A watch, wait, and rescan approach for incidental benign-appearing notochordal lesions of the skull base.

OBJECTIVE: The aim of this study was to describe the natural history of incidental benign-appearing notochordal lesions of the skull base with specific attention to features that can make differentiation from low-grade chordoma more difficult, namely contrast uptake and bone erosion. METHODS: In this retrospective case series, the authors describe the clinical outcomes of 58 patients with incidental benign-appearing notochordal lesions of the clivus, including those with minor radiological features of bone erosion or contrast uptake. RESULTS: All lesions remained stable during a median follow-up of almost 3 years. Thirty-seven (64%) patients underwent contrast-enhanced MRI; lesions in 14 (38%) of these patients exhibited minimal contrast enhancement. Twenty-seven (47%) patients underwent CT; lesions in 6 (22%) of these patients exhibited minimal bone erosion. CONCLUSIONS: These data make the case for monitoring selected cases of benign-appearing notochordal lesions of the clivus in the first instance even when there is minor contrast uptake or minimal bone erosion.

Quantitative assessment of global lung inflammation following radiation therapy using FDG PET/CT: a pilot study.

PURPOSE: Radiation pneumonitis is the most severe dose-limiting complication in patients receiving thoracic radiation therapy. The aim of this study was to quantify global lung inflammation following radiation therapy using FDG PET/CT. METHODS: We studied 20 subjects with stage III non-small-cell lung carcinoma who had undergone FDG PET/CT imaging before and after radiation therapy. On all PET/CT studies, the sectional lung volume (sLV) of each lung was calculated from each slice by multiplying the lung area by slice thickness. The sectional lung glycolysis (sLG) was calculated by multiplying the sLV and the lung sectional mean standardized uptake value (sSUVmean) on each slice passing through the lung. The lung volume (LV) was calculated by adding all sLVs from the lung, and the global lung glycolysis (GLG) was calculated by adding all sLGs from the lung. Finally, the lung SUVmean was calculated by dividing the GLG by the LV. The amount of inflammation in the lung parenchyma directly receiving radiation therapy was calculated by subtracting tumor measurements from GLG. RESULTS: In the lung directly receiving radiation therapy, the lung parenchyma SUVmean and global lung parenchymal glycolysis were significantly increased following therapy. In the contralateral lung (internal control), no significant changes were observed in lung SUVmean or GLG following radiation therapy. CONCLUSION: Global lung parenchymal glycolysis and lung parenchymal SUVmean may serve as potentially useful biomarkers to quantify lung inflammation on FDG PET/CT following thoracic radiation therapy.

Intraoperative diagnosis of facial schwannomas: a multicenter summation of clinical experience, preoperative avoidance, and intraoperative management protocol.

OBJECTIVE: Preoperative differentiation of facial nerve schwannoma (FNS) from vestibular schwannoma (VS) can be challenging, and failure to differentiate between these two pathologies can result in potentially avoidable facial nerve injury. This study presents the combined experience of two high-volume centers in the management of intraoperatively diagnosed FNSs. The authors highlight clinical and imaging features that can distinguish FNS from VS and provide an algorithm to help manage intraoperatively diagnosed FNS. METHODS: Operative records of 1484 presumed sporadic VS resections between January 2012 and December 2021 were reviewed, and patients with intraoperatively diagnosed FNSs were identified. Clinical data and preoperative imaging were retrospectively reviewed for features suggestive of FNS, and factors associated with good postoperative facial nerve function (House-Brackmann [HB] grade ≤ 2) were identified. A preoperative imaging protocol for suspected VS and recommendations for surgical decision-making following an intraoperative FNS diagnosis were created. RESULTS: Nineteen patients (1.3%) with FNSs were identified. All patients had normal facial motor function preoperatively. In 12 patients (63%), preoperative imaging demonstrated no features suggestive of FNS, with the remainder showing subtle enhancement of the geniculate/labyrinthine facial segment, widening/erosion of the fallopian canal, or multiple tumor nodules in retrospect. Eleven (57.9%) of the 19 patients underwent a retrosigmoid craniotomy, and in the remaining patients, a translabyrinthine (n = 6) or transotic (n = 2) approach was used. Following FNS diagnosis, 6 (32%) of the tumors underwent gross-total resection (GTR) and cable nerve grafting, 6 (32%) underwent subtotal resection (STR) and bony decompression of the meatal facial nerve segment, and 7 (36%) underwent bony decompression only. All patients undergoing subtotal debulking or bony decompression exhibited normal postoperative facial function (HB grade I). At the last clinical follow-up, patients who underwent GTR with a facial nerve graft had HB grade III (3 of 6 patients) or IV facial function. Tumor recurrence/regrowth occurred in 3 patients (16%), all of whom had been treated with either bony decompression or STR. CONCLUSIONS: Intraoperative diagnosis of an FNS during a presumed VS resection is rare, but its incidence can be reduced further by maintaining a high index of suspicion and undertaking further imaging in patients with atypical clinical or imaging features. If an intraoperative diagnosis does occur, conservative surgical management with bony decompression of the facial nerve only is recommended, unless there is significant mass effect on surrounding structures.

