Trastuzumab emtansine vs lapatinib and capecitabine in HER2-positive metastatic breast cancer brain metastases: A real-world study.

BACKGROUND: Trastuzumab emtansine (T-DM1) has demonstrated improvements in survival and neurological symptoms in patients with breast cancer with brain metastases (BCBM). This real-world study investigated the effectiveness of T-DM1 versus lapatinib plus capecitabine (LC) in patients with BCBM. METHODS: This retrospective, observational study evaluated patients with HER2-positive BCBM using a real-world database. Eligible patients had initiated T-DM1 or LC with a prior diagnosis of brain metastasis and ≥1 prior metastatic breast cancer treatment. The primary endpoint was overall survival (OS); secondary endpoints were time to next relevant treatment or death (TTNT) and real-world progression-free survival (rwPFS). An inverse probability of treatment weighting (IPTW) approach was used to account for differences in potential baseline characteristics between treatment groups. Outcomes were described using the Kaplan-Meier method, and the average treatment effect of initiating T-DM1 versus LC was estimated using weighted Cox proportional hazard models and hazard ratio (HR). RESULTS: A total of 214 patients were available for analysis (T-DM1, n = 161; LC, n = 53). Demographics and baseline characteristics were generally well-balanced between treatment groups after weighting. After weighting, median OS was 17.7 (T-DM1) versus 9.6 (LC) months (HR, 0.55 [95% CI, 0.34-0.89]; P=0.013). Median TTNT was 9.0 (T-DM1) versus 6.0 (LC) months (HR, 0.55 [95% CI, 0.36-0.85]; P = 0.005). After weighting, median rwPFS was 6.0 (T-DM1) versus 4.0 (LC) months (HR, 0.50 [95% CI, 0.36-0.69]; P < 0.001). CONCLUSIONS: These results support the superior effectiveness and clinical relevance of T-DM1 versus LC in patients with HER2-positive BCBM in the real world.

T-DM1 after Pertuzumab plus Trastuzumab: Treatment Sequence-Induced Selection Bias in HER2-Positive Metastatic Breast Cancer.

Real-world studies have suggested decreased trastuzumab emtansine (T-DM1) effectiveness in patients with metastatic breast cancer (mBC) who received prior trastuzumab plus pertuzumab (H + P). However, these studies may have been biased toward pertuzumab-experienced patients with more aggressive disease. Using an electronic health record-derived database, patients diagnosed with mBC on/after 1 January 2011 who initiated T-DM1 in any treatment line (primary cohort) or who initiated second-line T-DM1 following first-line H ± P (secondary cohort) from 22 February 2013 to 31 December 2019 were included. The primary outcome was time from index date to next treatment or death (TTNT). In the primary cohort (n = 757), the percentage of patients with prior P increased from 37% to 73% across the study period, while population characteristics and treatment effectiveness measures were generally stable. Among P-experienced patients from the secondary cohort (n = 246), median time from mBC diagnosis to T-DM1 initiation increased from 10 to 14 months (2013-2019), and median TTNT increased from 4.4 to 10.2 months (2013-2018). Over time, prior H + P prevalence significantly increased with no observable impact on T-DM1 effectiveness. Drug approval timing should be considered when assessing treatment effectiveness within a sequence.

Prevotella: A Key Player in Ruminal Metabolism.

Ruminants are foregut fermenters that have the remarkable ability of converting plant polymers that are indigestible to humans into assimilable comestibles like meat and milk, which are cornerstones of human nutrition. Ruminants establish a symbiotic relationship with their microbiome, and the latter is the workhorse of carbohydrate fermentation. On the other hand, during carbohydrate fermentation, synthesis of propionate sequesters H, thus reducing its availability for the ultimate production of methane (CH4) by methanogenic archaea. Biochemically, methane is the simplest alkane and represents a downturn in energetic efficiency in ruminants; environmentally, it constitutes a potent greenhouse gas that negatively affects climate change. Prevotella is a very versatile microbe capable of processing a wide range of proteins and polysaccharides, and one of its fermentation products is propionate, a trait that appears conspicuous in P. ruminicola strain 23. Since propionate, but not acetate or butyrate, constitutes an H sink, propionate-producing microbes have the potential to reduce methane production. Accordingly, numerous studies suggest that members of the genus Prevotella have the ability to divert the hydrogen flow in glycolysis away from methanogenesis and in favor of propionic acid production. Intended for a broad audience in microbiology, our review summarizes the biochemistry of carbohydrate fermentation and subsequently discusses the evidence supporting the essential role of Prevotella in lignocellulose processing and its association with reduced methane emissions. We hope this article will serve as an introduction to novice Prevotella researchers and as an update to others more conversant with the topic.

