Towards better mortality prediction in cancer patients in the ICU: a comparative analysis of prognostic scales: systematic literature review.

OBJECTIVE: To evaluate the predictive ability of mortality prediction scales in cancer patients admitted to intensive care units (ICUs). DESIGN: A systematic review of the literature was conducted using a search algorithm in October 2022. The following databases were searched: PubMed, Scopus, Virtual Health Library (BVS), and Medrxiv. The risk of bias was assessed using the QUADAS-2 scale. SETTING: ICUs admitting cancer patients. PARTICIPANTS: Studies that included adult patients with an active cancer diagnosis who were admitted to the ICU. INTERVENTIONS: Integrative study without interventions. MAIN VARIABLES OF INTEREST: Mortality prediction, standardized mortality, discrimination, and calibration. RESULTS: Seven mortality risk prediction models were analyzed in cancer patients in the ICU. Most models (APACHE II, APACHE IV, SOFA, SAPS-II, SAPS-III, and MPM II) underestimated mortality, while the ICMM overestimated it. The APACHE II had the SMR (Standardized Mortality Ratio) value closest to 1, suggesting a better prognostic ability compared to the other models. CONCLUSIONS: Predicting mortality in ICU cancer patients remains an intricate challenge due to the lack of a definitive superior model and the inherent limitations of available prediction tools. For evidence-based informed clinical decision-making, it is crucial to consider the healthcare team's familiarity with each tool and its inherent limitations. Developing novel instruments or conducting large-scale validation studies is essential to enhance prediction accuracy and optimize patient care in this population.

Africa must create centres of educational excellence for innovation and development.

This paper explores the following development questions that perplex most Africans: "Why do African countries rely on foreign companies and foreign experts for almost all our development projects? Why can't we build our own roads, process our own food, and mine our own minerals, oil, and gas? Why don't we have world-class hospitals and industries? How can we have so much natural wealth and yet be so poor? Why do we invent so little?" The answer lies in our failure to implement idea number two. There are two major ideas in educational policy. Idea number one is the obligation to educate all children because it is their fundamental human right as enshrined in the 1948 United Nations Declaration of Human Rights. Idea number two is the strategy of establishing and sustaining world class schools and universities for the education of the most highly gifted and highly talented citizens. Developed countries deploy both ideas aggressively. Underdeveloped countries in Africa have not implemented idea number two. Countries that have deployed idea number two have at least one university ranked among the top 200 in the world. The presence of great universities (top 200) in a country is a 21st century indicator of the presence of high levels of innovation, technology, development and wealth in that country. According to the three major rankings of world universities (Shanghai-ARWU, THE, and QS-topuniversities.com), none of the world's top 100 great universities is in Africa. Although Africa was a pioneer among the continents in innovations such as human language, domestication of fire, making of tools, invention of agriculture, development of writing, and creation of great centers of learning in ancient times, it has fallen behind other continents over the last 500 years and it has been disrupted by enslavement and colonization, and the structural adjustment programs (SAPs) of the IMF and the World Bank. Ancient African centers of innovation included the Ancient City of Benin and Timbuktu in Western Africa, the Kingdom of Kush and ancient Egypt in northern Africa, Axum in Eastern Africa, Mapungubwe and Great Zimbabwe in Southern Africa, and the Kingdom of Kongo in central-Africa. An African renaissance will only occur when we implement idea number two by establishing world class schools and at least one great university per African country.

