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1.
ESC Heart Fail ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605602

RESUMO

AIMS: Drug-refractory electrical storm (ES) is a life-threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in drug-refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking. METHODS AND RESULTS: Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug-refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti-arrhythmic drugs, requiring VA-ECMO for circulatory support. Thirty-four (6%) out of 552 patients with VA-ECMO for cardiogenic shock were included [71% men; 57 (44-62) years], 65% underwent cardiopulmonary resuscitation before VA-ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA-ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter-defibrillator. The drug-refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty-one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA-ECMO, and 29% had heart transplantation. Twenty-seven (79%) survived to hospital discharge (48 (33-82) days). Non-survivors were older [62 (58-67) vs. 54 (43-58); P < 0.01] and had a higher first rhythm disorder-to-ECMO interval [0 (0-2) vs. 2 (1-11) days; P = 0.02]. Seven (20%) had rehospitalization during follow-up [29 (12-48) months], with ES recurrence in 6%. CONCLUSIONS: VA-ECMO bridged drug-refractory ES without a reversible trigger with a high success rate. This required prolonged hospital stays and coordination between the ECMO centre, the electrophysiology laboratory, and the heart transplant programme.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38429541

RESUMO

AIMS: To characterize the register of a secondary diagnosis of mental illnesses in all chronic obstructive pulmonary disease (COPD) hospitalizations registered in Portugal from 2008 to 2015 and explore their impact on hospitalization outcomes. METHODS: A retrospective observational study was conducted. Hospitalizations of patients with at least 40 years old, discharged between 2008 and 2015 with a primary diagnosis of COPD (ICD-9-CM codes 491.x, 492.x and 496) were retrieved from a national administrative database. Comorbid psychiatric diagnoses were identified and defined by the HCUP Clinical Classification Software (CCS) category codes 650-670 (excluding 662). Length of hospital stay (LoS), admission type, in-hospital mortality, and estimated hospital charges were analyzed according to psychiatric diagnostic categories using sex and age-adjusted models. RESULTS: Of 66,661 COPD hospitalizations, 25,869 (38.8%) were episodes with a registered psychiatric comorbidity. These were more likely to correspond to younger inpatients (OR = 2.16, 95%CI 2.09-2.23; p < 0.001), to stay longer at the hospital (aOR = 1.08, 95%CI 1.05-1.12; p < 0.001), to incur in higher estimated hospital charges (aOR = 1.37, 95%CI 1.33-1.42; p < 0.001) and to be urgently admitted (aOR = 1.33, 95%CI 1.23-1.44; p < 0.001). After adjustment for age, in-hospital mortality was lower for episodes with psychiatric diagnoses (aOR = 0.90; 95%CI 0.84-0.96; p < 0.001), except for organic and neurodegenerative diseases category and developmental disorders, intellectual disabilities and disorders usually diagnosed in infancy, childhood, or adolescence category. DISCUSSION: These findings corroborate the additional burden placed by psychiatric disorders on COPD hospitalizations, highlighting the importance of individualizing care to address these comorbidities and minimize their impact on treatment outcomes.

3.
iScience ; 27(3): 109100, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38405606

RESUMO

Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells' proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.

4.
Aging Ment Health ; 28(1): 83-94, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36650751

RESUMO

OBJECTIVE: This rapid review aims to identify the types of technologies used by people with dementia and their supporters during the COVID-19 pandemic, and the issues which influenced technology adoption within their usual care routines. METHODS: PubMed, PsychInfo, Scopus, and Cochrane COVID reviews were searched to identify peer-review studies published since 2020. A total of 18 studies were included and synthesised thematically. RESULTS: Of these, most were conducted in the community (n = 15) with people with dementia only (n = 11) and involved qualitative methods (n = 11). The majority (n = 12) focused on digital off-the-shelf and low-cost solutions, such as free video conferencing platforms, to access care, socialise or take part in interventions. Whilst often well-accepted and associated with positive outcomes (such as improved social connectedness), lack of digital literacy or support to use technologies, limited access to appropriate technology, individuals' physical, cognitive, or sensory difficulties, were highlighted and likely to threaten the adoption of these solutions. The quality of the evidence was mixed, neither very robust nor easily generalisable which may be attributed to the challenges of conducting research during the pandemic or the need to rapidly adapt to a new reality. CONCLUSION: While COVID-19 has fast-tracked the adoption of technology, its use is likely to continue beyond the pandemic. We need to ensure this technology can leverage dementia support and care and that people with dementia are enabled and empowered to use it.


