Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with MET-dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy and MET status (MET exon 14 skipping mutation or MET amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS: A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients with MET amplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients with MET amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS: Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously. The efficacy in MET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).</p

Industrial, Collaborative and Mobile Robotics in Latin America: Review of Mechatronic Technologies for Advanced Automation

Mechatronics and Robotics (MaR) have recently gained importance in product development and manufacturing settings and applications. Therefore, the Center for Space Emerging Technologies (C-SET) has managed an international multi-disciplinary study to present, historically, the first Latin American general review of industrial, collaborative, and mobile robotics, with the support of North American and European researchers and institutions. The methodology is developed by considering literature extracted from Scopus, Web of Science, and Aerospace Research Central and adding reports written by companies and government organizations. This describes the state-of-the-art of MaR until the year 2023 in the 3 Sub-Regions: North America, Central America, and South America, having achieved important results related to the academy, industry, government, and entrepreneurship; thus, the statistics shown in this manuscript are unique. Also, this article explores the potential for further work and advantages described by robotic companies such as ABB, KUKA, and Mecademic and the use of the Robot Operating System (ROS) in order to promote research, development, and innovation. In addition, the integration with industry 4.0 and digital manufacturing, architecture and construction, aerospace, smart agriculture, artificial intelligence, and computational social science (human-robot interaction) is analyzed to show the promising features of these growing tech areas, considering the improvements to increase production, manufacturing, and education in the Region. Finally, regarding the information presented, Latin America is considered an important location for investments to increase production and product development, taking into account the further proposal for the creation of the LATAM Consortium for Advanced Robotics and Mechatronics, which could support and work on roboethics and education/R+D+I law and regulations in the Region. Doi: 10.28991/ESJ-2023-07-04-025 Full Text: PD

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Times and spaces of sociological and social theory: A simultaneous approach of "peripheries" and '"centers"

This chapter deploys the theoretical-methodological proposal of a “simultaneous approach,” which also assumes the purpose of “de-centering” social/sociological theory. This approach is sensitive to the relations between spatialities and temporalities, which is particularly suitable for comparative studies between productions from different latitudes that face certain theoretical and epochal crossroads, from the “peripheries” of the South to the “centers” of the North. The aim is to avoid the supposed “temporal distancing” promoted by other perspectives through the assertion that theoretical productions of the South are “delayed” compared to those of the North, or that there is such incommensurability between them that it renders any comparison impossible. In addition to presenting the features of the approach, it is used to analyze the case of Latin American theories of dependency in some detail. Second, focus is on two analytical tools that have proved useful in the framework of the simultaneous approach: the multiplicity of “dimensions” or “registers” and a “critical reflexivity on simultaneity.” It is expected that this contribution will show not only its analytical-practical usefulness but also its political potentiality, restoring for the South a capacity to legitimately produce theory, thus confronting existing inequalities and asymmetries.Fil: Bialakowsky, Alejandro Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; ArgentinaFil: de Marinis, Ernesto Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentin

The measurement of ammonia blood levels in patients taking valproic acid: Looking for problems where they do not exist?

Hyperammonemia (HA) commonly occurs with the use of valproic acid (VPA); while it has no clinical significance in most cases, the Physician Desk Reference recommends its discontinuation in the presence of HA. The purpose of this study is to review the literature in order to estimate the prevalence and magnitude of HA in VPA treated patients, to establish any association with hepatotoxicity and encephalopathy and to identify any factors associated with its occurrence. A search of MEDLINE and Cochrane Database of Systematic Reviews, between 1980 and 2005 was performed. Out of 183 studies, 24 met our inclusion criteria. The prevalence of HA in the prospective studies ranged between 70% and 100%, while in cross-sectional studies it varied between 16% and 100%. Ammonia (NH 3) blood levels increased by a two-fold average relative to the baseline levels. There was no association between HA and clinical symptoms. Concomitant administration of other antiepileptic drugs (AEDs) was the factor most frequently associated with HA

Comparing standard medical care for nonepileptic seizures in Chile and the United States

Objective: We sought to compare the diagnostic and treatment practices for psychogenic nonepileptic seizures (PNES) in the United States (US) to Chile. Methods: A survey on the diagnostic and treatment practices for PNES was administered to practicing clinicians in Chile. Results from 96 Chilean respondents were compared to results from 307 US clinicians. Type I error (alpha) was set to 0.005 for multiple comparisons. Results: Diagnosis: The diagnosis of PNES is made by inpatient video‐EEG/LTM in 89% of the US respondents compared to 25% of the Chilean respondents (p<0.0001). The diagnosis of PNES is made by history and exam alone at twice the rate in Chile (38%) than in the US (16%; p<0.0001). Treatment: A higher proportion of the Chilean respondents (65%) endorsed psychopharmacotherapy as potentially beneficial compared to the US respondents (31%; p<0.0001). Discussion: This cross-cultural multi‐site survey reveals some differences in PNES evaluation and management between neurologists and other clinicians in the US and in Chile. Access to video EEG may improve PNES diagnosis and treatment. ► NES diagnosis is made by history and exam alone at twice the rate in Chile than US. ► This survey reveals cross-cultural differences in NES evaluation in management. ► Access to video EEG may improve diagnosis and treatment of patients with PNES

Presurgical evaluation of temporal lobe epilepsy: Is an outpatient prolonged ambulatory EEG study sufficient to recommend a surgical resection?

•Inpatient VEEG study is the gold standard in patients with TLE undergoing presurgical evaluation.•VEEG is expensive and not available for a significant proportion of patients in developing countries.•AmbEEG may be used instead of VEEG to identify candidates for temporal lobectomy in selected patients with refractory TLE and concordant semiology, unilateral EEG, neuroimaging and neuropsychological data. Inpatient Video EEG Monitoring (VEM) is the typical study performed in presurgical evaluations. It is expensive and not widely available in developing countries. Recent studies suggested that in selected patients with mesial temporal lobe epilepsy secondary to unilateral mesial temporal sclerosis (MTS), the recording of unilateral interictal epileptiform activity ipsilateral to the MTS may yield sufficient presurgical EEG data. Outpatient prolonged ambulatory EEG (AEEG) could be an alternative in these cases. The purpose of this study was to compare the post-surgical seizure outcome and costs between patients evaluated with AEEG versus VEM. Thirty patients with TLE were included: 21 evaluated with VEM and 9 with AmbEEG and underwent surgery between 2011 and 2017. The minimum, post-surgical follow-up period was 1 year. Seven of nine patients who underwent AEEG had seizures ipsilateral to MTS. In two patients only unilateral interictal activity ipsilateral to the lesion was recorded. All patients were free of disabling seizures (Engel Class I) at last follow-up. The mean cost per patient of AEEG was $980 and was$4680 for VEM. AEEG may be used to identify candidates for temporal lobectomy in selected patients with unilateral lesional mesial TLE. This approach to EEG monitoring could make epilpesy surgery more affordable to some patients in developing countries

Exploraciones en teoría social : Ensayos de imaginación metodológica

Fil: Álvarez Ruiz, Fermín. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Alvaro, Daniel. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Bialakowsky, Alejandro. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Blanco, Ana. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: De Marinis, Pablo. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Fraga, Eugenia. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Grondona, Ana. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Haidar, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Sasín, Mariano. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Torterola, Emiliano. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Trovero, Juan Ignacio. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina