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Caregiving for a person with dementia is considered a situation of chronic stress, with consequences on caregivers' physical and psychological health. The usual challenges of dementia care were intensified during the pandemic due to the risk of contagion, social isolation measures, and decrease in healthcare resources. The COVID-19 pandemic increased the stress both in the persons with dementia and their caregivers. This commentary reflects on the long-term effects of the pandemic on caregivers' mental health, focusing on the study by Olavarría and colleagues and drawing future research lines for culturally diverse family caregivers.
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COVID-19 , Cuidadores , Demencia , Salud Mental , Estrés Psicológico , Humanos , COVID-19/psicología , COVID-19/epidemiología , Cuidadores/psicología , Demencia/psicología , Demencia/enfermería , Estrés Psicológico/psicología , Aislamiento Social/psicología , Pandemias , SARS-CoV-2 , Familia/psicologíaRESUMEN
The Aedes aegypti cadherin-like protein (Aae-Cad) and the membrane-bound alkaline phosphatase (Aae-mALP) are membrane proteins identified as putative receptors for the larvicidal Cry toxins produced by Bacillus thuringiensis subsp. israelensis bacteria. Cry toxins are the most used toxins in the control of different agricultural pest and mosquitos. Despite the relevance of Aae-Cad and Aae-mALP as possible toxin-receptors in mosquitoes, previous efforts to establish a clear functional connection among them and Cry toxins activity have been relatively limited. In this study, we used CRISPR-Cas9 to generate knockout (KO) mutations of Aae-Cad and Aae-mALP. The Aae-mALP KO was successfully generated, in contrast to the Aae-Cad KO which was obtained only in females. The female-linked genotype was due to the proximity of aae-cad gene to the sex-determining loci (M:m). Both A. aegypti KO mutant populations were viable and their insect-development was not affected, although a tendency on lower egg hatching rate was observed. Bioassays were performed to assess the effects of these KO mutations on the susceptibility of A. aegypti to Cry toxins, showing that the Aae-Cad female KO or Aae-mALP KO mutations did not significantly alter the susceptibility of A. aegypti larvae to the mosquitocidal Cry toxins, including Cry11Aa, Cry11Ba, Cry4Ba, and Cry4Aa. These findings suggest that besides the potential participation of Aae-Cad and Aae-mALP as Cry toxin receptors in A. aegypti, additional midgut membrane proteins are involved in the mode of action of these insecticidal toxins.
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Aedes , Fosfatasa Alcalina , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas , Sistemas CRISPR-Cas , Cadherinas , Endotoxinas , Proteínas Hemolisinas , Animales , Aedes/genética , Aedes/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/genética , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Endotoxinas/genética , Endotoxinas/metabolismo , Femenino , Cadherinas/genética , Cadherinas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas/genética , Técnicas de Inactivación de Genes , Larva/genética , Larva/crecimiento & desarrollo , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Masculino , Insecticidas/farmacologíaRESUMEN
OBJECTIVE: Compare prevalence and profile of post-intensive care patient (P-PICS) and family/caregiver (F-PICS) syndrome in two cohorts (COVID and non-COVID) and analyse risk factors for P-PICS. DESIGN: Prospective, observational cohort (March 2018-2023), follow-up at three months and one year. SETTING: 14-bed polyvalent Intensive Care Unit (ICU), Level II Hospital. PATIENTS OR PARTICIPANTS: 265 patients and 209 relatives. Inclusion criteria patients: age > 18 years, mechanical ventilation > 48 h, ICU stay > 5 days, delirium, septic shock, acute respiratory distress syndrome, cardiac arrest. Inclusion criteria family: those who attended. INTERVENTIONS: Follow-up 3 months and 1 year after hospital discharge. MAIN VARIABLES OF INTEREST: Patients: sociodemographic, clinical, evolutive, physical, psychological and cognitive alterations, dependency degree and quality of life. Main caregivers: mental state and physical overload. RESULTS: 64.9% PICS-P, no differences between groups. COVID patients more physical alterations than non-COVID (P = .028). These more functional deterioration (P = .005), poorer quality of life (P = .003), higher nutritional alterations (P = .004) and cognitive deterioration (P < .001). 19.1% PICS-F, more frequent in relatives of non-COVID patients (17.6% vs. 5.5%; P = .013). Independent predictors of PICS-P: first years of the study (OR: 0.484), higher comorbidity (OR: 1.158), delirium (OR: 2.935), several reasons for being included (OR: 3.171) and midazolam (OR: 4.265). CONCLUSIONS: Prevalence PICS-P and PICS-F between both cohorts was similar. Main factors associated with the development of SPCI-P were: higher comorbidity, delirium, midazolan, inclusion for more than one reason and during the first years.
