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.

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study.

OBJECTIVE: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection. DESIGN: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups. RESULTS: 1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection. CONCLUSION: Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.

Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience.

INTRODUCTION: The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic. METHODS: A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved. RESULTS: Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic. CONCLUSION: The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

Renal effects of novel antiretroviral drugs.

Chronic kidney disease (CKD) is a critical comorbidity for patients living with HIV, with an estimated prevalence between 2.4 and 17%. Such patients are increasingly affected by diseases associated with ageing, including cardiovascular disease and CKD, and the prevalence of risk factors such as smoking and dyslipidaemia is increased in this population. Proteinuria is also now recognized as a common finding in individuals living with HIV. While combination antiretroviral (ARV) treatments reduce CKD in the HIV-infected population overall, some ARV drugs have been shown to be nephrotoxic and associated with worsening renal function. Over the last few years, several highly efficacious new ARV agents have been introduced. This brief review will look at the novel agents dolutegravir, raltegravir, elvitegravir, cobicistat, tenofovir alafenamide fumarate and atazanavir, all of which have been licensed relatively recently, and describe issues relevant to renal function, creatinine handling and potential nephrotoxicity. Given the prevalence of CKD, the wide range of possible interactions between HIV, ARV therapy, CKD and its treatments, nephrologists need to be aware of these newer agents and their possible effect on kidneys.

Progressive weakness and intermittent low-grade fever in a Libyan man.

We present a diagnostically challenging case of a 61-year-old man presenting with progressive weakness and intermittent low-grade fever.

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.

No Surprises Act: Legal Challenges and Implications for Radiology.

When the word "surprise" is used as a noun, it generally describes an unexpected event. When "surprise" is used in conjunction with "billing", it conjures up images with which even the most hardened backroom medical administrator can empathize. One's first reaction is likely patient based, that a person received medical services from a health care provider or facility that are larger than anticipated in-network charges. As a result, the bill for services incorporates that, no-doubt unpleasant, surprise. The whole truth is understandably more complex. Radiology groups contract with insurance companies who for their own reasons, might have historically preferred progressively narrower networks. Nonetheless, these contracts allow providers the opportunity to negotiate reasonable payments for services rendered. Events have changed the historic dynamic between providers and insurance companies.

Neurointerventional payment for out-of-network mechanical thrombectomy in the era of the No Surprises Act.

BACKGROUND: Congress enacted the No Surprises Act (NSA) in 2021. The NSA relies on the ability for providers to appeal their out-of-network (OON) payment through an arbitration process known as Independent Dispute Resolution (IDR). This study was designed to evaluate the effective access to IDR for mechanical thrombectomy (MT). METHODS: This study uses a simulation to model the likelihood that neurointerventionalists have financially viable access to the NSA IDR process to seek adequate payment for MT OON claims. RESULTS: When evaluating professional claims, for only batches of four or more claims, would the expected payment recovery exceed the expected IDR costs. For global claims (both professional and technical components), a batch size of two claims would be required for the expected payment recovery to exceed expected IDR costs.For the 1000 simulations at large MT centers (300 MT annually), there were no instances where it would have been financially viable to submit professional-only OON claims to the IDR process. For global claims, it would have been financially viable to submit to IDR for only 13.2% of these claims. For smaller stroke centers, there were also no instances where it would have been financially viable to submit professional-only claims. For global claims, it would have been financially viable for only 3.3-6.1% of claims. CONCLUSIONS: The NSA process was designed to protect patients from unexpected bills following non-elective medical services. Given the emergent nature of many neuroendovascular cases and the lack of access to the IDR process as this model illustrates, the field is at risk for under-reimbursement due to NSA legislation.

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.

Higher intracranial positioning of an 8 Fr guide catheter improves efficacy of aspiration thrombectomy in large vessel occlusion stroke.

