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- Organ Crosstalk and Dysfunction in Sepsis.Publication . Borges, André; Bento, LuísSepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Sepsis-associated organ dysfunction involves multiple inflammatory mechanisms and complex metabolic reprogramming of cellular function. These mechanisms cooperate through multiple organs and systems according to a complex set of long-distance communications mediated by cellular pathways, solutes, and neurohormonal actions. In sepsis, the concept of organ crosstalk involves the dysregulation of one system, which triggers compensatory mechanisms in other systems that can induce further damage. Despite the abundance of studies published on organ crosstalk in the last decade, there is a need to formulate a more comprehensive framework involving all organs to create a more detailed picture of sepsis. In this paper, we review the literature published on organ crosstalk in the last 10 years and explore how these relationships affect the progression of organ failure in patients with septic shock. We explored these relationships in terms of the heart-kidney-lung, gut-microbiome-liver-brain, and adipose tissue-muscle-bone crosstalk in sepsis patients. A deep connection exists among these organs based on crosstalk. We also review how multiple therapeutic interventions administered in intensive care units, such as mechanical ventilation, antibiotics, anesthesia, nutrition, and proton pump inhibitors, affect these systems and must be carefully considered when managing septic patients. The progression to multiple organ dysfunction syndrome in sepsis patients is still one of the most frequent causes of death in critically ill patients. A better understanding and monitoring of the mechanics of organ crosstalk will enable the anticipation of organ damage and the development of individualized therapeutic strategies.
- Comparative Outcomes of Extracorporeal Membrane Oxygenation for COVID-19 Delivered in Experienced European Centres During Successive SARS-CoV-2 Variant Outbreaks (ECMO-SURGES): an International, Multicentre, Retrospective Cohort Study.Publication . Schmidt, Matthieu; Hajage, David; Landoll, Micha; Pequignot, Benjamin; Langouet, Elise; Amalric, Matthieu; Mekontso-Dessap, Armand; Chiscano-Camon, Luis; Surman, Katy; Finnerty, Dylan; Santa-Teresa, Patricia; Arcadipane, Antonio; Millán, Pablo; Roncon-Albuquerque, Roberto; Blandino-Ortiz, Aaron; Blanco-Schweizer, Pablo; Ricart, Pilar; Gimeno-Costa, Ricardo; Albacete, Carlos Luis; Fortuna, Philip; Schellongowski, Peter; Dauwe, Dieter; Winiszewski, Hadrien; Kimmoun, Antoine; Levy, Bruno; Hermans, Greet; Grasselli, Giacomo; Lebreton, Guillaume; Guervilly, Christophe; Martucci, Genarro; Karagiannidis, Christian; Riera, Jordi; Combes, AlainBackground: To inform future research and practice, we aimed to investigate the outcomes of patients who received extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to different variants of SARS-CoV-2. Methods: This retrospective study included consecutive adult patients with laboratory-confirmed SARS-CoV-2 infection who received ECMO for ARDS in 21 experienced ECMO centres in eight European countries (Austria, Belgium, England, France, Germany, Italy, Portugal, and Spain) between Jan 1, 2020, and Sept 30, 2021. We collected data on patient characteristics, clinical status, and management before and after the initiation of ECMO. Participants were grouped according to SARS-CoV-2 variant (wild type, alpha, delta, or other) and period of the pandemic (first [Jan 1-June 30] and second [July 1-Dec 31] semesters of 2020, and first [Jan 1-June 30] and second [July 1-Sept 30] semesters of 2021). Descriptive statistics and Kaplan-Meier survival curves were used to analyse evolving characteristics, management, and patient outcomes over the first 2 years of the pandemic, and independent risk factors of mortality were determined using multivariable Cox regression models. The primary outcome was mortality 90 days after the initiation of ECMO, with follow-up to Dec 30, 2021. Findings: ECMO was initiated in 1345 patients. Patient characteristics and management were similar for the groups of patients infected with different variants, except that those with the delta variant had a younger median age and less hypertension and diabetes. 90-day mortality was 42% (569 of 1345 patients died) overall, and 43% (297/686) in patients infected with wild-type SARS-CoV-2, 39% (152/391) in those with the alpha variant, 40% (78/195) in those with the delta variant, and 58% (42/73) in patients infected with other variants (mainly beta and gamma). Mortality was 10% higher (50%) in the second semester of 2020, when the wild-type variant was still prevailing, than in other semesters (40%). Independent predictors of mortality were age, immunocompromised status, a longer time from intensive care unit admission to intubation, need for renal replacement therapy, and higher Sequential Organ Failure Assessment haemodynamic component score, partial pressure of arterial carbon dioxide, and lactate concentration before ECMO. After adjusting for these variables, mortality was significantly higher with the delta variant than with the other variants, the wild-type strain being the reference. Interpretation: Although crude mortality did not differ between variants, adjusted risk of death was highest for patients treated with ECMO infected with the delta variant of SARS-CoV-2. The higher virulence and poorer outcomes associated with the delta strain might relate to higher viral load and increased inflammatory response syndrome in infected patients, reinforcing the need for a higher rate of vaccination in the population and updated selection criteria for ECMO, should a new and highly virulent strain of SARS-CoV-2 emerge in the future. Mortality was noticeably lower than in other large, multicentre series of patients who received ECMO for COVID-19, highlighting the need to concentrate resources at experienced centres.