Cet article explore les questions de développement suivantes qui intriguent la plupart des Africains : « Pourquoi les pays africains s'appuient-ils sur des entreprises et des experts étrangers pour presque tous nos projets de développement ? Pourquoi ne pouvons-nous pas construire nos propres routes, transformer nos propres aliments et extraire nos propres minéraux, pétrole et gaz ? Pourquoi n'avons-nous pas d'hôpitaux et d'industries de classe mondiale ? Comment pouvons-nous avoir autant de richesses naturelles et pourtant être si pauvres ? Pourquoi inventons-nous si peu ? La réponse réside dans notre échec à mettre en œuvre l'idée numéro deux. Il y a deux idées majeures en politique éducative. L'idée numéro un est l'obligation d'éduquer tous les enfants, car il s'agit de leur droit humain fondamental tel que consacré dans la Déclaration des droits de l'homme des Nations Unies de 1948. L'idée numéro deux est la stratégie consistant à créer et à maintenir des écoles et des universités de classe mondiale pour l'éducation des citoyens les plus doués et les plus talentueux. Les pays développés déploient ces deux idées de manière agressive. Les pays sous-développés d'Afrique n'ont pas mis en œuvre l'idée numéro deux. Les pays qui ont déployé l'idée numéro deux comptent au moins une université classée parmi les 200 meilleures au monde. La présence de grandes universités (les 200 meilleures) dans un pays est un indicateur du XXIe siècle de la présence de niveaux élevés d'innovation, de technologie, de développement et de richesse dans ce pays. Selon les trois principaux classements des universités mondiales (Shanghai-ARWU, THE et QS-topuniversities.com), aucune des 100 meilleures universités mondiales ne se trouve en Afrique. Bien que l'Afrique ait été un continent pionnier en matière d'innovations telles que le langage humain, la domestication du feu, la fabrication d'outils, l'invention de l'agriculture, le développement de l'écriture et la création de grands centres d'apprentissage dans l'Antiquité, elle a pris du retard sur les autres continents au fil du temps. Ces 500 dernières années ont été perturbées par l'esclavage et la colonisation, ainsi que par les programmes d'ajustement structurel (PAS) du FMI et de la Banque mondiale. Les anciens centres d'innovation de l'Afrique comprenaient l'ancienne ville du Bénin et Tombouctou en Afrique de l'Ouest, le royaume de Kouch et l'Égypte ancienne en Afrique du Nord, Axum en Afrique de l'Est, Mapungubwe et le Grand Zimbabwe en Afrique australe et le royaume de Kongo en Afrique centrale. . Une renaissance africaine ne se produira que lorsque nous mettrons en œuvre l'idée numéro deux en créant des écoles de classe mondiale et au moins une grande université par pays africain.

Synergizing Survival: Uniting Acute Gastrointestinal Injury Grade and Disease Severity Scores in Critical Care Prognostication.

How to cite this article: Patnaik RK, Karan N. Synergizing Survival: Uniting Acute Gastrointestinal Injury Grade and Disease Severity Scores in Critical Care Prognostication. Indian J Crit Care Med 2024;28(6):529-530.

Saps1-3 Antigens in Candida albicans: Differential Modulation Following Exposure to Soluble Proteins, Mammalian Cells, and Infection in Mice.

The secreted aspartic peptidases (Saps) of Candida albicans play crucial roles in various steps of fungal-host interactions. Using a flow cytometry approach, this study investigated the expression of Saps1-3 antigens after (i) incubation with soluble proteins, (ii) interaction with mammalian cells, and (iii) infection in immunosuppressed BALB/c mice. Supplementation strategies involving increasing concentrations of bovine serum albumin (BSA) added to yeast carbon base (YCB) medium as the sole nitrogenous source revealed a positive and significant correlation between BSA concentration and both the growth rate and the percentage of fluorescent cells (%FC) labeled with anti-Saps1-3 antibodies. Supplementing the YCB medium with various soluble proteins significantly modulated the expression of Saps1-3 antigens in C. albicans. Specifically, immunoglobulin G, gelatin, and total bovine/human sera significantly reduced the %FC, while laminin, human serum albumin, fibrinogen, hemoglobin, and mucin considerably increased the %FC compared to BSA. Furthermore, co-cultivating C. albicans yeasts with either live epithelial or macrophage cells induced the expression of Saps1-3 antigens in 78% (mean fluorescence intensity [MFI] = 152.1) and 82.7% (MFI = 178.2) of the yeast cells, respectively, compared to BSA, which resulted in 29.3% fluorescent cells (MFI = 50.9). Lastly, the yeasts recovered from the kidneys of infected immunosuppressed mice demonstrated a 4.8-fold increase in the production of Saps1-3 antigens (MFI = 246.6) compared to BSA, with 95.5% of yeasts labeled with anti-Saps1-3 antibodies. Altogether, these results demonstrated the positive modulation of Saps' expression in C. albicans by various key host proteinaceous components, as well as by in vitro and in vivo host challenges.

Catecholamine concentration as a predictor of mortality in emergency surgical patients.

BACKGROUND: Trauma and emergency surgery are major causes of morbidity and mortality. The objective of this study was to determine whether serum levels of epinephrine and norepinephrine are associated with aging and mortality. METHODS: This was a prospective observational cohort study conducted in a surgical critical care unit. We included 90 patients who were admitted for postoperative care, because of major trauma, or both. We collected demographic and clinical variables, as well as serum levels of epinephrine and norepinephrine. RESULTS: For patients in the > 60-year age group, the use of vasoactive drugs was found to be associated with an undetectable epinephrine level (OR [95% CI] = 6.36 [1.12, 36.08]), p = 0.05). For the patients with undetectable epinephrine levels, the in-hospital mortality was higher among those with a norepinephrine level ≥ 2006.5 pg/mL (OR [95% CI] = 4.00 [1.27, 12.58]), p = 0.03). CONCLUSIONS: There is an association between age and mortality. Undetectable serum epinephrine, which is more common in older patients, could contribute to poor outcomes. The use of epinephrine might improve the clinical prognosis in older surgical patients with shock.