Assuntos
COVID-19 , Demência , Humanos , Pandemias , Demência/psicologia , Tecnologia
5.
Arq. ciências saúde UNIPAR ; 27(2): 701-719, Maio-Ago. 2023.
Artigo em Português | LILACS | ID: biblio-1424879

RESUMO

Introdução: Estudos indicam que os profissionais de saúde têm alto risco de desenvolver sintomas relacionados à saúde mental, especialmente depressão, ansiedade e estresse. Objetivo: identificar e sintetizar os estudos sobre os preditores relacionados a saúde mental entre enfermeiros que atuam na linha de frente no combate ao COVID- 19. Método: Trata-se de uma revisão de escopo, sem limitação de linguagem e ano, nas bases BVS, PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, CAPES e ProQuest. Foi realizada síntese narrativa. Resultados: A pandemia da COVID-19 trouxe sérios impactos a saúde mental dos profissionais de enfermagem, os achados revelaram cinco temas principais sentimento de insegurança, falta de equipamentos de proteção individual, falta de exames diagnósticos, mudanças no fluxo de atendimento e medo do desconhecido. Existe uma associação significativa entre o bem-estar físico e metal e a produtividade laboral. Conclusão: Destaca-se os desafios enfrentados pelos enfermeiros no combate da COVID-19, mesmo com a repercussões no ambiente de trabalho os enfermeiros ainda padecem de reconhecimento adequado que incluem situações de estresse, ansiedade, depressão e estão diretamente relacionadas à frustração, esgotamento físico e mental, sentimento de impotência e insegurança profissional vivenciados durante a pandemia, principalmente por jovens profissionais sem experiência no cuidado de pacientes críticos.


Introduction: Studies indicate that health professionals are at high risk of developing symptoms related to mental health, especially depression, anxiety and stress. Objective: identify and synthesize studies on mental health-related predictors among nurses who work on the front line in the fight against COVID-19. Method: This is a scope review, without language and year limitations, in the VHL, PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, CAPES and ProQuest databases. Narrative synthesis was performed. Results: The COVID-19 pandemic had serious impacts on the mental health of nursing professionals, the findings revealed five main themes: feeling of insecurity, lack of personal protective equipment, lack of diagnostic tests, changes in the flow of care and fear of the unknown. There is a significant association between physical and mental well-being and labor productivity. Conclusion: The challenges faced by nurses in the fight against COVID-19 are highlighted, even with the repercussions in the work environment, nurses still suffer from adequate recognition and include situations of stress, anxiety and even depression, which are directly related to frustration , physical and mental exhaustion, feeling of helplessness and professional insecurity experienced during the pandemic, especially by young professionals with no experience in caring for critically ill patients.


Introducción: Los estudios indican que los profesionales de la salud tienen un alto riesgo de desarrollar síntomas relacionados con la salud mental, especialmente depresión, ansiedad y estrés. Objetivo: identificar y sintetizar estudios sobre predictores relacionados a la salud mental entre enfermeros que trabajan en primera línea en la lucha contra el COVID-19. Método: Se trata de una revisión de alcance, sin limitaciones de idioma y año, en las bases de datos BVS, PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, CAPES y ProQuest. Se realizó una síntesis narrativa. Resultados: La pandemia de COVID-19 tuvo graves impactos en la salud mental de los profesionales de enfermería, los hallazgos revelaron cinco temas principales: sensación de inseguridad, falta de equipo de protección personal, falta de pruebas diagnósticas, cambios en el flujo de atención y miedo a lo desconocido. Existe una asociación significativa entre el bienestar físico y mental y la productividad laboral. Conclusiones: Se destacan los retos a los que se enfrentan las enfermeras en la lucha contra la COVID-19, aún con las repercusiones en el ámbito laboral, las enfermeras siguen sufriendo un reconocimiento adecuado e incluyen situaciones de estrés, ansiedad e incluso depresión, que están directamente relacionadas con la frustración , el agotamiento físico y mental, la sensación de impotencia y la inseguridad profesional experimentada durante la pandemia, especialmente por profesionales jóvenes sin experiencia en el cuidado de pacientes críticos.


