[Tuberculous otitis media: A case presentation and review of european literature]. / Otitis media tuberculosa: Presentación de un caso y revisión de la literatura europea.

Tuberculous otitis media (TOM) is a rare affectation in our environment that represents a challenge in its diagnosis due to the non-specific symptoms that it usually presents. This paper presents our experience in the diagnosis of a case of TOM in a 66-year-old woman with hearing loss and chronic otorrhea of more than 6 months of evolution that did not respond to conventional treatments. In addition, a review of the cases published in the last 20 years (2000-2022) in countries of the European Union (EU) is carried out. The most common symptoms were otorrhea (n=43; 100%), hearing loss (n=37; 86.05%), eardrum perforation (n=19; 44.18%), facial paralysis (n=12, 27,91%) and ear pain (n=13; 30,23%). The most used sample for diagnosis was the biopsy obtained by mastoidectomy (n=34; 79.06%). All patients were given antituberculous therapy for a mean duration of 8.11 months (range, 6-12 months). The most frequent aftereffect was hearing loss (n=28; 65.12%). TOM should be included in the differential diagnosis of chronic suppurative otitis, since early diagnosis and treatment reduce the probability of suffering irreversible sequelae.

Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials.

BACKGROUND: Neoadjuvant ipilimumab plus nivolumab has yielded high response rates in patients with macroscopic stage III melanoma. These response rates translated to high short-term survival rates. However, data on long-term survival and disease recurrence are lacking. PATIENTS AND METHODS: In OpACIN, 20 patients with macroscopic stage III melanoma were randomized to ipilimumab 3 mg/kg plus nivolumab 1 mg/kg q3w four cycles of adjuvant or split two cycles of neoadjuvant and two adjuvant. In OpACIN-neo, 86 patients with macroscopic stage III melanoma were randomized to arm A (2× ipilimumab 3 mg/kg plus nivolumab 1 mg/kg q3w; n = 30), arm B (2× ipilimumab 1 mg/kg plus nivolumab 3 mg/kg q3w; n = 30), or arm C (2× ipilimumab 3 mg/kg q3w plus 2× nivolumab 3 mg/kg q2w; n = 26) followed by surgery. RESULTS: The median recurrence-free survival (RFS) and overall survival (OS) were not reached in either trial. After a median follow-up of 69 months for OpACIN, 1/7 patients with a pathologic response to neoadjuvant therapy had disease recurrence. The estimated 5-year RFS and OS rates for the neoadjuvant arm were 70% and 90% versus 60% and 70% for the adjuvant arm. After a median follow-up of 47 months for OpACIN-neo, the estimated 3-year RFS and OS rates were 82% and 92%, respectively. The estimated 3-year RFS rate for OpACIN-neo was 95% for patients with a pathologic response versus 37% for patients without a pathologic response (P < 0.001). In multiple regression analyses, pathologic response was the strongest predictor of disease recurrence. Of the 12 patients with distant disease recurrence after neoadjuvant therapy, 5 responded to subsequent anti-PD-1 and 8 to targeted therapy, although 7 patients showed progression after the initial response. CONCLUSIONS: Updated data confirm the high survival rates after neoadjuvant combination checkpoint inhibition in macroscopic stage III melanoma, especially for patients with a pathologic response. Pathologic response is the strongest surrogate marker for long-term outcome.

Genetic analysis of osteogenesis imperfecta in a large Brazilian cohort.

INTRODUCTION: Osteogenesis imperfecta (OI) is a genetically and clinically heterogeneous disorder caused by disruption of type I collagen synthesis. Previous Brazilian molecular OI studies have been restricted to case reports or small cohorts. The Brazilian OI Network (BOIN) is a multicenter study collecting clinical OI treatment data from five reference centers in three regions of Brazil. OBJECTIVE: To describe the molecular analysis of a large cohort of OI registered at BOIN. METHODS: Targeted next-generation sequencing (NGS) was performed at a centralized laboratory with the Ion Torrent platform, covering 99.6 % of the coding regions of 18 OI-associated genes. Clinical information was obtained from a clinical database. RESULTS: We included 156 subjects in the molecular analyses. Variants were detected in 121 subjects: 65 (53.7 %) in COL1A1, 42 (34.7 %) in COL1A2, 2 (1.7 %) in IFITM5, one (0.8 %) in CRTAP, three (2.5 %) in P3H1, two (1.7 %) in PPIB, four (3.3 %) FKBP10, one (0.8 %) in SERPINH1, and one (0.8 %) in TMEM38B. Ninety-one distinct variants were identified, of which 26 were novel. Of the 107 variants identified in COL1A1 and COL1A2, 24.5 % cause mild OI, while the remaining 75.5 % cause moderate, severe, or lethal OI, of which 49.3 % are glycine to serine substitutions. A single variant in FKBP10 (c.179A>C; p.Gln60Pro) was found in three unrelated and non-consanguineous participants living in the same geographic area in Northeast Brazil, suggesting a possible founder effect. CONCLUSION: Consistent with the literature, 88.4 % of the subjects had a variant in the COL1A1 and COL1A2 genes, with 10 % inherited in an autosomal recessive manner. Notably, one variant in FKBP10 with a potential founder effect requires further investigation. Data from this large cohort improves our understanding of genotype-phenotype correlations for OI in Brazil.

Factores asociados al desprendimiento de retina pseudofáquico: seguimiento a largo plazo en una población colombiana / Associated factors with pseudophakic retinal detachment: Long-term follow-up in a Colombian population

Objetivo Identificar factores asociados a la aparición de desprendimiento de retina pseudofáquico en pacientes con antecedente de cirugía de catarata. Métodos Estudio retrospectivo de casos y controles de 802 ojos de 783 pacientes con antecedente de cirugía de catarata. Los casos fueron pacientes con desprendimiento de retina pseudofáquico (n=258 ojos), mientras que los controles fueron pacientes con cirugía de cataratas que no desarrollaron desprendimiento de retina durante un período de seguimiento de 10 años (n=544 ojos). Resultados La edad de la cirugía de cataratas entre los casos fue menor que en el grupo control (57±13 vs. 67±14 años, respectivamente; p<0,0001). La edad al desprendimiento de retina fue de 59±13 años (rango 6-88) y el tiempo entre la cirugía de catarata y el desprendimiento de retina tuvo una mediana de 2 años (rango intercuartílico 1-4), con un rango de un mes a 14 años. Los factores asociados para el desprendimiento de retina pseudofáquico fueron la edad más joven (<50 años: razón de probabilidad ajustada [ORa]=18,03; intervalo de confianza del 95% [IC 95%]=5,92-54,87; 50-59 años: ORa=10,09, IC 95%=3,37-30,23 y 60-69 años: ORa=5,48, IC 95%=1,88-15,93), sexo masculino (ORa=3,71, IC 95%=2,54-5,44), vitrectomía anterior (ORa=3,26, IC 95%=1,16-9,16), antecedentes de desprendimiento de retina en el ojo contralateral (ORa=6,95, IC 95%=3,15-15,31) y complicaciones intraoperatorias durante la extracción de cataratas (ORa=7,45, IC 95%=3,54-15,69). Conclusiones Este es el primer artículo de factores asociados al desprendimiento de retina pseudofáquico en población colombiana. Se encontró que las complicaciones quirúrgicas, el sexo y la edad estaban asociados con el desprendimiento de retina. Los pacientes deben ser conscientes de estos riesgos potenciales para tomar decisiones informadas sobre su salud ocular (AU)

Objective To identify associated factors with the appearance of pseudophakic retinal detachment in patients with history of cataract surgery. Methods Retrospective case–control study of 802 eyes of 783 patients with history of cataract surgery. Cases were patients with pseudophakic retinal detachment (n=258 eyes), while controls were patients with cataract surgery who did not developed retinal detachment during a 10-year follow-up period (n=544 eyes). Results Age at cataract surgery among cases was lower than in the control group (57±13 vs. 67±14 years old, respectively; P<.0001). Age at retinal detachment was 59±13 years old (range 6–88) and the time between the cataract surgery and the retinal detachment had a median of 2 years (interquartile range 1–4) with a range of 1 month to 14 years. Associated factors for pseudophakic retinal detachment were younger age (<50 years: adjusted odds ratio [aOR]=18.03, 95% confidence interval [95% CI]=5.92–54.87; 50–59 years: aOR=10.09, 95% CI=3.37–30.23; and 60–69 years: aOR=5.48, 95% CI=1.88–15.93), male sex (aOR=3.71, 95% CI=2.54–5.44), anterior vitrectomy (aOR=3.26, 95% CI=1.16–9.16), history of retinal detachment in the fellow eye (aOR=6.95, 95% CI=3.15–15.31), and intraoperative complications during cataract extraction (aOR=7.45, 95% CI=3.54–15.69). Conclusions This is the first report of associated factors with pseudophakic retinal detachment in a Colombian population. Surgical complications, sex, and age were found to be associated with retinal detachment. Patients should be aware of these potential risks to make informed decisions about their eye health (AU)

