Postcooling But Not Precooling Benefits Motor Recovery by Suppressing Cell Death After Surgical Spinal Cord Injury in Rats.

BACKGROUND: Surgical spinal cord injury (SSCI) is often inevitable in patients with intramedullary lesions. Although regional hypothermia (RH) has been demonstrated neuroprotective, the value of priming RH in SSCI has never been studied. Herein, the authors investigated the impact of pre- and post-RH on neurologic recovery in a clinically relevant model. METHODS: An SSCI model was established at T10. RH was conducted by focal 4oC saline perfusion; room temperature (RT) saline was used as controls. Animals were randomized into 6 groups: SHAM-RT/RH, Pre-RT/RH, and Post-RT/RH. Motor and sensory functions were evaluated using the Basso, Beattie, and Bresnahan rating scale and Plantar test 2 weeks after surgery. TUNEL assay and Fluoro-Jade C staining were conducted to examine the cell death, and the alterations of apoptotic markers including total and cleaved casepase 3, Bcl-2, and Bax, as well as the pyroptotic proteins including NLRP3, ASC, and caspase 1, were determined. RESULTS: RH perfusion successfully created an intramedullary hypothermia approximately at 24oC, while RT controls remained above 30oC. Animals receiving postinjury RH had the least cell death and the best motor performance, while pre-RH showed the most dead cells and worst hind limb movements. Immunoblotting depicted that post-RH suppressed both apoptotic and pyroptotic death as the cleaved/total caspase 3, Bcl-2/Bax ratio, and NLRP3/ASC/caspase 1 signaling were inhibited. Priming cooling, on the contrary, elevated pyroptosis and did not affect apoptosis significantly. CONCLUSIONS: Priming RH before surgical incision could not be supported as it caused excessive cell death. In contrast, instant introduction of RH is beneficial in rescuing neurologic function.

Ophthalmological Considerations for COVID-19 Vaccination in Patients with Inflammatory Eye Diseases and Autoimmune Disorders.

The global impact imposed by the coronavirus disease 2019 (COVID-19) pandemic may be soon alleviated by the introduction and worldwide dissemination of safe and effective vaccines. This expedited timetable for development and approval of COVID-19 vaccines is an unprecedented extraordinary, concerted achievement by the scientific community. With the pending global rollout of vaccines, each with different mechanisms of action, physicians of various specialties will need to identify vulnerable patient groups for special considerations or advice. In this commentary, we analyse the important considerations for COVID-19 vaccines in patients with inflammatory eye diseases. Scrutiny of immunogenicity and adverse effects, particularly antibody-dependent enhancement, would better help in counselling these patients undergoing vaccination. More research on pharmacovigilance would allow for tailored guidelines and personalised management strategies.

Considerations for Use of Immune Checkpoint Inhibitors in Cancer Therapy for Patients with Co-Existing Thyroid Eye Disease.

Immune checkpoint inhibitors (ICIs) have revolutionised the field of oncology. While most ICIs are well-tolerated, severe and fatal immune-related adverse events (irAEs) have been documented, likely related to the strengthened immunity harnessed by ICIs against tumours. Endocrinopathies are some of the most common irAEs, with both hypothyroidism and hyperthyroidism encountered after ICI use. As such, patients with pre-existing autoimmune conditions, such as Graves' disease (GD) with clinically active thyroid eye disease (TED), are excluded from most clinical trials studying ICIs due to concerns of exacerbating pre-existing autoimmune conditions or of increasing the potential for irAE development. The limited information currently available on the safety and efficacy of ICIs in this population poses a clinical challenge for oncologists. The objective of this commentary is to highlight these challenges and provide treatment recommendations pertaining to two specific cohorts of patients with GD, namely GD patients with minimal eye complications and GD patients with previous TED who underwent radiotherapy, surgery or pulse methylprednisolone and whose disease is now quiescent, and to patients with subclinical autoimmune thyroid disease.

Does the COVID-19 Pandemic Spell the End for the Direct Ophthalmoscope?

Despite advances in ophthalmic diagnostics, the direct ophthalmoscope remains a key clinical skill taught to medical students and is the tool of choice for retina examination among non-ophthalmic physicians. However, in recent years viable alternatives have become available. The coronavirus disease 2019 (COVID-19) pandemic has forced a major re-thinking in medical education worldwide. In this commentary, we examined the current merits and limitations of the direct ophthalmoscope in both the clinical sense and in the context of infection control. Furthermore, we compared the direct ophthalmoscope with alternatives, including commercially available portable non-mydriatic fundus cameras, that would allow a change in focus during ophthalmic teaching. We concluded that the latter will better prepare our medical students for the age of telemedicine and deep-learning systems. While the COVID-19 pandemic will not be the sole reason for the 'death' of the direct ophthalmoscope, the global situation will inevitably serve to expedite long overdue changes in our teaching of ophthalmic skills to non-ophthalmic physicians.

Optimal Timing of External Ventricular Drainage after Severe Traumatic Brain Injury: A Systematic Review.

External ventricular drainage (EVD) may be used for therapeutic cerebrospinal fluid (CSF) drainage to control intracranial pressure (ICP) after traumatic brain injury (TBI). However, there is currently uncertainty regarding the optimal timing for EVD insertion. This study aims to compare patient outcomes for patients with early and late EVD insertion. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, MEDLINE/EMBASE/Scopus/Web of Science/Cochrane Central Register of Controlled Trials were searched for published literature involving at least 10 severe TBI (sTBI) patients from their inception date to December 2019. Outcomes assessed were mortality, functional outcome, ICP control, length of stay, therapy intensity level, and complications. Twenty-one studies comprising 4542 sTBI patients with an EVD were included; 19 of the studies included patients with an early EVD, and two studies had late EVD placements. The limited number of studies, small sample sizes, imbalance in baseline characteristics between the groups and poor methodological quality have limited the scope of our analysis. We present the descriptive statistics highlighting the current conflicting data and the overall lack of reliable research into the optimal timing of EVD. There is a clear need for high quality comparisons of early vs. late EVD insertion on patient outcomes in sTBI.

The Evolution of the Role of External Ventricular Drainage in Traumatic Brain Injury.

External ventricular drains (EVDs) are commonly used in neurosurgery in different conditions but frequently in the management of traumatic brain injury (TBI) to monitor and/or control intracranial pressure (ICP) by diverting cerebrospinal fluid (CSF). Their clinical effectiveness, when used as a therapeutic ICP-lowering procedure in contemporary practice, remains unclear. No consensus has been reached regarding the drainage strategy and optimal timing of insertion. We review the literature on EVDs in the setting of TBI, discussing its clinical indications, surgical technique, complications, clinical outcomes, and economic considerations.