Enhancing SAPS-3 Predictive Accuracy with Initial, Peak, and Last Lactate Measurements in Septic Shock.

Background/Objectives: Septic shock is a severe condition with high mortality necessitating precise prognostic tools for improved patient outcomes. This study aimed to evaluate the collective predictive value of the Simplified Acute Physiology Score 3 (SAPS-3) and lactate measurements (initial, peak, last, and clearance rates within the first 24 h) in patients with septic shock. Specifically, it sought to determine how these markers enhance predictive accuracy for 28-day mortality beyond SAPS-3 alone. Methods: This retrospective cohort study analyzed data from 66 septic shock patients at two ICUs of Vienna General Hospital (2017-2019). SAPS-3 and lactate levels (initial, peak, last measurement within 24 h, and 24 h clearance) were obtained from electronic health records. Logistic regression models were constructed to identify predictors of 28-day mortality, and receiver operating characteristic (ROC) curves assessed predictive accuracy. Results: Among 66 patients, 36 (55%) died within 28 days. SAPS-3 scores significantly differed between survivors and non-survivors (76 vs. 85 points; p = 0.016). First, last, and peak lactate were significantly higher in non-survivors compared to survivors (all p < 0.001). The combination of SAPS-3 and first lactate produced the highest predictive accuracy (AUC = 80.6%). However, 24 h lactate clearance was not predictive of mortality. Conclusions: Integrating SAPS-3 with lactate measurements, particularly first lactate, improves predictive accuracy for 28-day mortality in septic shock patients. First lactate serves as an early, robust prognostic marker, providing crucial information for clinical decision-making and care prioritization. Further large-scale studies are needed to refine these predictive tools and validate their efficacy in guiding treatment strategies.

Secreted Aspartic Proteinases: Key Factors in Candida Infections and Host-Pathogen Interactions.

Extracellular proteases are key factors contributing to the virulence of pathogenic fungi from the genus Candida. Their proteolytic activities are crucial for extracting nutrients from the external environment, degrading host defenses, and destabilizing the internal balance of the human organism. Currently, the enzymes most frequently described in this context are secreted aspartic proteases (Saps). This review comprehensively explores the multifaceted roles of Saps, highlighting their importance in biofilm formation, tissue invasion through the degradation of extracellular matrix proteins and components of the coagulation cascade, modulation of host immune responses via impairment of neutrophil and monocyte/macrophage functions, and their contribution to antifungal resistance. Additionally, the diagnostic challenges associated with Candida infections and the potential of Saps as biomarkers were discussed. Furthermore, we examined the prospects of developing vaccines based on Saps and the use of protease inhibitors as adjunctive therapies for candidiasis. Given the complex biology of Saps and their central role in Candida pathogenicity, a multidisciplinary approach may pave the way for innovative diagnostic strategies and open new opportunities for innovative clinical interventions against candidiasis.

Clavicle fractures do not increase the occurrence of later subacromial pain syndrome. A registry-based case-control study with 15-25 years of follow-up of 131.838 persons from the Danish National Patient Register.

Background: A clavicle fracture often changes the mechanical axes of the shoulder girdle due to displacement and shortening, potentially leading to scapular protraction and decreased subacromial space. If protraction of the scapula is a major risk factor for developing subacromial pain syndrome (SAPS), a previous clavicle fracture could increase the risk of later SAPS. The purpose of this study was to investigate if a previous clavicle fracture correlates with a higher occurrence or earlier diagnosis of SAPS. Methods: In this retrospective case-control study with data from the Danish National Patient Register, all persons aged 18-60 years, with any hospital contact due to a clavicle fracture (DS420) between January 1, 1996, and December 31, 2005, were identified as cases. For each case, five controls, matched on age and sex, were identified. Primary outcome was the first hospital contact with a SAPS diagnosis (DM751-755) registered more than 180 days following the fracture. Follow-up was until November 01, 2021. Results: 21.973 cases and 109.865 controls were included. The incidence of clavicle fractures was 76 fractures per 100.000 persons per year. Twenty-three percent were female. 1.640 (7.46%) cases and 8.072 (7.35%) controls received a SAPS diagnosis within the following 15-25 years, demonstrating no significant difference in the occurrence of SAPS (P = .56). The mean time from fracture to SAPS diagnosis was shorter for cases compared to controls (4040 vs. 4442 days, P < .001), and cases were slightly younger when receiving the diagnosis (51.3 vs. 53.6 years, P < .001). 1614 cases underwent surgical fixation. This subgroup had a statistically significant higher occurrence of later SAPS diagnosis (205 cases, 13%, P < .001). Conclusions: Persons with a previous clavicle fracture did not have an increased occurrence of receiving a SAPS diagnosis compared to matched controls. However, the diagnosis was given 1-2 years earlier for people with a previous fracture. Based on these findings, no strong argument for protraction of the scapula as a major risk factor for the development of SAPS was found.

