Novel human recombinant N-acetylgalactosamine-6-sulfate sulfatase produced in a glyco-engineered Escherichia coli strain.

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), resulting in the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Previously, it was reported the production of an active human recombinant GALNS (rGALNS) in E. coli BL21(DE3). However, this recombinant enzyme was not taken up by HEK293 cells or MPS IVA skin fibroblasts. Here, we leveraged a glyco-engineered E. coli strain to produce a recombinant human GALNS bearing the eukaryotic trimannosyl core N-glycan, Man3GlcNAc2 (rGALNSoptGly). The N-glycosylated GALNS was produced at 100 mL and 1.65 L scales, purified and characterized with respect to pH stability, enzyme kinetic parameters, cell uptake, and KS clearance. The results showed that the addition of trimannosyl core N-glycans enhanced both protein stability and substrate affinity. rGALNSoptGly was capture through a mannose receptor-mediated process. This enzyme was delivered to the lysosome, where it reduced KS storage in human MPS IVA fibroblasts. This study demonstrates the potential of a glyco-engineered E. coli for producing a fully functional GALNS enzyme. It may offer an economic approach for the biosynthesis of a therapeutic glycoprotein that could prove useful for MPS IVA treatment. This strategy could be extended to other lysosomal enzymes that rely on the presence of mannose N-glycans for cell uptake.

One-year survival of patients admitted for sepsis to intensive care units in Colombia.

BACKGROUND: Sepsis is a frequent cause of admission to intensive care units (ICUs). High mortality rates are estimated globally, and in our country, few studies have reported one-year survival. The objective of this study is to determine one-year survival in patients with sepsis admitted to the ICU in Colombia, compared with the survival of patients admitted for other conditions. METHODS: Retrospective cohort study using administrative databases from the Ministry of Health of Colombia. One-year survival and the adjusted hazard ratio for survival, adjusted for comorbidities included in the Charlson Index, were determined using a Cox proportional hazards model for patients admitted for other causes as well as for those admitted for sepsis. This was then compared with an inverse propensity score weighting model. RESULTS: A total of 116.407 patients were initially admitted to the ICUs, with 12.056 (10.36%) diagnosed with sepsis. Within the first year, 4.428 (36.73%) patients died due to sepsis. Age and male gender were associated with an increased risk of death from sepsis, and the covariates associated with one-year mortality were as follows: age over 80 years with HR 9.91 (95% CI: 9.22-10.65), renal disease with HR 3.16 (95% CI: 3.03-3.29), primary tumoral disease with HR 2.07 (95% CI: 1.92-2.23), liver disease with HR 2.27 (95% CI: 2.07-2.50), and metastatic solid tumor with HR 2.03 (95% CI: 1.92-2.15). CONCLUSION: This study revealed a high one-year sepsis mortality rate in the population, associated with variables such as age over 80 years, the presence of renal disease, liver disease, connective tissue diseases, and cancer. Men exhibited higher mortality compared to women.

Performance of risk scores in predicting mortality at 3, 6, and 12 months in patients diagnosed with community-acquired pneumonia.

BACKGROUND: Risk scores (RS) evaluate the likelihood of short-term mortality in patients diagnosed with community-acquired pneumonia (CAP). However, there is a scarcity of evidence to determine the risk of long-term mortality. This article aims to compare the effectiveness of 16 scores in predicting mortality at three, six, and twelve months in adult patients with CAP. METHODS: A retrospective cohort study on individuals diagnosed with CAP was conducted across two hospitals in Colombia. Receiver Operating Characteristic (ROC) curves were constructed at 3, 6, and 12 months to assess the predictive ability of death for the following scoring systems: CURB-65, CRB-65, SCAP, CORB, ADROP, NEWS, Pneumonia Shock, REA-ICU, PSI, SMART-COP, SMRT-CO, SOAR, qSOFA, SIRS, CAPSI, and Charlson Comorbidity Index (CCI). RESULTS: A total of 3688 patients were included in the final analysis. Mortality at 3, 6, and 12 months was 5.2%, 8.3%, and 16.3% respectively. At 3 months, PSI, CCI, and CRB-65 scores showed ROC curves of 0.74 (95% CI: 0.71-0.77), 0.71 (95% CI: 0.67-0.74), and 0.70 (95% CI: 0.66-0.74). At 6 months, PSI and CCI scores showed performances of 0.74 (95% CI: 0.72-0.77) and 0.72 (95% CI: 0.69-0.74), respectively. Finally at 12 months, all evaluated scores showed poor discriminatory capacity, including PSI, which decreased from acceptable to poor with an ROC curve of 0.64 (95% CI: 0.61-0.66). CONCLUSION: When predicting mortality in patients with CAP, at 3 months, PSI, CCI, and CRB-65 showed acceptable predictive performances. At 6 months, only PSI and CCI maintained acceptable levels of accuracy. For the 12-month period, all evaluated scores exhibited very limited discriminatory ability, ranging from poor to almost negligible.

