Carotid Intima-Media Thickness, Overweight, and Poor Sleep Quality in Commercial Airline Pilots: A Cross-Sectional Study.

Background Cardiovascular disease is a leading cause of premature career termination in commercial airline pilots (APs). In this cross-sectional study, we sought to investigate the relationship between intima-media thickness (IMT), a marker of subclinical atherosclerosis, and cardiovascular risk factors in APs, focusing on overweight status and sleep quality. Methods A total of 140 male APs were categorized into four groups based on body mass index (BMI) and Pittsburgh Sleep Quality Index (PSQI) score: overweight poor sleepers (OW-PS), overweight good sleepers (OW-GS), normal weight poor sleepers (NW-PS), and normal weight good sleepers (NW-GS). IMT was quantified in the common carotid artery (CCA) and carotid bulb using ultrasound, yielding a composite IMT (IMTcom) measure. Common cardiovascular risk factors were assessed in all participants. Results The prevalence of overweight and poor sleep quality was 43.6% and 32.9%, respectively. The OW-PS group had significantly higher age, heart rate, total cholesterol, and low-density lipoprotein (LDL) cholesterol compared to other groups (p<0.05). Overweight pilots, regardless of sleep quality, had increased IMTcom compared to normal-weight pilots (p<0.001). Age and LDL cholesterol were independent predictors of IMTcom in the OW-PS and OW-GS groups (p<0.05). Conclusions Overweight status, irrespective of sleep quality, is associated with increased IMT in APs, suggesting a higher burden of subclinical atherosclerosis. Interventions focused on reducing LDL cholesterol levels and managing age-related cardiovascular risk factors could be advantageous in mitigating the risk of atherosclerotic vascular disease in overweight pilots.

Magneto-optical Particles in Isotropic Spinning Fields Mimic Magnetic Monopoles.

In contrast with the typical electric currents accelerated under the influence of a Coulombic force, there are only a few condensed matter examples of particles experiencing a force proportional to a constant, external magnetic field. In this Letter, we present a new alternative, based on an isotropic radiation spinning field and the magneto-optical effect, in which a particle is propelled by a magnetic field just like a magnetic monopole will do. This is a purely nonreciprocal effect as the reciprocal equivalent (a chiral dipole), despite presenting a dichroic response, does not experience any force when illuminated by the spinning field. The "magnetic charge" induced by impinging radiation on the magneto-optical dipole is found to depend linearly on the helicity of the field. In addition, this artificial monopole experiences a dichroic permanent optical torque and does not interact with an external electric field.

Photonic and Nanomechanical Modes in Acoustoplasmonic Toroidal Nanopropellers.

Non-conventional resonances, both acoustic and photonic, are found in metallic particles with a toroidal nanopropeller geometry, which is generated by sweeping a three-lobed 2D shape along a spiral with twisting angle α. For both optical and acoustic cases, the spectral location of resonances experiences a red-shift as a function of α. We demonstrate that the optical case can be understood as a natural evolution of resonances as the spiral length of the toroidal nanopropeller increases with α, implying a huge helicity-dependent absorption cross-section. In the case of acoustic response, two red-shifting breathing modes are identified. Additionally, even a small α allows the appearance of new low-frequency resonances, whose spectral dispersion depends on a competition between the length of the generative spiral and the pitch of the toroidal nanopropeller.

Effects of a Resistance Exercise Program in Patients with Colorectal Cancer Undergoing Chemotherapy Treatment: A Randomized Controlled Trial Study Protocol.