Effectiveness of Copeptin, MR-proADM and MR-proANP in Predicting Adverse Outcomes, Alone and in Combination with Traditional Severity Scores, a Secondary Analysis in COVID-19 Patients Requiring Intensive Care Admission.

Objective: To investigate whether copeptin, MR-proADM and MR-proANP, alone or integrated with the SOFA, MuLBSTA and SAPS II scores, are capable of early recognition of COVID-19 ICU patients at increased risk of adverse outcomes. Methods: For this predefined secondary analysis of a larger cohort previously described, all consecutive COVID-19 adult patients admitted between March and December 2020 to the ICU of a referral, university hospital in Northern Italy were screened, and clinical severity scores were calculated upon admission. A blood sample for copeptin, MR-proADM and MR-proANP was collected within 48 h (T1), on day 3 (T3) and 7 (T7). Outcomes considered were ICU and in-hospital mortality, bacterial superinfection, recourse to renal replacement therapy (RRT) or veno-venous extracorporeal membrane oxygenation, need for invasive mechanical ventilation (IMV) and pronation. Results: Sixty-eight patients were enrolled, and in-hospital mortality was 69.1%. ICU mortality was predicted by MR-proANP measured at T1 (HR 1.005, 95% CI 1.001-1.010, p = 0.049), although significance was lost if the analysis was adjusted for procalcitonin and steroid treatment (p = 0.056). Non-survivors showed higher MR-proADM levels than survivors at all time points, and an increase in the ratio between values at baseline and at T7 > 4.9% resulted in a more than four-fold greater risk of in-hospital mortality (HR 4.417, p < 0.001). Finally, when considering patients with any reduction in glomerular filtration, an early copeptin level > 23.4 pmol/L correlated with a more than five-fold higher risk of requiring RRT during hospitalization (HR 5.305, p = 0.044). Conclusion: Timely evaluation of MR-proADM, MR-proANP and copeptin, as well as changes in the former over time, might predict mortality and other adverse outcomes in ICU patients suffering from severe COVID-19.

Complicaciones y mortalidad en pacientes neurocríticos / Complications and mortality in neurocritic patients

Objetivo: Relacionar las complicaciones y el riesgo de muerte en pacientes neurocríticos admitidos en la unidad de cuidados intensivos (UCI) del Hospital Universitario de Caracas durante un período de 5 meses. Métodos: investigación observacional, prospectiva, descriptiva. La muestra estuvo conformada por 65 pacientes neurocríticos, ≥ 18 años, con patologías médicas o quirúrgicas, ingresados en la UCI. El análisis estadístico incluyó la determinación de frecuencias, promedios, porcentajes y medias para descripción de variables y el T de Student. Resultados: La edad promedio fue 50,98 ± 16,66 años; la población masculinarepresentó el 50,76%. Entre las complicaciones, la mayor incidencia correspondió a las no infecciosas (70,77 %) y los trastornos ácido-básicos de tipo metabólico, la anemia y las alteraciones electrolíticas fueron las más frecuentes; el 29,23% de los pacientes presentaron complicaciones infecciosas, y la neumonía asociada a ventilación mecánica fue la más frecuente (73,91 %). La comorbilidad con mayor incidencia fue hipertensión arterial sistémica (53,84%). El 90.70% requirió ventilación mecánica y el tiempo en VM fue 4.29 ± 6.43 días. La estancia en UCI fue 5.96 ± 7.72 días. El 29,23% presentó un puntaje en la escala APACHE II entre 5-9; el SAPS II presentó mayor incidencia entre los 6-21 y 22-37 puntos con (66,70%); el SOFA al ingreso se reportó < 15 puntos en 98,46% y > 15 en 1,53%. La mortalidad del grupo fue 23,08 % (n=15). Conclusiones: Las complicaciones no infecciosas predominaron sobre las infecciosas las primeras íntimamente relacionadas con la mortalida(AU)

Objective: To relate complications and the risk of death in neurocritical patients admitted to the intensive care unit (ICU) of the University Hospital of Caracas during a period of 5 months. Methods: observational, prospective, descriptive research. The sample was made up of 65 neurocritical patients, ≥ 18 years old, with medical or surgical pathologies, admitted to the ICU.The statistical analysis included the determination of frequencies, averages, percentages and meansfor description of variables and Student's T.Results: The average age was 50.98 ± 16.66 years; the male population represented 50.76%. Among the complications, the highest incidence corresponded to non-infectious complications (70.77%) and metabolic acid-base disorders, anemia and electrolyte alterations were the most frequent; 29.23% of patients presented infectious complications, and pneumonia associated with mechanical ventilation was the most frequent (73.91%). The comorbidity with the highest incidence was systemic arterial hypertension (53.84%), 90.70% required mechanical ventilation and the time on MV was 4.29 ± 6.43 days. The ICU stay was 5.96 ± 7.72 days. 29.23% had a score on the APACHE II scale between 5-9; SAPS II presented the highest incidence between 6-21 and 22-37 points with (66.70%); The SOFA upon admission was reported to be < 15 points in 98.46% and > 15 in 1.53%. The mortality of the group was 23.08% (n=15). Conclusions: Non-infectious complications predominated over infectious complications, the former being closely related to mortalit(AU)

