Experiencia institucional en pacientes con cáncer de pulmón de células no pequeñas con mutaciones de inserción del exón 20 del receptor del factor de crecimiento epidérmico (EGFR)

En el cáncer de pulmón de células no pequeñas (CPCNP) con mutación clásica de EGFR, los inhibidores de la tirosina quinasa (TKI) de EGFR produce mejores resultados que la quimioterapia basada en platino. Sin embargo, la eficacia terapéutica es bastante diferente en pacientes con mutaciones de inserción del exón 20 del EGFR (ex20ins) versus mutaciones comunes. Los pacientes con mutaciones ex20ins son insensibles a los EGFR-TKI y tienen mal pronóstico. Es importante conocer las características demográficas y clínicas en este grupo de pacientes y la prevalencia en nuestra región. Metodología: Revisión retrospectiva, única instituciónal, serie de casos de pacientes con cáncer de pulmón de células no pequeñas con mutaciones de inserción del exón 20 desde 2017-2023. Los pacientes habían recibido terapia de primera línea para enfermedad avanzada y tuvieron estudios de imágenes para evaluar la respuesta. Se registraron los datos demográficos, las características y tratamiento de cada paciente. La respuesta al tratamiento se evaluó utilizando los criterios RECIST v1.1 y la supervivencia global se calculó mediante el método de Kaplan Meier. Resultados: Entre los 15 pacientes identificados con cáncer de pulmón de células no pequeñas con mutaciones de inserción del exón 20 en nuestra institución, la incidencia para la mutación fue del 1.5%. La edad promedio fue de 60 años, el 46,7% eran mujeres, 14 pacientes hispanos y 1 paciente asiático, solo 3 pacientes tenían antecedentes de tabaquismo. El 40% de los pacientes tuvo una escala funcional según el Grupo Cooperativo de Oncología Oriental (ECOG) de 2. El subtipo histológico fue adenocarcinoma en todos los casos. De los 13 (86.7%) pacientes que recibieron tratamiento de primera línea, se les realizaron exploraciones evaluables para determinar la respuesta, 11 progresaron, 1 paciente obtuvo enfermedad estable y otro tuvo respuesta parcial. La mediana de supervivencia global (SG) fue de 5 meses. Conclusiones: Los pacientes con mutaciones de inserción del exón 20 tienen resistencia a los inhibidores de tirosina quinasa, lo cual le confiere un peor pronóstico. Es vital conocer en nuestra región la incidencia de la mutación y las características de los pacientes para ofrecer un diagnóstico y tratamiento oportuno. Nuestros resultados proporcionan un contexto importante para el desarrollo de nuevas terapias que puedan aprobarse en primera línea de tratamiento y no en líneas subsecuentes. (provisto por Infomedic International)

In non-small cell lung cancer (NSCLC) with classical EGFR mutation, EGFR tyrosine kinase inhibitors (TKIs) produce better results than platinum-based chemotherapy. However, therapeutic efficacy is quite different in patients with EGFR exon 20 insertion mutations (ex20ins) versus common mutations. Patients with ex20ins mutations are insensitive to EGFR-TKIs and have poor prognosis. It is important to know the demographic and clinical characteristics in this group of patients and the prevalence in our region. Methodology: retrospective, single institution, case series review of patients with non-small cell lung cancer with exon 20 insertion mutations from 2017-2023. Patients had received first-line therapy for advanced disease and had imaging studies to assess response. Demographics, characteristics, and treatment of each patient were recorded. Treatment response was assessed using RECIST v1.1 criteria and overall survival was calculated using the Kaplan Meier method. Results: Among the 15 patients identified with non-small cell lung cancer with exon 20 insertion mutations at our institution, the incidence for the mutation was 1.5%. The mean age was 60 years, 46.7% were women, and the incidence of the mutation was 1.5%. The average age was 60 years, 46.7% were women, 14 patients were Hispanic and 1 patient was Asian, only 3 patients had a history of smoking. Forty percent of the patients had an Eastern Cooperative Oncology Group (ECOG) functional score of 2. The histologic subtype was adenocarcinoma in all cases. Of the 13 (86.7%) patients who received first-line treatment had evaluable scans to determine response, 11 progressed, 1 patient had stable disease, and 1 patient had a partial response. The median overall survival (OS) was 5 months. Conclusions: Patients with exon 20 insertion mutations have resistance to tyrosine kinase inhibitors, which confers a worse prognosis. It is vital to know in our region the incidence of the mutation and patient characteristics to provide timely diagnosis and treatment. Our results provide an important context for the development of new therapies that can be approved in the first line of treatment and not in subsequent lines. (provided by Infomedic International)