Lower methane emissions were associated with higher abundance of ruminal Prevotella in a cohort of Colombian buffalos.

BACKGROUND: Ruminants burp massive amounts of methane into the atmosphere and significantly contribute to the deposition of greenhouse gases and the consequent global warming. It is therefore urgent to devise strategies to mitigate ruminant's methane emissions to alleviate climate change. Ruminal methanogenesis is accomplished by a series of methanogen archaea in the phylum Euryarchaeota, which piggyback into carbohydrate fermentation by utilizing residual hydrogen to produce methane. Abundance of methanogens, therefore, is expected to affect methane production. Furthermore, availability of hydrogen produced by cellulolytic bacteria acting upstream of methanogens is a rate-limiting factor for methane production. The aim of our study was to identify microbes associated with the production of methane which would constitute the basis for the design of mitigation strategies. RESULTS: Moderate differences in the abundance of methanogens were observed between groups. In addition, we present three lines of evidence suggesting an apparent higher abundance of a consortium of Prevotella species in animals with lower methane emissions. First, taxonomic classification revealed increased abundance of at least 29 species of Prevotella. Second, metagenome assembly identified increased abundance of Prevotella ruminicola and another species of Prevotella. Third, metabolic profiling of predicted proteins uncovered 25 enzymes with homology to Prevotella proteins more abundant in the low methane emissions group. CONCLUSIONS: We propose that higher abundance of ruminal Prevotella increases the production of propionic acid and, in doing so, reduces the amount of hydrogen available for methanogenesis. However, further experimentation is required to ascertain the role of Prevotella on methane production and its potential to act as a methane production mitigator.

Validity of ophthalmology surgical competency assessment rubric for strabismus surgery in resident training.

The Accreditation Council for Graduate Medical Education (ACGME) requires US residency programs to assess ophthalmology residents for competency in 6 core areas. Ophthalmic surgical skills are currently part of the ACGME "Patient Care" competency, although some have advocated for a seventh competency, "Surgical Skills." The Ophthalmology Surgical Competency Assessment Rubric for Strabismus Surgery in Resident Training ( OSCAR: Strabismus) tool was designed to aid in the assessment of surgical skills using procedure specific behavioral anchors. The present study evaluated inter-rater agreement of the OSCAR: Strabismus tool in the assessment of resident performance. OSCAR: Strabismus evaluations of resident surgical strabismus cases were performed by a multinational group of faculty strabismus surgeons. Cronbach α statistical analysis of the completed evaluations revealed high inter-rater agreement, indicating the OSCAR: Strabismus is a reliable tool to facilitate assessment of resident strabismus surgical skills.

Identification of two distinct carcinoma-associated fibroblast subtypes with differential tumor-promoting abilities in oral squamous cell carcinoma.

Heterogeneity of carcinoma-associated fibroblasts (CAF) has long been recognized, but the functional significance remains poorly understood. Here, we report the distinction of two CAF subtypes in oral squamous cell carcinoma (OSCC) that have differential tumor-promoting capability, one with a transcriptome and secretome closer to normal fibroblasts (CAF-N) and the other with a more divergent expression pattern (CAF-D). Both subtypes supported higher tumor incidence in nonobese diabetic/severe combined immunodeficient (NOD/SCID) Ilγ2(null) mice and deeper invasion of malignant keratinocytes than normal or dysplasia-associated fibroblasts, but CAF-N was more efficient than CAF-D in enhancing tumor incidence. CAF-N included more intrinsically motile fibroblasts maintained by high autocrine production of hyaluronan. Inhibiting CAF-N migration by blocking hyaluronan synthesis or chain elongation impaired invasion of adjacent OSCC cells, pinpointing fibroblast motility as an essential mechanism in this process. In contrast, CAF-D harbored fewer motile fibroblasts but synthesized higher TGF-ß1 levels. TGF-ß1 did not stimulate CAF-D migration but enhanced invasion and expression of epithelial-mesenchymal transition (EMT) markers in malignant keratinocytes. Inhibiting TGF-ß1 in three-dimensional cultures containing CAF-D impaired keratinocyte invasion, suggesting TGF-ß1-induced EMT mediates CAF-D-induced carcinoma cell invasion. TGF-ß1-pretreated normal fibroblasts also induced invasive properties in transformed oral keratinocytes, indicating that TGF-ß1-synthesizing fibroblasts, as well as hyaluronan-synthesizing fibroblasts, are critical for carcinoma invasion. Taken together, these results discern two subtypes of CAF that promote OSCC cell invasion via different mechanisms.

Spectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma.