Cell-intrinsic defects in the proliferative response of antiviral memory CD8 T cells in aged mice upon secondary infection.

Although previous studies have demonstrated delayed viral clearance and blunted effector T cell responses in aged mice during infection, memory CD8 T cells and especially secondary responses have received less attention. In this study, we show that modest differences in the number of memory CD8 T cells formed in aged versus young animals were associated with altered memory CD8 T cell differentiation. Aged immune mice had increased morbidity and mortality upon secondary viral challenge, suggesting changes in T cell immunity. Indeed, virus-specific memory CD8 T cells from aged mice showed substantially reduced proliferative expansion upon secondary infection using multiple challenge models. In addition, this defect in recall capacity of aged memory CD8 T cells was cell-intrinsic and persisted upon adoptive transfer into young mice. Thus, the poor proliferative potential of memory T cells and altered memory CD8 T cell differentiation could underlie age-related defects in antiviral immunity.

Augmentation of primary influenza A virus-specific CD8+ T cell responses in aged mice through blockade of an immunoinhibitory pathway.

Immune responses diminish with age resulting in an increased susceptibility of the elderly to infectious agents and an inability to mount protective immune responses to vaccines. Immunosenescence affects multiple aspects of the immune system, including CD8(+) T cells, which control viral infections and are assumed to prevent the development of cancers. In this study, we tested if CD8(+) T cell responses in aged mice could be enhanced through a vaccine that concomitantly expresses Ag and a molecule that blocks an immunoinhibitory pathway. Specifically, we tested a vaccine based on a replication-defective chimpanzee-derived adenovirus vector expressing the nucleoprotein (NP) of influenza A virus as a fusion protein with the HSV type 1 glycoprotein D, which through binding to the herpes virus entry mediator, blocks the immunoinhibitory herpes virus entry mediator B and T lymphocyte attenuator/CD160 pathways. Our results show that the vaccine expressing a fusion protein of NP and glycoprotein D induces significantly higher NP-specific CD8(+) T cell responses in young and aged mice compared with the vaccine expressing NP only.

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens.

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.

Encapsulation Capacity of ß-Cyclodextrin Stabilized Silver Nanoparticles towards Creatinine Enhances the Colorimetric Sensing of Hydrogen Peroxide in Urine.