Critically ill patients with high predicted mortality: Incidence and outcome / Pacientes en cuidados intensivos con alta mortalidad prevista: Incidencia y evolución

Objective As calculated by the severity scores, an unknown number of patients are admitted to the Intensive Care Unit (ICU) with a very high risk of death. Clinical studies have poorly addressed this population, and their prognosis is largely unknown. Design Post hoc analysis of a multicenter, cohort, longitudinal, observational, retrospective study (CIMbA). Setting Sixteen Portuguese multipurpose ICUs. Patients Patients with a Simplified Acute Physiology Score II (SAPS II) predicted hospital mortality above 80% on admission to the ICU (high-risk group); A comparison with the remaining patients was obtained. Interventions None. Main Variables of Interest Hospital, 30 days, 1 year mortality. Results We identified 4546 patients (59.9% male), 12.2% of the whole population. Their SAPS II predicted hospital mortality was 89.0±5.8%, whilst the observed mortality was lower, 61.0%. This group had higher mortality, both during the first 30 days (aHR 3.52 [95% CI 3.34–3.71]) and from day 31 to day 365 after ICU admission (aHR 1.14 [95%CI 1.04–1.26]), respectively. However, their hospital standardized mortality ratio was similar to the other patients (0.69 vs. 0.69, P=.92). At one year of follow-up, 30% of patients in the high-risk group were alive. Conclusions Roughly 12% of patients admitted to the ICU for more than 24h had a SAPS II score predicted mortality above 80%. Their hospital standardized mortality was similar to the less severe population and 30% were alive after one year of follow-up. (AU)

Objetivo Según las escalas de gravedad, un número indeterminado de pacientes ingresan en la Unidad de Cuidados Intensivos (UCI) con riesgo de muerte muy elevado. Este grupo ha sido poco abordado en los estudios clínicos y se desconoce en gran medida su pronóstico. Diseño Análisis post-hoc de estudio multicéntrico, de cohortes, longitudinal, observacional y retrospectivo (CIMbA). Âmbito Dieciséis UCI polivalentes portuguesas. Pacientes Pacientes con mortalidad hospitalaria prevista en el Simplified Acute Physiology Score II (SAPS II) superior al 80% nel ingreso en la UCI (grupo de alto riesgo); se compararon con los restantes. Intervenciones Ninguna. Variables de interés principals Mortalidad hospitalaria, a 30 días y 1 año. Resultados Se identificaron 4546 pacientes (59.9% hombres), 12.2% da población. La mortalidad hospitalaria estimada por lo SAPS II fue de 89.0±5.8%, aunque la observada fue inferior, 61.0%. Este grupo presentó mayor mortalidad, tanto durante los primeros 30 días (aHR 3.52 [IC 95%: 3.34–3.71]) y desde el día 31 hasta el día 365 después del ingreso en UCI (aHR 1.14 [IC 95%: 1.04–1.26]). Sin embargo, su índice de mortalidad hospitalaria estandarizada fue similar a los otros pacientes (0.69 vs. 0.69; P=.92). Al primer año de seguimiento, 30% de los pacientes de alto riesgo estaban vivos. ConclusionesAproximadamente 12% de los pacientes ingresados en la UCI durante más de 24 horas tenían una mortalidad prevista por SAPS II superior al 80%. Su mortalidad hospitalaria estandarizada fue similar a la de la población menos grave y el 30% estaban vivos después de un año de seguimiento. (AU)

The value of five scoring systems in predicting the prognosis of patients with sepsis-associated acute respiratory failure.