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COVID-19 , Familia , Humanos , COVID-19/epidemiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Factores de Riesgo , Cuidadores/estadística & datos numéricos , Cuidados Críticos , Unidades de Cuidados Intensivos , Factores de Tiempo , Prevalencia , Calidad de Vida , Delirio/epidemiología , Delirio/etiología , Enfermedad CríticaRESUMEN
BACKGROUND: Despite the recognized advantages of Peer-Assisted Learning (PAL) in academic settings, there is a notable absence of research analyzing its effects on students' Academic Burnout. This study aims to cover this gap by assessing the underlying effectiveness of Informal Peer-Assisted Learning (IPAL) as a cooperative learning method, focusing on its potential to mitigate academic burnout among medical students. METHODS: In 2022, a cross-sectional study was conducted at the School of Medicine, Universidad Central del Caribe, in Puerto Rico. The research team gathered data from 151 participants, 49.19% of 307 total student body. This cohort included 76 female students, 71 male students, and 4 individuals saying other. The School Burnout Inventory questionnaire (SBI-9) was employed to assess Academic Burnout, along with an added query about self-reported IPAL. The SBI-9 underwent validation processes to ascertain its reliability and validity, incorporating the Exploratory Factor Analysis and Confirmatory Factor Analysis. Following this, the investigators conducted an analysis to determine the correlation between academic burnout levels and involvement in IPAL. RESULTS: The validation process of the questionnaire affirmed its alignment with an eight-item inventory, encapsulating two principal factors that elucidate academic burnout. The first factor pertains to exhaustion, while the second encompasses the combined subscales of cynicism and inadequacy. The questionnaire shows high reliability (Cronbach's alpha = 0.829) and good fit indices (Comparative Fit Index = 0.934; Tucker-Lewis Index = 0.902; Standardized Root Mean Squared Residual = 0.0495; Root Mean Squared Error of Approximation = 0.09791; p-value < 0.001). The factors proven in the selected model were used to evaluate the correlation between Academic Burnout and IPAL. Students engaged in IPAL showed significantly lower academic burnout prevalence compared to those who never participated in such practices, with a mean academic burnout score of 44.75% (SD 18.50) for IPAL engaged students versus 54.89% (SD 23.71) for those who never engaged in such practices (p-value < 0.013). Furthermore, within the group engaged in IPAL, students displayed lower levels of cynicism/inadequacy 41.98% (SD 23.41) compared to exhaustion 52.25% (SD 22.42) with a p-value < 0.001. CONCLUSIONS: The results of this study underscore a notable issue of academic burnout among medical students within the surveyed cohort. The investigation reveals a significant correlation between Academic Burnout and IPAL, suggesting that incorporating IPAL strategies may be beneficial in addressing burnout in medical education settings. However, further research is needed to explore potential causal mechanisms.