- The Accuracy of PiCCO® in Measuring Cardiac Output in Patients Under Therapeutic Hypothermia: Comparison With Transthoracic EchocardiographyPublication . Souto Moura, T; Aguiar Rosa, S; Germano, N; Cavaco, R; Sequeira, T; Alves, M; Papoila, AL; Bento, LBackground: Invasive cardiac monitoring using thermodilution methods such as PiCCO® is widely used in critically ill patients and provides a wide range of hemodynamic variables, including cardiac output (CO). However, in post-cardiac arrest patients subjected to therapeutic hypothermia, the low body temperature possibly could interfere with the technique. Transthoracic Doppler echocardiography (ECHO) has long proved its accuracy in estimating CO, and is not influenced by temperature changes. Objective: To assess the accuracy of PiCCO® in measuring CO in patients under therapeutic hypothermia, compared with ECHO. Design and patients: Thirty paired COECHO/COPiCCO measurements were analyzed in 15 patients subjected to hypothermia after cardiac arrest. Eighteen paired measurements were obtained at under 36°C and 12 at ≥36°C. A value of 0.5l/min was considered the maximum accepted difference between the COECHO and COPiCCO values. Results: Under conditions of normothermia (≥36°C), the mean difference between COECHO and COPiCCO was 0.030 l/min, with limits of agreement (-0.22, 0.28) - all of the measurements differing by less than 0.5 l/min. In situations of hypothermia (<36°C), the mean difference in CO measurements was -0.426 l/min, with limits of agreement (-1.60, 0.75), and only 44% (8/18) of the paired measurements fell within the interval (-0.5, 0.5). The calculated temperature cut-off point maximizing specificity was 35.95°C: above this temperature, specificity was 100%, with a false-positive rate of 0%. Conclusions: The results clearly show clinically relevant discordance between COECHO and COPiCCO at temperatures of <36°C, demonstrating the inaccuracy of PiCCO® for cardiac output measurements in hypothermic patients.
- Pancreatic Stone Protein As a Biomarker of SepsisPublication . Lopes, D; Chumbinho, B; Bandovas, JP; Faria, P; Espírito Santo, C; Ferreira, B; Val-Flores, L; Pereira, R; Germano, N; Bento, L
- Risk Factors for Mortality in Patients With COVID-19 Needing Extracorporeal Respiratory SupportPublication . Riera, J; Alcántara, S; Bonilla, C; Fortuna, P; Blandino Ortiz, A; Vaz, A; Albacete, C; Millán, P; Ricart, P; Boado, MV; Ruiz de Gopegui, P; Santa Teresa, P; Sandoval, E; Pérez-Chomón, H; González-Pérez, A; Duerto, J; Gimeno, R; Colomina, J; Gómez, V; Renedo, G; Naranjo, J; García, MA; Rodríguez-Ruiz, E; Silva, PE; Pérez, D; Veganzones, J; Voces, R; Martínez, S; Blanco-Schweizer, P; García, M; Villanueva-Fernández, H; Fuset, MP; Luna, S; Martínez-Martínez, M; Argudo, E; Chiscano, L; Roncon-Albuquerque, RWhen indicating ECMO in patients with COVID-19, centre case volume, age, driving pressure and the duration of symptoms (not the length of MV) should be taken into account. Large drainage cannula and high PEEP levels during the first days are recommended.
- Simplifying Data Analysis in Biomedical Research: an Automated, User-Friendly ToolPublication . Araújo, R; Ramalhete, L; Viegas, A; Von Rekowski, C; Fonseca, T; Calado, C; Bento, LRobust data normalization and analysis are pivotal in biomedical research to ensure that observed differences in populations are directly attributable to the target variable, rather than disparities between control and study groups. ArsHive addresses this challenge using advanced algorithms to normalize populations (e.g., control and study groups) and perform statistical evaluations between demographic, clinical, and other variables within biomedical datasets, resulting in more balanced and unbiased analyses. The tool's functionality extends to comprehensive data reporting, which elucidates the effects of data processing, while maintaining dataset integrity. Additionally, ArsHive is complemented by A.D.A. (Autonomous Digital Assistant), which employs OpenAI's GPT-4 model to assist researchers with inquiries, enhancing the decision-making process. In this proof-of-concept study, we tested ArsHive on three different datasets derived from proprietary data, demonstrating its effectiveness in managing complex clinical and therapeutic information and highlighting its versatility for diverse research fields.