Our study aimed to identify the optimal scoring system for predicting the prognosis of patients with sepsis-associated acute respiratory failure (SA-ARF). All data were taken from the fourth version of the Markets in Intensive Care Medicine (MIMIC-IV) database. Independent risk factors for death in hospitals were confirmed by regression analysis. The predictive value of the five scoring systems was evaluated by receiving operating characteristic (ROC) curves. Kaplan‒Meier curves showed the impact of acute physiology score III (APSIII) on survival and prognosis in patients with SA-ARF. Decision curve analysis (DCA) identified a scoring system with the highest net clinical benefit. ROC curve analysis showed that APS III (AUC: 0.755, 95% Cl 0.714-0.768) and Logical Organ Dysfunction System (LODS) (AUC: 0.731, 95% Cl 0.717-0.7745) were better than Simplified Acute Physiology Score II (SAPS II) (AUC: 0.727, 95% CI 0.713-0.741), Oxford Acute Severity of Illness Score (OASIS) (AUC: 0.706, 95% CI 0.691-0.720) and Sequential Organ Failure Assessment (SOFA) (AUC: 0.606, 95% CI 0.590-0.621) in assessing in-hospital mortality. Kaplan‒Meier survival analysis patients in the high-APS III score group had a considerably poorer median survival time. The DCA curve showed that APS III may provide better clinical benefits for patients. We demonstrated that the APS III score is an excellent predictor of in-hospital mortality.

PgxSAVy: A tool for comprehensive evaluation of variant peptide quality in proteogenomics - catching the (un)usual suspects.

Variant peptides resulting from single nucleotide polymorphisms (SNPs) can lead to aberrant protein functions and have translational potential for disease diagnosis and personalized therapy. Variant peptides detected by proteogenomics are fraught with high number of false positives, but there is no uniform and comprehensive approach to assess variant quality across analysis pipelines. Despite class-specific FDR along with ad-hoc filters, the problem is far from solved. These protocols are typically manual and tedious, and thus not uniform across labs. We demonstrate that variant peptide rescoring, integrated with intensity, variant event information and search result features, allows better discrimination of correct variant peptides. Implemented into PgxSAVy - a tool for quality control of variant peptides, this method can tackle the high rate of false positives. PgxSAVy provides a rigorous framework for quality control and annotations of variant peptides on the basis of (i) variant quality, (ii) isobaric masses, and (iii) disease annotation. PgxSAVy demonstrated high accuracy by identifying true variants with 98.43% accuracy on simulated data. Large-scale proteogenomic reanalysis of ∼2.8 million spectra (PXD004010 and PXD001468) resulted in 12,705 variant peptide spectrum matches (PSMs), of which PgxSAVy evaluated 3028 (23.8%), 1409 (11.1%) and 8268 (65.1%) as confident, semi-confident and doubtful respectively. PgxSAVy also annotates the variants based on their pathogenicity and provides support for assisted manual validation. The analysis of proteins carrying variants can provide fine granularity in discovering important pathways. PgxSAVy will advance personalized medicine by providing a comprehensive framework for quality control and prioritization of proteogenomics variants. PgxSAVy is freely available at https://pgxsavy.igib.res.in/ as a webserver and https://github.com/anuragraj/PgxSAVy as a stand-alone tool.

Heart rate complexity helps mortality prediction in the intensive care unit: A pilot study using artificial intelligence.

BACKGROUND: In intensive care units (ICUs), accurate mortality prediction is crucial for effective patient management and resource allocation. The Simplified Acute Physiology Score II (SAPS-2), though commonly used, relies heavily on comprehensive clinical data and blood samples. This study sought to develop an artificial intelligence (AI) model utilizing key hemodynamic parameters to predict ICU mortality within the first 24 h and assess its performance relative to SAPS-2. METHODS: We conducted an analysis of select hemodynamic parameters and the structure of heart rate curves to identify potential predictors of ICU mortality. A machine-learning model was subsequently trained and validated on distinct patient cohorts. The AI algorithm's performance was then compared to the SAPS-2, focusing on classification accuracy, calibration, and generalizability. MEASUREMENTS AND MAIN RESULTS: The study included 1298 ICU admissions from March 27th, 2015, to March 27th, 2017. An additional cohort from 2022 to 2023 comprised 590 patients, resulting in a total dataset of 1888 patients. The observed mortality rate stood at 24.0%. Key determinants of mortality were the Glasgow Coma Scale score, heart rate complexity, patient age, duration of diastolic blood pressure below 50 mmHg, heart rate variability, and specific mean and systolic blood pressure thresholds. The AI model, informed by these determinants, exhibited a performance profile in predicting mortality that was comparable, if not superior, to the SAPS-2. CONCLUSIONS: The AI model, which integrates heart rate and blood pressure curve analyses with basic clinical parameters, provides a methodological approach to predict in-hospital mortality in ICU patients. This model offers an alternative to existing tools that depend on extensive clinical data and laboratory inputs. Its potential integration into ICU monitoring systems may facilitate more streamlined mortality prediction processes.

A methodological approach by capillary electrophoresis coupled to mass spectrometry via electrospray interface for the characterization of short synthetic peptides towards the conception of self-assembled nanotheranostic agents.