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Grupo Paritario , Estudiantes de Medicina , Humanos , Estudiantes de Medicina/psicología , Femenino , Masculino , Estudios Transversales , Agotamiento Profesional , Encuestas y Cuestionarios , Puerto Rico , Adulto Joven , Adulto , Reproducibilidad de los Resultados , Educación de Pregrado en MedicinaRESUMEN
The identification of large vessel occlusion with underlying intracranial atherosclerotic disease (ICAS-LVO) before endovascular treatment (EVT) continues to be a challenge. We aimed to analyze baseline clinical-radiological features associated with ICAS-LVO that could lead to a prompt identification. We performed a retrospective cross-sectional study of consecutive patients with stroke treated with EVT from January 2020 to April 2022. We included anterior LVO involving intracranial internal carotid artery and middle cerebral artery. We analyzed baseline clinical and radiological variables associated with ICAS-LVO and evaluated the diagnostic value of a multivariate logistic regression model to identify ICAS-LVO before EVT. ICAS-LVO was defined as presence of angiographic residual stenosis or a trend to re-occlusion during EVT procedure. A total of 338 patients were included in the study. Of them, 28 patients (8.3%) presented with ICAS-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 9.33, 95% CI 1.11-78.42; p = 0.040), lower hypoperfusion intensity ratio (HIR [Tmax > 10 s/Tmax > 6 s ratio], (OR 0.69, 95% CI 0.50-0.95; p = 0.025), symptomatic intracranial artery calcification (IAC, OR .15, 95% CI 1.64-26.42, p = 0.006), a more proximal occlusion (ICA, MCA-M1: OR 4.00, 95% CI 1.23-13.03; p = 0.021), and smoking (OR 2.91, 95% CI 1.08-7.90; p = 0.035) were associated with ICAS-LVO. The clinico-radiological model showed an overall well capability to identify ICAS-LVO (AUC = 0.88, 95% CI 0.83-0.94; p < 0.001). In conclusion, a combination of clinical and radiological features available before EVT can help to identify an ICAS-LVO. This approach could be useful to perform a rapid assessment of underlying etiology and suggest specific pathophysiology-based measures. Prospective studies are needed to validate these findings in other populations.
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Procedimientos Endovasculares , Arteriosclerosis Intracraneal , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Estudios Transversales , Arteria Carótida Interna , Procedimientos Endovasculares/métodos , Arteriosclerosis Intracraneal/etiologíaRESUMEN
Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.
OBJECTIVES: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. DESIGN: Retrospective observational study. METHODS: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). RESULTS: Overall, 473 UC patients were included (330 IVi, 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4%, in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. CONCLUSION: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.
Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents. Data from the ENEIDA registry Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC), but little is known when it is used as the second anti-TNF.
RESUMEN
RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.
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Aspirina , Accidente Cerebrovascular Isquémico , Trombosis , Tirofibán , Humanos , Aspirina/efectos adversos , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Tirofibán/efectos adversos , Tirofibán/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Bacillus thuringiensis (Bt) produces crystals composed mainly of Cry pesticidal proteins with insecticidal activity against pests but are highly susceptible to degradation by abiotic factors. In this sense, encapsulation techniques are designed to improve their performance and lifetime. However, the effects of polymeric matrix encapsulation such as gum arabic and maltodextrin by spray-dryer in the mechanisms of action of Bt kurstaki and Bt aizawai are unknown. We analyzed crystal solubilization, protoxin activation, and receptor binding after microencapsulation and compared them with commercial non-encapsulated products. Microencapsulation did not alter protein crystal solubilization, providing 130 kDa (Cry1 protoxin) and 70 kDa (Cry2 protoxin). Activation with trypsin, chymotrypsin, and larval midgut juice was analyzed, showing that this step is highly efficient, and the protoxins were cleaved producing similar ~ 55 to 65 kDa activated proteins for both formulations. Binding assays with brush border membrane vesicles of Manduca sexta and Spodoptera frugiperda larvae provided a similar binding for both formulations. LC50 bioassays showed no significant differences between treatments but the microencapsulated treatment provided higher mortality against S. frugiperda when subjected to UV radiation. Microencapsulation did not affect the mechanism of action of Cry pesticidal proteins while enhancing protection against UV radiation. These data will contribute to the development of more efficient Bt biopesticide formulations. KEY POINTS: ⢠Microencapsulation did not affect the mechanisms of action of Cry pesticidal proteins produced by Bt. ⢠Microencapsulation provided protection against UV radiation for Bt-based biopesticides. ⢠The study's findings can contribute to the development of more efficient Bt biopesticide formulations.
