Persistent COVID-19: a case report of an immunocompromised patient and a literature review.

Introduction Immunocompromised patients can show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and persistent symptoms, which is called persistent COVID-19. Case presentation We report a case of an immunocompromised patient who was treated for mantle cell lymphoma and was suffering from B-cell depletion. The patient developed persistent COVID-19, which was confirmed by real-time polymerase chain reaction (RT-PCR) tests in only sputum and bronchoalveolar fluid which remained positive for at least 112 days. The patient was successfully treated with SARS-CoV-2 convalescent plasma. Conclusion It could be of interest to investigate the RT-PCR results of SARS-CoV-2 in sputum/bronchoalveolar lavage samples from immunocompromised patients with unexplained pneumonia.

Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo.

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

Salmonella Infection in Mesenteric Lymph Nodes of Breeding Sows.

Salmonellosis is one of the main foodborne diseases worldwide. Breeding sows asymptomatically infected with Salmonella can transmit the pathogen to piglets and humans. The isolation of Salmonella from mesenteric lymph nodes (MLNs) is considered a demonstration of asymptomatic infection in swine. As previous breeding sow studies have been performed using feces, the aim of this work was to study the occurrence of Salmonella infections by sampling MLNs, in comparison to their serological status. First, Salmonella fecal shedding was studied in 12/16 large breeding farms to establish the framework of study. Then, MLN (n = 264) and blood (n = 237) samples were obtained at an abattoir from sows of 15 of these 16 breeding farms. Additionally, risk factors associated with Salmonella MLN infection were analyzed. A total of 6.1% (16/264) sows, distributed in 40% (6/15) of the farms, had the pathogen in MLN. Salmonella Typhimurium was the most frequent serovar isolated. Interestingly, 43.8% (7/16) of MLN isolates were susceptible to all the antimicrobials tested and were found distributed throughout all farms with at least one sow positive. As well, one isolate of the emerging DT195 clone was detected and found to be resistant to six antibiotic families (ASSuTNx-Cfx). The serovars and the resistance profiles of the Salmonella isolates from feces were completely different to those obtained from MLNs. The seroprevalence (41.8% of sows and 100% of farms) was higher than that of MLN infections, showing no concordance (k = 0.15) between these two diagnostic tests in sows. Strategies directed to correct two risk factors (i.e., administration of dry food and old premises) would most likely help to reduce Salmonella infections in breeding sows.

Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aß) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activation is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer's disease) mice and found specifically expressed in microglia associated with Aß plaques. Single-nucleotide polymorphisms in the LGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar Aß. Gal3 deletion decreased the Aß burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aß monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aß aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was shown by a fluorescence anisotropy assay involving the gal3 carbohydrate recognition domain. Furthermore, gal3 was shown to stimulate TREM2-DAP12 signaling in a reporter cell line. Overall, our data support the view that gal3 inhibition may be a potential pharmacological approach to counteract AD.

Basic Abdominal Point-of-Care Ultrasound Training in the Undergraduate: Students as Mentors.

OBJECTIVES: To analyze the ability of medical students to be integrated in the teaching of basic abdominal ultrasound using a peer-mentoring design. METHODS: Thirty medical students previously trained in basic abdominal ultrasound (mentors) had to teach all fourth-year students (n = 136) from a single academic year the same training they had received. There were 3 stages to the ultrasound teaching: theoretical (online course); basic training (3 practical sessions in which students were guaranteed to have had a minimum of 15 hours of practical experience with ultrasound and performed at least 20 basic abdominal ultrasound studies); and evaluation (objective structured clinical examination in which students had to obtain the basic abdominal views and to identify 17 structures). RESULTS: The mean grade ± SD obtained was 8.71 ± 1.53 of a possible 10 points. Only 2 students (1.56%) obtained a grade lower than 5, and 14 students (10.86%) obtained a grade lower than 7. A total of 33 students (25.5%) achieved the maximum grade. The structures most easily identified were the liver, the right kidney, and the urinary bladder, with 97.7% of correct answers. Students obtained the poorest results when trying to identify the left and right cardiac cavities (subxiphoid view), with only 53.5% and 55.8% of correct answers, respectively. CONCLUSIONS: Teaching based on peer mentoring achieved an adequate level of training in basic abdominal ultrasound. The students acquired these skills in a relatively short training period. These results suggest that peer mentoring can facilitate the large-scale implementation of ultrasound teaching in undergraduate students.

In vivo monitoring of Staphylococcus aureus biofilm infections and antimicrobial therapy by [18F]fluoro-deoxyglucose-MicroPET in a mouse model.