Evaluation of gender differences in postoperative sore throat and hoarseness following the use of Ambu AuraGain laryngeal mask: the randomised controlled LadyLAMA trial study protocol.

INTRODUCTION: Postoperative sore throat (POST) is a comparatively minor but very common side effect of general anaesthesia with a supraglottic airway device. The patient considers these side effects a mirror of the quality of anaesthesia. The aims of this study are to evaluate gender-specific differences in the incidence of POST and to assess whether the effects of known risk factors vary between genders. METHODS AND ANALYSIS: The LadyLAMA trial is a single-centre, patient-blinded, randomised controlled trial. Consecutive patients requiring ophthalmological surgery under general anaesthesia with a second generation Ambu AuraGain laryngeal mask are randomly allocated to either cuff pressure of 45 cmH2O or cuff pressure of 60 cmH2O. We estimate the difference in POST between the genders at 20% and we hypothesised that a reduction of cuff pressure would reduce POST by 10%. A total of 800 patients will be recruited, with each subgroup including 200 patients to achieve 80% power for detecting a difference at the 5% significance level. Primary endpoints are gender differences in the incidence of POST within 24 hours postoperatively, as well as comparison of cuff pressure 45 cmH2O to 60 cmH2O with respect to POST. The main secondary objective is the effect of cuff pressure on POST stratified by gender. Further secondary endpoints are gender-specific differences in POST and hoarseness in postanaesthesia care unit (PACU) at 48 and 72 hours (or until freedom of discomfort). The parameter cuff pressure serves as key-secondary endpoint. ETHICS AND DISSEMINATION: The project is approved by the local ethics committee of the Medical Association of the Rhineland Palatine state (Nr. 2021-15835). The results of this study will be made available in the form of manuscripts for publication and presentations at national and international meetings. TRIAL REGISTRATION NUMBER: NCT04915534.

Blockade of 5-Ht3 receptors in the septal area increases Fos expression in selected brain areas.

Serotonin is widely distributed throughout the brain and is involved in a multiplicity of visceral, cognitive and behavioral responses. It has been previously shown that injections of different doses of ondansetron, a 5-HT3 receptor antagonist, into the medial septum/vertical limb of the diagonal band complex (MS/vDB) induce a hypertensive response in rats. On the other hand, administration of m-CPBG, a 5-HT3 agonist, into the MS/vDB inhibits the increase of blood pressure during restraint stress. However, it is unclear which neuronal circuitry is involved in these responses. The present study investigated Fos immunoreactive nuclei (Fos-IR) in different brain areas following the blockade of 5-HT3 receptors located in the MS/vDB in sham and in sinoaortic denervated (SAD) rats. Ondansetron injection into the MS/vDB increases Fos-IR in different brain areas including the limbic system (central amygdala and ventral part of the bed nucleus of the stria terminalis), hypothalamus (medial parvocellular parts of the paraventricular nucleus, anterodorsal preoptic area, dorsomedial hypothalamic nucleus), mesencephalon (ventrolateral periaqueductal gray region) and rhombencephalon (lateral parabrachial nucleus) in sham rats. Barodenervation results in higher Fos expression at the parvocellular and magnocellular part of the paraventricular nucleus, the lateral parabrachial nucleus, the central nucleus of amygdala, the locus coeruleus, the medial part of the nucleus of the solitary tract, the rostral ventrolateral medulla and the caudal ventrolateral medulla following 5-HT3receptor blockade in the MS/vDB. Based on the present results and previous data showing a hypertensive response to ondansetron injected into the MS/vDB, it is reasonable to suggest that 5-HT3receptors in the MS/vDB exert an inhibitory drive that may oscillate as a functional regulatory part of the complex central neuronal network participating in the control of blood pressure.