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Bacillus thuringiensis , Plaguicidas , Polisacáridos , Animales , Plaguicidas/farmacología , Goma Arábiga , Agentes de Control Biológico , Larva , Control de PlagasRESUMEN
Importance: Using race and ethnicity in clinical prediction models can reduce or inadvertently increase racial and ethnic disparities in medical decisions. Objective: To compare eligibility for lung cancer screening in a contemporary representative US population by refitting the life-years gained from screening-computed tomography (LYFS-CT) model to exclude race and ethnicity vs a counterfactual eligibility approach that recalculates life expectancy for racial and ethnic minority individuals using the same covariates but substitutes White race and uses the higher predicted life expectancy, ensuring that historically underserved groups are not penalized. Design, Setting, and Participants: The 2 submodels composing LYFS-CT NoRace were refit and externally validated without race and ethnicity: the lung cancer death submodel in participants of a large clinical trial (recruited 1993-2001; followed up until December 31, 2009) who ever smoked (n = 39â¯180) and the all-cause mortality submodel in the National Health Interview Survey (NHIS) 1997-2001 participants aged 40 to 80 years who ever smoked (n = 74â¯842, followed up until December 31, 2006). Screening eligibility was examined in NHIS 2015-2018 participants aged 50 to 80 years who ever smoked. Data were analyzed from June 2021 to September 2022. Exposure: Including and removing race and ethnicity (African American, Asian American, Hispanic American, White) in each LYFS-CT submodel. Main Outcomes and Measures: By race and ethnicity: calibration of the LYFS-CT NoRace model and the counterfactual approach (ratio of expected to observed [E/O] outcomes), US individuals eligible for screening, predicted days of life gained from screening by LYFS-CT. Results: The NHIS 2015-2018 included 25â¯601 individuals aged 50 to 80 years who ever smoked (2769 African American, 649 Asian American, 1855 Hispanic American, and 20â¯328 White individuals). Removing race and ethnicity from the submodels underestimated lung cancer death risk (expected/observed [E/O], 0.72; 95% CI, 0.52-1.00) and all-cause mortality (E/O, 0.90; 95% CI, 0.86-0.94) in African American individuals. It also overestimated mortality in Hispanic American (E/O, 1.08, 95% CI, 1.00-1.16) and Asian American individuals (E/O, 1.14, 95% CI, 1.01-1.30). Consequently, the LYFS-CT NoRace model increased Hispanic American and Asian American eligibility by 108% and 73%, respectively, while reducing African American eligibility by 39%. Using LYFS-CT with the counterfactual all-cause mortality model better maintained calibration across groups and increased African American eligibility by 13% without reducing eligibility for Hispanic American and Asian American individuals. Conclusions and Relevance: In this study, removing race and ethnicity miscalibrated LYFS-CT submodels and substantially reduced African American eligibility for lung cancer screening. Under counterfactual eligibility, no one became ineligible, and African American eligibility increased, demonstrating the potential for maintaining model accuracy while reducing disparities.
