiento sobre el uso y abuso de los estupefacientes así como mantener actualizado a todo el personal sanitario para lograr el óptimo control sobre estas sustancias.

Background: in practice, the term narcotic is applied to pharmaceutical specialties that contain active ingredients that act on the central nervous system, modifying it, and to master formulas with the same active ingredients. Objective: to characterize clinically and epidemiologically the patients who consume carbamazepine in a health area of the Santa Clara municipality. Methods: descriptive, cross-sectional study in patients consuming carbamazepine, belonging to the Marta Abreu Teaching Polyclinic, from January the 1st, 2021 to April the 1st, 2022. 209 patients were included and the following variables were measured: age, sex, number of patients according to diagnoses, number of patients according to new protocols and time of consumption of the treatment. Results: the age group from 51 to 60 predominated with 43 patients (20.5%), within this group the female sex (11.0% of the total); the predominant diagnosis was generalized epilepsy with a total of 93 patients. The female sex predominated with a total of 59 patients and in them the largest number of expired files was found, with a total of 16. According to new protocols, patients with a diagnosis of trigeminal, glossopharyngeal or facial neuralgia (7 patients) predominated. Regarding the time of consumption, patients with the same diagnosis as the previous ones and behavioral disorder due to a medical illness predominated, both groups with treatments of up to three years. Conclusions: knowledge about the use and abuse of narcotic drugs is important, as well as keeping all health personnel updated to achieve optimal control over these substances.

Surgical Resection of an Intravascular Lipoma of the Superior Vena Cava.

Intravascular lipomas (IVL) located in the superior vena cava (SVS) are rare benign primary venous tumors with less than 15 cases reported in the literature. We report a case of a 64-year-old woman with IVL of the SVC extending to the right brachiocephalic vein. She was treated successfully using a hybrid procedure which involved endovascular control of the right subclavian vein and surgical approach via median sternotomy followed by mass resection and use of pericardial patch for vein defect closure.

Clinical features and severe acute respiratory syndrome-coronavirus-2 structural protein-based serology of Mexican children and adolescents with coronavirus disease 2019.

Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection in children and adolescents primarily causes mild or asymptomatic coronavirus disease 2019 (COVID-19), and severe illness is mainly associated with comorbidities. However, the worldwide prevalence of COVID-19 in this population is only 1%-2%. In Mexico, the prevalence of COVID-19 in children has increased to 10%. As serology-based studies are scarce, we analyzed the clinical features and serological response (SARS-CoV-2 structural proteins) of children and adolescents who visited the Hospital Infantil de México Federico Gómez (October 2020-March 2021). The majority were 9-year-old children without comorbidities who were treated as outpatients and had mild-to-moderate illness. Children aged 6-10 years and adolescents aged 11-15 years had the maximum number of symptoms, including those with obesity. Nevertheless, children with comorbidities such as immunosuppression, leukemia, and obesity exhibited the lowest antibody response, whereas those aged 1-5 years with heart disease had the highest levels of antibodies. The SARS-CoV-2 spike receptor-binding domain-localized peptides and M and E proteins had the best antibody response. In conclusion, Mexican children and adolescents with COVID-19 represent a heterogeneous population, and comorbidities play an important role in the antibody response against SARS-CoV-2 infection.

Presence of Human Papillomavirus DNA in Malignant Neoplasia and Non-Malignant Breast Disease.

Breast cancer is the leading cause of cancer death among women worldwide. Multiple extrinsic and intrinsic factors are associated with this disease's development. Various research groups worldwide have reported the presence of human papillomavirus (HPV) DNA in samples of malignant breast tumors. Although its role in mammary carcinogenesis is not fully understood, it is known that the HPV genome, once inserted into host cells, has oncogenic capabilities. The present study aimed to detect the presence of HPV DNA in 116 breast tissue biopsies and classify them according to their histology. It was found that 50.9% of the breast biopsies analyzed were malignant neoplasms, of which 74.6% were histologically classified as infiltrating ductal carcinoma. In biopsies with non-malignant breast disease, fibroadenoma was the most common benign neoplasm (39.1%). Detection of HPV DNA was performed through nested PCR using the external primer MY09/11 and the internal primer GP5+/6+. A hybridization assay genotyped HPV. HPV DNA was identified in 20.3% (12/59) of malignant neoplasms and 35% non-malignant breast disease (16/46). It was also detected in 27.3% (3/11) of breast tissue biopsies without alteration. However, there are no statistically significant differences between these groups and the existence of HPV DNA (p = 0.2521). Its presence was more frequent in non-malignant alterations than in malignant neoplasias. The most frequent genotypes in the HPV-positive samples were low-risk (LR) HPV-42 followed by high-risk (HR) HPV-31.

Ability of Two Strains of Lactic Acid Bacteria To Inhibit Listeria monocytogenes by Spot Inoculation and in an Environmental Microbiome Context.

We evaluated the ability of two strains of lactic acid bacteria (LAB) to inhibit L. monocytogenes using spot inoculation and environmental microbiome attached-biomass assays. LAB strains (PS01155 and PS01156) were tested for antilisterial activity toward 22 phylogenetically distinct L. monocytogenes strains isolated from three fruit packing environments (F1, F2, and F3). LAB strains were tested by spot inoculation onto L. monocytogenes lawns (108 and 107 CFU/mL) and incubated at 15, 20, 25, or 30°C for 3 days. The same LAB strains were also cocultured at 15°C for 3, 5, and 15 days in polypropylene conical tubes with L. monocytogenes and environmental microbiome suspensions collected from F1, F2, and F3. In the spot inoculation assay, PS01156 was significantly more inhibitory toward less concentrated L. monocytogenes lawns than more concentrated lawns at all the tested temperatures, while PS01155 was significantly more inhibitory toward less concentrated lawns only at 15 and 25°C. Furthermore, inhibition of L. monocytogenes by PS01156 was significantly greater at 15°C than higher temperatures, whereas the temperature did not have an effect on the inhibitory activity of PS01155. In the assay using attached environmental microbiome biomass, L. monocytogenes concentration was significantly reduced by PS01156, but not PS01155, when cocultured with microbiomes from F1 and F3 and incubated for 3 days at 15°C. Attached biomass microbiota composition was significantly affected by incubation time but not by LAB strain. This study demonstrates that LAB strains that may exhibit inhibitory properties toward L. monocytogenes in a spot inoculation assay may not maintain antilisterial activity within a complex microbiome. IMPORTANCE Listeria monocytogenes has previously been associated with outbreaks of foodborne illness linked to consumption of fresh produce. In addition to conventional cleaning and sanitizing, lactic acid bacteria (LAB) have been studied for biocontrol of L. monocytogenes in food processing environments that are challenging to clean and sanitize. We evaluated whether two specific LAB strains, PS01155 and PS01156, can inhibit the growth of L. monocytogenes strains in a spot inoculation and in an attached-biomass assay, in which they were cocultured with environmental microbiomes collected from tree fruit packing facilities. LAB strains PS01155 and PS01156 inhibited L. monocytogenes in a spot inoculation assay, but the antilisterial activity was lower or not detected when they were grown with environmental microbiota. These results highlight the importance of conducting biocontrol challenge tests in the context of the complex environmental microbiomes present in food processing facilities to assess their potential for application in the food industry.

Características clínicas de pacientes pediátricos con síndrome de dificultad respiratoria aguda asociado con COVID-19 / Clinical characteristics of pediatric patients with acute respiratory distress syndrome due to COVID-19

Resumen Introducción: Existen pocos reportes de síndrome de dificultad respiratoria aguda (SDRA) con COVID-19 en pacientes pediátricos. El objetivo de este estudio fue describir las características de los pacientes pediátricos críticamente enfermos con COVID-19, la frecuencia del SDRA, la mecánica ventilatoria y los resultados de la posición prona. Métodos: Se llevó a cabo un estudio retrospectivo y observacional de los pacientes ingresados del 1 de abril al 30 de septiembre de 2020. Resultados: Ingresaron 34 pacientes a la unidad de terapia intensiva pediátrica (UTIP) con prueba positiva para SARS-CoV-2. De ellos, 13 presentaron SDRA, 11 requirieron ventilación mecánica invasiva y siete fueron pronados como estrategia de oxigenación. Todos los pacientes clasificados como SDRA graves fueron pronados. La obesidad fue la comorbilidad más importante. Las complicaciones asociadas con SDRA fueron el síndrome inflamatorio multisistémico (p < 0.05) y la lesión renal aguda (p < 0.05). La procalcitonina fue mayor en los pacientes con SDRA, al igual que los días de estancia en la UTIP (p < 0.05). El éxito de la maniobra de pronación se alcanzó 8 horas después.Los resultados observados fueron los siguientes relación presión arterial de oxígeno/fracción inspirada de oxígeno 128 vs. 204, índice de oxigenación 8.9 vs. 5.9, distensibilidad pulmonar estática 0.54 vs. 0.70 ml/cmH2O/kg, y presión meseta 24 vs. 19 cmH2O (p < 0.05). El uso de narcóticos fue mayor en el grupo de SDRA más pronación que en los no pronados (124 vs. 27 h; p < 0.01). La mortalidad asociada con SARS-CoV-2 fue del 5.8%. Conclusiones: El SDRA se presentó en el 38.2% de los niños admitidos a UTIP, y con mayor frecuencia en los pacientes con obesidad. La maniobra de pronación aplicada en los casos severos, mejoró la oxigenación de la mécanica pulmonar. Ninguno de los pacientes falleció por SDRA.