A targeted likelihood estimation comparing cefepime and piperacillin/tazobactam in critically ill patients with community-acquired pneumonia (CAP).

Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01-1.27], p = 0.03), (OR 1.14 95% CI [1.03-1.26], p = 0.009), (OR 1.1 95% CI [1.01-1.22], p = 0.039) and (OR 1.13 95% CI [1.03-1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions.

Computed tomography perfusion as an early predictor of malignant cerebral infarction.

INTRODUCTION: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks. MATERIALS AND METHODS: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F-score was calculated as an indicator of precision and sensitivity. RESULTS: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F-score 0.52, Youden's index 6), than with perfusion-based measures: relative cerebral blood volume threshold <40% (AUC 0.87, F-score 0.71, Youden's index 34 mL) or relative cerebral blood flow threshold <35% (AUC 0.87, F-score 0.62, Youden's index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS. DISCUSSION AND CONCLUSION: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment.

Hospital-acquired bacterial pneumonia in critically ill patients: from research to clinical practice.

INTRODUCTION: Hospital-acquired pneumonia (HAP) represents a significant cause of mortality among critically ill patients admitted to Intensive Care Units (ICUs). Timely and precise diagnosis is imperative to enhance therapeutic efficacy and patient outcomes. However, the diagnostic process is challenged by test limitations and a wide-ranging list of differential diagnoses, particularly in patients exhibiting escalating oxygen requirements, leukocytosis, and increased secretions. AREAS COVERED: This narrative review aims to update diagnostic modalities, facilitating the prompt identification of nosocomial pneumonia while guiding, developing, and assessing therapeutic interventions. A comprehensive literature review was conducted utilizing the MEDLINE/PubMed database from 2013 to April 2024. EXPERT OPINION: An integrated approach that integrates clinical, microbiological, and imaging tools is paramount. Progress in diagnostic techniques, including novel molecular methods, the expanding utilization and accuracy of bedside ultrasound, and the emergence of Artificial Intelligence, coupled with an improved comprehension of lung microbiota and host-pathogen interactions, continues to enhance our capability to accurately and swiftly identify HAP and its causative agents. This advancement enables the refinement of treatment strategies and facilitates the implementation of precision medicine approaches.

Dataset of breast thermography images for the detection of benign and malignant masses.

Thermographic image analysis is a subfield of diagnostic image processing aimed at detecting breast abnormalities in women at an early stage. It is a developing field of research and its effectiveness and scope require scientific assessment to be determined. An open-access dataset has been created for the scientific community to test and develop techniques for computational detection of normal and abnormal breast conditions from thermograms. This dataset is a valuable resource for researchers due to the scarcity of publicly available datasets of breast thermographic images. It includes thermographic images of the female chest area in three capture positions: anterior, left oblique and right oblique. The data set comes from 119 women ranging from 18 to 81 years of age. A table is attached to the dataset with the diagnosis of breast pathology, showing that 84 patients had benign pathology and 35 patients had malignant pathology. The diagnoses of women with healthy breast pathology are not included.

Personalized medicine and nutrition in hepatology for preventing chronic liver disease in Mexico.

Chronic liver disease is a global health issue. Patients with chronic liver disease require a fresh approach that focuses on the genetic and environmental factors that contribute to disease initiation and progression. Emerging knowledge in the fields of Genomic Medicine and Genomic Nutrition demonstrates differences between countries in terms of genetics and lifestyle risk factors such as diet, physical activity, and mental health in chronic liver disease, which serves as the foundation for the implementation of Personalized Medicine and Nutrition (PerMed-Nut) strategies. Most of the world's populations have descended from various ethnic groupings. Mexico's population has a tripartite ancestral background, consisting of Amerindian, European, and African lineages, which is common across Latin America's regional countries. The purpose of this review is to discuss the genetic and environmental components that could be incorporated into a PerMed-Nut model for metabolic-associated liver disease, viral hepatitis B and C, and hepatocellular carcinoma in Mexico. Additionally, the implementation of the PerMed-Nut approach will require updated medicine and nutrition education curricula. Training and equipping future health professionals and researchers with new clinical and investigative abilities focused on preventing liver illnesses in the field of genomic hepatology globally is a vision that clinicians and nutritionists should be concerned about.

PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

BACKGROUND: Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. METHODS: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. RESULTS: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. CONCLUSIONS: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

The development and implementation of a low-cost mechanical ventilator in a low-middle-income country during the COVID-19 pandemic: The Unisabana-HERONS.