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Detección Precoz del Cáncer , Determinación de la Elegibilidad , Neoplasias Pulmonares , Tamizaje Masivo , Humanos , Detección Precoz del Cáncer/estadística & datos numéricos , Etnicidad , Hispánicos o Latinos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etnología , Grupos Minoritarios , Tamizaje Masivo/estadística & datos numéricos , Determinación de la Elegibilidad/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Modelos Estadísticos , Factores Raciales , Negro o Afroamericano , Asiático , Blanco , Medición de Riesgo , Esperanza de VidaRESUMEN
In Central Europe the most common allergies are provoked by grass or birch pollen allergens. We determined the intra-daily behavior of airborne pollen grains of grasses (Poaceae) and birch (Betula ssp.) in Central Europe, based on data obtained from a network of automatic pollen monitors over Europe (www.pollenscience.eu). Our aim was to determine the time of day when the lowest concentrations occur, to provide allergic individuals the optimal time to ventilate their homes. The study was carried out in three Central European capitals, Berlin (Germany), Paris-Saclay (France), and Luxembourg (Luxembourg), as well as in eight stations in Germany (Altötting, Feucht, Garmisch-Partenkirchen, Hof, Marktheidenfeld, Mindelheim, Munich and Viechtach). The diurnal rhythm of these eleven locations was analyzed for either the complete, first week, peak week, peak day and last week of the pollen season. The data studied were reported as pollen/m3 measured in 3 h periods. Stations were classified as city, semi-populated or countryside areas using land-use and population density criteria. Grass pollen has a more pronounced diurnal rhythm than birch pollen concentrations. A significant difference was observed when comparing day (6-21 h) versus night (21-6 h) for all stations. No difference was detected between city and countryside for both pollen types, although for Poaceae a longer period of maximum concentrations was observed in big cities and higher day/night-time differences were registered in the countryside (6.4) than in cities (3.0). The highest pollen concentrations were observed between 9 and 18 h for grass, but the rhythm was less pronounced for birch pollen. For allergic individuals who want to bring in fresh air in their homes, we recommend opening windows after 21 h, but even better early in the morning between 6 and 9 h before pollinations (re)starts.
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Hipersensibilidad , Poaceae , Humanos , Betula , Polen , Alérgenos , Europa (Continente) , Estaciones del AñoRESUMEN
PURPOSE OF REVIEW: Urinary pH is an important factor related to renal stone disease, and it plays an essential role in stone prevention. Monitoring of urinary pH by patients at home provides information that can help to assess the treatment needed by each patient. We conducted a systematic review is to assess the available evidence concerning urinary pH monitoring methods along with their accuracy, cost, and usefulness by patients with urolithiasis. RECENT FINDINGS: A total of 9 articles were included (1886 urinary pH measurements). They reported information about urinary dipsticks, portable electronic pH meters and electronic strip readers, amongst other methods. Accuracy was compared with a laboratory pH meter (gold standard). Urinary dipsticks were found to be not accurate enough to guide clinical decision making and portable electronic pH meters showed promising results. Urinary dipsticks are neither precise nor accurate enough. Portable electronic pH meters seem to be more accurate, easy to use, and cost-effective. They are a reliable source for patients to use at home in order to prevent future episodes of nephrolithiasis.
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Cálculos Renales , Sistema Urinario , Urolitiasis , Humanos , Concentración de Iones de Hidrógeno , Cálculos Renales/diagnóstico , PredicciónRESUMEN
INTRODUCTION: Taking care of a relative with dementia may be linked to negative consequences for the caregiver. One of the processes that can be experienced is anticipatory grief, that is defined as the feelings of pain and loss that appear in the caregiver before the death of the person cared for. OBJECTIVES: The review aimed to conceptualize anticipatory grief in this population, to study the related psychosocial variables, and to know the repercussions for the health of the caregiver. METHOD: A systematic search was made under the directives of PRISMA statement in the ProQuest, PubMed, Web of Science (WOS), and Scopus databases, including studies published in the last 10 years (2013-2023). RESULTS: A total of 160 articles were obtained, 15 being finally selected. It is observed that anticipatory grief is defined as an ambiguous process since it appeared before the death of the sick family member. Being a female caregiver, spouse of a family member with dementia, having a closer relationship with him and/or having an important responsibility in care, are associated with a greater chance of experiencing anticipatory grief. In relation to the person cared for, if he or she is in a severe phase of the disease, is younger, and/or presents problematic behaviours, there is also greater anticipatory grief in the family caregiver. Anticipatory grief has a significant impact on caregivers' physical, psychological, and social health, being associated with greater burden, depressive symptomatology, and social isolation. CONCLUSIONS: Anticipatory grief turns out to be a relevant concept in the context of dementia, being necessary to include it in intervention programs for this population.
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Cuidadores , Demencia , Humanos , Masculino , Femenino , Cuidadores/psicología , Pesar , Dolor , Aislamiento Social , Demencia/psicologíaRESUMEN
BACKGROUND: Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed. OBJECTIVES: To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. MATERIAL AND METHODS: We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC + EMDA, BCG, BCG, MMC + EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. RESULTS: Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. CONCLUSION: Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases.
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Mitomicina , Neoplasias de la Vejiga Urinaria , Anciano , Humanos , Administración Intravesical , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéutico , Inmunoterapia , Mitomicina/administración & dosificación , Mitomicina/uso terapéutico , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/inducido químicamente , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Trombosis , Humanos , Tirofibán/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Isquemia Encefálica/inducido químicamente , Resultado del Tratamiento , Aspirina/efectos adversos , Trombectomía/efectos adversos , Trombosis/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase IV como AsuntoRESUMEN
Iron is the most abundant micronutrient in plant mitochondria, and it has a crucial role in biochemical reactions involving electron transfer. It has been described in Oryza sativa that Mitochondrial Iron Transporter (MIT) is an essential gene and that knockdown mutant rice plants have a decreased amount of iron in their mitochondria, strongly suggesting that OsMIT is involved in mitochondrial iron uptake. In Arabidopsis thaliana, two genes encode MIT homologues. In this study, we analyzed different AtMIT1 and AtMIT2 mutant alleles, and no phenotypic defects were observed in individual mutant plants grown in normal conditions, confirming that neither AtMIT1 nor AtMIT2 are individually essential. When we generated crosses between the Atmit1 and Atmit2 alleles, we were able to isolate homozygous double mutant plants. Interestingly, homozygous double mutant plants were obtained only when mutant alleles of Atmit2 with the T-DNA insertion in the intron region were used for crossings, and in these cases, a correctly spliced AtMIT2 mRNA was generated, although at a low level. Atmit1 Atmit2 double homozygous mutant plants, knockout for AtMIT1 and knockdown for AtMIT2, were grown and characterized in iron-sufficient conditions. Pleiotropic developmental defects were observed, including abnormal seeds, an increased number of cotyledons, a slow growth rate, pinoid stems, defects in flower structures, and reduced seed set. A RNA-Seq study was performed, and we could identify more than 760 genes differentially expressed in Atmit1 Atmit2. Our results show that Atmit1 Atmit2 double homozygous mutant plants misregulate genes involved in iron transport, coumarin metabolism, hormone metabolism, root development, and stress-related response. The phenotypes observed, such as pinoid stems and fused cotyledons, in Atmit1 Atmit2 double homozygous mutant plants may suggest defects in auxin homeostasis. Unexpectedly, we observed a possible phenomenon of T-DNA suppression in the next generation of Atmit1 Atmit2 double homozygous mutant plants, correlating with increased splicing of the AtMIT2 intron containing the T-DNA and the suppression of the phenotypes observed in the first generation of the double mutant plants. In these plants with a suppressed phenotype, no differences were observed in the oxygen consumption rate of isolated mitochondria; however, the molecular analysis of gene expression markers, AOX1a, UPOX, and MSM1, for mitochondrial and oxidative stress showed that these plants express a degree of mitochondrial perturbation. Finally, we could establish by a targeted proteomic analysis that a protein level of 30% of MIT2, in the absence of MIT1, is enough for normal plant growth under iron-sufficient conditions.