A mouse model was developed for in vivo monitoring of infection and the effect of antimicrobial treatment against Staphylococcus aureus biofilms, using the [(18)F]fluoro-deoxyglucose-MicroPET ([(18)F]FDG-MicroPET) image technique. In the model, sealed Vialon catheters were briefly precolonized with S. aureus strains ATCC 15981 or V329, which differ in cytotoxic properties and biofilm matrix composition. After subcutaneous implantation of catheters in mice, the S. aureus strain differences found in bacterial counts and the inflammatory reaction triggered were detected by the regular bacteriological and histological procedures and also by [(18)F]FDG-MicroPET image signal intensity determinations in the infection area and regional lymph node. Moreover, [(18)F]FDG-MicroPET imaging allowed the monitoring of the rifampin treatment effect, identifying the periods of controlled infection and those of reactivated infection due to the appearance of bacteria naturally resistant to rifampin. Overall, the mouse model developed may be useful for noninvasive in vivo determinations in studies on S. aureus biofilm infections and assessment of new therapeutic approaches.

Simultaneous infections by different Salmonella strains in mesenteric lymph nodes of finishing pigs.

BACKGROUND: Salmonellosis is a major worldwide zoonosis, and Salmonella-infected finishing pigs are considered one of the major sources of human infections in developed countries. Baseline studies on salmonellosis prevalence in fattening pigs in Europe are based on direct pathogen isolation from mesenteric lymph nodes (MLN). This procedure is considered the most reliable for diagnosing salmonellosis in apparently healthy pigs. The presence of simultaneous infections by different Salmonella strains in the same animal has never been reported and could have important epidemiological implications. RESULTS: Fourteen finishing pigs belonging to 14 farms that showed high salmonellosis prevalence and a variety of circulating Salmonella strains, were found infected by Salmonella spp, and 7 of them were simultaneously infected with strains of 2 or 3 different serotypes. Typhimurium isolates showing resistance to several antimicrobials and carrying mobile integrons were the most frequently identified in the colonized MLN. Four animals were found infected by Salmonella spp. of a single serotype (Rissen or Derby) but showing 2 or 3 different antimicrobial resistance profiles, without evidence of mobile genetic element exchange in vivo. CONCLUSION: This is the first report clearly demonstrating that pigs naturally infected by Salmonella may harbour different Salmonella strains simultaneously. This may have implications in the interpretation of results from baseline studies, and also help to better understand human salmonellosis outbreaks and the horizontal transmission of antimicrobial resistance genes.

Role of wild bird and rodents in the epidemiology of subclinical salmonellosis in finishing pigs.

Wild birds and rodents may play an important role in the dynamics of subclinical pig salmonellosis, either as the introducers of the bacteria into the farm or as receptors of an infection already established in the farm. We tried to gain further insight into the epidemiology of this infection by studying the phenotypic (i.e., serotype and antimicrobial resistance patterns) and molecular characteristics of Salmonella strains isolated from samples collected from pigs and wildlife captured in the vicinity of pig farms. Salmonella-positive pig fecal samples were identified in 56.1% of the 41 farms investigated. Birds shedding Salmonella spp. were detected in 21.4% of the farms despite the low numbers of birds captured in many farms. Most Salmonella isolates from birds (74%) did not show any antimicrobial resistance (AR) pattern and belonged to phage types rarely seen in the pig population (U310, DT56, DT137, DT164), supporting the likely avian source of infection for most birds. The proportion of farms showing Salmonella-infected rodents was higher (46.2%), with Salmonella isolates showing a high homology with those likely originated from pigs. Salmonella-positive environmental samples were found in >50% of the farms, and the characteristics of these Salmonella strains supported the idea of pigs as a major source of Salmonella contamination of the farm environment. Dissemination of Salmonella in pig farms from areas of high Salmonella prevalence appeared to depend to some extent upon rodents and wild birds present in the farm, but the role of rodents in its maintenance seemed to be somewhat more relevant than that of birds. In conclusion, activities aimed at reducing the contact of these wild species with pigs will probably assist in the control of pig salmonellosis. Strict hygienic measures should be considered in areas of high prevalence of infection to lower the high load of environmental contamination.

[Geriatric failure to thrive: between illusory diagnosis and clinical reality]. / Syndrome de glissement : entre diagnostic illusoire et réalité clinique.

The geriatric failure to thrive, a controversial French concept not present in the international literature, was first characterized by Jean Carrié in 1956. It is described as a process of aging and physical and psychological decline associated with advanced age, manifesting as a pronounced overall deterioration. In this case report, we present the case of an 88-year-old patient, admitted to a general medicine service for geriatric failure to thrive, whose management eventually leads to the diagnosis of endocarditis with digestive cancer complicated by a characterized depressive episode. This case prompts us to consider the geriatric failure to thrive with extreme caution and challenges the legitimacy of such a diagnosis in the context of an aging population and the progress of medical sciences.