Abstract Background: There are only a few reports of acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 in pediatrics. This study aimed to describe the characteristics of critically ill pediatric patients with COVID-19, the frequency of ARDS, ventilatory mechanics and results of prone position. Methods: We conducted a retrospective, observational study of patients admitted to the pediatric intensive care unit (PICU) between April 1 to September 30, 2020. Results: Thirty-four patients were admitted to pediatric intensive care unit, 31.7% were SARS-CoV-2 positive. 13 presented ARDS, 11 required invasive mechanical ventilation, and seven were pronated as an oxygenation strategy. All patients classified as severe ARDS were pronated. Obesity was the most important comorbidity. The complications associated with ARDS were multisystemic inflammatory syndrome (8 vs. 4; p < 0.05) and acute kidney injury (8 vs. 3; p < 0.05). Procalcitonin was higher in patients with ARDS, as were the days of stay in PICU (p < 0.05). The success of the pronation maneuver was achieved 8 hours later , with the following results: arterial oxygen partial pressure to fractional inspired oxygen ratio 128 vs. 204, oxygenation index 8.9 vs. 5.9, static lung compliance 0.54 vs. 0.70 ml/cmH2O/kg, plateau pressure 24 vs. 19 cmH2O (p < 0.05). The use of narcotics was higher in the group with ARDS plus pronation 124 vs. 27 hours in the non-pronated (p < 0.01). Mortality associated with SARS-CoV-2 was 5.8%. Conclusions: ARDS was presented in 38.2% of the children admitted to PICU and was more frequent in obese patients. Pronation, performed in severe cases, improved oxygenation and lung mechanics indexes. No patient died of ARDS.

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America.

Objectives: Venetoclax combinations are a new standard for patients with acute myeloid leukemia (AML). We aimed to evaluate the safety and efficacy of these combinations in a period of accelerated approval in Latin-America.Methods: This observational study evaluated adults with acute myeloid leukemia who received venetoclax-based therapy in 11 public or private centers in Mexico and Peru for both newly diagnosed or relapsed and refractory AML.Results: Fifty patients were included; 28 with newly diagnosed (ND) AML and 22 with relapsed/refractory (RR) disease. ND patients were older (64 vs. 40 years; p < 0.001) with a lower functional capacity (ECOG ≥2 64.3% vs 9%; p < 0.001). Venetoclax was frequently combined with azacytidine (60%) and prophylactic azoles (82%) with a median maximum dose of 200 mg (range, 100-600 mg). Hematologic toxicities were common. Complete response rates including patients with incomplete hematopoietic recovery were 78.6% in ND and 45.5% in RR patients, with a median overall survival of 9.6 (95% CI 3.7-15.5) and 8 months (95% CI 4.8-11.2).Discussion: Our study showed a preferred use of venetoclax plus azacytidine over cyatrabine. Patients in the first-line setting were similar to those in the landmark studies, while most patients with relapsed disease had received prior intensive therapies. Responses were favorable, with a median survival in agreement to other reports, albeit shorter than that observed in the randomized phase-3 trials.Conclusion: Venetoclax-based therapy in AML was effective despite dose reductions and prophylactic antifungals in two middle-income countries outside of a clinical trial setting.

Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study.

Background: Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19. Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. Results: About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29-4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01-4.87) and serum IL-6. In-silico clinical trials supported these findings. Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype. Funding: Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021).