Nanostructures formed by the self-assembling peptide building blocks are attractive materials for the design of theranostic objects due to their intrinsic biocompatibility, accessible surface chemistry as well as cavitary morphology. Short peptide synthesis and modification are straightforward and give access to a great diversity of sequences, making them very versatile building blocks allowing for the design of thoroughly controlled self-assembled nanostructures. In this work, we developed a new CE-DAD-ESI-MS method to characterize short synthetic amphiphilic peptides in terms of exact sequence and purity level in the low 0.1 mg.mL-1 range, without sample treatment. This study was conducted using a model sequence, described to have pH sensitive self-assembling property. Peptide samples obtained from different synthesis processes (batch or flow, purified or not) were thus separated by capillary zone electrophoresis (CZE). The associated dual UV and MS detection mode allowed to evidence the exact sequence together with the presence of impurities, identified as truncated or non-deprotected sequences, and to quantify their relative proportion in the peptide mixture. Our results demonstrate that the developed CE-DAD-ESI-MS method could be directly applied to the characterization of crude synthetic peptide products, in parallel with the optimization of peptide synthetic pathway to obtain controlled sequences with high synthetic yield and purity, which is crucial for further design of robust peptide based self-assembled nanoarchitectures.

Critically ill patients with high predicted mortality: Incidence and outcome.

OBJECTIVE: As calculated by the severity scores, an unknown number of patients are admitted to the Intensive Care Unit (ICU) with a very high risk of death. Clinical studies have poorly addressed this population, and their prognosis is largely unknown. DESIGN: Post hoc analysis of a multicenter, cohort, longitudinal, observational, retrospective study (CIMbA). SETTING: Sixteen Portuguese multipurpose ICUs. PATIENTS: Patients with a Simplified Acute Physiology Score II (SAPS II) predicted hospital mortality above 80% on admission to the ICU (high-risk group); A comparison with the remaining patients was obtained. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Hospital, 30 days, 1 year mortality. RESULTS: We identified 4546 patients (59.9% male), 12.2% of the whole population. Their SAPS II predicted hospital mortality was 89.0±5.8%, whilst the observed mortality was lower, 61.0%. This group had higher mortality, both during the first 30 days (aHR 3.52 [95% CI 3.34-3.71]) and from day 31 to day 365 after ICU admission (aHR 1.14 [95%CI 1.04-1.26]), respectively. However, their hospital standardized mortality ratio was similar to the other patients (0.69 vs. 0.69, P=.92). At one year of follow-up, 30% of patients in the high-risk group were alive. CONCLUSIONS: Roughly 12% of patients admitted to the ICU for more than 24h had a SAPS II score predicted mortality above 80%. Their hospital standardized mortality was similar to the less severe population and 30% were alive after one year of follow-up.

Is Carboxyhaemoglobin an Effective Bedside Prognostic Tool for Sepsis and Septic Shock Patients?

Introduction: Proper management of sepsis poses a challenge even today, with early diagnosis and targeted treatment being the most important steps. Easy, cost-effective bedside tools are needed in order to pinpoint towards the outcome of sepsis or septic shock. Aim of study: This study aims to find a correlation between Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) severity scores, the Neutrophil-Lymphocytes Ratio (NLR) and carboxyhaemoglobin (COHb) levels in septic or septic shock patients with the scope of establishing a bed side cost-effective prognostic tool. Materials and methods: A pilot, prospective, observational, and ongoing study was conducted on 61 patients admitted with sepsis or septic shock according to the SEPSIS 3 Consensus definition. We followed clinical and paraclinical parameters on day 1 (D1) and day 5 (D5) after meeting the inclusion criteria. Results: On D1 we found a statistically significant positive correlation between each severity score (p <0.0001), r = 0.7287 for SOFA vs. APACHE II with CI: 0.5841-0.8285, r = 0.6862 for SOFA vs. SAPS II with CI: 0.5251-0.7998 and r = 0.8534 for APACHE II vs. SAPS II with CI: 0.7663 to 0.9097. On D5 we observed similar results: a significant positive correlation between each severity score (p <0.0001), with r = 0.7877 for SOFA vs. APACHE II with CI: 0.6283 to 0.8836, r = 0.8210 for SOFA vs. SAPS II with CI: 0.6822 to 0.9027 and r = 0.8880 for APACHE II vs. SAPS II., CI: 0.7952 to 0.9401. Nil correlation was found between the severity scores, NLR and COHb on D1 and D5. Conclusion: Cost-effective bedside tools to pinpoint towards the outcome of sepsis are yet to be found, however the positive correlation between the severity scores point out to a combination of such tools for prognosis prediction of septic or septic shock patients.

Relationship between clinical-epidemiological parameters and outcomes of patients with COVID-19 admitted to the intensive care unit: a report from a Brazilian hospital.

