Summary of Research: Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

This is a summary of the original article ?Overall survival with osimertinib in resected EGFR-mutated NSCLC.Ë® Osimertinib blocks the activity of the epidermal growth factor receptor (EGFR) on cancer cells, causing cancer cell death and tumor shrinkage, and is an effective treatment for EGFR-mutated non-small cell lung cancer (NSCLC). The ADAURA study assessed the effects of osimertinib versus placebo in patients with EGFR-mutated (exon 19 deletion or L858R) early stage (IB-IIIA) NSCLC removed by surgery (resected). Previous results from ADAURA demonstrated that patients treated with osimertinib stayed alive and cancer-free (disease-free survival) significantly longer than patients who received placebo. Recent data showed the overall length of time patients were alive after starting treatment (overall survival). In both the primary stage II-IIIA and overall stage IB-IIIA populations, patients in the osimertinib group had a significant 51% reduction in the risk of death compared with the placebo group. The data demonstrated that osimertinib after surgery significantly improved overall survival in patients with resected, EGFR-mutated, stage IB-IIIA NSCLC.

Adjuvant Osimertinib in Patients With Stage IB to IIIA EGFR Mutation-Positive NSCLC After Complete Tumor Resection: ADAURA China Subgroup Analysis.

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People's Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People's Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13-0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17-0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21-1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

Presence of methanogenic archaea in necrotic root canals of patients with or without type 2 diabetes mellitus.

Theoretically, a necrotic root canal fulfils all requirements as a niche for methanogens to inhabit. However, their presence in it and its implication in apical periodontitis (AP) is controversial. Therefore, to contribute to ending the controversy, this study aimed to detect and compare methanogens' presence in two distinct niches with supposedly different microenvironments; both were necrotic root canals associated with AP but one from patients with type 2 diabetes mellitus (T2DM) while the other from non-diabetic patients. A clinical examination was performed on 65 T2DM patients and 73 non-diabetic controls. Samples from necrotic root canals were obtained, and methanogens were identified. The presence of methanogens was three times higher (27.6%) in the T2DM group than in non-diabetic patients (8.2%). In addition, methanogens' presence was associated with a higher prevalence of periapical symptoms.

Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

BACKGROUND: Among patients with resected, epidermal growth factor receptor (EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival. METHODS: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis. CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial.

PURPOSE: The phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P < .001). We report an updated exploratory analysis of final DFS data. METHODS: Overall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test; following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points. RESULTS: At data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo); the DFS HR was 0.23 (95% CI, 0.18 to 0.30); 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34); 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had local/regional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis. CONCLUSION: These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

Pericarditis Aguda asociada a infección por COVID-19 / Acute pericarditis associated with COVID-19 infection

RESUMEN La infección por el coronavirus de tipo 2 causante del síndrome respiratorio agudo grave (SARS-COV2, por sus siglas en inglés), ha sido asociada con múltiples manifestaciones cardiovasculares. El mecanismo por el cual el virus afecta el corazón es objeto de discusión; sin embargo, se ha planteado que el receptor de la enzima convertidora de angiotensina (ACE2) sirve como entrada directa del virus. Así mismo, un estado de inflamación mediado por una tormenta de citoquinas puede generar falla multiorgánica y explicar algunas manifestaciones cardíacas. Las principales asociaciones al sistema cardiovascular reportadas en la infección por COVID-19 son el síndrome coronario agudo, la falla cardiaca aguda, el choque cardiogénico y las arritmias. La pericarditis aguda es un síndrome inflamatorio de etiología principalmente viral, pero su relación con la infección por SARS-COV2 parece ser infrecuente, con pocos reportes en la literatura. Se presenta el caso de una paciente que desarrolló pericarditis concomitante a la infección por SARS-COV2.

SUMMARY Infection by coronavirus type 2 that causes severe acute respiratory syndrome (SARS-CoV-2) has been associated with multiple cardiovascular manifestations. The mechanism by which the virus affects the heart is under discussion; however, it has been proposed that the angiotensinconverting enzyme 2 (ACE2) serves as a direct entry point for the virus; likewise, the state of inflammation mediated by cytokine storm can generate multiorgan failure, explaining some cardiac manifestations. The main associations to the cardiovascular system reported in COVID-19 infection are acute coronary syndrome, acute heart failure, cardiogenic shock and arrhythmias. Acute pericarditis is an inflammatory syndrome of mainly viral etiology, and its relationship to SARS-CoV-2 infection seems infrequent, with few reports in the literature. We present the case of a patient who developed pericarditis, concomitant with SARS-CoV-2 infection.