Sex differences in serum CK activity but not in glomerular filtration rate after resistance exercise: is there a sex dependent renal adaptative response?

We investigated differences in sex responses in serum CK activity and renal function measured by glomerular filtration rate (GFR) after an exercise session. Twenty-two healthy and trained volunteers (11 males and 11 females) performed 17 resistance exercises with 3 × 12 repetitions in a circuit training fashion. Subjects provided blood samples prior to exercise session, and at 24, 48, and 72 h following exercise sessions for creatine kinase and creatinine. Twenty-four-hour urine samples were collected before and 72 h after the exercise. Estimate (e) GFR was obtained by using the Chronic Kidney Disease Epidemiology Collaboration equation adjusted for males and females. After the exercise session, males showed greater serum CK activity than females (p < 0.02), serum creatinine increased 31.3 % for males and 29.8 % for females, and urinary creatinine decreased on average 5.4 % for males and 0.6 % for females, with no significant differences (p > 0.05) between sex for serum and urinary creatinine. eGFR decreased significantly for males (~10 %) and females (~8 %), but also without a difference between the sexes (p > 0.05). The correlation between CK and eGFR was significant for males (r = -0.794; p = 0.003), and females (r = -0.8875; p < 0.001). A significant negative correlation between CK activity and the eGFR indice of renal function in both males and females was observed. Additionally, the renal function compromise was similar for both sexes, despite males presenting greater exercise-induced skeletal muscle damage when compared to females.

Comparison of explosive force between young and elderly women: evidence of an earlier decline from explosive force.

The aging process causes many changes in muscle strength, and analysis of explosive force from handgrip strength seems to be useful and promising in studying the aging musculoskeletal system. Therefore, the purpose of this study was to investigate if explosive force parameters [rate of force development (RFD) and contractile impulse (CI) over the time interval of 0-200 ms from the onset of contraction] during handgrip efforts decline differently than maximum handgrip strength with increasing age. Twenty healthy young women (20-27 years) and 65 healthy elderly women, assigned into three age groups (50-64, 65-74, and 75-86 years), participated in this study. All participants performed two maximal grip attempts. Handgrip data were recorded as force-time curves, peak force, and explosive force parameters. Our results revealed that peak force decreased significantly (p < 0.05) for those who are 65 years old, while explosive force parameters decreased significantly (p < 0.05) for those aged 50 years. These data indicate that the decline in explosive grip force-generating capacity may begin earlier (i.e., for those aged 50 years old) than peak force during the aging process. Our findings suggest that the aging process reduces the explosive grip force-generating capacity before affecting peak force.

Hand dominance during constant force isometric contractions: evidence of different cortical drive commands.

