Neuroinvasion of emerging and re-emerging arboviruses: A scoping review.

Background: Arboviruses are RNA viruses and some have the potential to cause neuroinvasive disease and are a growing threat to global health. Objectives: Our objective is to identify and map all aspects of arbovirus neuroinvasive disease, clarify key concepts, and identify gaps within our knowledge with appropriate future directions related to the improvement of global health. Methods: Sources of Evidence: A scoping review of the literature was conducted using PubMed, Scopus, ScienceDirect, and Hinari. Eligibility Criteria: Original data including epidemiology, risk factors, neurological manifestations, neuro-diagnostics, management, and preventive measures related to neuroinvasive arbovirus infections was obtained. Sources of evidence not reporting on original data, non-English, and not in peer-reviewed journals were removed. Charting Methods: An initial pilot sample of 30 abstracts were reviewed by all authors and a Cohen's kappa of κ = 0.81 (near-perfect agreement) was obtained. Records were manually reviewed by two authors using the Rayyan QCRI software. Results: A total of 171 records were included. A wide array of neurological manifestations can occur most frequently, including parkinsonism, encephalitis/encephalopathy, meningitis, flaccid myelitis, and Guillain-Barré syndrome. Magnetic resonance imaging of the brain often reveals subcortical lesions, sometimes with diffusion restriction consistent with acute ischemia. Vertical transmission of arbovirus is most often secondary to the Zika virus. Neurological manifestations of congenital Zika syndrome, include microcephaly, failure to thrive, intellectual disability, and seizures. Cerebrospinal fluid analysis often shows lymphocytic pleocytosis, elevated albumin, and protein consistent with blood-brain barrier dysfunction. Conclusions: Arbovirus infection with neurological manifestations leads to increased morbidity and mortality. Risk factors for disease include living and traveling in an arbovirus endemic zone, age, pregnancy, and immunosuppressed status. The management of neuroinvasive arbovirus disease is largely supportive and focuses on specific neurological complications. There is a need for therapeutics and currently, management is based on disease prevention and limiting zoonosis.

Budd-Chiari syndrome in myeloproliferative neoplasms: A review of literature.

Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e., polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g., portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations (e.g., the V617F point mutation in the JAK2 gene), microparticles, circulating endothelial cells, and other factors, to name a few. Herein, we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs, with a particular focus on its epidemiology, pathogenesis, histopathology, risk factors, classification, clinical presentation, diagnosis, and management.

Stealth invaders: unraveling the mystery of neurotropic viruses and their elusive presence in cerebrospinal fluid - a comprehensive review.

Neurotropic viruses are a threat to human populations due to ongoing zoonosis. A wide array of neurological manifestations can occur most often including parkinsonism, encephalitis/encephalopathy, flaccid myelitis, and Guillain-Barré syndrome. Neuroinvasion occurs through: transneural transmission, blood brain barrier (BBB) dysfunction, and 'trojan horse' mechanism or infected immune cell trafficking into the central nervous system (CNS). Transneural transmission occurs through virus mediated hijacking of intracellular transport proteins allowing retrograde viral transport. BBB dysfunction occurs through cytokine storm increasing membrane permissibility. Increased chemokine expression allows leukocyte trafficking to the BBB. Virally infected leukocytes may successfully pass through the BBB allowing the pathogen to infect microglia and other CNS cell types. We define cerebrospinal fluid (CSF) nondetection as a virus' ability to evade direct CSF detection but still causing significant neurological symptoms and disease. Mechanisms of CSF nondetection include: transneuronal propagation through trans-synaptic transmission, and synaptic microfusion, as well as intrathecal antibody synthesis and virus neutralization. Direct virus detection in CSF is associated with an increased neurological disease burden. However, the lack of CSF detection does not exclude CNS involvement due to possible neuroevasive mechanisms.

Prognosis of Spontaneous Pneumothorax/Pneumomediastinum in Coronavirus Disease 2019: The CoBiF Score.