Background: The COVID-19 pandemic in Latin America generated the need to develop low-cost, fast-manufacturing mechanical ventilators. The Universidad de La Sabana and the Fundacion Neumologica Colombiana designed and manufactured the Unisabana-HERONS (USH) ventilator. Here, we present the preclinical and clinical study results to evaluate its effectiveness and safety characteristics in an animal model (Yorkshire Sow) and five patients with acute respiratory failure receiving mechanical ventilatory support for 24 h. Methods: The effectiveness and safety outcomes included maintaining arterial blood gases and pulse oximetry saturation (SpO2), respiratory pressures and volumes (during continuous monitoring) in the range of ARDS and lung-protective strategy goals, and the occurrence of barotrauma. A significance level of 0.05 was used for statistical tests. This clinical trial was registered on Clinicaltrials.gov (NCT04497623) and approved by the ethics committee. Results: Among patients treated with the Unisabana-HERONS, the most frequent causes of acute respiratory failure were pneumonia in 3/5 (60 %) and ARDS in 2/5 (40 %). During the treatment, the ventilatory parameters related to lung protection protocols were kept within the safety range, and vital signs and blood gas were stable. The percentage of time that the respiratory pressures or volumes were out of safety range were plateau pressure >30 cm H2O: 0.00 %; driving pressure >15 cm H2O: 0.06 %; mechanical power >15 J/min: 0.00 %; and Tidal volume >8 mL/kg: 0.00 %. There were no adverse events related to the ventilator. The usability questionnaire retrieved a median score for all items between 9 and 10 (best score: 10), indicating great ease of use. Conclusion: The Unisabana-HERONS ventilator effectively provided adequate gas exchange and maintained the ventilatory parameters in the range of lung protection strategies in humans and an animal model. Furthermore, it is straightforward to use and is a low-cost medical device.

Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia.

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.

Data challenges for international health emergencies: lessons learned from ten international COVID-19 driver projects.

The COVID-19 pandemic highlighted the importance of international data sharing and access to improve health outcomes for all. The International COVID-19 Data Alliance (ICODA) programme enabled 12 exemplar or driver projects to use existing health-related data to address major research questions relating to the pandemic, and developed data science approaches that helped each research team to overcome challenges, accelerate the data research cycle, and produce rapid insights and outputs. These approaches also sought to address inequity in data access and use, test approaches to ethical health data use, and make summary datasets and outputs accessible to a wider group of researchers. This Health Policy paper focuses on the challenges and lessons learned from ten of the ICODA driver projects, involving researchers from 19 countries and a range of health-related datasets. The ICODA programme reviewed the time taken for each project to complete stages of the health data research cycle and identified common challenges in areas such as data sharing agreements and data curation. Solutions included provision of standard data sharing templates, additional data curation expertise at an early stage, and a trusted research environment that facilitated data sharing across national boundaries and reduced risk. These approaches enabled the driver projects to rapidly produce research outputs, including publications, shared code, dashboards, and innovative resources, which can all be accessed and used by other research teams to address global health challenges.

Engineering the cellulolytic bacterium, Clostridium thermocellum, to co-utilize hemicellulose.

Consolidated bioprocessing (CBP) of lignocellulosic biomass holds promise to realize economic production of second-generation biofuels/chemicals, and Clostridium thermocellum is a leading candidate for CBP due to it being one of the fastest degraders of crystalline cellulose and lignocellulosic biomass. However, CBP by C. thermocellum is approached with co-cultures, because C. thermocellum does not utilize hemicellulose. When compared with a single-species fermentation, the co-culture system introduces unnecessary process complexity that may compromise process robustness. In this study, we engineered C. thermocellum to co-utilize hemicellulose without the need for co-culture. By evolving our previously engineered xylose-utilizing strain in xylose, an evolved clonal isolate (KJC19-9) was obtained and showed improved specific growth rate on xylose by ∼3-fold and displayed comparable growth to a minimally engineered strain grown on the bacteria's naturally preferred substrate, cellobiose. To enable full xylan deconstruction to xylose, we recombinantly expressed three different ß-xylosidase enzymes originating from Thermoanaerobacterium saccharolyticum into KJC19-9 and demonstrated growth on xylan with one of the enzymes. This recombinant strain was capable of co-utilizing cellulose and xylan simultaneously, and we integrated the ß-xylosidase gene into the KJC19-9 genome, creating the KJCBXint strain. The strain, KJC19-9, consumed monomeric xylose but accumulated xylobiose when grown on pretreated corn stover, whereas the final KJCBXint strain showed significantly greater deconstruction of xylan and xylobiose. This is the first reported C. thermocellum strain capable of degrading and assimilating hemicellulose polysaccharide while retaining its cellulolytic capabilities, unlocking significant potential for CBP in advancing the bioeconomy.