Associated factors with pseudophakic retinal detachment: Long-term follow-up in a Colombian population.

OBJECTIVE: To identify associated factors with the appearance of pseudophakic retinal detachment in patients with history of cataract surgery. METHODS: Retrospective case-control study of 802 eyes of 783 patients with history of cataract surgery. Cases were patients with pseudophakic retinal detachment (n = 258 eyes), while controls were patients with cataract surgery who did not developed retinal detachment during a 10-year follow-up period (n = 544 eyes). RESULTS: Age at cataract surgery among cases was lower than in the control group (57 ± 13 vs. 67 ± 14 years old, respectively; p < 0.0001). Age at retinal detachment was 59 ± 13 years old (range 6-88) and the time between the cataract surgery and the retinal detachment had a median of 2 years (interquartile range 1-4) with a range of 1 month to 14 years. Associated factors for pseudophakic retinal detachment were younger age (<50 years: adjusted odds ratio [aOR] = 18.03, 95% confidence interval [95%CI] = 5.92-54.87; 50-59 years: aOR = 10.09, 95%CI = 3.37-30.23; and 60-69 years: aOR = 5.48, 95%CI = 1.88-15.93), male sex (aOR = 3.71, 95%CI = 2.54-5.44), anterior vitrectomy (aOR = 3.26, 95%CI = 1.16-9.16), history of retinal detachment in the fellow eye (aOR = 6.95, 95%CI = 3.15-15.31), and intraoperative complications during cataract extraction (aOR = 7.45, 95%CI = 3.54-15.69). CONCLUSIONS: This is the first report of associated factors with pseudophakic retinal detachment in a Colombian population. Surgical complications, sex, and age were found to be associated with retinal detachment. Patients should be aware of these potential risks to make informed decisions about their eye health.

Molecular phylogeny of Cosmetocleithrum Kritsky, Thatcher & Boeger, 1986 (Monogenoidea: Dactylogyridae), gill parasites of Neotropical catfishes (Siluriformes).

Cosmetocleithrum Kritsky, Thatcher & Boeger, 1986 (Dactylogyridae) represents one of the most species-rich groups (22 species currently recognized as valid) of all dactylogyrid parasites infecting Neotropical catfishes. Species of Cosmetocleithrum exhibit a remarkable affinity towards catfishes of the Doradidae and the Auchenipteridae. However, phylogenetic relationships between members of this genus have not been yet analysed. This study analysed newly obtained partial sequences of the 28S ribosomal RNA gene of seven species of Cosmetocleithrum, including its type species C. gussevi Kritsky, Thatcher & Boeger, 1986, along with several other dactylogyrids infecting siluriform, gymnotiform, perciform and characiform fishes. Cosmetocleithrum appeared as an evolutionary recent group, composed of two well-defined lineages: lineage 1 includes parasites of doradids - namely, C. bulbocirrus, C. confusum, C. parvum and C. bifurcum - whereas lineage 2 is composed of species from doradids - that is, C. rarum, C. gussevi, C. gigas, C. trachydorasi and C. falsunilatum - together with parasites of auchenipterids - namely, C. laciniatum and C. baculum. The search for synapomorphies to characterize taxonomic groups within Cosmetocleithrum appears challenging, since the morphology of their haptoral elements is quite conservative, and that of the copulatory complex is highly variable between species. The results of the present study support the recent synonymization of Paracosmetocleithrum Acosta, Scholz, Blasco-Costa, Alves & Silva, 2018 with Cosmetocleithrum. Whereas the 28S ribosomal DNA data resolved Cosmetocleithrum as monophyletic, the statistical support for the lineage was low, rendering its phylogenetic position between other Neotropical dactylogyrids yet undefined.