BACKGROUND: Higher positioning of a large bore guide catheter during endovascular thrombectomy (EVT) is hypothesized to potentially improve thrombectomy success. OBJECTIVE: To evaluate the safety and efficacy of intracranial guide catheter placement during EVT using a multicenter database. METHODS: We reviewed data on consecutive patients undergoing EVT for anterior circulation large vessel occlusion (LVO) at three comprehensive stroke centers between October 2019 and December 2022. Participants were allocated to one of two cohorts: intracranial (n=141)-guide catheter tip positioned in the petrous carotid or further distal; and control (n=285)-guide catheter tip below the petrous carotid. Primary outcome was excellent reperfusion (Thrombolysis in Cerebral Ischemia (TICI) 2c or better), first pass effect (TICI 2c or better after one pass), and arterial access to final reperfusion time. The unpaired t-test, Mann-Whitney U test, and Fisher's exact test were used to compare themeans, medians and proportions of the two groups, respectively. P values & lt;0.05 were considered statistically significant two cohorts. RESULTS: A total of 426 patients were included in the analysis. Patients with guide catheter location in the petrous segment or further distal had a significantly higher first-pass effect (111/284, 39.1% vs 37/141, 26.2%, P=0.009). There was no significant difference in final excellent recanalization rates between groups (202/285, 70.9% vs 92/141, 65.2%, P=0.266). Furthermore, intracranial positioning of the guide catheter was associated with significantly shorter time to final recanalization (median 21.0 (13.0-38.0) min vs 30.0 (17.0-48.0) min, P<0.001). CONCLUSION: Positioning a large bore guide catheter in the petrous segment or further distal resulted in a significantly higher rate of first pass effect, faster procedural times, and equivalent final excellent reperfusion rates compared with more proximal guide catheter placement for patients with anterior circulation LVO.

The Impact of GeneXpert Cerebrospinal Fluid Testing on Tuberculous Meningitis Diagnosis in Routine Care in Botswana.

Background: Tuberculous meningitis (TBM) disproportionately impacts high-HIV prevalence, resource-limited settings where diagnosis is challenging. The GeneXpert platform has utility in TBM diagnosis, but uptake remains limited. In Botswana, before the introduction of GeneXpert, tuberculosis (TB) testing was only available through mycobacterial culture at the National TB Reference Laboratory. Data describing routine use of Xpert MTB/RIF for cerebrospinal fluid (CSF) testing in resource-limited settings are scarce. Methods: Electronic records for patients with CSF tested in government facilities in Botswana between 2016 and 2022 were obtained from a central online repository as part of ongoing national meningitis surveillance. Samples were excluded from 1 site where Xpert MTB/RIF is performed universally. The proportion receiving TB-specific investigation on CSF and the number positive for Mycobacterium tuberculosis following increased Xpert MTB/RIF capacity were determined. Results: The proportion of CSF samples receiving TB-specific investigation increased from 4.5% (58/1288) in 2016 to 29.0% (201/693) in 2022, primarily due to increased analysis with Xpert MTB/RIF from 0.9% (11/1288) to 23.2% (161/693). There was an overall decline in the annual number of CSF samples analyzed, but the proportion with microbiologically confirmed TBM increased from 0.4% to 1.2%. The proportion of samples tested for TB that were collected from health care facilities >100 km from the National TB Reference Laboratory increased with Xpert MTB/RIF rollout from 65.9% (87/132) to 78.0% (494/633). Conclusions: In Botswana, access to TB culture is challenging in remote populations; more accessible near-patient testing using Xpert MTB/RIF increased the number of patients receiving TB-specific testing on CSF and the number of confirmed TBM cases.

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.

Neonatal high-flow anterior circulation dural arteriovenous fistulae successfully treated with subtotal endovascular embolization; A case report.

High-flow grade-III dural arteriovenous fistulae(dAVF) represent rare abnormal vascular connections with a high risk of rupture. Management involves obliteration of both the fistulous connection as well as the draining venous network with preservation of normal vasculature. We describe and multiple neonatal dAVFs inducing cardiomyopathy via high-flow grade III shunting in the anterior circulation successfully treated via transvenous and transarterial embolization.

The Influence of Extracurricular Activities on Radiology Resident Selection Decisions.