The purpose of this study was to investigate force variability and sensoriomotor strategies of dominant and nondominant hands of right and left-handed subjects during a submaximal isometric force production task. Twelve right-handed adults (9 men and 3 women; 23 ± 3 year) and twelve left-handed adults (4 men and 8 women; 24 ± 3 year) performed an isometric constant force contraction sustained at 30 and 50% of maximal force for 10 s. Surface EMG signals were obtained from forearm flexors and extensors. Force signals were analyzed in the time (CV of force) and frequency (0-10 Hz) domain. The neural activation of the involved muscles was investigated from the EMG structure using the cross-wavelet spectra of the interference EMG signals of six different frequency bands of the EMG signals were quantified (5-13, 13-30, 30-60, 60-100, 100-150 and 150-200 Hz). The major findings were: (1) dominant and nondominant hands of right- and left-handed subjects exhibited similar CV of force; (2) the power spectrum of force is influenced by handedness, with greater 1-3 Hz oscillations for left-handed subjects when compared to right-handed subjects; (3) right-handed subjects have greater 30-60 Hz neuromuscular activation when compared to left-handed subjects. Our results indicate that right-handed individuals may rely preferentially in visual feedback to carry out a task with visual and proprioceptive feedback because of the left hemisphere specialization on the visuomotor control.

Compreendendo as restrições dos técnicos de enfermagem sobre a permanência de acompanhantes em Unidade de Terapia Intensiva aberta / Understanding nursing technicians' objections to patients' companions staying in the Intensive Care Unit / Comprendiendo las restricciones de los técnicos en enfermería ante la permanencia de acompañantes en Unidad de Terapia Intensiva abierta

A presente pesquisa teve como objetivo compreender as restrições dos técnicos de enfermagem sobre a permanência de acompanhantes em Unidade de Terapia Intensiva. Trata-se de uma pesquisa qualitativa do tipo exploratória. Os sujeitos foram 11 técnicos de enfermagem de todos os turnos. A coleta de dados se deu em dois encontros no mês de março de 2008. Para a análise, foi utilizada a técnica do Discurso do Sujeito Coletivo. Após análise foi possível apreender duas ancoragens: a Ancoragem I mostra que os acompanhantes representam uma sobrecarga para os técnicos e a Ancoragem II que os técnicos se sentem desprotegidos em relação aos familiares. Conclui-se que as razões que supostamente geram o conflito não é a relação com o acompanhante ou o desenvolvimento de técnicas sob observação, mas a pouca valorização profissional e a falta de suporte para executar as atividades diárias.

The objective of this qualitative, exploratory research was to better understand nursing technicians' objections to patients' companions staying in the Intensive Care Unit. The subjects were 11 nursing technicians from all shifts. Data was collected in two meetings in March, 2008. The Discourse of the Collective Subject technique was used for analysis. After analysis, 2 main ideas (or anchor ideas) were apprehended: Anchor idea I shows that patients' companions represent a burden for technicians, and Anchor idea II shows that technicians feel unprotected in relation to them. It is concluded that the reasons which supposedly generate the conflict are not the relationship with the companion or the development of techniques under observation, but the professional undervaluing and the lack of support to perform daily tasks.

La presente investigación tuvo como objetivo comprender las restricciones de los técnicos en enfermería ante la permanencia de acompañantes en la Unidad de Terapia Intensiva. Se trata de una investigación cualitativa, de tipo exploratorio. Los sujetos fueron 11 técnicos en enfermería de todos los turnos. La recolección de los datos se realizó mediante dos encuentros en el mes de marzo de 2008. Para el análisis se utilizó la técnica del Discurso de Sujeto Colectivo. Con el análisis fue posible reconocer dos tópicos : el Tópico I, revela que los acompañantes representan una sobrecarga para los técnicos, y el Tópico II muestra que los técnicos se sienten desprotegidos frente a ellos. Se concluye que las razones que supuestamente generan el conflicto no es la relación con el acompañante o el desarrollo de técnicas de observación, sino la poca valorización profesional y la falta de apoyo para ejecutar las actividades diarias.