Pitiriasis rosada como manifestación dermatológica de infección por SARS-CoV-2: a propósito de un caso / Pityriasis rosea as a cutaneous manifestation associated with SARS-CoV-2 infection: case report

Las manifestaciones cutáneas relacionadas a la infección por el coronavirus SARS-CoV-2, causante de COVID-19, se han descrito entre el 0,2% y 20,4% de las personas que cursan con esta enfermedad. Las más frecuentemente descritas son: lesiones maculopapulares (47%), lesiones acrales eritematosas con vesículas o pústulas (pseudoperniosis) (19%), urticariales (19%), lesiones vesiculosas (9%) y livedo/necrosis (6%). En particular, la pitiriasis rosada es una dermatosis autolimitada de etiología desconocida, sin embargo, se ha visto asociada a la infección por SARS-CoV-2, con algunos reportes de casos en la literatura. El mecanismo fisiopatológico de las lesiones cutáneas en COVID-19 no es claro, y se han planteado algunas teorías, entre las cuales está el papel que juega la enzima convertidora de angiotensina 2 (ACE2) utilizada por el virus para infectar las células, los infiltrados linfocíticos, los depósitos de factores del complemento en la piel, y la reactivación de virus latentes como los herpes virus humanos. Se presenta el caso de una paciente con pitiriasis rosada asociada a COVID-19 y se describen los casos reportados hasta la fecha

Endodontic set sealer eluates promote cytokine production in human mononuclear and periodontal ligament cells.

Endodontic freshly mixed sealers display toxic effects; however, these are significantly reduced and most become relatively inert in the set state but there is no information about the possible inflammatory reaction promoted by them. Four contemporary and different formulated endodontic set sealers (MTA Fillapex, BioRoot RCS, AH Plus, and Pulp Canal Sealer) were evaluated. Human periodontal ligament cells and human peripheral blood mononuclear cells were stimulated for 3, 6, 12 and 24 h. Interleukin-6, tumour necrosis factor-alpha, interleukin-8 and interleukin-10 concentrations were measured by enzyme-linked immunosorbent assay. All endodontic set sealer eluates promoted a similar production (P ˃ 0.05) of the four cytokines. However, their concentrations decreased within a short time period to nearly undetectable concentrations after 24 h, suggesting that the studied endodontic set sealers do not possess inflammatory properties which has favoured their long-term use in clinical practice.

Infección de un muñón por Leuconostoc spp, reporte de un caso y revisión de la literatura / Infection of a stump by Leuconostoc, a case report and review of the literature

Resumen La infección del muñón después de amputaciones traumáticas tiene una prevalencia hasta del 34%. Las bacterias más frecuentemente aisladas son Staphylococcus aureus, Enterobacterales como Escherichia coli; Pseudomonas aeruginosa, entre otras. Estas infecciones ocurren por la inoculación directa en el momento del trauma o por gérmenes nosocomiales; la realización de curaciones de las heridas con emplastos vegetales es una práctica aún frecuente en zonas rurales de nuestro país pero su relación con infección del sitio operatorio ha sido poco explorada en la literatura. Leuconostoc spp. es un coco Gram positivo encontrado en territorio agrícola y utilizado en la industria de alimentos. Se presenta un caso de infección de un muñón transfemoral por Leuconostoc, después de una amputación traumática del miembro inferior en una paciente previamente sana con una posible asociación a curaciones con emplastos vegetales.

Abstract Infection of a traumatic amputation stump has a prevalence of 34%. The most common bacteria isolated are Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacterales such as Escherichia coli. These infections occur by direct inoculation in the moment of the trauma or by nosocomial germs. Infections secondary to manipulation of the wounds with vegetable plasters have few case reports in the literature. Leuconostoc spp. is a Gram-positive coccobacillus commonly found in agricultural territory and used in the food industry. There are few case reports in the literature about bone infections by Leuconostocs pp. We present a case of an infection of the operative site of a transfemoral stump by Leuconostoc spp. after a traumatic amputation of the lower limb in a previously healthy patient who had a possible association to cures with vegetable plasters.

A motor learning therapeutic intervention for a child with cerebral palsy through a social assistive robot.