Objectives: Pneumothorax and pneumomediastinum are associated with high mortality in invasively ventilated coronavirus disease 2019 (COVID-19) patients; however, the mortality rates among non-intubated patients remain unknown. We aimed to analyze the clinical features of COVID-19-associated pneumothorax/pneumomediastinum in non-intubated patients and identify risk factors for mortality. Methods: We searched PubMed Scopus and Embase from January 2020 to December 2021. We performed a pooled analysis of 151 patients with no invasive mechanical ventilation history from 17 case series and 87 case reports. Subsequently, we developed a novel scoring system to predict in-hospital mortality; the system was further validated in multinational cohorts from ten countries (n = 133). Results: Clinical scenarios included pneumothorax/pneumomediastinum at presentation (n = 68), pneumothorax/pneumomediastinum onset during hospitalization (n = 65), and pneumothorax/pneumomediastinum development after recent COVID-19 treatment (n = 18). Significant differences were not observed in clinical outcomes between patients with pneumomediastinum and pneumothorax (±pneumomediastinum). The overall mortality rate of pneumothorax/pneumomediastinum was 23.2%. Risk factor analysis revealed that comorbidities bilateral pneumothorax and fever at pneumothorax/pneumomediastinum presentation were predictors for mortality. In the new scoring system, i.e., the CoBiF system, the area under the curve which was used to assess the predictability of mortality was 0.887. External validation results were also promising (area under the curve: 0.709). Conclusions: The presence of comorbidity bilateral pneumothorax and fever on presentation are significantly associated with poor prognosis in COVID-19 patients with spontaneous pneumothorax/pneumomediastinum. The CoBiF score can predict mortality in clinical settings as well as simplify the identification and appropriate management of patients at high risk.

Changes in Running Economy, Respiratory Exchange Ratio and VO2max in Runners following a 10-day Altitude Training Camp.

Running economy (RE) and VO2max are important predictors of endurance performance for elite and semi-elite endurance athletes, with RE being an appropriate predictor in a homogenous running population. Altitude training has been observed to change RE (mL.kg-1.min-1), and VO2max due to alterations resulting from acclimatization. This study tracked changes in RE and VO2max before and after a 10-day altitude training camp at 1828 meters. VO2max, RE expressed calorically, and respiratory exchange ratio (RER), were measured below anaerobic threshold (AT) to observe differences between pre-and post-altitude training. Eight varsity cross-country runners between the ages of 18 and 22 years performed an incremental treadmill test, pre- and post-10-day altitude training. Paired samples t-tests were used to statistically analyze the data. Average RE (VO2 mL.kg-1.min-1) improved following altitude intervention (M= 56.44 ± 4.28) compared to pre-altitude training (61.30 ± 7.56). These differences were statistically significant t(7)= 2.71, p =.014. RE expressed as kcals.kg-1.km-1 improved following altitude training (16.73 ± 2.96) compared to (18.44 ± 4.04) pre-altitude training and was statistically significant t(7) =3.08, p = .008. RER taken during the last minute of steady-state was higher (0.97, ± .019) post-altitude training, compared to (0.90 ± .043) pre-altitude. These differences were statistically significant t(7) -3.62, p =.008. VO2max (mL.kg-1.min-1) was lower in 6 out of 8 participants (63.91, ± 8.65) post-altitude compared to (69.90, ± 10.80) pre-altitude and was statistically significant t(7) = 2.33, p =.026. The observed improvements in RE may be beneficial for endurance athletes competing and/or training at moderate altitudes near 1828 meters.

The Effects of a 10-day Altitude Training Camp at 1828 Meters on Varsity Cross-Country Runners.

Altitude training has been shown to alter blood lactate (BL) levels due to alterations resulting from acclimatization. This study aims to estimate the impact of altitude training on BL changes immediately following an incremental treadmill test and during recovery before and after 10-day altitude training at approximately 1828 meters. Eight varsity cross-country runners performed an incremental treadmill test (ITT), pre and post-altitude training. Resting and post-warm-up BL values were recorded. During ITT, heart rate (HR), oxygen saturation (SpO2), and time to exhaustion were monitored. BL was also measured post-ITT at 0, 2, 4, 6, and 8 minutes. The average of all BL values was higher following altitude intervention (8.8 ± 4.6 mmol/L) compared to pre-intervention (7.4 ± 3.3 mmol/L). These differences were statistically significant (t(6) = -2.40, p = .026). BL immediately (0 minutes) after the ITT was higher following the altitude intervention (13.6 ± 3.6 mmol/L) compared to pre-intervention (9.7 ± 3.8 mmol/L) and was statistically significant (t(7) = -3.30, p = .006). Average HR during the ITT was lower following the altitude intervention (176.9 ± 11.1 bpm) compared to pre (187 ± 9.5 bpm), these differences were statistically significant (t(28)= 18.07, p= <.001. Time to exhaustion was longer after the intervention, however was not statistically significant p = 0.13. These findings indicate that a 10 - day altitude intervention at 1828 meters may benefit varsity cross-country runners. The higher post-exercise BL may be attributed to more anaerobic contributions. Lower HR may suggest a larger stroke volume and/or more efficient O2 carrying capacity.