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study.

OBJECTIVE: Pembrolizumab demonstrated a clinically meaningful objective response rate in patients with previously treated, advanced MSI-H/dMMR endometrial cancer in the multicohort phase 2 KEYNOTE-158 study (ClinicalTrials.gov, NCT02628067). We present health-related quality of life (HRQoL) results for these patients. METHODS: This analysis included patients from cohorts D (endometrial cancer with any MSI status) and K (any MSI-H/dMMR solid tumor except colorectal) who had previously treated, advanced MSI-H/dMMR endometrial cancer. Patients received pembrolizumab 200 mg Q3W for 35 cycles. EORTC QLQ-C30 and EQ-5D-3L questionnaires were administered at baseline, at regular intervals during treatment, and 30 days after treatment discontinuation. Pre-specified exploratory analyses included changes from baseline to week 9 in QLQ-C30 global health status (GHS)/QoL and EQ-5D-3L visual analog scale (VAS) score for all patients and by best overall response. RESULTS: 84 of 90 enrolled patients completed ≥1 HRQoL questionnaire and were included in the analysis. QLQ-C30 and EQ-5D-3L compliance rates were 90% and 94%, respectively, at baseline, and 92% and 93% at week 9. Mean (95% CI) QLQ-C30 GHS/QoL scores improved from baseline to week 9 by 6.08 (0.71-11.46) points in the overall population, with greater improvement in patients who achieved complete or partial response (11.67 [5.33-18.00]-point increase). Mean (95% CI) EQ-5D-3L VAS scores improved by 6.00 (2.25-9.75) points in the overall population and 9.11 (5.24-12.98) points in patients with CR/PR. CONCLUSIONS: Pembrolizumab maintained or improved HRQoL in patients with previously treated, advanced MSI-H/dMMR endometrial cancer, further supporting efficacy and safety results from KEYNOTE-158 and pembrolizumab use in this setting.

Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study.

BACKGROUND: Pembrolizumab demonstrated durable antitumor activity in 233 patients with previously treated advanced microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors in the phase II multicohort KEYNOTE-158 (NCT02628067) study. Herein, we report safety and efficacy outcomes with longer follow-up for more patients with previously treated advanced MSI-H/dMMR noncolorectal cancers who were included in cohort K of the KEYNOTE-158 (NCT02628067) study. PATIENTS AND METHODS: Eligible patients with previously treated advanced noncolorectal MSI-H/dMMR solid tumors, measurable disease as per RECIST v1.1, and Eastern Cooperative Oncology Group performance status of 0 or 1 received pembrolizumab 200 mg Q3W for 35 cycles or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as per RECIST v1.1 by independent central radiologic review. RESULTS: Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%). Median time from first dose to database cut-off (5 October 2020) was 37.5 months (range, 0.2-55.6 months). ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cut-off date) was 30.8% [95% confidence interval (CI) 25.8% to 36.2%]. Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months; '+' indicates no progressive disease by the time of last disease assessment). Median progression-free survival was 3.5 months (95% CI 2.3-4.2 months) and median overall survival was 20.1 months (95% CI 14.1-27.1 months). Treatment-related adverse events (AEs) occurred in 227 patients (64.7%). Grade 3-4 treatment-related AEs occurred in 39 patients (11.1%); 3 (0.9%) had grade 5 treatment-related AEs (myocarditis, pneumonia, and Guillain-Barre syndrome, n = 1 each). CONCLUSIONS: Pembrolizumab demonstrated clinically meaningful and durable benefit, with a high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.