The ß-cyclodextrin shell of synthesized silver nanoparticles (ßCD-AgNPs) are found to enhance the detection of hydrogen peroxide in urine when compared to the Horse Radish Peroxidase assay kit. Nanoparticles are confirmed by the UV-Vis absorbance of their localized surface plasmonic resonance (LSPR) at 384 nm. The mean size of the ßCD-AgNPs is 53 nm/diameter; XRD analysis shows a face-centered cubic structure. The crystalline structure of type 4H hexagonal nature of the AgNPs with 2.4 nm ß-CD coating onto is confirmed using aberration corrected high-resolution transmission electron microscopy (HRTEM). A silver atomic lattice at 2.50 Å and 2.41 Å corresponding to (100) and (101) Miller indices is confirmed using the HRTEM. The scope of ßCD-AgNPs to detect hydrogen peroxide (H2O2) in aqueous media and human urine is investigated. The test is optimized by examining the effect of volumes of nanoparticles, the pH of the medium, and the kinetic and temperature effect on H2O2 detection. The ßCD-AgNPs test is used as a refined protocol, which demonstrated improved sensitivity towards H2O2 in urine compared to the values obtained by the Horse Radish Assay kit. Direct assessment of H2O2 by the ßCD-AgNPs test presented always with a linear response in the nM, µM, and mM ranges with a limit of detection of 1.47 nM and a quantitation limit of 3.76 nM. While a linear response obtained from 1.3 to 37.3 nmoles of H2O2/mole creatinine with a slope of 0.0075 and regression coefficient of 0.9955 when the ßCD-AgNPs is used as refined test of creatinine. Values ranging from 34.62 ± 0.23 nmoles of H2O2/mole of creatinine and 54.61 ± 1.04 nmoles of H2O2/mole of creatinine when the matrix is not diluted and between 32.16 ± 0.42 nmoles of H2O2/mole of creatinine and 49.66 ± 0.80 nmoles of H2O2/mole of creatinine when the matrix is twice diluted are found in freshly voided urine of seven apparent healthy men aged between 20 and 40 years old.

Short- and Long-Term Geriatric Mortality After Acute Traumatic Subdural Hemorrhage.

BACKGROUND: Acute subdural hemorrhage often occurs in those ≥65 years of age after trauma and tends to yield poor clinical outcomes. Previous studies have demonstrated a propensity toward high in-hospital mortality rates in this population; however, postdischarge mortality data are limited. The objective of the present study was to analyze short- and long-term mortality data after acute traumatic subdural hemorrhage in the geriatric population as well as review the impact of associated clinical variables including mechanism of injury, pre-morbid antithrombotic use, and need for surgical decompression on mortality rates. METHODS: We retrospectively reviewed 455 patients who presented with an isolated traumatic acute subdural hemorrhage to our level-1 trauma center over a 5 year period using our data registry. Patients were then cross-referenced in the National Social Security Death Index for postdischarge mortality rates. United States life tables were used for peer-controlled actuarial comparisons. RESULTS: Acute traumatic subdural hemorrhage is often a fatal injury in the geriatric population, especially if taking antithrombotics or requiring surgical decompression. Specifically, they have greater in-hospital mortality rates than adults with similar injuries and have significantly lower survival rates for several years following discharge compared with their peer-matched controls. CONCLUSIONS: Here, we found that age is a significant predictor of both short- and long-term survival after acute traumatic subdural hemorrhage. Moreover, the present study corroborates that the need for surgical decompression or the use of pre-morbid antithrombotic medications is associated with increased overall mortality.

Studying the Effects of Semaphorins on Oligodendrocyte Lineage Cells.

Oligodendrocytes are the myelinating cells of the central nervous system. The role of oligodendrocytes in health and disease has been considerably enhanced by the development of methods to isolate and culture oligodendrocytes from central nervous system tissue. The cellular and molecular mechanisms involved in oligodendrocyte differentiation can be identified by challenging oligodendrocyte progenitors cells (OPCs) by altering their extracellular environment and intrinsic differentiation pathways. To address these issues, it is imperative to develop an in vitro protocol where pure OPCs are isolated and cultured in the presence of inhibitory developmental and differentiation cues like Semaphorin 3A. In this chapter, we describe methods to isolate and culture OPCs from neonatal rat brain tissue and further characterise their differentiation into oligodendrocytes. The described protocol is relatively simple in comparison to existing protocols and can be used to study the effect of lesion-associated inhibitors like Semaphorin 3A on oligodendrocyte differentiation.