Post-injury multiple organ failure and late outcome. Is it just an association?

Multiple organ failure (MOF) is associated with a high rate of mortality in trauma patients. Several studies focused on long-term outcome in these patients, and showed that MOF is related to both in-hospital and late mortality and functional status. Exact mechanism of sequelae in MOF is still unclear. The distinction between early and late MOF probably helps to separate two different clinical conditions and find a stronger relationship with outcome

Editors' comments on a new trial of activated protein C for persistent septic shock

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Noninvasive mechanical ventilation during the weaning process: facilitative, curative, or preventive?

To avoid the complications associated with endotracheal intubation, noninvasive positive-pressure ventilation (NPPV) has been proposed in the management of ventilator weaning in patients with acute respiratory failure (ARF) of various etiologies. Several studies have been performed to assess the benefit of NPPV in various weaning strategies, including permitting early extubation in patients who fail to meet standard extubation criteria (facilitation use), avoiding reintubation in patients who fail extubation (curative use), and preventing extubation failure in nonselected and selected patients (preventive use). NPPV has been successfully used in facilitating early extubation, particularly in patients with chronic obstructive pulmonary disease. In contrast, applying curative NPPV to treat postextubation ARF in nonselected populations may not be effective and could even be deleterious. Early use of NPPV was successful in preventing ARF after extubation, and decreased the need for reintubation in selected patients at risk of developing postextubation ARF. It is important that caregivers clearly differentiate among these application modalities of NPPV. The skills and expertise of both medical and nonmedical personnel are crucial predictive factors for the success of NPPV in the ventilator weaning process

Clinical review: Noninvasive ventilation in the clinical setting – experience from the past 10 years

This brief review analyses the progress of noninvasive ventilation (NIV) over the last decade. NIV has gained the dignity of first line intervention for acute exacerbation of chronic obstructive pulmonary disease, assuring reduction of the intubation rate, rate of infection and mortality. Despite positive results, NIV still remains controversial as a treatment for acute hypoxemic respiratory failure, largely due to the different pathophysiology of hypoxemia. The infection rate reduction effect achieved by NIV application is crucial for immunocompromised patients for whom the endotracheal intubation represents a high risk. Improvements in skills acquired with experience over time progressively allowed successful treatment of more severe patients

An Adaptable and Unsupervised TinyML Anomaly Detection System for Extreme Industrial Environments

Industrial assets often feature multiple sensing devices to keep track of their status by monitoring certain physical parameters. These readings can be analyzed with machine learning (ML) tools to identify potential failures through anomaly detection, allowing operators to take appropriate corrective actions. Typically, these analyses are conducted on servers located in data centers or the cloud. However, this approach increases system complexity and is susceptible to failure in cases where connectivity is unavailable. Furthermore, this communication restriction limits the approach’s applicability in extreme industrial environments where operating conditions affect communication and access to the system. This paper proposes and evaluates an end-to-end adaptable and configurable anomaly detection system that uses the Internet of Things (IoT), edge computing, and Tiny-MLOps methodologies in an extreme industrial environment such as submersible pumps. The system runs on an IoT sensing Kit, based on an ESP32 microcontroller and MicroPython firmware, located near the data source. The processing pipeline on the sensing device collects data, trains an anomaly detection model, and alerts an external gateway in the event of an anomaly. The anomaly detection model uses the isolation forest algorithm, which can be trained on the microcontroller in just 1.2 to 6.4 s and detect an anomaly in less than 16 milliseconds with an ensemble of 50 trees and 80 KB of RAM. Additionally, the system employs blockchain technology to provide a transparent and irrefutable repository of anomalies

Safety and efficacy of colistin versus meropenem in the empirical treatment of ventilator-associated pneumonia as part of a macro-project funded by the Seventh Framework Program of the European Commission studying off-patent antibiotics. study protocol for a randomized controlled trial

Background: Ventilator-associated pneumonia (VAP) is one of the most common and severe hospital-adquired infections, and multidrugresistant gram-negative bacilli (MDR-GNB) constitute the main etiology in many countries. Inappropriate empiric antimicrobial treatment is associated with increased mortality. In this context, the empirical treatment of choice for VAP is unknown. Colistin, is now the antimicrobial with greatest in vitro activity against MDR-GNB. Methods/Design: The MagicBullet clinical trial is an investigator-driven clinical study, funded by the Seventh Framework Program of the European Commission. This is designed as a phase IV, randomized, controlled, open label, non-inferiority and international trial to assess the safety and efficacy of colistin versus meropenem in late onset VAP. The study is conducted in a total of 32 centers in three European countries (Spain, Italy and Greece) with specific high incidences of infections caused by MDR-GNB. Patients older than 18 years who develop VAP with both clinical and radiological signs, and are on mechanical ventilation for more than 96 hours, or less than 96 hours but with previous antibiotic treatment plus one week of hospitalization, are candidates for inclusion in the study. A total sample size of 496 patients will be randomized according to a severity clinical score (at the time of VAP diagnosis in a 1:1 ratio to receive either colistin 4.5 MU as a loading dose, followed by 3 MU every eight hours (experimental arm), or meropenem 2 g every eight hours (control arm), both combined with levofloxacin. Mortality from any cause at 28 days will be considered as the main outcome. Clinical and microbiological cure will be evaluated at 72 hours, eight days, the finalization of antibiotic treatment, and 28 days of follow-up. The efficacy evaluation will be performed in every patient who receives at least one study treatment drug, and with etiologic diagnosis of VAP, intention-to-treat population and per protocol analysis will be performed

CTLA-4 and PD-1 ligand gene expression in epithelial thyroid cancers

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80 and CD86 was evaluated at mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the down-regulation of CD80 was observed in above all ATC. In addition, the increased expression of CD80 associated to longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 down-regulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC

Frequent detection of high human papillomavirus DNA loads in oral potentially malignant disorders

Human papillomavirus (HPV) is estimated to be the cause of 40-80% of the squamous cell carcinoma of the oropharynx but only of a small fraction of the oral cavity cancers. The prevalence of oral HPV infection has significantly increased in the last decade, raising concerns about the HPV role in progression of oral potentially malignant disorders (OPMD) toward squamous cell carcinomas. We sought to study HPV infection in patients with oral lesions, and in control individuals, using non-invasive and site-specific oral brushing and sensitive molecular methods. HPV DNA positivity and viral loads were evaluated in relation to patient data and clinical diagnosis. We enrolled 116 individuals attending Dental Clinics: 62 patients with benign oral lesions (e.g. fibromas, papillomatosis, ulcers) or OPMD (e.g. lichen, leukoplakia) and 54 controls. Oral cells were collected with Cytobrush and HPV-DNA detected with quantitative real-time PCR (qPCR) for the more common high-risk (HR) and low-risk (LR) genotypes. HPV detection rate, percentage of HR HPVs and HPV-DNA loads (namely HPV16 and in particular, HPV18) were significantly higher in patients than in controls. Lichen planus cases had the highest HPV positive rate (75.0%), hairy leukoplakia the lowest (33.3%). This study detected unexpectedly high rates of HPV infection in cells of the oral mucosa. The elevated HR HPV loads found in OPMD suggest the effectiveness of qPCR in testing oral lesions. Prospective studies are needed to establish whether elevated viral loads represent a clinically useful marker of the risk of malignant progression

Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial

Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice