Effect of manual hyperinflation on recurrent atelectasis in a ventilator-dependent C3 complete spinal cord injury patient: A case report.

CLINICAL CASE: We present here the case of a ventilator-dependent 76-year-old man with C3 complete spinal cord injury (SCI) who presented with recurrent left lung atelectasis managed with manual hyperinflation (MH). Atelectasis was primarily assessed with chest X-ray (CXR). Additional monitoring included blood gas analysis, serum procalcitonin, and the Modified Borg Dyspnea Scale (MBS), as an objective measure of reported dyspnea. We found that MH successfully reversed the radiographic appearance of atelectasis after the first treatment and maintained this effect for the duration of the 2-week intervention period as well as at 2 weeks of follow-up post-intervention. Furthermore, MH decreased the patient's oxygen requirements and was associated with a decrease in serum procalcitonin. Clinically, the patient reported reduced subjective dyspnea post-MH, which was reflected as an improvement on the MBS. We conclude that MH may represent a therapeutic modality for consideration in the routine management of recurrent atelectasis in mechanically ventilated patients.

Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as "reactive astrogliosis." Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions.

BCG immunomodulation: From the 'hygiene hypothesis' to COVID-19.

The century-old tuberculosis vaccine BCG has been the focus of renewed interest due to its well-documented ability to protect against various non-TB pathogens. Much of these broad spectrum protective effects are attributed to trained immunity, the epigenetic and metabolic reprogramming of innate immune cells. As BCG vaccine is safe, cheap, widely available, amendable to use as a recombinant vector, and immunogenic, it has immense potential for use as an immunotherapeutic agent for various conditions including autoimmune, allergic, neurodegenerative, and neoplastic diseases as well as a preventive measure against infectious agents. Of particular interest is the use of BCG vaccination to counteract the increasing prevalence of autoimmune and allergic conditions in industrialized countries attributable to reduced infectious burden as described by the 'hygiene hypothesis.' Furthermore, BCG vaccination has been proposed as a potential therapy to mitigate spread and disease burden of COVID-19 as a bridge to development of a specific vaccine and recombinant BCG expression vectors may prove useful for the introduction of SARS-CoV-2 antigens (rBCG-SARS-CoV-2) to induce long-term immunity. Understanding the immunomodulatory effects of BCG vaccine in these disease contexts is therefore critical. To that end, we review here BCG-induced immunomodulation focusing specifically on BCG-induced trained immunity and how it relates to the 'hygiene hypothesis' and COVID-19.

Neuroprotective effects of a ketogenic diet in combination with exogenous ketone salts following acute spinal cord injury.

We have previously shown that induction of ketosis by ketogenic diet (KD) conveyed neuroprotection following spinal cord injury in rodent models, however, clinical translation may be limited by the slow raise of ketone levels when applying KD in the acute post-injury period. Thus we investigated the use of exogenous ketone supplementation (ketone sodium, KS) combined with ketogenic diet as a means rapidly inducing a metabolic state of ketosis following spinal cord injury in adult rats. In uninjured rats, ketone levels increased more rapidly than those in rats with KD alone and peaked at higher levels than we previously demonstrated for the KD in models of spinal cord injury. However, ketone levels in KD + KS treated rats with SCI did not exceed the previously observed levels in rats treated with KD alone. We still demonstrated neuroprotective effects of KD + KS treatment that extend our previous neuroprotective observations with KD only. The results showed increased neuronal and axonal sparing in the dorsal corticospinal tract. Also, better performance of forelimb motor abilities were observed on the Montoya staircase (for testing food pellets reaching) at 4 and 6 weeks post-injury and rearing in a cylinder (for testing forelimb usage) at 6 and 8 weeks post-injury. Taken together, the findings of this study add to the growing body of work demonstrating the potential benefits of inducing ketosis following neurotrauma. Ketone salt combined with a ketogenic diet gavage in rats with acute spinal cord injury can rapidly increase ketone body levels in the blood and promote motor function recovery. This study was approved by the Animal Care Committee of the University of British Columbia (protocol No. A14-350) on August 31, 2015.

Neuroprotection and secondary damage following spinal cord injury: concepts and methods.

Neuroprotection refers to the attenuation of pathophysiological processes triggered by acute injury to minimize secondary damage. The development of neuroprotective treatments represents a major goal in the field of spinal cord injury (SCI) research. In this review, we discuss the strengths and limitations of the methodologies employed to assess secondary damage and neuroprotection in preclinical models of traumatic SCI. We also discuss modelling issues and how new tools might be exploited to study secondary damage and neuroprotection.