Patients with severe COVID-19 often need mechanical ventilation to help them breathe and other types of intensive care. The outcome for many of these patients depends on how their immune system reacts to the infection. If the inflammatory response triggered by the immune system is too strong, this can cause further harm to the patient. One gene that plays an important role in inflammation is IFIH1 which encodes a protein that helps the body to recognize viruses. There are multiple versions of this gene which each produce a slightly different protein. It is possible that this variation impacts how the immune system responds to the virus that causes COVID-19. To investigate, Amado-Rodríguez, Salgado del Riego et al. analyzed the IFIH1 gene in 227 patients admitted to an intensive care unit in Spain for severe COVID-19 between March and December 2020. They found that patients with a specific version of the gene called TT experienced less inflammation and were more likely to survive the infection. Physicians typically treat patients with moderate to severe COVID-19 with corticosteroid drugs that reduce the inflammatory response. However, Amado-Rodríguez, Salgado del Riego et al. found that patients with the TT version of the IFIH1 gene were at greater risk of dying if they received corticosteroids. The team then applied the distribution of IFIH1 variants among different ethnic ancestries to data from a previous clinical trial, and simulated the effects of corticosteroid treatment. This 'mock' clinical trial supported their findings from the patient-derived data, which were also validated by laboratory experiments on immune cells from individuals with the TT gene. The work by Amado-Rodríguez, Salgado del Riego et al. suggests that while corticosteroids benefit some patients, they may cause harm to others. However, a real-world clinical trial is needed to determine whether patients with the TT version of the IFIH1 gene would do better without steroids.

Mechanical ventilation promotes lung tumour spread by modulation of cholesterol cell content.

BACKGROUND: Mechanical stretch of cancer cells can alter their invasiveness. During mechanical ventilation, lungs may be exposed to an increased amount of stretch, but the consequences on lung tumours have not been explored. METHODS: To characterise the influence of mechanical ventilation on the behaviour of lung tumours, invasiveness assays and transcriptomic analyses were performed in cancer cell lines cultured in static conditions or under cyclic stretch. Mice harbouring lung melanoma implants were submitted to mechanical ventilation and metastatic spread was assessed. Additional in vivo experiments were performed to determine the mechanodependent specificity of the response. Incidence of metastases was studied in a cohort of lung cancer patients that received mechanical ventilation compared with a matched group of nonventilated patients. RESULTS: Stretch increases invasiveness in melanoma B16F10luc2 and lung adenocarcinoma A549 cells. We identified a mechanosensitive upregulation of pathways involved in cholesterol processing in vitro, leading to an increase in pro-protein convertase subtilisin/kexin type 9 (PCSK9) and LDLR expression, a decrease in intracellular cholesterol and preservation of cell stiffness. A course of mechanical ventilation in mice harbouring melanoma implants increased brain and kidney metastases 2 weeks later. Blockade of PCSK9 using a monoclonal antibody increased cell cholesterol and stiffness and decreased cell invasiveness in vitro and metastasis in vivo. In patients, mechanical ventilation increased PCSK9 abundance in lung tumours and the incidence of metastasis, thus decreasing survival. CONCLUSIONS: Our results suggest that mechanical stretch promote invasiveness of cancer cells, which may have clinically relevant consequences. Pharmacological manipulation of cholesterol endocytosis could be a novel therapeutic target in this setting.

Diagnostic concordance of pathological methods and reports of hematopathologists compared to local nonspecialized pathologists in the diagnosis of lymphoma in Mexico.

OBJECTIVES: To assess the concordance between lymphoma diagnoses made via tissue biopsy by local pathologists and also to assess the after review of these specimens by more specialized hematopathologists. METHODS: A prospective, non-interventional and multicenter study was conducted at seven sites in Mexico from January 2017 to October 2017. Eligible biopsies were sampled from patients with a previous diagnosis of lymphoma on lymph node biopsy or a diagnosis of extranodal lymphoma, with adequate amount and tissue preservation for the review analysis. The biopsy tissues reviewed by local pathologists were also reviewed by hematopathologists participating in the study. The concordance in diagnosis results was classified into three categories: diagnostic agreement, minor discrepancy and major discrepancy. RESULTS: Out of 111 samples received, 105 samples met the eligibility criteria and were included for full analysis. The median patient age (range) was 54 (16-94) years. A diagnostic agreement was observed in 23 (21.9%) biopsies, minor discrepancies were observed in 32 (30.5%) biopsies and major discrepancies were observed in 50 (47.6%) biopsies. Diagnostic concordance varied across the seven study sites; the rate of major discrepancies ranged from 0% to 100% and the rate of diagnostic agreement ranged from 0% to 81.8%. Out of the 105 reviewed biopsies, a total of 89 cases were diagnosed as lymphoma by hematopathologists. CONCLUSIONS: This study showed that major discrepancies were observed following the review by hematopathologists compared with that of the local pathologist's initial diagnosis in nearly one-half cases. In addition, there was a wide variation in the percentage of diagnostic agreements and discrepancies among different study sites.