Background: Colorectal cancer is a leading cause of morbidity and mortality worldwide, with chemotherapy being a crucial treatment despite its significant side effects, such as chemotherapy-induced peripheral neuropathy (CIPN). Physical exercise has shown potential benefits in mitigating these side effects and improving patients' overall well-being. Objective: This study aims to evaluate the efficacy of a strength exercise program in reducing CIPN in patients with colorectal cancer undergoing chemotherapy, along with secondary objectives including impacts on quality of life, body mass index, oxygen consumption, anxiety and depression, fatigue, sleep quality, and various analytical parameters. Methods: A double-blind randomized controlled trial was conducted with 44 participants, divided into an intervention group (supervised resistance training twice a week and home exercises) and a control group (home exercises only). The primary outcome measure was CIPN, assessed using the EORTC QLQ-CIPN20 questionnaire. Secondary outcomes included assessments using the EORTC QLQ-C30, the 6-minute walk test, HADS, FACT-F, and MISS, along with various blood parameters. Results and Conclusions: The study will provide insights into the effectiveness of physical exercise in managing CIPN and improving various health parameters in colorectal cancer patients. By developing tailored exercise protocols, this research aims to enhance patient quality of life, optimize treatment outcomes, and reduce the incidence of debilitating side effects, thereby supporting the integration of physical exercise into standard oncological care.

Guide RNA structure design enables combinatorial CRISPRa programs for biosynthetic profiling.

Engineering metabolism to efficiently produce chemicals from multi-step pathways requires optimizing multi-gene expression programs to achieve enzyme balance. CRISPR-Cas transcriptional control systems are emerging as important tools for programming multi-gene expression, but poor predictability of guide RNA folding can disrupt expression control. Here, we correlate efficacy of modified guide RNAs (scRNAs) for CRISPR activation (CRISPRa) in E. coli with a computational kinetic parameter describing scRNA folding rate into the active structure (rS = 0.8). This parameter also enables forward design of scRNAs, allowing us to design a system of three synthetic CRISPRa promoters that can orthogonally activate (>35-fold) expression of chosen outputs. Through combinatorial activation tuning, we profile a three-dimensional design space expressing two different biosynthetic pathways, demonstrating variable production of pteridine and human milk oligosaccharide products. This RNA design approach aids combinatorial optimization of metabolic pathways and may accelerate routine design of effective multi-gene regulation programs in bacterial hosts.

Identifying Gaps in the Treatment Guidelines for Hepatitis C in Peru to Meet International Standards: A Narrative Review.

Hepatitis C virus still represents a major cause of morbidity and mortality worldwide. In Peru, two national practice guidelines for the management of this infection were published more than 5 years ago; however, the latest breakthroughs in the treatment make it necessary to update these guidelines. We reviewed the most recent recommendations of the international guidelines and compared them with the current Peruvian guidelines. We found major differences, such as the use of Glecaprevir/Pibrentasvir as a first-line therapy, which is contemplated in the World Health Organization guideline, and recommended by American and European guidelines, but is not considered in the Peruvian guidelines. Another crucial difference lies in the management of patients with chronic kidney disease, who are treated nowadays with a variety of direct-acting antivirals, with no restrictions on the use of Sofosbuvir-based regimens in first-world countries, an approach that has not been adopted in Peru. We believe that standardization of the recommendations of the Peruvian guidelines is imperative, including the new therapeutic strategies that have emerged in recent years. We also suggest conducting a cost effectiveness analysis in the Peruvian context to allow for the implementation of new antivirals, and to achieve a better control of hepatitis C in the country.

Biological Rhythms Generated by a Single Activator-Repressor Loop with Inhomogeneity and Diffusion.

Common models of circadian rhythms are typically constructed as compartmental reactions of well-mixed biochemicals, incorporating a negative-feedback loop consisting of several intermediate reaction steps essentially required to produce oscillations. Spatial transport of each reactant is often represented as an extra compartmental reaction step. Contrary to this traditional understanding, in this Letter we demonstrate that a single activation-repression biochemical reaction pair is sufficient to generate sustained oscillations if the sites of both reactions are spatially separated and molecular transport is mediated by diffusion. Our proposed scenario represents the simplest configuration in terms of the participating chemical reactions and offers a conceptual basis for understanding biological oscillations and inspiring in vitro assays aimed at constructing minimal clocks.

Deformity correction from the convexity of the curve in neuromuscular scoliosis.