PURPOSE: Extracurricular activities (EAs) listed on radiology residency applications can signal traits and characteristics desired in holistic reviews. The authors conducted an objective analysis to determine the influence of EAs on resident selection decisions. METHODS: A discrete-choice experiment was designed to model radiology resident selection and determine the relative weights of EAs among academic and demographic application factors. Faculty members involved in resident selection at 30 US radiology programs chose between hypothetical pairs of applicant profiles between October 2021 and February 2022. Each applicant profile included one of 22 EAs chosen for study. A conditional logistic regression model assessed the relative weights of the attributes and odds ratios (ORs) were calculated. RESULTS: Two hundred forty-four participants completed the exercise. Community-service EAs were ranked most highly by participants. LGBTQ Pride Alliance (OR, 1.56; 95% confidence interval [CI], 1.14-2.15; P = .006) and Young Republicans (OR, 0.60; 95% CI, 0.43-0.82; P = .001) significantly influenced decisions. The highest ranked EAs were significantly preferred over the lowest ranked EAs (OR, 1.916; 95% CI, 1.671-2.197; P < .001). Participants preferred EAs that reflected active over passive engagement (OR, 1.154; 95% CI, 1.022-1.304; P = .021) and progressive over conservative ideology (OR, 1.280; 95% CI, 1.133-1.447; P < .001). Participants who ranked progressive EAs more highly preferred applicants with progressive EAs (P < .05 for all). CONCLUSIONS: The influence of EAs on resident selection decisions is significant and likely to gain importance in resident selection as medical student performance metrics are further eliminated. Applicants and selection committees should consider this influence and the bias that EAs can bring to resident selection decisions.

Human Herpesvirus-6 Detection in Cerebrospinal Fluid on the BioFire FilmArray Meningitis/Encephalitis Panel in a High Human Immunodeficiency Virus-Prevalence African Setting.

The prevalence and clinical relevance of human herpesvirus-6 (HHV-6) detection in cerebrospinal fluid (CSF) using multiplex polymerase chain reaction (PCR) testing in patients with suspected meningoencephalitis in high human immunodeficiency virus-prevalence African settings are not known. We describe the clinical and laboratory characteristics of 13 patients with HHV-6 CSF PCR positivity in Botswana.

The Evolving Status of Fellowships and Mini-Fellowships in Diagnostic Radiology: A Survey of Program Directors and Chief Residents.

RATIONALE AND OBJECTIVES: Recent changes in radiology fellowships include musculoskeletal radiology adopting a match system, interventional radiology transitioning away from diagnostic radiology to offer direct-entry programs, and a common fellowship application timeline created by the Society for Chairs of Academic Radiology Departments (SCARD). The concept of mini-fellowships has also emerged with the elimination of the oral American Board of Radiology examinations that had been administered in the final year of residency training prior to 2014. This paper seeks to assess the opinions of fellowship program directors, residency program directors, and chief residents regarding these recent changes. MATERIALS AND METHODS: This is a cross-sectional study using a web-based survey posed to fellowship program directors, residency program directors, and chief residents in 2020. Questions sought to explore current attitudes toward the following topics: (1) a common fellowship application timeline; (2) a common fellowship match; and (3) the status of mini-fellowships in diagnostic radiology. In addition, the number of fellowship positions for each subspecialty was estimated using subspecialty society directories, Accreditation Council for Graduate Medical Education (ACGME) data, and individual program websites. RESULTS: Deidentified responses were collected electronically and aggregated. The three respondent groups preferred a common fellowship application timeline at rates of 67% among fellowship program directors, 80% residency program directors, and 74% residents. A common match system across all subspecialties was preferred at rates of 50% fellowship program directors, 74% residency program directors, and 26% chief residents. There was widespread reported compliance with the SCARD fellowship timeline policy. Subspecialty programs using the match system reported interviewing greater numbers of applicants per position. Fellowship directors and chief residents reported that the most common duration of mini-fellowship experiences was 2 to 3 months. CONCLUSION: There is a division between chief residents and program directors regarding the preference for a common radiology match. Adopting a radiology-wide fellowship match would increase the number of interviews required. The SCARD fellowship timeline policy has been successful, and there is support across stakeholders regarding the common timeline. Mini-fellowships are highly variable in length and structure.