Maternal Supplementation with Polyphenols and Omega-3 Fatty Acids during Pregnancy: Prenatal Effects on Growth and Metabolism.

Maternal supplementation with antioxidants and n-3 PUFAs may be a promising strategy to reduce the risk of intrauterine growth restriction and preterm delivery, which may diminish the appearance of low-birth-neonates. A previous studies showed beneficial outcomes of the combination of hydroxytyrosol and linoleic acid, but there is no data of its prenatal effects. The present study aimed to determine the possible prenatal implications of such maternal supplementation at prenatal stages in swine, a model of IUGR pregnancies. Results showed effects on litter size, with treated sows having larger litters and, therefore, smaller fetuses. However, the brain/head weight ratio showed a positive effect of the treatment in development, as well as in some other major organs like lungs, spleen, or kidneys. On the other hand, treated piglets showed better glycemic and lipidemic profiles, which could explain postnatal effects. However, further research on the implications of the treatment on litter size and prenatal and postnatal development must be done before practical recommendation can be given.

Acute Promyelocytic Leukemia: A Long-Term Retrospective Study in Mexico.

BACKGROUND: The present retrospective study reviewed acute promyelocytic leukemia (APL) cases recorded in Mexico between January 2007 and January 2017. The primary objective of the study was to evaluate overall survival (OS) in Mexican patients with APL. Secondary objective was to evaluate the impact of induction treatment with different anthracyclines on OS, event-free survival (EFS) and complications in this patient population. METHODS: The medical charts of patients referred to medical institutions in Mexico from January 2007 through January 2017 for the treatment of suspected APL were reviewed retrospectively. Patients aged 15 - 75 years, in whom the diagnosis of APL was confirmed, who had an Eastern Cooperative Group performance status of 0 - 2, and who were eligible for combined treatment with intensive chemotherapy and all-trans retinoic acid (ATRA), were included in the study. Study participants received induction and consolidation treatment with ATRA plus either daunorubicin or idarubicin, followed by 2 years of single-agent ATRA as maintenance therapy. Patients who were unable to pay for ATRA treatment received anthracycline-based induction and consolidation, with methotrexate plus mercaptopurine as maintenance therapy. RESULTS: A total of 360 patients from 21 public and private hospitals were included in the study. The median age of the population was 37 years, and 51% were male. Of the 360 patients, 205 (57%) vs. 155 (43%) received daunorubicin vs. idarubicin as induction treatment for APL. ATRA was administered to 201 (98%) patients in the daunorubicin group vs. 138 (89%) in the idarubicin group (P = 0.001), and was initiated at diagnosis in 92% vs. 73% of recipients, respectively (P = 0.0001). At 150 months, OS and EFS for the entire population were 84% and 79%, respectively. Both OS (90% vs. 76%, P = 0.003) and EFS (85% vs. 72%, P = 0.001) were significantly prolonged in daunorubicin vs. idarubicin recipients. Rates of complications were similar in the two groups. CONCLUSIONS: As arsenic trioxide (ATO) is not currently available in Mexico, anthracycline plus ATRA is the mainstay of treatment for APL here. Our results confirm the efficacy of this strategy, with high OS and EFS rates being observed 12.5 years after diagnosis.

Treatment of paroxysmal nocturnal hemoglobinuria in pregnancy with eculizumab: A case report.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease caused by mutations in hematopoietic stem cells leading to pancytopenia and a predisposition for thromboembolic events. In pregnancy, these manifestations can be amplified, leading to increased neonatal and maternal morbidity and mortality. Although data are limited, eculizumab has emerged as a potential treatment of PNH in pregnancy. This report describes a case of a woman with PNH successfully treated with eculizumab during two pregnancies. Although during both pregnancies she experienced breakthrough hemolysis requiring intermittent blood transfusions, she had no thromboembolic events and had term vaginal births. Granted more research is needed, eculizumab may be an acceptable therapy for PNH in pregnancy.

Prescription Patterns of Daratumumab in Patients with Multiple Myeloma in Underprivileged Circumstances: A Multicenter Experience in Mexico.