Background: Children with cerebral palsy have difficulty to sit, stand, walk, run and jump independently. Therapy is an important factor in improving these aspects, and if applied in early intervention treatments, when the child is growing, it could have many benefits. These therapies require intensive and extended sessions, which in turn demand dedication and effort. New strategies that provide interesting and motivating interventions are often incorporated to improve the participation and performance of the children in the therapies. Therapies using social assistive robots can be alternative and complementary methods to promote the participation and motivation of children with cerebral palsy.Methods: The objective of this work is to validate the effectiveness of a 16-session physical therapy program to improve the participation and fulfillment of therapeutic objectives on an 8 year-old boy with dyskinetic cerebral palsy for motor learning to walk using a social assistive robot. The therapy program was carried out through a methodological proposal that uses SMART objectives (Specific, Measurable, Achievable, Realistic and Timed), Goal-Directed Therapy (GDT) and its evaluation through Goal Attainment Scaling (GAS). Results: A NAO robot was used as a social assistive robot to support a physical therapy for a child with cerebral palsy. In this work, it was observed that the motivation generated by the interaction with the social assistive robot facilitated the persistence in the walking and the fulfillment of the objectives. Conclusion: Using humanoid robots as social assistive robots may benefit therapeutic processes on children with motor disabilities. The methodology developed provides a formal way to achieve objectives in therapeutic processes for children with cerebral palsy.Implications for rehabilitationIt requires researchers to conduct more studies to validate the potential of the use of social robots in therapeutic interventions that promote development in children with motor disabilities, such as cerebral palsy.Promoting the use of new technologies in therapeutic processes such as humanoid robots allows us to create new strategies to know the impact of this technology in the area of rehabilitation.The use of formal methodologies focused on the patient, along with multidisciplinary teams, could increase the possibilities of using social robots to improve cognitive and motor outcomes in children with cerebral palsy.The formulation of SMART objectives and their quantification through the GAS scale can be used as recommendations to improve the formulation of goals in therapeutic interventions for children with cerebral palsy.

Changes in lipid class and fatty acid composition during development in white seabream (Diplodus sargus) eggs and larvae.

To establish the changes which occur during embryogenesis and early larvae development, eggs, yolk-sac larvae (one day old larvae) and absorbed yolk-sac larvae (three day old larvae) of white sea bream were examined for lipid class and fatty acid composition. The development was characterized by a decrease in all lipid classes with the exception of phosphatidylserine (PS) and fatty free acids (FFA) which increased, and sphingomyelin (SM) which remained unchanged. The changes observed in lipid class content and the decrease in fatty acids in total lipid (TL) reflect the utilization and mobilization of lipids during both embryogenesis and early larvae development. Fluctuations in the relative composition of fatty acids in phosphatidylcholine (PC) during development suggest a selective bulk uptake and catabolism of fatty acids in this lipid class. Unlike PC, catabolism of triacylglycerol (TG) fatty acid appears to be non-selective. During development, the decrease in levels of polyunsaturated fatty acids (PUFA) eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) in total lipid denotes their utilization as energy substrate by Diplodus sargus larvae.

Lipid and fatty acid composition of muscle and liver from wild and captive mature female broodstocks of white seabream, Diplodus sargus.

Total lipids (TL), lipid classes, and their associated fatty acids from muscle and liver of captive and wild mature female broodstocks were investigated in order to estimate the fatty acid requirements of white seabream (Diplodus sargus). The results showed that the percentage of triacylglycerol was higher in liver and muscle of captive fish than in wild fish. The distribution of phospholipid classes in liver and muscle of both fish groups was similar, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol being the predominant lipid classes. The general pattern of fatty acid distribution in total lipid of liver and muscle from captive and wild fish was similar. However, the relative percentage of specific fatty acids differed in captive and wild fish. The most noteworthy difference was the lower proportion of arachidonic acid (20:4n-6, AA) and the higher proportion of eicosapentaenoic acid (20:5n-3, EPA) in liver and muscle of captive fish with respect to those of wild fish. The proportion of docosahexaenoic acid (22:6n-3, DHA) did not differ between the two fish groups. The differences in EPA and AA proportions between captive and wild fish implied that captive fish presented a higher EPA/AA ratio and a lower DHA/EPA ratio than wild fish. In general terms, in both liver and muscle, the differences in fatty acid composition observed for TL were extended to all lipid classes. The results suggest that the different AA, EPA and DHA proportions in liver and muscle between captive and wild broodstocks are attributed to different levels of these fatty acids in broodstock diets.