The role of bacterial translocation in sepsis: a new target for therapy.

Sepsis is a leading cause of death in critically ill patients, primarily due to multiple organ failures. It is associated with a systemic inflammatory response that plays a role in the pathogenesis of the disease. Intestinal barrier dysfunction and bacterial translocation (BT) play pivotal roles in the pathogenesis of sepsis and associated organ failure. In this review, we describe recent advances in understanding the mechanisms by which the gut microbiome and BT contribute to the pathogenesis of sepsis. We also discuss several potential treatment modalities that target the microbiome as therapeutic tools for patients with sepsis.

A Case Report of Mycoplasma hominis Subdural Empyema Following Decompressive Craniotomy, and a Review of Central Nervous System Mycoplasma hominis Infections.

Background: Mycoplasma hominis is a small cell-wall-free organism, part of the normal microbiota of the genitourinary tract. It is rarely involved in extragenital infections, mainly joint, surgical-site, and respiratory infections. Methods: We describe a case of M. hominis subdural empyema and lower limb surgical site infections, following decompressive craniotomy, after traumatic brain and extremities injury. In addition, a literature review of 34 cases M. hominis CNS infections was done. Results: Our case depicts a 25-years old patient who developed subdural empyema and surgical site infections in his cranium and fibula. Both sites were cultured, and small pinpoint colonies grew on blood agar. MALDI-TOF MS identified M. hominis. Simultaneously 16S-rDNA PCR from CSF detected M. hominis. Antimicrobial treatment was switched to doxycycline with improvement. Literature review revealed 21 adults and 13 pediatric cases of M. hominis CNS infection. Risk factors in adults were head trauma, neurosurgery, or post-partum period. Conclusions: Based upon the literature reviewed, we postulate that adult patients with head trauma or neurosurgical procedure, rarely are infected either through direct contamination during the trauma, or by undergoing urgent, urinary catheterization, and may experience distant infection due to translocation of M. hominis into the bloodstream. In such cases diagnosis is delayed due to difficulties in growing and identifying the bacteria. Empiric antimicrobials are usually not effective against mycoplasmas. These factors contributed to the mortality in adult cases (15%). Our rare case highlights the necessity of combining classical microbiology routines with advanced molecular techniques to establish a diagnosis in complicated cases.

Native aortic valve Staphylococcus warneri endocarditis after COVID-19 infection: a case report and a review of literature.

We report a case of Staphylococcus warneri native valve endocarditis in an immunocompetent healthy adult, without known risk factors for infective endocarditis, two months following COVID-19 infection, who recovered with conservative treatment. Additionally, we reviewed previous cases of native valve endocarditis caused by Staphylococcus warneri and summarized the main clinical implications.

Augmented antiviral T cell immunity by oral administration of IMM-124E in preclinical models and a phase I/IIa clinical trial: A method for the prevention and treatment of COVID-19.

Biological adjuvants that target the gut immune system are being developed for modulating the immune system. Hyperimmune bovine colostrum (HBC), produced by harvesting the bovine colostrum of dairy cows immunized to exogenous antigens, has been shown to modulate the immune responses and alleviate immune-mediated organ damages. The aim of the present study was to determine the ability of HBC to promote antiviral interferonγ (IFNγ) T cell responses. In a preclinical study, mice were orally administered with HBC for 5 days and tested for the number of T cell clones secreting IFNγ in response to viral antigens of the swine flu, New Caledonia influenza, and cytomegalovirus. In a phase I/IIa clinical trial, five healthy volunteers were treated for 5 days with HBC followed by testing the anti-coronavirus disease (COVID-19) immunity. In the preclinical study, oral administration of HBC augmented the number of T cell clones secreting IFNγ in response to viral antigens. In the clinical trial, oral administration of HBC to healthy males significantly increased the number of anti-COVID-19 spike protein IFNγ positive T cell clones. Oral administration of HBC provides a novel method for augmenting antiviral responses. Its high-safety profile makes it ideal for all disease stages and for pre-emptive therapy among medical personnel and other workers who are at a high risk of exposure to infections. The relatively low cost of HBC is expected to minimize care provider burdens, costs, and enable its global application.

A digital health platform for assisting the diagnosis and monitoring of COVID-19 progression: An adjuvant approach for augmenting the antiviral response and mitigating the immune-mediated target organ damage.

Coronavirus disease 2019 (COVID-19), which is a respiratory illness associated with high mortality, has been classified as a pandemic. The major obstacles for the clinicians to contain the disease are limited information availability, difficulty in disease diagnosis, predicting disease prognosis, and lack of disease monitoring tools. Additionally, the lack of valid therapies has further contributed to the difficulties in containing the pandemic. Recent studies have reported that the dysregulation of the immune system leads to an ineffective antiviral response and promotes pathological immune response, which manifests as ARDS, myocarditis, and hepatitis. In this study, a novel platform has been described for disseminating information to physicians for the diagnosis and monitoring of patients with COVID-19. An adjuvant approach using compounds that can potentiate antiviral immune response and mitigate COVID-19-induced immune-mediated target organ damage has been presented. A prolonged beneficial effect is achieved by implementing algorithm-based individualized variability measures in the treatment regimen.

The role of chronobiology in drug-resistance epilepsy: The potential use of a variability and chronotherapy-based individualized platform for improving the response to anti-seizure drugs.

Despite progress in the development of anti-seizure drugs, drug-resistant epilepsy (DRE) occurs in a third of patients. DRE is associated with poor quality of life and increased risk of sudden, unexplained death. The autonomic nervous system and chronobiology play a role in DRE. In the present paper, we provide a narrative review the mechanisms that underlie DRE and characterize some of the autonomic- and chronotherapy-associated parameters that contribute to the degree of response to therapy. Variability describes the functions of many biological systems, which are dynamic and continuously change over time. These systems are required for responses to continuing internal and external triggers, in order to maintain homeostasis and normal function. Both intra- and inter-subject variability in biological systems have been described. We present a platform, which comprises a personalized-based machine learning closed loop algorithm built on epilepsy-related signatures, autonomic signals, and chronotherapy, as a means for overcoming DRE, improving the response, and reducing the toxicity of current therapies.