Assuntos
Pandemias , Revisões Sistemáticas como Assunto , Bem-Estar Psicológico/psicologia , Enfermeiras e Enfermeiros/psicologia , Ansiedade/psicologia , Saúde Mental , Bibliotecas Digitais , Emoções , Esgotamento Psicológico/psicologia , COVID-19/psicologia
7.
Epilepsy Behav ; 148: 109447, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37804601

RESUMO

BACKGROUND: Psychiatric comorbidities are highly frequent in people with epilepsy and were found to be markers of poorer prognosis. These comorbidities increase the use of healthcare resources, including emergency department visits and inpatient care. Despite this, there is little information on healthcare utilization associated with a wide range of comorbid mental disorders in people with epilepsy (PWE). OBJECTIVE: To characterize registered mental disorders among all hospitalizations with a primary diagnosis of epilepsy and to analyze their association with crucial hospitalization outcomes. METHODS: An observational retrospective study was performed using administrative data from hospitalization episodes with epilepsy as the primary diagnosis discharged between 2008 and 2015. Mental disorder categories 650 to 670 from Clinical Classification Software were selected as secondary diagnoses. Mann-Whitney U, Kruskall-Wallis, and Chi-squared tests were used to establish comparisons. For each episode, data regarding hospitalization outcomes was retrieved, including length of stay (LoS), in-hospital mortality (IHM), 8-year period readmissions, and total estimated charges. RESULTS: Overall, 27,785 hospitalizations were analyzed and 33.9% had registered mental disorders, with alcohol-related disorders being the most prevalent (11.7%). For episodes with a concomitant register of a mental disorder, LoS was significantly longer (5.0 vs. 4.0 days, P <0.001), and IHM was higher (2.8% vs. 2.2%, P <0.001), as were readmissions (25.5% vs. 23.7%, P <0.001), and median episodes' charges (1,578.7 vs. 1,324.4 euros, P <0.001). CONCLUSION: Epilepsy-related hospitalizations with registered mental disorders heightened the utilization of healthcare resources, stressing the importance of diagnosing and treating mental disorders in PWE.


Assuntos
Epilepsia , Transtornos Mentais , Humanos , Estudos Retrospectivos , Portugal/epidemiologia , Hospitalização , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Epilepsia/epidemiologia , Epilepsia/terapia
8.
Ann Intensive Care ; 13(1): 86, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723384

RESUMO

BACKGROUND: Extubation during extracorporeal oxygenation (ECMO) in severe acute respiratory distress syndrome (ARDS) has not been well studied. Despite the potential benefits of this strategy, weaning from ECMO before liberation from invasive mechanical ventilation remains the most frequent approach. Our aim was to evaluate the safety and feasibility of a standardized approach for extubation during ECMO in patients with severe ARDS. RESULTS: We conducted a prospective observational study to assess the safety and feasibility of a standardized approach for extubation during ECMO in severe ARDS among 254 adult patients across 4 intensive care units (ICU) from 2 tertiary ECMO centers over 6 years. This consisted of a daily assessment of clinical and gas exchange criteria based on an Extracorporeal Life Support Organization guideline, with extubation during ECMO after validation by a dedicated intensive care medicine specialist. Fifty-four (21%) patients were extubated during ECMO, 167 (66%) did not reach the clinical criteria, and in 33 (13%) patients, gas exchange precluded extubation during ECMO. At ECMO initiation, there were fewer extrapulmonary organ dysfunctions (lower SOFA score [OR, 0.88; 95% CI, 0.79-0.98; P = .02] with similar PaO2/FiO2) when compared with patients not extubated during ECMO. Extubation during ECMO associated with shorter duration of invasive mechanical ventilation (7 (4-18) vs. 32 (18-54) days; P < .01) and of ECMO (12 (7-25) vs. 19 (10-41) days; P = .01). This was accompanied by a lower incidence of hemorrhagic shock (2 vs. 11%; P = .05), but more cannula-associated deep vein thrombosis (49 vs. 31%; P = .02) and failed extubation (20 vs. 6%; P < .01). There were no increased major adverse events. Extubation during ECMO is associated with a lower risk of all-cause death, independently of measured confounding (adjusted logistic regression OR 0.23; 95% confidence interval 0.08-0.69, P = .008). CONCLUSIONS: A standardized approach was safe and feasible allowing extubation during ECMO in 21% of patients with severe ARDS, selecting patients who will have a shorter duration of invasive mechanical ventilation, ECMO course, and ICU stay, as well as fewer infectious complications, and high hospital survival.