Background: "Convex Pedicle Screw Technique" reduces the theoretical risk of neurovascular injury. Our aim is to evaluate the efficacy of this technique in patients with neuromuscular scoliosis (NMS). Methods: Retrospective study of 12 patients who underwent a Convex Pedicle Screw Technique and were diagnosed with NMS. Patients who had undergone previous spinal surgery were excluded. The minimum follow-up required was 24 months. Demographic data, intraoperative data, neurovascular complications and neurophysiological events requiring implant repositioning, as well as pre- and postoperative radiological variables were collected. Results: Twelve patients diagnosed with NMS underwent surgery. The median operative time was 217 minutes. Mean blood loss was 3.8±1.1 g/dL hemoglobin (Hb). The median postoperative stay was 8.8±4 days. A reduction of the Cobb angle in primary curve of 49.1% (from 52.8°±18° to 26.5°±12.6°; P<0.001) and in secondary curve of 25.2% (from 27.8°±18.9° to 18.3°±13.3°; P=0.10) was achieved. Coronal balance improved by 69.4% (7.5±46.2 vs. 2.3±20.9 mm; P=0.72) and sagittal balance by 75% (from -14.1±71.8 vs. -3.5±48.6 mm; P=0.50). There were no neurovascular complications. There were no intraoperative neurophysiological events requiring implant repositioning, nor during reduction maneuvers. No infections were reported. Conclusions: The correction of the deformity from convexity in NMS achieves similar results to other techniques, and a very low complication rate.

Multi-step regulation of microRNA expression and secretion into small extracellular vesicles by insulin.

Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells. Insulin regulated this process in part by phosphorylating hnRNPA1, causing it to bind to AU-rich motifs in miRNAs, mediating their secretion into sEVs. Importantly, 43% of insulin-regulated sEV-miRNAs are implicated in obesity and insulin resistance. These include let-7 and miR-103, which we show regulate insulin signaling in AML12 hepatocytes. Together, these findings demonstrate an important layer to insulin's regulation of adipose biology and provide a mechanism of tissue crosstalk in obesity and other hyperinsulinemic states.

Stochastic journeys of cell progenies through compartments and the role of self-renewal, symmetric and asymmetric division.

Division and differentiation events by which cell populations with specific functions are generated often take place as part of a developmental programme, which can be represented by a sequence of compartments. A compartment is the set of cells with common characteristics; sharing, for instance, a spatial location or a phenotype. Differentiation events are transitions from one compartment to the next. Cells may also die or divide. We consider three different types of division events: (i) where both daughter cells inherit the mother's phenotype (self-renewal), (ii) where only one of the daughters changes phenotype (asymmetric division), and (iii) where both daughters change phenotype (symmetric division). The self-renewal probability in each compartment determines whether the progeny of a single cell, moving through the sequence of compartments, is finite or grows without bound. We analyse the progeny stochastic dynamics with probability generating functions. In the case of self-renewal, by following one of the daughters after any division event, we may construct lifelines containing only one cell at any time. We analyse the number of divisions along such lines, and the compartment where lines terminate with a death event. Analysis and numerical simulations are applied to a five-compartment model of the gradual differentiation of hematopoietic stem cells and to a model of thymocyte development: from pre-double positive to single positive (SP) cells with a bifurcation to either SP4 or SP8 in the last compartment of the sequence.

Prospective One-Health investigation into low-abundant extended-spectrum ß-lactamase producing Enterobacterales enables detection of potential dissemination events and persistence.

