-
Frontiers in Immunology 2024Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and...
Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus.
Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.
Topics: Chlorocebus aethiops; Animals; Cats; Humans; Influenza Vaccines; Cowpox virus; Vero Cells; Coinfection; Superinfection; Vaccinia virus; Vaccines, Synthetic; Whole Genome Sequencing
PubMed: 38633245
DOI: 10.3389/fimmu.2024.1277447 -
The Journal of Veterinary Medical... Jun 2024The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral...
The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral copy numbers less or greater than the number of bovine nucleated cells. EBL cattle with BLV copy numbers less than the number of bovine nucleated cells showed monoclonal and biclonal proliferation of B-cells with one BLV provirus integration site. On the other hand, EBL cattle with BLV copy numbers greater than the number of bovine nucleated cells showed monoclonal proliferation of B-cells with two BLV provirus integration sites. These results suggest that superinfection of BLV can occur in EBL cattle.
Topics: Animals; Leukemia Virus, Bovine; Enzootic Bovine Leukosis; Cattle; Proviruses; DNA, Viral; B-Lymphocytes; Virus Integration; Cell Proliferation
PubMed: 38631888
DOI: 10.1292/jvms.24-0037 -
Experimental and Therapeutic Medicine May 2024The connection between vasculitis and infection is complex. The present study described a typical situation for a patient with unbalanced type 2 diabetes and chronic...
The connection between vasculitis and infection is complex. The present study described a typical situation for a patient with unbalanced type 2 diabetes and chronic complications, in which a lack of adherence to the protection and care measures ultimately led to the appearance of some of the worst consequences of the condition, namely, ulceration, gangrene and amputation. In the context of an unstable condition with significant metabolic imbalance there was an impaired response to infections in the present patient, and the amputation resulted in wound persistence and ulcer development, followed by superinfection with methicillin-resistant according to the antibiogram performed. In this case, an episode of vasculitis was triggered without evidence of bacteraemia. The present case report highlighted the importance of proper hygiene and good metabolic control in patients with diabetes that suffer from amputations and conditions that expose them to certain complications, including vasculitis.
PubMed: 38628659
DOI: 10.3892/etm.2024.12522 -
PloS One 2024Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many...
Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa-a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years-a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies.
Topics: Humans; Clinical Trials as Topic; Anti-Bacterial Agents; Anti-Infective Agents; Pseudomonas Infections; Intensive Care Units
PubMed: 38626111
DOI: 10.1371/journal.pone.0301944 -
VideoGIE : An Official Video Journal of... Apr 2024Superinfected intragastric balloon removal.
Superinfected intragastric balloon removal.
PubMed: 38618621
DOI: 10.1016/j.vgie.2023.12.010 -
Journal of Clinical Medicine Mar 2024To investigate whether copeptin, MR-proADM and MR-proANP, alone or integrated with the SOFA, MuLBSTA and SAPS II scores, are capable of early recognition of COVID-19...
Effectiveness of Copeptin, MR-proADM and MR-proANP in Predicting Adverse Outcomes, Alone and in Combination with Traditional Severity Scores, a Secondary Analysis in COVID-19 Patients Requiring Intensive Care Admission.
To investigate whether copeptin, MR-proADM and MR-proANP, alone or integrated with the SOFA, MuLBSTA and SAPS II scores, are capable of early recognition of COVID-19 ICU patients at increased risk of adverse outcomes. For this predefined secondary analysis of a larger cohort previously described, all consecutive COVID-19 adult patients admitted between March and December 2020 to the ICU of a referral, university hospital in Northern Italy were screened, and clinical severity scores were calculated upon admission. A blood sample for copeptin, MR-proADM and MR-proANP was collected within 48 h (T1), on day 3 (T3) and 7 (T7). Outcomes considered were ICU and in-hospital mortality, bacterial superinfection, recourse to renal replacement therapy (RRT) or veno-venous extracorporeal membrane oxygenation, need for invasive mechanical ventilation (IMV) and pronation. Sixty-eight patients were enrolled, and in-hospital mortality was 69.1%. ICU mortality was predicted by MR-proANP measured at T1 (HR 1.005, 95% CI 1.001-1.010, = 0.049), although significance was lost if the analysis was adjusted for procalcitonin and steroid treatment ( = 0.056). Non-survivors showed higher MR-proADM levels than survivors at all time points, and an increase in the ratio between values at baseline and at T7 > 4.9% resulted in a more than four-fold greater risk of in-hospital mortality (HR 4.417, < 0.001). Finally, when considering patients with any reduction in glomerular filtration, an early copeptin level > 23.4 pmol/L correlated with a more than five-fold higher risk of requiring RRT during hospitalization (HR 5.305, = 0.044). Timely evaluation of MR-proADM, MR-proANP and copeptin, as well as changes in the former over time, might predict mortality and other adverse outcomes in ICU patients suffering from severe COVID-19.
PubMed: 38610784
DOI: 10.3390/jcm13072019 -
Case Reports in Surgery 2024Cold atmospheric plasma (CAP) has shown promising potential in promoting wound healing. This case report presents the successful application of CAP in a 42-year-old...
Cold atmospheric plasma (CAP) has shown promising potential in promoting wound healing. This case report presents the successful application of CAP in a 42-year-old female patient with extensive wound healing disorders and superinfections following the excision of an abscess in the left thoracic region. After several failed split skin graft attempts, the implementation of CAP led to significant improvements in wound healing. This report highlights the wound healing-promoting effects of CAP and discusses its potential mechanisms of action.
PubMed: 38601320
DOI: 10.1155/2024/1013445 -
La Clinica Terapeutica 2024The Influenza A H1N1 subtype can present with a wide spectrum of severity, from mild symptoms of influenza to severe respiratory distress. The morbidity and mortality...
The Influenza A H1N1 subtype can present with a wide spectrum of severity, from mild symptoms of influenza to severe respiratory distress. The morbidity and mortality connected to influenza are mostly associated with secondary bacterial infections. The influenza syndrome alone can cause a massive release of cytokines with dysregulation of the immune system, and it can act in synergy with other bacteria which can enhance cytokines secretion. This article deals with a case of severe pneumonia of H1N1 in a 17-year-old woman with bacterial superinfection with Staphylococcus aureus characterized by a high level of interleukine-6 (105900 pg/mL) and the appearance of severe leukopenia with immuno-suppression, such that HIV infection and hematological diseases were included in the initial differential diagnosis. After death, the autopsy confirmed the presence of severe pneumonia, in addition to an hepatic steatosis in absence of other risk factors. This case reports the rapid and lethal course of influenza A /H1N1 in a young and healthy subject without comorbidities, in an age group in which mortality is about 0.3 deaths per 100,000. The case underlines the importance of quickly diagnosis of viral infections and the differential diagnoses with other immunosuppressive diseases, which can be fatal even in adolescent and healthy subjects.
Topics: Female; Adolescent; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; HIV Infections; Sepsis; Autopsy; Pneumonia; Cytokines
PubMed: 38571465
DOI: 10.7417/CT.2024.5039 -
Critical Care Explorations Apr 2024We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and... (Review)
Review
OBJECTIVES
We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness.
DATA SOURCES
We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials.
STUDY SELECTION
We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP.
DATA EXTRACTION
We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia, superinfections/secondary infections, neuropsychiatric effects, and neuromuscular weakness.
DATA SYNTHESIS
We included 47 RCTs ( = 13,893 patients). Corticosteroids probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95% CI, 0.87-1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or secondary infections (RR, 0.97; 95% CI, 0.89-1.05; absolute risk reduction, 0.5%; moderate certainty) and may have no effect on neuromuscular weakness (RR, 1.22; 95% CI, 1.03-1.45; ARI, 1.4%; low certainty) or neuropsychiatric events (RR, 1.19; 95% CI, 0.82-1.74; ARI, 0.5%; low certainty). Conversely, they increase the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11-1.31; ARI, 5.4%; high certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI, 1.29-1.96; ARI, 2.3%; moderate certainty).
CONCLUSIONS
In ARDS, sepsis, and CAP, corticosteroids are associated with hyperglycemia and probably with hypernatremia but likely have no effect on gastrointestinal bleeding or secondary infections. More data examining effects of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular weakness, would clarify the safety of this class of drugs in critical illness.
PubMed: 38567382
DOI: 10.1097/CCE.0000000000001071 -
Cureus Feb 2024The coronavirus disease 2019 (COVID-19) pandemic favors cognitive biases such as anchoring and availability biases. The first refers to overvaluing some of the initial...
The coronavirus disease 2019 (COVID-19) pandemic favors cognitive biases such as anchoring and availability biases. The first refers to overvaluing some of the initial information and establishing a diagnosis too early, with resistance to future adjustments. The latter happens when diagnoses more frequently considered are regarded as more common in reality. This case, in which the correct diagnosis was delayed due to these biases, highlights the need to remain aware of them as a means toward timely diagnosis and therapeutic success of pneumonia cases. An 84-year-old woman presented with a mild non-productive cough for two months and fever. She had a history of breast carcinoma treated with radiotherapy in the previous year. Computerized tomography (CT) showed extensive bilateral consolidation foci with ground-glass-opacification areas and bilateral pleural effusion, CO-RADS 3. COVID-19 with bacterial superinfection was suspected and levofloxacin was initiated. Nasopharyngeal swab polymerase chain reaction (PCR) was carried out three times, always negative for SARS-CoV-2. As the patient remained with fever and cough, the antibiotic was escalated to piperacillin/tazobactam and then to meropenem/vancomycin. She underwent bronchofibroscopy and alveolar lavage, with negative SARS-CoV-2 PCR. The re-evaluation CT scan maintained bilateral consolidations, with an aerial bronchogram. The biopsy of pulmonary consolidation allowed the diagnosis of radiation-induced organizing pneumonia. Prednisolone was initiated and achieved clinical remission and radiological improvement. This case highlights the need to remain aware of cognitive biases both when COVID-19 is suspected or ruled out and to consider other diagnoses when there is a lack of therapeutic response.
PubMed: 38558668
DOI: 10.7759/cureus.55144