Background: People in low-income countries, especially those with low socio-economic conditions, are likelier to test positive for SARS-CoV-2. The unequal conditions of public health systems also increase the infection rate and make early identification and treatment of at-risk patients difficult. Here, we aimed to characterize the epidemiological profile of COVID-19 patients in intensive care and identify laboratory and clinical markers associated with death. Materials and methods: We conducted an observational, descriptive, and cross-sectional study in a reference hospital for COVID-19 treatment in the Southern Region of Bahia State, in Brazil, to evaluate the epidemiological, clinical, and laboratory characteristics of COVID-19 patients admitted to the intensive care unit (ICU). Additionally, we used the area under the curve (AUC) to classify survivors and non-survivors and a multivariate logistic regression analysis to assess factors associated with death. Data was collected from the hospital databases between April 2020 and July 2021. Results: The use of bladder catheters (OR 79.30; p < 0.0001) and central venous catheters (OR, 45.12; p < 0.0001) were the main factors associated with death in ICU COVID-19 patients. Additionally, the number of non-survivors increased with age (p < 0.0001) and prolonged ICU stay (p < 0.0001). Besides, SAPS3 presents a higher sensibility (77.9%) and specificity (63.1%) to discriminate between survivors and non-survivor with an AUC of 0.79 (p < 0.0001). Conclusion: We suggest that multi-laboratory parameters can predict patient prognosis and guide healthcare teams toward more assertive clinical management, better resource allocation, and improved survival of COVID-19 patients admitted to the ICU.

Association between nutritional status scores and the 30-day mortality in patients with acute kidney injury: an analysis of MIMIC-III database.

BACKGROUND: Studies have proven that the risk of acute kidney injury (AKI) increased in patients with malnutrition. Prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) were general tools to predict the risk of mortality, but the prognostic value of them for in-hospital mortality among patients with AKI have not been validated yet. Herein, this study aims to explore the association between PNI and GNRI and 30-day mortality in patients with AKI. METHODS: Demographic and clinical data of 863 adult patients with AKI were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database in 2001-2012 in this retrospective cohort study. Univariate and multivariate Cox proportional regression analyses were used to explore the association between PNI and GNRI and 30-day mortality. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of age, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology (SAPS-II) score were also performed. RESULTS: Totally, 222 (26.71%) patients died within 30 days. After adjusting for covariates, PNI ≥ 28.5 [HR = 0.71, 95%CI: (0.51-0.98)] and GNRI ≥ 83.25 [HR = 0.63, 95%CI: (0.47-0.86)] were both associated with low risk of 30-day mortality. These relationships were also found in patients who aged ≥ 65 years old. Differently, high PNI level was associated with low risk of 30-day mortality among patients with SOFA score < 6 or SAPS-II score < 43, while high GNRI was associated with low risk of 30-day mortality among those who with SOFA score ≥ 6 or SAPS-II score ≥ 43 (all P < 0.05). CONCLUSION: PNI and GNRI may be potential predictors of 30-day mortality in patients with AKI. Whether the PNI is more recommended for patients with mild AKI, while GNRI for those with severe AKI is needed further exploration.

Altered Heart Rate Variability During Rest in Schizophrenia: A State Marker.

BACKGROUND: Autonomic nervous system (ANS) imbalance has been reported in a number of psychiatric disorders such as depression, schizophrenia, panic disorder, etc. Autonomic dysfunction in schizophrenia has been associated with the symptoms and manifestation of psychosis. Heart rate variability (HRV) as a tool has been widely used to assess ANS activity and the effect of disease on the sympathovagal balance. Therefore, in the present study, HRV derived from electrocardiogram (ECG) lead II at rest was investigated in order to understand the changes in frequency domain measures in patients with schizophrenia and their first-degree relatives compared to healthy controls. METHODS: Twenty-five patients with schizophrenia, 24 first-degree relatives of patients, and 24 healthy controls (Diagnostic and Statistical Manual of Mental Disorders (DSM)-5; 18-45 years) were included in the study. HRV of the subjects was measured after five minutes of rest. ECG lead II was recorded for five minutes and HRV was analysed in the frequency domain: low frequency (LF), high frequency (HF), total power, and LF/HF ratio. HRV parameters and heart rate were statistically analysed for group comparisons using general linear model multivariate analysis. RESULTS: Patients had significantly higher minimum heart rate and lower HF (normalized units (nu)) compared to their first-degree relatives. A trend was observed in HF (nu) with the lowest in patients followed by healthy controls and first-degree relatives and LF/HF ratio was the highest in patients followed by healthy controls and first-degree relatives, although not statistically significant. No significant difference was found between first-degree relatives and healthy controls. CONCLUSION: The alteration of HRV in schizophrenia could be attributed to reduction in vagal tone and sympathetic dominance, which in turn could serve as state markers of schizophrenia.