Resiliencia y sobrecarga en cuidadores familiares de enfermos con demencias en Navarra / Resilience and burden in family caregivers of patients with dementias in Navarre

Objetivos: Evaluar la adaptación de los cuidadores familiares de enfermos con demencias. Otros objetivos son establecer una relación entre sobrecarga y resiliencia, analizar las diferencias significativas de sexo entre cuidadores, detectar diferencias económicas y comparar las estrategias de afrontamiento utilizadas frente al estrés. Metodología: Se han utilizado cuatro cuestionarios distintos. El primero consta de una entrevista sociodemográfica de diseño propio; el cuestionario CD-RISC 10 (Connor-Davidson Resilience Scale), el cual mide el grado de resiliencia del paciente; el tercer formulario es la Escala de Carga del Cuidador, con el cual se consiguen evaluar los diferentes grados de sobrecarga, y el último instrumento es el cuestionario COPE-28, que evalúa las diferentes formas de respuesta ante el estrés. Resultados: El perfil más común del cuidador es una mujer de entre 50 y 60 años de edad, que lleva alrededor de 6 años cuidando a un enfermo de Alzheimer. Además, la mayoría de las personas encuestadas tienen resiliencia y sobrecarga medias, aunque los hombres obtuvieron mayor resiliencia (con significación estadística) y menor sobrecarga que las mujeres (sin ella). Respecto a la resiliencia, predominan las estrategias de aceptación, afrontamiento activo y planificación, de acuerdo con los resultados en CD-RISC-10, confirmados por los de COPE-28. Conclusiones: Se ha conseguido ofrecer datos dirigidos a mejorar los enfoques de intervención psicológica en familiares cuidadores de enfermos con demencia, específicamente en el ámbito de Navarra, ya que establecen estrategias que COPE-28 ha probado que tienen correlación con la resiliencia. En definitiva, obtener evidencia científica sobre la que modificar los programas terapéuticos (AU)

Objectives: To assess the adaptation of family caregivers of patients with dementias. Other objectives are to establish a relationship between burden and resilience, to analyze significant gender differences among caregivers, to detect economic differences and to compare strategies used in order to deal with stress. Methods: Four different tests have been used. The first one consists of a sociodemographic interview made by ourselves; the CD-RISC-10 (Connor-Davidson Resilience Scale) questionnaire, which measures the degree of patient resilience; the Caregiver Burden Interview, which measures the different degrees of burden; the last one is the COPE-28 questionnaire, which evaluates the different ways of stress response. Results: It has been obtained that the most common profile of the caregiver is a woman between 50 and 60 years of age who has been caring for an Alzheimer's patient for about 6 years. Furthermore, most of the people surveyed have medium resilience and overload, although men obtained greater resilience (with statistical significance) and less overload than women (without it). Regarding resilience, acceptance, active coping and planning strategies predominate, according to the results in CDRISC-10, confirmed by those of COPE-28. Conclusions: It has been possible to offer data aimed at improving psychological intervention approaches in family caregivers of patients with dementia, specifically in the area of Navarra, since they establish strategies that COPE-28 has proven to correlate with resilience. Definitely, obtaining scientific evidence on the basis of which to modify therapeutic programs (AU)

Emergence of genital infections due to Haemophilus pittmaniae and Haemophilus sputorum.

BACKGROUND: We report for the first time the association of Haemophilus pittmaniae and Haemophilus sputorum with urethritis in men who have sex with men and who engage in unprotected intercourse. PATIENTS AND METHODS: A search for genital pathogens was conducted using urethral exudate cultures and PCR tests for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma spp., and Ureaplasma spp. Recovered microorganisms were identified by MALDI-TOF mass spectrometry, and their susceptibility was evaluated by diffusion gradient test. RESULTS: H. pittmaniae and H. sputorum were isolated. They both proved susceptible to ampicillin, cefixime, and trimethoprim/sulfamethoxazole. H. pittmaniae was also susceptible to tetracycline and H. sputorum to moxifloxacin. CONCLUSION: The increased frequency of potentially resistant Haemophilus spp. isolates in genital exudates highlights the need for greater surveillance of these microorganisms and for their consideration in the differential diagnosis of genital system infections.

Carpobrotus spp. patches as trap for litter: Evidence from a Mediterranean beach.

Dunal plants may affect the patterns of deposition of beach litter. In this study, we aimed at evaluating if Carpobrotus spp. patches may act as a litter trap in coastal dune systems. To do so, we counted the number of macrolitter occurring in both Carpobrotus and control (embryo dune vegetation) patches classifying each item into categories according to the Marine Strategy. Totally, we observed a significant difference between litter trapped in Carpobrotus (331 items, representing 62.4% of the total beach litter) and control (199, 37.6%). Plastic fragments were the most trapped items by both Carpobrotus (46.2%) and control patches (47.2%). We also calculated the item co-occurrence, obtaining a random aggregated 'litter community'. The main emerging output is that Carpobrotus patches act as filter in respect to different anthropogenic materials (overall plastics), suggesting that alien plant management actions may contribute to solve beach litter issues as well.