Estudo do envolvimento dos receptores serotoninérgicos 5-HT3 e 5-HT2C localizados na amígdala no controle da ingestão de sal em ratos / Study of the involvement of serotonin receptors 5-HT3 and 5-HT2C located in the amygdala in controlling the intake of salt in rats

Diferentes áreas do sistema nervoso central estão envolvidas no controle da ingestão de água e sal, formando uma extensa rede neural que permite respostas corretivas viscerais e comportamentais, de forma a manter a homeostasia hidrossalina. Vários estudos têm demonstrado que a ativação de algumas vias neurotransmissoras centrais tais como a serotoninérgica, a colinérgica, a angiotensinérgica, a adrenérgica, a opiatérgica, a glutamatérgica e a GABAérgica, leva a mudanças no comportamento de ingestão de água e sal. No presente trabalho, verificamos a participação dos receptores serotoninéricos dos tipos 5-HT 3 e 5-HT 2C localizados na amígdala medial (MeA) e I central (CeA) no controle da ingestão de sal em ratos sódio-depletados. Verificamos que a administração do m-CPBG, agonista dos receptores 5-HT3, na MeA inibe a ingestão de sal em ratos sódio-depletados. Este efeito antinatriorexigênico do m-CPBG parece ser devido à sua ação nos receptores 5-IHT 3, uma vez que o pré-tratamento com a ondansetrona, antagonista específico destes receptores, bloqueia a resposta antinatrioréxica do m-CPBG. A administração da ondansetrona sozinha não foi capaz de alterar a ingestão de sal em ratos sódio-depletados. Além disso, verificamos que a injeção do m-CPP, agonista dos receptores 5-HT 2C, na MeA não alterou a ingestão de sal induzida por depleção de sódio. Ao contrário, o tratamento com o SDZ-SER082, antagonista dos receptores 5-HT 2C, inibiu a ingestão de sal quando injetado na MeA. O efeito inibitório do m-CPBG e do SDZ-SER 082 na MeA não parece ser conseqüência de efeitos aversivos ou de alterações locomotoras produzidas pela administração destas drogas. Na CeA, a administração do m-CPBG também induziu uma redução na ingestão de sal e este efeito também foi bloqueado pelo pré-tratamento com a ondansetrona. A administração de ondansetrona sozinha na CeA não alterou a ingestão de sal em ratos sódio-depletados. Além disso, verificamos que o efeito inibitório na ingestão de sal induzido pela administração do m-CPBG na CeA não está relacionado a efeitos aversivos, deficits locomotores ou ao aumento na pressão arterial. O m-CPP e o SDZ SER 082 não modificaram j a ingestão de sal em animais depletados de Sódio, quando injetados na CeA. Desta forma, podemos dizer que a estimulação farmacológica dos receptores 5-HT 3 localizados na MeA e CeA induz um significante efeito antinatriorexigênico em ratos sodio-depletados e que a integridade funcional dos receptores 5-HT 2C localizados na MeA é importante para a expressão do apetite por sódio neste modelo experimental.

Role of 5-HT3 and 5-HT2C receptors located within the medial amygdala in the control of salt intake in sodium-depleted rats.

In the present study, we investigated the role of 5-HT(3) and 5-HT(2C) receptors located within the medial amygdala (MeA) in the control of water and salt intake in sodium-depleted rats. Pharmacological activation of 5-HT(3) receptors located in the medial amygdala by the selective 5-HT(3) receptor agonist m-CPBG significantly reduced salt intake in sodium-depleted rats, an effect that is reverted by pretreatment with the selective 5-HT(3) receptor antagonist ondansetron. In addition, the injection of ondansetron alone into the medial amygdala had no effect on salt intake in sodium-depleted and in sodium-repleted rats. Pharmacological stimulation of 5-HT(2C) receptors located in the medial amygdala by the selective 5-HT(2C) receptor agonist m-CPP failed to modify salt intake in sodium-depleted rats, whereas the blockade of these receptors by the selective 5-HT(2C) receptor antagonist SDZ SER 082 significantly reduced salt intake in this same group of animals. These results lead to the conclusion that the pharmacological activation of 5-HT(3) receptors located within the MeA inhibits salt intake in sodium-depleted rats and that, in this same brain region, the functional integrity of 5-HT(2C) receptors is required to achieve the full expression of sodium appetite in sodium-depleted rats.