Rev1Δwzm vaccine candidate is safe in young and adult sheep and protects against Brucella ovis infection in rams.

Small ruminants affected by brucellosis, caused mainly by Brucella melitensis and B. ovis, suffer reproductive disorders, leading to significant economic losses worldwide. Vaccination is an essential tool to prevent the disease in ovine and caprine livestock, but the only vaccine recommended to date is B. melitensis Rev1, which in sheep is only safe for use in lambs aged 3-4 months. This restriction poses considerable practical challenges for the implementation of Rev1 in countries with endemic brucellosis and/or limited resources, where there is a need for mass vaccination with a safe vaccine to control the disease in both animals and humans. We recently developed a B. melitensis strain Rev1Δwzm showing superior vaccine properties in mice and safety in pregnant ewes. Here, we report that Rev1Δwzm (i) is safe in young and adult sheep, both male and female; (ii) induces a transient serological response in the Rose Bengal test in ≤50 % of sheep, confirmed to some extent by the complement fixation test, and a stronger, more persistent anti- rough-LPS response; and (iii) protects rams against a B. ovis challenge 25 weeks after vaccination. To resolve the problem of serological interference, the use of green fluorescent protein tagging strategy allowed us to identify vaccinated sheep with only a single inoculation. These results, together with the previously reported safety in pregnant ewes, position Rev1Δwzm as a firm vaccine candidate and a promising alternative to Rev1. Further experiments are warranted to assess its efficacy against B. melitensis in pregnant ewes.

Sleep disturbances in Alzheimer's disease are associated with neuropsychiatric symptoms and antidementia treatment.

Sleep disturbances (SDs) in Alzheimer's disease (AD) may significantly affect the behavioral, functional, and cognitive capacities of patients to the point of becoming a major determinant of caregiver burden. We conducted a cross-sectional study in 125 patients with probable AD to assess the association of SDs with neuropsychiatric symptoms, cognitive and functional status of patients, and severity and duration of dementia and to ascertain the role of antidementia drugs in the treatment of SD. SDs were assessed using the questionnaire on sleep disorders in the Neuropsychiatric Inventory. The prevalence of SDs in this sample was 36%. SDs in patients with AD are significantly associated with depression (Wald's test, 3.983; p < 0.05), disinhibition (Wald's test, 5.522; p < 0.05), and aberrant motor behavior (Wald's test, 7.430; p < 0.01). The patients treated with memantine presented lower mean SDs scores (t = 2.76; p < 0.001). These results highlight the need for a standardized and validated approach to the assessment of SDs in AD.

The experience of caregiving: the influence of coping strategies on behavioral and psychological symptoms in patients with Alzheimer's disease.

OBJECTIVES: To determine whether caregiver coping strategies are independently associated with behavioral and psychological symptoms (BPS) in Alzheimer's disease (AD) after accounting for patient characteristics. METHODS: Cross-sectional data analysis of 80 patients with AD and their primary caregivers. The presence of BPS was recorded using the Neuropsychiatric Inventory (NPI). The relationship between caregiver characteristics and BPS was assessed through one-way analysis of variance, two-tailed student t-tests or correlation coefficients. Multivariate linear regression was used to determine the combined effect of all caregiver factors that were significant on bivariate analysis regarding coping and BPS controlling for patient characteristics. RESULTS: Caregivers were on average 62 years old, 77% female, and most were the children or the spouse of the patient. Over 50% had significant depression or anxiety. Patients were on average 77 years old and 62% were female, and most had moderate to severe dementia. After adjusting for patient characteristics, patients cared for by more depressed, more burdened, or those using more disengagement coping strategies showed higher NPI mean composite scores. CONCLUSION: Coping strategies are associated with BPS regardeless of patient characteristics. Interventions to reduce BPS should focus on which psychological coping strategies caregivers use. Understanding how coping strategies influence BPS may help tailor specific interventions for caregivers.

High-Flow Nasal Cannula Therapy as an Adjuvant Therapy for Respiratory Support during Endoscopic Techniques: A Narrative Review.

High-flow nasal cannula (HFNC) is a respiratory support technique that delivers a controlled concentration of oxygen with high flow, heat, and humidity via the nasal pathway. As it has many physiological effects, its use has increased for a variety of clinical indications; however, there is limited guidance on using HFNC as a respiratory support tool during endoscopic procedures. We conducted a narrative review to evaluate the effect of HFNC as an adjuvant tool during fiberoptic bronchoscopy (FOB), upper gastrointestinal tract endoscopy, and surgical procedures in adults. A search of the PubMed and Cochrane databases were performed. Approximately 384 publications were retrieved, and 99 were selected (93 original works and 6 case reports with a literature review). In patients who underwent FOB, HFNC appears to be superior to conventional oxygen therapy (COT) in preventing hypoxaemia. In contrast, for gastrointestinal endoscopy, the current evidence is insufficient to recommend HFNC over COT in a cost-effective manner. Finally, in surgical procedures such as laryngeal microsurgery or thoracic surgery, HFNC has been shown to be a safe and effective alternative to orotracheal intubation. As the results are heterogeneous, we advocate for the need for more quality studies to understand the effectiveness of HFNC during endoscopic procedures.

Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms.

Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality when associated with Pseudomonas aeruginosa biofilms. After validating the biosafety of an attenuated M. pneumoniae chassis in mice, we introduced four transgenes into the chromosome by transposition to implement bactericidal and biofilm degradation activities. We show that this engineered strain has high efficacy against an acute P. aeruginosa lung infection in a mouse model. In addition, we demonstrated that the engineered strain could dissolve biofilms formed in endotracheal tubes of patients with ventilator-associated pneumonia and be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against Gram-positive and Gram-negative bacteria. We expect our M. pneumoniae-engineered strain to be able to treat biofilm-associated infections in the respiratory tract.

Diagnosis and Treatment of Pleural Effusion. Recommendations of the Spanish Society of Pulmonology and Thoracic Surgery. Update 2022.

Pleural effusion (PE) is a common yet complex disease that requires specialized, multidisciplinary management. Recent advances, novel diagnostic techniques, and innovative patient-centered therapeutic proposals have prompted an update of the current guidelines. This document provides recommendations and protocols based on a critical review of the literature on the epidemiology, etiology, diagnosis, prognosis, and new therapeutic options in PE, and addresses some cost-effectiveness issues related to the main types of PE.

Tocilizumab versus anakinra in COVID-19: results from propensity score matching.

Background: Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra. Methods: Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation. Results: Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44). Conclusion: Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.

The extradomain a of fibronectin enhances the efficacy of lipopolysaccharide defective Salmonella bacterins as vaccines in mice.

The Extradomain A from fibronectin (EDA) has an immunomodulatory role as fusion protein with viral and tumor antigens, but its effect when administered with bacteria has not been assessed. Here, we investigated the adjuvant effect of EDA in mice immunizations against Salmonella enterica subspecies enterica serovar Enteritidis (Salmonella Enteritidis). Since lipopolysaccharide (LPS) is a major virulence factor and the LPS O-polysaccharide (O-PS) is the immunodominant antigen in serological diagnostic tests, Salmonella mutants lacking O-PS (rough mutants) represent an interesting approach for developing new vaccines and diagnostic tests to differentiate infected and vaccinated animals (DIVA tests). Here, antigenic preparations (hot-saline extracts and formalin-inactivated bacterins) from two Salmonella Enteritidis rough mutants, carrying either intact (SEΔwaaL) or deep-defective (SEΔgal) LPS-Core, were used in combination with EDA. Biotinylated bacterins, in particular SEΔwaaL bacterin, decorated with EDAvidin (EDA and streptavidin fusion protein) improved the protection conferred by hot-saline or bacterins alone and prevented significantly the virulent infection at least to the levels of live attenuated rough mutants. These findings demonstrate the adjuvant effect of EDAvidin when administered with biotinylated bacterins from Salmonella Enteritidis lacking O-PS and the usefulness of BEDA-SEΔwaaL as non-live vaccine in the mouse model.

Anxiety and depression are associated with coping strategies in caregivers of Alzheimer's disease patients: results from the MÁLAGA-AD study.

BACKGROUND: Caregiving for people with Alzheimer's disease (AD) is highly stressful and has significant negative consequences, such as anxiety and depression. Previous research offers conflicting findings as to whether coping strategies are associated with greater psychological distress or not. We conducted this study with a view to obtaining new data regarding the association of coping strategies and psychological distress in AD caregivers. METHODS: Eighty people with AD and their primary caregivers living in the community were recruited from local health services. Purposive recruitment was carried out to ensure that the sample was representative of people living with dementia in terms of dementia severity, gender, and care setting. We used the State-Trait Anxiety Inventory to measure anxiety, the Beck Depression Inventory to measure depression, and the Coping Strategies Inventory to measure coping strategies. RESULTS: Most caregivers reported higher anxiety and depression levels. Use of disengagement coping strategies (Wald = 3.35, p = 0.01) and higher caregiver burden (Wald = 4.83, p = 0.02) predicted anxiety on logistic regression. In turn, use of disengagement coping strategies (Wald = 12.48, p = 0.001) and higher caregiver burden (Wald = 6.91, p = 0.009) predicted depression on logistic regression. CONCLUSION: These results may be useful for designing treatment interventions that aim to modify the use of coping strategies and thus reduces caregiver anxiety and depression.