Ex vivo host transcriptomics during Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans infection of PBMCs from South African volunteers.

Cryptococcus neoformans, Cryptococcus gattii and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of HIV-related deaths globally, with the majority occurring in Africa. The human immune response to C. albicans infection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied. Here we investigated the transcriptional response of immune cells after in vitro stimulation with in vitro C. neoformans, C. gattii and C. albicans infection of peripheral blood mononuclear cells (PBMCs) collected from healthy South African volunteers. We found a lower transcriptional response to cryptococcal stimuli compared to C. albicans and unique expression signatures from all three fungal stimuli. This work provides a starting point for further studies comparing the transcriptional signature of CM in immunocompromised patients, with the goal of identifying biomarkers of disease severity and possible novel treatment targets.

Tracking Cryptococcal Meningitis to Monitor HIV Program Success During the Treat All Era: An Analysis of National Data in Botswana.

BACKGROUND: Cryptococcal meningitis (CM) causes substantial mortality in African countries with a high prevalence of human immunodeficiency virus (HIV), despite advances in disease management and increasing antiretroviral therapy (ART) coverage. Reliable diagnosis of CM is cheap and more accessible than other indicators of advanced HIV disease burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring CM incidence has the potential to serve as a valuable metric of HIV programmatic success. METHODS: Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analyzed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. CM case frequency was enumerated using a case definition and incidence calculated using national census data. RESULTS: A total of 1744 episodes of CM were identified; incidence declined from 15.0 (95% confidence interval [CI], 13.4-16.7) cases/100 000 person-years in 2015 to 7.4 (95% CI, 6.4-8.6) cases/100 000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44 years. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. CONCLUSIONS: CM incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test, highlighting the potential of using CM as key metric of program success in the Treat All era.

The use of diffusion tensor imaging in spinal pathology: a comprehensive literature review.

STUDY DESIGN: We reviewed the available literature systematically without meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. OBJECTIVE: To evaluate contemporary literature on use of spinal diffusion tensor imaging(sDTI) in spinal pathology. BACKGROUND: sDTI reveals the location and functional state of critical long tracts and is a potentially useful adjunct in disease management. METHODS: Studies were included if they presented or discussed data from investigative or therapeutic procedures involving sDTI on human subjects in the setting of surgically amenable spinal pathology. Studies were excluded if they were (1) restricted to computational models investigating parameters using data not obtained clinically, (2) about cranial DTI methods, (3) about spinal pathology data not related to surgical management, (4) discussions or overviews of methods/techniques with minimal inclusion of objective experimental or clinical data. RESULTS: Degenerative pathologies of interest were restricted to either cervical myelopathy (22/29,75.9%) or lumbar spondylosis 7/29,24.1%). Mass-occupying lesions included intradural pathology and discussed preoperative (7/9,77.8%) and intraoperative imaging(2/9,22.2%) as an adjunct to surgery 22.2%. Traumatic pathology focused on spinal cord injury prognosis and severity grading. CONCLUSIONS: sDTI seems useful in surgical decision making and outcome measurements and in establishing clinical prognoses over a wide range of surgical pathologies. Further research is warranted with longer follow-up and larger population sizes in a prospective and controlled protocol.

The diagnosis of central nervous system infections in resource-limited settings and the use of novel and molecular diagnostic platforms to improve diagnosis.

INTRODUCTION: Central nervous system infections (CNSI) disproportionately affect individuals in low-resource settings where diagnosis is challenging; large proportions of patients never receive a confirmed microbiological diagnosis resulting in inadequate management and high mortality. The epidemiology of CNSI varies globally and conventional diagnostics deployed in resource-limited settings have significant limitations, with an urgent need for improved diagnostic strategies. AREAS COVERED: This review describes molecular platforms and other novel diagnostics used in the diagnosis of CNSI that are applicable to resource-limited settings. An extensive literature search of Medline and PubMed was performed. The emphasis is on investigations targeting infections of relevance to resource-limited settings either due to variation in regional CNSI epidemiology or due to increased prevalence in patients with immunosuppression. This includes commercially available multiplex PCR platforms, mycobacterial PCR platforms, and rapid diagnostics tests. To offer a framework for the optimal implementation in clinical settings, existing evidence highlighting the advantages and limitations of available platforms is reviewed. EXPERT OPINION: The implementation of molecular platforms and other novel diagnostics has the potential to transform CNSI diagnosis in resource-limited settings, with several examples of successful rollout of novel diagnostics such as Xpert MTB/RIF Ultra and cryptococcal antigen testing.

Intrafacet Spacer Placement as a Mobility-Sparing Bailout Option in Atlantoaxial Fusion Construct Salvage.

Background: Salvage revisions of atlantoaxial (AA) joint complex posterior segmental instrumented fusion constructs require careful individualized planning to prevent occipital extension. In this case report, we describe the use of bilateral intrafacet spacer placement as a mobility-sparing bailout option for the revision surgery. Case Report: A 64-year-old male with a history of diffuse idiopathic skeletal hyperostosis, extremely limited baseline cervical mobility, and prior AA posterior segmental instrumented fusion presented with increasing pain at his 6-month follow-up. Imaging showed fusion and hardware failures and dynamic instability. To prevent occipitocervical fixation, AA intra-articular fusion via a DTRAX spinal system (Providence Medical Technology, Inc) was used as an adjunct to a navigated C1 lateral mass and C2 pars screw posterior segmental instrumented fusion construct. The patient had an uneventful postoperative course and was discharged with resolution of symptoms. Three-month postoperative follow-up confirmed persistent resolution of symptoms and absence of complaints, along with successful arthrodesis on imaging. Conclusion: AA posterior segmental instrumented fusion revision is technically challenging, particularly when partial preservation of craniovertebral junction mobility is required. Bilateral intra-articular cages may be used as an adjunct to hardware revision in construct salvage when sturdy arthrodesis is desired without occipital extension and may represent a major potential strength of intra-articular cages.

Training Cerebrovascular and Neuroendovascular Surgery Residents: A Systematic Literature Review and Recommendations.

Background: The rapid evolution of neuroendovascular intervention has resulted in the inclusion of endovascular techniques as a core competency in neurosurgical residency training. Methods: We conducted a literature review of studies involving the training of neurosurgical residents in cerebrovascular and endovascular neurosurgery. We reviewed the evolution of cerebrovascular neurosurgery and the effects of these changes on residency, and we propose interventions to supplement contemporary training. Results: A total of 48 studies were included for full review. Studies evaluated trainee education and competency (29.2%, 14/48), neuroendovascular training models (20.8%, 10/48), and open cerebrovascular training models (52.1%, 25/48), with some overlap. We used a qualitative analysis of reviewed reports to generate a series of suggested training supplements to optimize cerebrovascular education. Conclusion: Cerebrovascular neurosurgery is at a crossroads where trainees must develop disparate skill sets with inverse trends in volume. Continued longitudinal exposure to both endovascular and open cerebrovascular surgical fields should be mandated in general resident education, and blended learning tactics using adjunct simulation systems and models should be incorporated with didactics to both optimize learning and alleviate restraints placed by decreased volume and autonomy.

Endovascular Mechanical Thrombectomy for Right Hemispheric Stroke Syndrome Due to Acute Left A1-A2 Junction Thromboembolic Occlusion.

Background: Endovascular mechanical thrombectomy (EVT) for large vessel occlusions has had a dramatic impact on the management of acute ischemic stroke. Extended use of EVT beyond American Heart Association guidelines has been successful in carefully selected cases. Case Report: A 71-year-old male presented to our comprehensive stroke center upon awakening with mild left hemiparesis. He was found to have a chronic occlusion of the right supraclinoid segment of the internal carotid artery. Angiography demonstrated large vessel occlusion of the contralateral A1-A2 junction that was successfully recanalized. Imaging at 24 hours displayed no evidence of infarct, the patient rapidly improved during hospitalization, and he was discharged on postoperative day 7 with a National Institutes of Health Stroke Scale score of zero. Conclusion: We describe successful EVT of a patient presenting with false-localizing symptoms consistent with a right hemispheric acute ischemic stroke secondary to left A1-A2 junction large vessel occlusion. This case demonstrates the importance of a high index of suspicion when evaluating atypical stroke presentations and the effectiveness of EVT in the treatment of distal small-caliber vessels.