Latex vascular injection as method for enhanced neurosurgical training and skills.

Background: Tridimensional medical knowledge of human anatomy is a key step in the undergraduate and postgraduate medical education, especially in surgical fields. Training simulation before real surgical procedures is necessary to develop clinical competences and to minimize surgical complications. Methods: Latex injection of vascular system in brain and in head-neck segment is made after washing out of the vascular system and fixation of the specimen before and after latex injection. Results: Using this latex injection technique, the vascular system of 90% of brains and 80% of head-neck segments are well-perfused. Latex-injected vessels maintain real appearance compared to silicone, and more flexible vessels compared to resins. Besides, latex makes possible a better perfusion of small vessels. Conclusions: Latex vascular injection technique of the brain and head-neck segment is a simulation model for neurosurgical training based on real experiencing to improve surgical skills and surgical results.

Major alteration of Lung Microbiome and the Host Reaction in critically ill COVID-19 Patients with high viral load.

Background: Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. Materials and methods: In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 hours of intubation and again at 72 hours post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. Results: In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1ß, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. Conclusions: This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients, with elevated SARS-CoV-2 levels and metabolic changes, providing novel insights into the underlying mechanisms of VAP with potential management and prevention implications.

Streptococcus pneumoniae as a colonizing agent of the Nasopharynx - Oropharynx in adults: A systematic review and meta-analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) is a commensal pathogen that usually colonizes the upper respiratory tract of children. Likewise, Spn colonization has been considered a critical factor in the development of pneumococcal invasive disease. However, Spn prevalence in adults remains unclear. This study performs a systematic review and meta-analysis to explore the prevalence of Spn Nasopharynx - Oropharynx Colonization (NOC) in adults. METHODS: A Systematic review of scientific databases was utilized to identify eligible studies that follow strict selection criteria. Subsequently, a meta-analysis was conducted to establish NOC prevalence in adults (≥18 years old). The heterogeneity and sensitivity analyses were assessed using the microorganism identification technique, sample type, and age subgroups. RESULTS: Initial selection includes 69 studies, with 37 selected for the meta-analysis, involving 23,724 individuals. The overall prevalence (95 % CI) of Spn NOC among adults was 6 % (5-9). The subgroup analysis revealed that young adults (YA), 18-64 years old, had a prevalence of 10 %, whereas older adults (OA), ≥65 years old, had a prevalence of 2 %. The identification of Spn NOC may vary depending on the method of diagnosis used. High heterogeneity (I2 > 90 %) was observed but diminished to 70 % when the analysis was restricted to oropharyngeal swabs as an identification method. Furthermore, heterogeneity decreased to 58 % when exclusively employing traditional culture as the identification method. CONCLUSIONS: This study found a low prevalence of Spn NOC in adults. Notably, the prevalence of Spn NOC was higher in younger adults than in older adults. It is essential to highlight a significant heterogeneity among studies, which indicates there is no standardized method of Spn NOC identification.

The Vertebrobasilar Trunk and Its Anatomical Variants: A Microsurgical Anatomical Study.

BACKGROUND: The trunk of the basilar artery has not been included in microanatomy studies. Anatomical variants of the perforant branches of the vertebrobasilar trunk and their relationship with neural structures are very important in surgical approaches. Surgical dissection for the treatment of vascular lesions requires a perfect knowledge of the microsurgical anatomy. METHODS: We conducted a descriptive analysis of 50 brains, which were fixed with formalin at 10% for 2 weeks, and the arterial system was injected with colored latex. After microsurgical dissection, it was divided into three segments: the lower portion went from the anterior spinal artery to the anteroinferior cerebellar artery, the middle segment was raised from the upper limit of the lower portion to the origin of the superior cerebellar artery, and the upper segment ranged from the previous portion until the origin of the posterior cerebral artery. RESULTS: The basilar artery had an average length of 30 mm. The average diameter at its junction with the vertebral arteries was 4.05 mm. The average middle segment was 3.4 mm in diameter and 15.2 mm in length. The diameter of the upper segment was 4.2 mm, and its average length was 3.6 mm. The average number of bulbar arteries was three, and their average diameter was 0. 66 mm. The number of caudal perforator arteries were five on average, with a diameter of 0.32 mm. We found three rare cases of anatomical variants in the vertebra-basilar junction. CONCLUSIONS: The basilar artery emits penetrating branches in its lower, middle, and upper portions. The origin of penetrating branches was single or divided after forming a trunk. However, we observed long branches from perforant arteries.

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.