RESUMEN
We propose a novel biomarker that can identify patients at high risk of early progression after chimeric antigen receptor (CAR) T cell therapy. Calculation of cell-free DNA (cfDNA) with a pre-apheresis (PA) and pre-lymphodepletion (PL) sample allows monitoring of tumor dynamics (∆cfDNA). In the present study, ∆cfDNA and other biomarkers and clinical variables were evaluated in 58 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). ∆cfDNA (>11 ng/mL plasma; P =.003), C-reactive protein (CRP) PL (>1.06 mg/dL; P = .004), lactate dehydrogenase (LDH) PL (>304; P = .006), disease status PL (progressive disease; P = .035) and sex (male; P = .016) were highly correlated with 1 month progression. After adjusting for ∆cfDNA, CRP PL, and LDH PL, disease status PL, and sex, ∆cfDNA remained associated with 1-month progression after CAR T cell infusion.
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Ácidos Nucleicos Libres de Células , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Masculino , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/uso terapéutico , Ácidos Nucleicos Libres de Células/uso terapéutico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia , Inmunoterapia Adoptiva/efectos adversos , Biomarcadores , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
INTRODUCTION: The aim of this study was to compare the perioperative outcomes of routine drainage insertion vs. no drainage in patients undergoing robot-assisted radical prostatectomy (RARP), robot-assisted partial nephrectomy (RAPN), and robot-assisted radical cystectomy (RARC). EVIDENCE ACQUISITION: A literature search was conducted through April 2022 using PubMed/Medline, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. EVIDENCE SYNTHESIS: Eleven studies comprising 8447 RARPs and 1890 RAPNs met our inclusion criteria. Our search strategy did not identify any studies within the RARC framework. In RARP, patients without postoperative drainage had lower rate of postoperative ileus (OR 0.53, 95% CI: 0.38 to 0.74; P<0.001) and similar low-grade (Clavien 1-2, P=0.41) and high-grade (Clavien ≥3; P=0.85) complications, urinary leakage (P=0.07), pelvic hematoma (P=0.35), symptomatic lymphocele (P=0.13), fever (P=0.25), incisional hernia (P=0.31), reintervention (P=0.57), length of hospital stay (P=0.22), and readmission (P=0.74) compared with routinely drained patients. In RAPN, patients without postoperative drainage had shorter length of hospital stay (mean difference: -0.84 days, 95% CI: -1.06 to -0.63; P<0.001) and similar low-grade (P=0.94) and high-grade (P=0.31) complications, urinary leakage (P=0.49), hemorrhage (P=0.39), reintervention (P=0.69), and readmission (P=0.20) compared with routinely drained patients. CONCLUSIONS: In our study, patients without drainage had similar perioperative course to patients with prophylactic drain insertion after RARP and RAPN. Omission of drain insertion was associated with a lower rate of postoperative ileus for RARP and a shorter hospital stay for RAPN. In the era of robotic surgery, routine drain placement is no longer indicated in unselected patients.
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Laparoscopía , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Laparoscopía/efectos adversos , Próstata , Prostatectomía/efectos adversos , Cistectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
Microplastics have appeared as emerging pollutants due to the diverse applications of plastics in today's world. Growing evidence points to the negative impacts that airborne microplastics have on human health, as they can enter the human body through respiration. Our aim was to quantify polystyrene airborne microplastics in smaller fractions, thoracic (PM10) and alveolar (PM2.5), as they have scarcely been studied. In this work, we proposed a methodology based on thermogravimetric analysis coupled with mass spectrometry that requires minimal sample preparation and does not limit particle size. We applied this methodology to quantify the airborne polystyrene in PM10 and PM2.5 fractions in mass units of microplastics per m3 of air in an urban and agricultural region during the summer of 2021. The mean concentrations of polystyrene found in the PM10 and PM2.5 fractions were 2.09 and 1.81 ng m-3, respectively. Therefore, the majority of airborne polystyrene microplastics are found in the alveolar fraction which, is associated with severe cardiopulmonary and respiratory diseases. According to air mass backward trajectories, it was noted that the main sources of these emerging pollutants could be related to local agricultural practices.