BACKGROUND: Following a one-health approach, we sought to determine reservoirs of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), other than Escherichia coli or Klebsiella pneumoniae complex species (i.e., low-abundant species), and their associated ESBL genes and plasmid-replicon profiles. METHODS: From 06/2017-05/2019, ESBL-PE isolates were recovered from clinical samples routinely collected at the University Hospital Basel (Basel, Switzerland), as well as from wastewater and foodstuffs collected monthly at predefined locations throughout the city of Basel. Whole-genome sequencing was performed for characterization of ESBL-PE isolates. RESULTS: Among 1634 isolates recovered, 114 (7%) belonged to 17 low-abundant ESBL-PE species. Seven species originated from more than one compartment, mainly from clinical and wastewater samples (6/17). Sixteen different ESBL genes were identified, with blaCTX-M-15 (27%), blaFONA-6 (23%) and blaSHV-12 (16%) being most frequent. The blaCTX-M-1 gene was the only ESBL gene recovered from all three compartments. Putative plasmids constituted 60% of ESBL gene-containing contigs, while chromosomes comprised 40%. Foodstuff isolates showed the highest proportion (91%, 41/45) of ESBL genes located on chromosomes, whereas wastewater isolates had the highest proportion (95%, 37/39) of putative plasmids. Multi-replicon combinations were identified in 81% of the isolates. Epidemiological links were found among some clinical and wastewater isolates. CONCLUSIONS: The dominance of blaCTX-M-15 among low-abundant ESBL-PE species supports its species-independent transmission potential beyond the E. coli and K. pneumoniae complex, and blaCTX-M-1 may be transmitted between strains recovered from different compartments. The substantial overlap between low-abundant ESBL-PE present in wastewater and clinical samples supports the utility of wastewater surveillance for antibiotic resistance monitoring.

Elucidating the Impact of Li3InCl6-Coated LiNi0.8Co0.15Al0.05O2 on the Electro-Chemo-Mechanics of Li6PS5Cl-Based Solid-State Batteries.

Li6PS5Cl has attracted significant attention due to its high Li-ion conductivity and processability, facilitating large-scale solid-state battery applications. However, when paired with high-voltage cathodes, it experiences adverse side reactions. Li3InCl6 (LIC), known for its higher stability at high voltages and moderate Li-ion conductivity, is considered a catholyte to address the limitations of Li6PS5Cl. To extend the stability of Li6PS5Cl toward LiNi0.8Co0.15Al0.05O2 (NCA), we applied nanocrystalline LIC as a 180 nm-thick protective coating in a core-shell-like fashion (LIC@NCA) via mechanofusion. Solid-state batteries with LIC@NCA allow an initial discharge specific capacity of 148 mA h/g at 0.1C and 80% capacity retention for 200 cycles at 0.2C with a cutoff voltage of 4.2 V (vs Li/Li+), while cells without LIC coating suffers from low initial discharge capacity and poor retention. Using a wide spectrum of advanced characterization techniques, such as operando XRD, XPS, FIB-SEM, and TOF-SIMS, we reveal that the superior performance of solid-state batteries employing LIC@NCA is related to the suppression of detrimental interfacial reactions of NCA with Li6PS5Cl, delamination, and particle cracking compared to uncoated NCA.

Behavioral therapy in migraine: Expanding the therapeutic arsenal.

BACKGROUND AND PURPOSE: The US Headache Consortium developed evidence-based guidelines for the treatment of migraine and found grade A evidence in support of behavior therapy (BT). Understanding the mechanisms of BT may improve the management of migraine and reduce its burden. METHODS: We performed a narrative review to define the current evidence of BT and determine its usefulness in migraine management. RESULTS: The information was obtained from 116 publications, with 56 of them retrieved through direct searches in PubMed (2011-2020) and the remainder selected by the authors to complete the content. BT might reduce migraine impact by decreasing the sympathetic nervous system's response to stress and increasing pain tolerance. Acting in headache-related surroundings can be improved, together with headache duration and self-efficacy. Applications such as mobile health and electronic health applications can help to carry out healthier lifestyle patterns. Regarding medication overuse, BT seems to be a good choice, with similar results to pharmacological prophylaxis. Advantages of using BT are the lack of adverse effects and the unrestricted use in children, where BT is postulated to be even more effective than the standardized pharmacopeia. CONCLUSIONS: BT is an interesting tool that can be used as an add-on therapy in migraine. Through BT, the autonomy and empowerment of migraine patients is enhanced. BT may not cure migraine, but it could help to reduce pain severity perception, disability, and migraine impact, adding an emotive and cognitive approach to the perceptive role of pharmacopeia. Thus, a better approach in migraine, implementing specific therapeutic management, can improve migraine control.