10.
J Vasc Bras ; 22: e20220161, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37416092

RESUMO

Superior mesenteric artery syndrome designates compression of the third part of the duodenum between the superior mesenteric artery and the aorta. This condition has a low incidence, being more common in thin young women. Nutcracker syndrome is compression of the left renal vein between the superior mesenteric artery and the aorta. Both entities are rare, and their coexistence has been reported in a few cases. Conservative treatment targeting weight gain is sufficient in most cases. An association between the superior mesenteric artery syndrome and acute pancreatitis has rarely been reported. We intend to describe the case of an 18-year-old girl who was admitted to the emergency room with epigastric pain and emesis. Our investigation revealed acute acalculous pancreatitis. During work-up, we discovered superior mesenteric artery syndrome and a compressed left renal vein. The patient is on conservative treatment, and her symptoms have improved.


A síndrome da artéria mesentérica superior designa compressão da terceira parte do duodeno pela artéria mesentérica superior e a aorta. Essa condição tem uma baixa incidência, sendo mais comum em mulheres jovens magras. A síndrome de quebra-nozes resulta da compressão da veia renal esquerda pela artéria mesentérica superior e a aorta. Ambas as entidades são raras, e a sua coexistência foi descrita em poucos casos. Tratamento conservador com o objetivo de ganho ponderal é suficiente na maioria dos casos. A associação entre a síndrome da artéria mesentérica superior e a pancreatite aguda foi raramente relatada. Pretendemos descrever o caso de uma jovem de 18 anos que recorreu ao serviço de urgência com epigastralgia e vômitos. A investigação realizada revelou pancreatite aguda alitiásica. Durante o estudo complementar, foi identificada a síndrome da artéria mesentérica superior, bem como uma veia renal esquerda comprimida. A paciente encontra-se em tratamento conservador, apresentando melhora clínica.

11.
Rev Bras Enferm ; 76(2): e20220120, 2023.
Artigo em Inglês, Português | MEDLINE | ID: mdl-37162043

RESUMO

OBJECTIVES: to analyze the implications of precarious work for the organization of work and for the health of nursing professionals in a surgical center. METHODS: qualitative, descriptive study in which the interview technique was applied on 30 nursing professionals from a surgical center in a university hospital located in the Southeast region of Brazil. The project was approved by the research ethics committee. Thematic content analysis was applied in the categorization of speeches. RESULTS: precarious work in the surgical center negatively affects the organization of work due to staff turnover, loss of skilled talent, and the need for continuous training of temporary workers. It also affects the quality of care, leading to risks to patient safety and workers' health.Final Considerations: it is important to make work conditions less precarious in order to minimize staff turnover and promote the quality of the service offered and the health of the worker.


Assuntos
Recursos Humanos de Enfermagem , Humanos , Organizações , Brasil , Hospitais Universitários , Segurança do Paciente
13.
Cell Death Dis ; 14(5): 338, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221162

RESUMO

Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy's cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3/g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P < 0.0001), weight loss (P < 0.05), daily activity (P < 0.02) and maintenance of body composition (P < 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing diversity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury (P = 0.001) and diarrhea (P < 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.


Assuntos
Microbioma Gastrointestinal , Soro do Leite , Humanos , Proteínas do Soro do Leite , Metotrexato , Dieta , Mucosa Intestinal , Triglicerídeos , Diarreia
14.
Eur J Case Rep Intern Med ; 10(4): 003817, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051481

RESUMO

Introduction: The Fontan procedure is used to treat congenital heart defects and has improved long-term survival. Long-term complications include liver disease due to congestive hepatopathy. Fontan-related cirrhosis can manifest with ascites, gastrointestinal bleeding and encephalopathy. Case description: A 43-year-old man with history of Fontan surgery was admitted with COVID-19 pneumonia. There was rapid clinical and neurological deterioration, with coma and shock. CT imaging showed thrombosis of the Fontan conduit. The patient was successfully subjected to recanalization of the Fontan circulation, with progressive improvement of coma. Discussion: Fontan-associated liver disease is a major complication following the Fontan procedure. Clinicians must be aware of this pathology during patient follow-up. LEARNING POINTS: The Fontan procedure has improved the long-term survival of patients with single ventricle pathology.Fontan-associated liver disease is a result of haemodynamic changes associated with Fontan circulation; complications include hepatic encephalopathy and coma.Patients with Fontan circulation should be evaluated over time in order prevent and treat systemic complications.

15.
Methods Mol Biol ; 2643: 271-294, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36952192

RESUMO

The general interest in the study of the interplay between peroxisomes and viruses has increased in recent years, with different reports demonstrating that distinct viruses modulate peroxisome-related mechanisms to either counteract the cellular antiviral response or support viral propagation. Nevertheless, mechanistical details are still scarce, and information is often incomplete. In this chapter, we present an overview of the current knowledge concerning the interplay between peroxisomes and different viruses. We furthermore present, compare, and discuss the most relevant experimental approaches and tools used in the different studies. Finally, we stress the importance of further, more detailed, and spatial-temporal analyses that encompass all the different phases of the viruses' infection cycles. These studies may lead to the discovery of novel peroxisome-related cellular mechanisms that can further be explored as targets for the development of novel antiviral therapies.


Assuntos
Peroxissomos , Vírus , Antivirais/farmacologia , Antivirais/uso terapêutico
16.
Methods Mol Biol ; 2643: 295-307, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36952193

RESUMO

The importance of peroxisomes in the context of viral infections has been increasingly demonstrated in recent years. The discovery that MAVS localizes at peroxisomes and that peroxisomal and mitochondrial MAVS perform complementing functions within the antiviral response has raised the interest in studying the peroxisome-dependent signaling in the context of infection by different viruses. To that end, specific experimental procedures should be applied, taking into consideration the endogenous localization of MAVS at both organelles. The analysis of peroxisomal MAVS activation requires, hence, the preliminar generation and validation of cell lines where MAVS localizes solely at peroxisomes, as well as other specific cellular tools. Here, we present a detailed protocol to analyse the peroxisome-dependent antiviral response, using virus-specific and virus-unspecific stimuli.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Antivirais , Antivirais/farmacologia , Antivirais/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Peroxissomos/metabolismo , Transdução de Sinais , Mitocôndrias/metabolismo , Imunidade Inata
17.
Methods Mol Biol ; 2643: 309-319, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36952194

RESUMO

Peroxisomes have recently been shown to play important roles in the context of viral infections. However, further and more detailed studies should be performed to unravel the specific mechanisms involved. The analysis of the relevance of particular peroxisomal components, such as peroxisomal proteins, for viral infections can be performed by comparing the production of new virus particles in the absence and presence of those specific components. Different methodologies are used to quantify the production of infectious virus particles, depending on the virus, cell type, and the specific characteristics of the viral infection to be analyzed. Here we provide a detailed protocol to study the importance of a putative peroxisomal protein on infection by viruses that induce the death of their host cells. We use the influenza A virus (IAV) infection in A549 cells as a model, and the quantification of the newly produced infectious virus particles is performed by a plaque assay.