BACKGROUND: Despite novel therapies, multiple myeloma (MM) remains an incurable malignancy, daratumumab (DARA) being a major game changer, may be a good option for treatment. AIMED OF THE STUDY: To assess the prescription patterns of DARA in patients with MM in Mexico. METHODS: 47 patients with MM were analyzed in 13 different hospitals in Mexico. RESULTS: Five (10.5%) of patients received DARA as first line therapy, 13 (27.5%) as second line, whereas 29 (62%) received its in ≥3rd line. In 32% DARA was used in combination with dexamethasone, 64% received DARA on a triple combination, and 4% as a 4 drug combination. Eighty three percent of patients had a response, including 32% in complete remission. Progression free survival (PFS) was higher in patients in ISS stage 1, and in patients achieving ≥PR. Overall survival (OS) was lower in patients not achieving ≥PR, in patients having increased LDH, and extramedullary disease. Grade 1-2 infusion related reactions were present in 34%, and grade 3-4 neutropenia and lymphopenia in 25 and 17% of the patients. CONCLUSIONS: In Mexico, 62% of patients with MM received DARA as a third or further line of treatment. DARA employed as a doublet or triplet combination is useful in relapsed/refractory patients with tolerable adverse events.

SARS-CoV-2 infection in a pediatric patient with cystic fibrosis.

Background: Cystic fibrosis (CF) is a potentially mortal disease characterized by a chronic pulmonary disease with persistent airway infection. Children with this disease are more susceptible to respiratory infections due to the limitation in mucociliary transport and anatomical disruption of the bronchial tree. SARS-CoV-2 causes COVID-19, a respiratory illness related to exacerbations of chronic pulmonary pathologies in children, such as CF and asthma. There are not enough case reports on pediatric patients with SARS-CoV-2 infection and CF, for which we share our experience. Case report: A 22-month-old male patient diagnosed with CF presented in the hospital with cough, fever, and increased respiratory work. The patient received supplemental oxygen and antibiotic and antiviral therapy. Positive results for type B influenza and RT-PCR (reverse transcription-polymerase chain reaction) for SARS-CoV-2 were obtained. Due to the persistence of respiratory difficulty, high-flow therapy was initiated, with a good response. After an episode of hypoxemia, bradycardia, and increased respiratory work secondary to accumulated secretions, orotracheal intubation and invasive mechanical ventilation were performed. The patient evolved with clinical and gasometric improvement. After 10 days of in-hospital antibiotic management with adequate clinical evolution, the patient was discharged to complete oral treatment and home isolation. Conclusions: We present a case of chronic respiratory disease and SARS-CoV-2 infection with severity criteria in a pediatric patient. The evolution was favorable with timely support management and antibiotic therapy in a third-level hospital.

Introducción: La fibrosis quística es una afección potencialmente mortal caracterizada por enfermedad pulmonar crónica con infección persistente de las vías aéreas. Los niños con esta enfermedad son más susceptibles a infecciones respiratorias debido a la limitación en el transporte mucociliar y la distorsión anatómica del árbol bronquial. El SARS-CoV-2 (coronavirus tipo 2 del síndrome agudo respiratorio grave) es el virus causante de la COVID-19, enfermedad respiratoria que puede estar relacionada con exacerbaciones de patologías pulmonares crónicas en niños, como la fibrosis quística y el asma. No hay suficientes reportes de casos de pacientes pediátricos con infección por SARS-CoV-2 y fibrosis quística, por lo cual se comparte la presente experiencia. Caso clínico: Paciente de sexo masculino de 22 meses de edad con diagnóstico de fibrosis quística que presentó tos, fiebre y aumento en el trabajo respiratorio. A su ingreso se inició manejo con oxígeno suplementario y tratamiento antibiótico y antiviral. Se obtuvo prueba positiva para influenza tipo B y para SARS-CoV-2 por RT-PCR (reacción en cadena de la polimerasa de transcriptasa inversa). Ante un episodio de hipoxemia, bradicardia y mayor trabajo respiratorio, requirió intubación orotraqueal y ventilación mecánica invasiva. El paciente evolucionó con mejoría clínica y gasométrica. Después de 10 días de manejo antibiótico intrahospitalario, con adecuada evolución clínica, egresó para completar tratamiento por vía oral y aislamiento en casa. Conclusiones: Se presenta el caso de un paciente pediátrico con enfermedad respiratoria crónica de base e infección por SARS-CoV-2 con criterios de gravedad. El paciente evolucionó favorablemente con el manejo de soporte oportuno y terapia de antibióticos en un hospital de tercer nivel.