Aislamiento social, tecnología y salud mental

Introducción:hace varios meses el mundo se enfrenta a una situación de confinamiento para librar una intensa batalla relacionada con la COVID-19, causada por el SARS-CoV-2. A raíz de lo que ha representado este aislamiento social ya comienza a visibilizarse los daños a la salud mental de quienes lo enfrentan, principalmente los niños y adolescentes. El uso de la tecnología ha sido una opción para muchos y quienes han abusado de la misma hoy sufren la repercusión psicológica que puede generar cualquier adicción.Objetivo:describir las alteraciones psicológicas de los niños y adolescentes relacionada con el abuso de la tecnología en tiempos de COVID-19.Métodos:se realizó una búsqueda bibliográfica en bases de datos Medline/Pubmed, Elseiver, Scielo y Google académico. Se utilizó descriptores como pandemia, confinamiento, tecnología, adicciones, salud mental.Resultados:la medida de confinamiento en el mundo ha demostrado ser la acción más efectiva contra el SARS-CoV-2. Los niños y adolescentes son los que más problemas psicológicos pueden presentar a raíz de esta medida. El uso y abuso de la tecnología durante el confinamiento exacerba manifestaciones psicopatológicas por la pérdida en el control de los impulsos y la poca capacidad de adherirse a actividades más saludables y placenteras.Conclusiones:el confinamiento genera estrés, esto lleva al abuso de tecnología en los más jóvenes. Los trastornos del sueño, la agresividad, la ira, el pobre control de los impulsos, trastornos alimentarios, ansiedad, hiperactividad que aparecen se relacionan con la pérdida del control de estas conductas riesgos.[AU]

Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)☆.

BACKGROUND: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. PATIENTS AND METHODS: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. RESULTS: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895). CONCLUSION: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.

Post-mating gene expression of Mexican fruit fly females: disentangling the effects of the male accessory glands.

Mating has profound physiological and behavioural consequences for female insects. During copulation, female insects typically receive not only sperm, but a complex ejaculate containing hundreds of proteins and other molecules from male reproductive tissues, primarily the reproductive accessory glands. The post-mating phenotypes affected by male accessory gland (MAG) proteins include egg development, attraction to oviposition hosts, mating, attractiveness, sperm storage, feeding and lifespan. In the Mexican fruit fly, Anastrepha ludens, mating increases egg production and the latency to remating. However, previous studies have not found a clear relationship between injection of MAG products and oviposition or remating inhibition in this species. We used RNA-seq to study gene expression in mated, unmated and MAG-injected females to understand the potential mating- and MAG-regulated genes and pathways in A. ludens. Both mating and MAG-injection regulated transcripts and pathways related to egg development. Other transcripts regulated by mating included those with orthologs predicted to be involved in immune response, musculature and chemosensory perception, whereas those regulated by MAG-injection were predicted to be involved in translational control, sugar regulation, diet detoxification and lifespan determination. These results suggest new phenotypes that may be influenced by seminal fluid molecules in A. ludens. Understanding these influences is critical for developing novel tools to manage A. ludens.

El estudio y trabajo independientes en la mira de la educación médica superior cubana

Introducción:El estudio y trabajo independientes como unidad dialéctica en el proceso pedagógico desarrollan la actividad cognoscitiva del estudiante.Objetivo:Identificar las aproximaciones teóricas sobre el estudio y el trabajo independientes del estudiante en el contexto de las ciencias médicas en Cuba.Métodos:La gestión de información se enmarcó en la biblioteca virtual electrónica de las revistas médicas cubanas durante 2011-2018, a partir de los descriptores: “estudio independiente” y “trabajo independiente”. El análisis de la información se realizó con los siguientes indicadores: autor, año, propósitos, muestra, medición, intervención, resultados y hallazgos. La unidad de análisis tuvo en cuenta al estudiante y al profesor en la formación inicial y continua. Para el tratamiento matemático de la información se empleó el cálculo porcentual.Resultados:Se consultaron en total 28 artículos sobre ambas categorías: el 78,5 Porciento referidos al trabajo independiente y el resto al estudio independiente. Estos se centraron en la dirección del trabajo independiente y las orientaciones metodológicas, fundamentalmente, en la carrera de medicina (31,8 Porciento). Los principales resultados se revelaron a nivel descriptivo (45,4 Porciento) y de transformación social (18,1 Porciento). Los hallazgos se enfocaron en la efectividad de ambas categorías en el rendimiento académico, la motivación, la independencia, la creatividad y responsabilidad ante las tareas docentes de carácter profesional, problematizador e integral, así como en la preparación docente para su dirección.Conclusiones:Ambas categorías mostraron limitaciones en la formación inicial y continua, lo cual significó un reto pedagógico, ante la necesidad de preparar al docente para que forme a un profesional con la calidad requerida.[AU]

Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma.

Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies1,2. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P < 0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-γ score/high TMB; patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma.

Wavelet-based method for spectral interferometry filtering.

In this work, we study the effects of noise present on spectral interferometry signals, for femtosecond pulse retrieval such as in the SPIDER technique (spectral phase interferometry for direct e-field reconstruction). Although previous works report SPIDER robustness, we have found that noisy signals with low signal-to-noise ratio (SNR), in the acquired spectral interferogram, could cause variations in the temporal pulse intensity retrieval. We demonstrate that even in a filtered SPIDER signal, following standard procedures, at some point the noise on the spectral interferogram could affect the spectral phase retrieval. As a novel alternative for spectral interferograms filtering, we have applied the wavelet transform and propose a target criterion to automatize the optimization algorithm. We apply this method on SPIDER signals and analyze its effectiveness on the spectral phase retrieval. We present numerical and experimental results to show the improvement in the phase retrieval and the temporal pulse reconstruction after applying this filtering method and compare the results with a standard method.

Development of an immunochromatographic lateral flow dipstick for the detection of Mycobacterium tuberculosis 16 kDa antigen (Mtb-strip).

Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium that causes tuberculosis (TB). This contagious disease remains a severe health problem in the world. The disease is transmitted via inhalation of airborne droplets carrying Mtb from TB patients. Early detection of the disease is vital to prevent transmission of the infection to people in close contact with the patients. To date, there is a need of a simple, rapid, sensitive and specific diagnostic test for TB. Previous studies showed the potential of Mtb 16 kDa antigen (Ag16) in TB diagnosis. In this study, lateral flow immunoassay, also called simple strip immunoassay or immunochromatographic test (ICT) for detection of Ag16 was developed (Mtb-strip) and assessed as a potential rapid TB diagnosis method. A monoclonal antibody against Ag16 was optimized as the capturing and detection antibody on the Mtb-strip. Parameters affecting the performance of the Mtb-strip were also optimized before a complete prototype was developed. Analytical sensitivity showed that Mtb-strip was capable to detect as low as 125 ng of purified Ag16. The analytical sensitivity of Mtb-strip suggests its potential usefulness in different clinical applications.

Atividade antibacteriana de nanopartículas de polipirrol diante de Staphylococcus aureus isolados de amostras de leite de vacas e cabras com mastite / Antibacterial behavior of polypyrrole nanoparticles against Staphylococcus aureus isolated from cows and goats with mastitis

The aim of the present study was to evaluate the antibacterial behavior of polypyrrole nanoparticles (PPy-NPs) in water against biofilm producer or not S. aureus isolated from cows and goats with mastitis. One hundred and thirty-eight isolates of S. aureus were initially evaluated for biofilm formation by spectrophotometry in microplates. In addition, the minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) of PPy-NPs in water for planktonic S. aureus were determined. From the bovine samples analyzed, 5 (4.46%) S. aureus isolates showed a strong biofilm production, 17 (15.18%) moderate production, 36 (32.14%) with weak production and 54 (48.21%) did not produce biofilms. Strains from goats (26) showed no biofilm production in 18 (69.23%) strains and weak biofilm production in 8 (30.76%) strains. The MIC and MBC of S. aureus to PPy-NPs were found in the same concentration (125搭/mL) in all strains tested, regardless of biofilm production or not. This finding provides a new insight into the interaction between PPy-NPs and S. aureus, and will offer potential benefits for the control of mastitis.(AU)