Shar-Pei autoinflammatory disease with skin necrosis due to neutrophilic vasculitis: a case report.

A 4-month-old female Shar-pei dog was admitted with apathy, anorexia, and vomiting. The patient had an appropriate vaccination protocol, with the last vaccine administered 2.5 weeks prior to the onset of clinical signs. Physical examination revealed tachycardia, fever and swelling of the tibiotarsal joints. Several diagnostic tests including complete blood cell count, biochemistry profile, urinalysis, thoracic radiographs, hind limbs radiographs, abdominal ultrasound, and infectious diseases tests, were conducted to determine the underlying cause. Shar-Pei Auto-inflammatory Disease (SPAID) was diagnosed. Additionally, the patient developed skin necrosis in the inner aspect of the tibiotarsal joints as a complication. A skin biopsy revealed cutaneous vasculopathy causing degeneration, abrupt ulceration, and ischemic necrosis with intense neutrophilic inflammation of the dermis and subcutis. Moreover, a hospital-acquired infection was identified by skin culture. Debridement of the necrotic skin was performed, and due to its' severity and extent, the wound was closed by secondary intention. A diagnostic protocol and the therapeutic dose of acetylsalicylic acid, which led to clinical improvement, are recommended here. The patient has continued to present episodic manifestations of SPAID mainly fever and swelling of the tibiotarsal joints, but there has been no recurrence of necrosis or other cutaneous lesion in the last two years.

Study on the additional financial burden of breast cancer disease on cancer patients and their families. Financial toxicity in cancer.

Introduction: Breast cancer is among the most frequently diagnosed cancers worldwide, with 2.3 million new cases reported annually. The condition causes a social and economic impact known as financial toxicity of cancer. The study aims to explore the extra expenses borne by patients and their families on being diagnosed with breast cancer. Methodology: An observational, descriptive, cross-sectional study was conducted. The data was collected between November 2021 and March 2022 at the Medical Oncology Service in Complejo Asistencial Universitario de Salamanca, Spain. The variables under investigation were additional economic costs, physical disability (as measured by the Barthel Index), instrumental activities of daily living (as measured by the Lawton-Brody Scale), and caregiver burden (measured using the ZARIT scale). Results: The final sample size was N = 107. The study yielded the following outcomes: the median age was 55 years old and the majority of participants were female, with a proportion of 99.1%. The incidence rates for stage I and II were 31.8 and 35.5%, respectively. The median Barthel score was 100 points, while the Lawton and Brody score were 8 points and the ECOG score was 2 points. The analysis of primary caregiver burden resulted in a median ZARIT score of 15 points. The expenses related solely to the cancer diagnosis totaled 1511.22 euros per year (316.82 euros for pharmaceuticals; 487.85 euros for orthopedic equipment; 140.19 euros for home help; and 566.36 euros for housing adaptation or transfer to a hospital). The average annual income before diagnosis was 19962.62 euros. However, after being diagnosed with breast cancer, there is a significant income decrease of 15.91%, resulting in a reduced average annual income of 16785.98 euros. Additionally, a significant correlation was found between total expenditure and the level of dependency (p = 0.032) and functional status (p = 0.045). Conclusion: These findings indicate that breast cancer patients experience a considerable economic burden, which worsens as their functional status deteriorates. Therefore, we believe policies should be implemented to help control this economic deterioration resulting from a serious health condition.

Bipolar hybrid posterior instrumentation tecnique for the correction of Scheuermann's kyphosis.