- Sequential Use of High-Volume Plasma Exchange and Continuous Renal Replacement Therapy in Hepatitis B Virus-Related Acute Liver Failure: A Case ReportPublication . Bragança, S; Ferraz, M; Germano, NBackground: Acute liver failure (ALF) may represent an indication for liver transplantation (LT). However, in patients who do not meet the criteria or who have contraindications for LT, support measures remain indicated since they may improve survival. Continuous renal replacement therapy (CRRT) can be considered in the presence of hyperammonemia, 3 times above the upper normal limit, and hepatic encephalopathy (HE), even in the absence of the classic indications. High-volume plasma exchange (HVPE) is an artificial liver support system with proven benefits in ALF, allowing ammonia and inflammatory mediator clearance. Both techniques, HVPE and CRRT, are associated with an increase in transplant-free survival. Case summary: We share a case of a 51-year-old male, without relevant personal history, diagnosed with severe acute hepatitis B which progressed to ALF, with grade IV HE (West-Haven criteria) and hyperammonemia (423 μg/dL). Due to the simultaneously diagnosed malignant neoplasm, he was not a candidate for LT. After refractory to medical therapy, HVPE was started, followed by CRRT. There was a significant improvement in liver tests, allowing surgical treatment of malignancy. After recovery, the patient returned to his everyday life. Conclusion: The authors present a successful case in which an early and invasive approach to ALF was revealed to be a game changer. The lack of response to the measures instituted, as well as the contraindication for LT, motivated the institution of HVPE and CRRT. Both techniques proved to be an asset, allowing complete clinical recovery, reaffirming their role in ALF.
- Time of Admission to Intensive Care Unit, Strained Capacity, and Mortality: a Retrospective Cohort StudyPublication . Sousa Cardoso, F; Germano, N; Bento, L; Fortuna, PPurpose: We sought to study the association between afterhours ICU admission and ICU mortality considering measures of strained ICU capacity. Materials and methods: Retrospective analysis of 4141 admissions to 2 ICUs in Lisbon, Portugal (06/2016-06/2018). Primary exposure was ICU admission on 20:00 h-07:59 h. Primary outcome was ICU mortality. Measures of strained ICU capacity were: bed occupancy rate ≥ 90% and cluster of ICU admissions 2 h before or following index admission. Results: There were 1581 (38.2%) afterhours ICU admissions. Median APACHE II score (19 vs. 20) was similar between patients admitted afterhours and others (P = .27). Patients admitted afterhours had higher crude ICU mortality (15.4% vs. 21.9%; P < .001), but similar adjusted ICU mortality (aOR [95%CI] = 1.15 [0.97-1.38]; P = .12). While bed occupancy rate ≥ 90% was more frequent in patients admitted afterhours (23.1% vs. 29.1%) or deceased in ICU (23.6% vs. 33.7%), cluster of ICU admissions was more frequent in patients admitted during daytime hours (75.2% vs. 58.9%) or that survived the ICU stay (70.1% vs. 63.9%; P ≤ .001 for all). These measures of strained ICU capacity were not associated with adjusted ICU mortality (P ≥ .10 for both). Conclusions: Afterhours ICU admission and measures of strained ICU capacity were associated with crude but not adjusted ICU mortality.
- Trapped Lung from Calcified FibrothoraxPublication . Barosa, M; Trindade, M; Marques, R
- Repair of Ruptured Abdominal Aortic Aneurysm after Cardiac Arrest: a Case ReportPublication . Branco Ribeiro, S; Bento, LThe management of abdominal aortic aneurysms, especially ruptured abdominal aortic aneurysms, continues to challenge vascular surgeons. A ruptured abdominal aortic aneurysm is associated with a high mortality rate. If cardiopulmonary resuscitation is required before surgical repair, mortality rates are said to be even higher. However, cardiac arrest in patients with ruptured abdominal aortic aneurysm does not accurately predict a nonsalvageable state or preclude functional survival. In these cases, agressive management may be the only hope for survival, and cardiac arrest should not as such contraindicate repair. The objective of this study is to present a successful case of repair of ruptured abdominal aortic aneurysm after cardiac arrest.
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