PURPOSE: To identify functionally related prognostic gene sets for head and neck squamous cell carcinoma (HNSCC) by unsupervised statistical analysis of microarray data. PATIENTS AND METHODS: Microarray analysis was performed on 14 normal oral epithelium and 71 HNSCCs from patients with outcome data. Spectral clustering (SC) analysis of the data set identified multiple vectors representing distinct aspects of gene expression heterogeneity between samples. Gene ontology (GO) analysis of vector gene lists identified gene sets significantly enriched within defined biologic pathways. The prognostic significance of these was established by Cox survival analysis. RESULTS: The most influential SC vectors were V2 and V3. V2 separated normal from tumor samples. GO analysis of V2 gene lists identified pathways with heterogeneous expression between HNSCCs, notably focal adhesion (FA)/extracellular matrix remodeling and cytokine-cytokine receptor (CR) interactions. Similar analysis of V3 gene lists identified further heterogeneity in CR pathways. V2CR genes represent an innate immune response, whereas high expression of V3CR genes represented an adaptive immune response that was not dependent on human papillomavirus status. Survival analysis demonstrated that the FA gene set was prognostic of poor outcome, whereas classification for adaptive immune response by the CR gene set was prognostic of good outcome. A combined FA&CR model dramatically exceeded the performance of current clinical classifiers (P < .001 in our cohort and, importantly, P = .007 in an independent cohort of 60 HNSCCs). CONCLUSION: The application of SC and GO algorithms to HNSCC microarray data identified gene sets highly significant for predicting patient outcome. Further large-scale studies will establish the usefulness of these gene sets in the clinical management of HNSCC.

Semiotécnicas aplicadas en la práctica odontológica. Investigación documental / Semi-techniques applied in dental practice. Documentary research

La presente investigación documental denominada "Semiotécnicas aplicadas en la práctica odontológica" tiene como finalidad revisar las técnicas semiológicas que pueden ser aplicadas en la profesión odontológica, así también dar a conocer algunos aspectos como el ético, social, cultural, etc., que entran en juego en la relación odontólogo-paciente; de igual manera se estudiaron algunos exámenes complementarios como por ejemplo: exámenes de laboratorio y técnicas radiográficas, que contribuyen a realizar un diagnóstico certero. Para llevar a cabo esta investigación documental se recopilo información sobre el tema consultando libros, revistas, páginas de Internet, folletos, etc.; y reclasificando la información de acuerdo al tema en estudio. Concluyendo las semiotécnicas que se aplican en la práctica odontológica deben ser siempre complementadas con una adecuada anamnesis y exámenes de laboratorio y radiográficos complementarios para realizar un buen diagnóstico y dar un tratamiento integral al paciente.

The present documentary research called "Semiotechnics applied in dental practice" aims to review the semiological techniques that can be applied in the dental profession, as well as to make known some aspects such as ethical, social, cultural, etc., that enter into play in the dentist-patient relationship; in the same way, some complementary tests were studied, such as: laboratory tests and radiographic techniques, which contribute to making an accurate diagnosis. To carry out this documentary research, information on the subject was collected by consulting books, magazines, Internet pages, brochures, etc .; and reclassifying the information according to the subject under study. Concluding the semi-techniques that are applied in dental practice, they must always be complemented with an adequate anamnesis and complementary laboratory and radiographic examinations to make a good diagnosis and give a comprehensive treatment to the patient.

Prevalencia de pterigio y exploración de posibles factores de riesgo asociados, en dos poblaciones con altitudes diferentes / Prevalence of pterygium and possible risk factors

El objetivo de este estudio fué establecer la prevalencia del pterigio en dos poblaciones colombianas ubicadas en altitudes diferentes y comparar varios factores de riesgo que han sido poco estudiados en el pais. Es un estudio descriptivo que analiza la consulta oftalmológica durante 6 meses en el ISS de Bogotá y Barranquilla entre Abril 1 y Octubre 30 de 1993. La consulta fué de 2169 paciente en Barranquilla (0 metros), de los cuales 116 (5.34 por ciento) tenían pterigio y en Bogotá (2360 metros sobre el mar) fué de 3681, de los cuales 73 (1.98 por ciento) tenían pterigio. Esta diferencia fue estadísticamente significativa (p<0.0003). En los dispensarios del ISS de las dos ciudades se utilizó un formato de historia clínica para recolección de datos y una hoja-tabla para calcular la prevalencia. Usamos el mismo formato el análisis de los factores de riesgo con los pacientes de control. El análisis estadístico fue realizado con el programa SPSS (V.5.01) utilizando regresión logística para los factores de riesgo y ji-cuadrado para la prevalencia. Encontrando relación de la actividad y la presencia de pterigio con variables como antecedentes familiares de pterigio, exposición solar, procedencia rural. Destacando que no hallando relación con alergias ni con el uso de gafas