Scheuermann´s kyphosis (SK) is the most common cause of painful and progressive structural hyperkyphosis in adolescents. Surgical treatment should be considered in cases of refractory pain or progressive deformities. We present the clinical and radiological results obtained using a bipolar, hybrid posterior instrumentation tecnique. We analysed 12 males and 6 females, with mean age of 15.8 years. Minimum follow-up was 2 years. We used transverse process hooks at the cranial level and polyaxial screws for the remaining levels. We did not instrument the periapical segment. We used the sagittal stable vertebra (SSV) as the lower instrumented vertebra (LIV) in most cases, the "barely touched SSV" if the above disc space is lordotic. The mean preoperative kyphosis was 73.6º, mean postoperative kyphosis 44.7º, and mean correction of 28.9º (p = 0.0002). The mean reduction in lumbar lordosis (LL) was 8.9º (p = 0.0018). There were no significant differences in the spinopelvic parameters or sagittal balance. The mean number of instrumented levels was 8.9. Type II osteotomies were necessary in only three patients. Three patients had a cranial sagittal angle greater than 10°, all of them asymptomatic. Postoperatively, all patients had VAS scores less than 2 and SRS-22 scores greater than 4. Hybrid bipolar posterior instrumentation offers adequate curve correction, less operative time, implant density, bleeding, material protrusion and risk of spinal cord injury, leaving a large periapical bed for graft supply. We propose to measure the flexibility of the curve in MRI. In flexible curves (those that correct at least 20% in the supine decubitus position), wide facetectomies offer adequate correction of the deformity.

Metagenomic Analysis of Rhizospheric Bacterial Community of Citrus Trees Expressing Phloem-Directed Antimicrobials.

Huanglongbing, also known as citrus greening, is currently the most devastating citrus disease with limited success in prevention and mitigation. A promising strategy for Huanglongbing control is the use of antimicrobials fused to a carrier protein (phloem protein of 16 kDa or PP16) that targets vascular tissues. This study investigated the effects of genetically modified citrus trees expressing Citrus sinensis PP16 (CsPP16) fused to human lysozyme and ß-defensin-2 on the soil microbiome diversity using 16S amplicon analysis. The results indicated that there were no significant alterations in alpha diversity, beta diversity, phylogenetic diversity, differential abundance, or functional prediction between the antimicrobial phloem-overexpressing plants and the control group, suggesting minimal impact on microbial community structure. However, microbiota diversity analysis revealed distinct bacterial assemblages between the rhizosphere soil and root environments. This study helps to understand the ecological implications of crops expressing phloem-targeted antimicrobials for vascular disease management, with minimal impact on soil microbiota.

Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization.

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.

Orbital trochleitis: Literature review.

Trochleitis is clinically and/or radiologically evidenced inflammation of the trochlea or orbital pulley. Clinically it is characterized by pain and hypersensitivity in the superomedial orbital angle, which is increased or triggered by direct palpation of the area and/or eye movements. During the REM (rapid eye movements) phase of sleep, patients with trochleitis suffer from nocturnal micro-awakenings that impede their rest, and pain is often associated with visual symptoms (diplopia or Brown's syndrome). The lack of common guidelines for diagnosis and treatment of this disease, its low prevalence and the lack of knowledge of the different entities associated with trochlear pain, leads to underdiagnosis or misdiagnosis. It is essential to know the characteristics of this pathology and to diagnose it correctly, differentiating it from other trochlear pain entities, in order to be able to carry out an adequate therapeutic and prognostic approach. The lack of consensus on the therapeutic protocol means that various treatments are used, in different order and often with a combination of several without a firm scientific basis. This comprehensive review of previous studies concludes that nonsteroidal anti-inflammatory drugs (NSAIDs) achieve an overall complete cure rate of 77%, although this rate decreases to 30% in case of motility restriction or diplopia. Intratrochlear corticosteroid injection achieves an overall complete cure rate of 86%, even in the worst prognosis trochleitis, being the only effective option in NSAID-refractory trochleitis and currently being questioned as the first treatment option.

The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19.

BACKGROUND: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. METHODS: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). FINDINGS: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. INTERPRETATION: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. FUNDING: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).