Assuntos
Vírus da Influenza A , Influenza Humana , Animais , Humanos , Células Cultivadas , Células A549 , Mamíferos , Replicação Viral
18.
Membranes (Basel) ; 13(2)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36837642

RESUMO

Cationic antimicrobial peptides (CAMPs) offer a promising strategy to counteract bacterial resistance, mostly due to their membrane-targeting activity. W-BP100 is a potent broad-spectrum cecropin-melittin CAMP bearing a single N-terminal Trp, which was previously found to improve its antibacterial activity. W-BP100 has high affinity toward anionic membranes, inducing membrane saturation at low peptide-to-lipid (P/L) ratios and membrane permeabilization, with the unique property of promoting the aggregation of anionic vesicles only at specific P/L ratios. Herein, we aimed to investigate this unusual behavior of W-BP100 by studying its aggregation and fusion properties with negatively-charged large (LUVs) or giant (GUVs) unilamellar vesicles using biophysical tools. Circular dichroism (CD) showed that W-BP100 adopted an α-helical conformation in anionic LUVs, neutralizing its surface charge at the aggregation P/L ratio. Its fusion activity, assessed by Förster resonance energy transfer (FRET) using steady-state fluorescence spectroscopy, occurred mainly at the membrane saturation/aggregation P/L ratio. Confocal microscopy studies confirmed that W-BP100 displays aggregation and detergent-like effects at a critical P/L ratio, above which it induces the formation of new lipid aggregates. Our data suggest that W-BP100 promotes the aggregation and fusion of anionic vesicles at specific P/L ratios, being able to reshape the morphology of GUVs into new lipid structures.

19.
Ann Hematol ; 102(2): 421-427, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36648505

RESUMO

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.


Assuntos
Anti-Infecciosos , Microbioma Gastrointestinal , Mucosite , Humanos , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Projetos Piloto , Fluconazol/efeitos adversos , Seguimentos , Estudos Prospectivos , Citrulina/farmacologia , Transplante de Células-Tronco , Anti-Infecciosos/efeitos adversos , Ciprofloxacina/efeitos adversos
20.
Aging Ment Health ; 27(2): 380-388, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35466829

RESUMO

OBJECTIVES: To characterize all hospitalizations held in mainland Portugal (2010-2015) with dementia-related agitation based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding, and to investigate whether there is a relationship between agitation and hospitalization outcomes. METHODS: A retrospective observational study was conducted using an administrative dataset containing data from all mainland Portuguese public hospitals. Only hospitalization episodes for patients aged over 65 years who have received a dementia diagnosis ascertained by an ICD-9-CM code of dementia with behavioral disturbance (294.11 and 294.21) and dementia without behavioral disturbance (294.10 and 294.20) were selected. Episodes were further grouped according to the presence of an agitation code. For each episode, demographic data and hospitalization outcomes, including length of stay (LoS), in-hospital mortality, discharge destination and all-cause hospital readmissions, were sourced from the dataset. Comparative analyses were performed and multivariable logistic methods were used to estimate the adjusted associations between agitation (exposure) and outcomes. RESULTS: Overall, 53,156 episodes were selected, of which 6,586 had an agitation code. These were mostly related to male, younger inpatients (mean 81.19 vs. 83.29 years, p < 0.001), had a higher comorbidity burden, stayed longer at the hospital (median 9.00 vs. 8.00 days, p < 0.001) and frequently ended being transferred to another facility with inpatient care. Agitation was shown to independently increase LoS (aOR = 1.385; 95%CI:1.314-1.461), but not the risk of a fatal outcome (aOR = 0.648; 95%CI:0.600-0.700). CONCLUSION: These results support the importance of detecting and managing agitation early on admission, since its prompt management may prevent lengthy disruptive hospitalizations.


Assuntos
Demência , Hospitalização , Humanos , Masculino , Idoso , Tempo de Internação , Alta do Paciente , Comorbidade , Estudos Retrospectivos , Demência/epidemiologia
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