Pain management in cervical cancer.

Cervical cancer (CC) occupies the second place in incidence and mortality among women in México. Despite this, Cervical Cancer continues to have a late diagnosis which leads to a high rate of complications. Pain represents the most feared and disabling symptom, being present in up to 86% of patients with advanced disease. The approach to managing pain in this population has not been studied and described to a full extent. In addition, there is a pressing need to provide concise recommendations to promote adequate pain control. We performed a review of the literature in CC and had experts in the field of pain management evaluate the evidence found. We then issued relevant recommendations on pharmacology and interventional pain management. Thus, the approach to pain management must be comprehensive and individualized, considering the timely and appropriate use of pharmacologic treatment as well as interventional procedures.

The dynamic impact of location and resection on the glioma CSF proteome.

While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints for patients with glioma. Paired lumbar-versus-intracranial glioma CSF samples were also obtained (n=14). Using aptamer-based proteomics, we identify significant differences in the CSF proteome between lumbar, subarachnoid, and ventricular CSF. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome. Proteomic data are provided with individual clinical annotations as a resource for the field. One Sentence Summary: Glioma cerebrospinal fluid (CSF) accessed intra-operatively and longitudinally via devices can reveal impacts of treatment and anatomical location.

Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial.

BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).

The longitudinal risk of hemorrhage of melanoma brain metastases after Gamma Knife radiosurgery.

OBJECTIVE: The objective of this study was to analyze the hemorrhagic risk of melanoma brain metastases after Gamma Knife radiosurgery (GKRS). METHODS: A prospective institutional database was retrospectively queried to identify patients who underwent GKRS for melanoma brain metastases between 1990 and 2021. Lesional hemorrhage was defined as definite or possible based on radiologists' readings, and severity was graded according to Common Terminology Criteria for Adverse Events. RESULTS: Two hundred ninety-one patients with 1083 lesions treated in 419 sessions were identified. The mean (± SD) patient age was 60 ± 15 years, and 61% were male. The median follow-up period for overall survival (OS) was 11 (range 0-214) months with 581 patient-years. Definite/possible lesional hemorrhages occurred in 13% of lesions, with grade 3 hemorrhages observed in 4% of lesions. Surgical intervention was required in 2% of cases (5% of patients), and all resected lesions were pathologically consistent with melanoma. A decreased risk of definite/possible lesional hemorrhage was associated with a later time period between 2015 and 2021 (OR 0.45, 95% CI 0.266-0.75, p = 0.0021), increased marginal dose (OR 0.91, 95% CI 0.83-0.99, p = 0.037), antiplatelet use post-GKRS (OR 0.195, 95% CI 0.083-0.46, p < 0.001), and whole-brain radiotherapy (WBRT; OR 0.53, 95% CI 0.344-0.82, p = 0.0042). After 2015, more patients received anticoagulation, B-Raf proto-oncogene inhibitors, and immune checkpoint inhibitors, and fewer received bevacizumab (p < 0.001). The cumulative risk of lesional hemorrhage was 17%-20% at 36 months from GKRS, with 95%-96% of cases occurring within 12 months. The median patient OS was 11 (95% CI 9-13) months, and multivariate Cox regression analysis revealed that antiplatelet agents (hazard ratio [HR] 0.66, 95% CI 0.45-0.96, p = 0.031) and immune checkpoint inhibitors (HR 0.35, 95% CI 0.26-0.48, p < 0.001) were associated with longer OS, while WBRT (HR 1.36, 95% CI 1.02-1.81, p = 0.037) and definite/possible hemorrhage (HR 1.39, 95% CI 1.04-1.85, p = 0.024) were associated with shorter OS. CONCLUSIONS: The definite hemorrhage risk of melanoma brain metastases after GKRS was 17% in the first 3 years and 95% of the lesional hemorrhage occurred within the 1st year. Surgical intervention was needed in 5% of patients. Antiplatelet agents and immune checkpoint inhibitors were associated with improved OS, while definite/possible hemorrhage was associated with worse OS.

Methodological and analytical considerations for intra-operative microdialysis.

BACKGROUND: Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight catheters (HMW, 100 kDa) and a variable flow rate pump to perform microdialysis at flow rates amenable to an intra-operative setting. We herein report on the lessons and insights obtained during our intra-operative HMW microdialysis trial, both in regard to methodological and analytical considerations. METHODS: Intra-operative HMW microdialysis was performed during 15 clinically indicated glioma resections in fourteen patients, across three radiographically diverse regions in each patient. Microdialysates were analyzed via targeted and untargeted metabolomics via ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Use of albumin and lactate-containing perfusates impacted subsets of metabolites evaluated via global metabolomics. Additionally, focal delivery of lactate via a lactate-containing perfusate, induced local metabolic changes, suggesting the potential for intra-operative pharmacodynamic studies via reverse microdialysis of candidate drugs. Multiple peri-operatively administered drugs, including levetiracetam, cefazolin, caffeine, mannitol and acetaminophen, could be detected from one microdialysate aliquot representing 10 min worth of intra-operative sampling. Moreover, clinical, radiographic, and methodological considerations for performing intra-operative microdialysis are discussed. CONCLUSIONS: Intra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis. Trial registration NCT04047264.

Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas.

The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05-10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.

MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series.

We present three cases of O6-Methylguanine-DNA Methyl-transferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

[Multiple myeloma with laryngeal affectation: an uncommon cause of dysphonia].

Plasma cell proliferation leads to the formation of a single tumour (plasmacytoma) or to systemic disease (myeloma). Plasma cell myeloma involving laryngeal cartilage is unusual and clinical manifestations are similar to those of laryngeal carcinoma. We report the case of a 70-year-old man with disphonia after a recent diagnosis of multiple myeloma. Radiological and immunohistochemical studies showed laryngeal involvement. The patient is currently under treatment with lenalidomide, dexamethasone, and bortezomib.

INPH and parkinsonism: A positive shunt response with a negative tap test.

Introduction: The aim of this study was to compare clinical and functional performances of idiopathic normal pressure hydrocephalus (INPH) patients with and without parkinsonism at the initial evaluation, 72 h after the cerebrospinal fluid tap test (CSF TT), and 6 months after ventriculoperitoneal shunt (VPS) surgery. Materials and methods: This is an observational prospective study on patients with INPH who underwent VPS. Patients were classified into INPH with parkinsonism (INPH-P+) and without parkinsonism (INPH-P-). We used the time up and go (TUG) test, Tinetti Performance-Oriented Mobility Assessment (POMA) test, INPH grading scale (INHPGS), and modified Rankin scale (mRS) at baseline, 72 h after CSF TT, and 6 months after VPS surgery. Results: A total of 64 patients with probable INPH were included, 12 patients with INPH-P+ and 52 controls with INPH-P-. Patients with INPH showed significant improvement in all clinical and neurological parameters after VPS including TUG, Tinetti POMA, INPHGS, and mRS (p < 0.001) with the exception of mRS where there was no significant change 72 h after CSF TT compared to baseline for patients with INPH (p = 0.182). Patients with INPH-P+ performed significantly worse than patients with INPH-P- on Tinetti POMA and mRS at baseline, at 72 h post-CSF TT, and at 6 months post-VPS with INPHGS being worst at 72 h post-CSF TT. There was no difference between patients with INPH-P+ and patients with INPH-P- for TUG at baseline (p = 0.270), at 72 h post-CSF TT (p = 0.487), and at 6 months post-VPS (p = 0.182). Patients with INPH-P+ did not show any change in any of the parameters at 72 h post-CSF TT compared to baseline; however, there was a trend toward improvement on TUG (p = 0.058), Tinetti gait (p = 0.062), and Tinetti total (p = 0.067). INPH-P+ significantly improved in all parameters 6 months post-VPS compared to baseline except for mRS (p = 0.124). Patients with INPH-P- significantly improved in all parameters at 72 h post-CSF TT and at 6 months post-VPS compared to baseline, respectively, except on mRS 72 h after CSF TT (p = 0.299). Conclusion: Patients with INPH and parkinsonism overall do worse than patients without parkinsonism. An unsatisfying response to the CSF tap test in INPH patients with parkinsonism should not be used as an exclusion criterion from VPS surgery since patients with and without parkinsonism showed significant improvement post-VPS.

Objective assessment of patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement using activity-monitoring data: pilot study.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) results in significant morbidity in the elderly with symptoms of dementia, gait instability, and urinary incontinence. In well-selected patients, ventriculoperitoneal shunt (VPS) placement often results in clinical improvement. Most postshunt assessments of patients rely on subjective scales. The goal of this study was to assess the utility of remote activity monitoring to provide objective evidence of gait improvement following VPS placement for iNPH. METHODS: Patients with iNPH were prospectively enrolled and fitted with 5 activity monitors (on the hip and bilateral thighs and ankles) that they wore for 4 days preoperatively within 30 days of surgery and for 4 days within 30 days postoperatively. Monitors collected continuous data for number of steps, cadence, body position (upright, prone, supine, and lateral decubitus), gait entropy, and the proportion of each day spent active or static. Data were retrieved from the devices and a comparison of pre- and postoperative movement assessment was performed. The gait data were also correlated with formal clinical gait assessments before and after lumbar puncture and with motion analysis laboratory testing at baseline and 1 month and 1 year after VPS placement. RESULTS: Twenty patients fulfilled the inclusion and exclusion criteria (median age 76 years). The baseline median number of daily steps was 1929, the median percentage of the day spent inactive was 70%, the median percentage of the day with a static posture was 95%, the median gait velocity was 0.49 m/sec, and the median number of steps required to turn was 8. There was objective improvement in median entropy from pre- to postoperatively, increasing from 0.6 to 0.8 (p = 0.002). There were no statistically significant differences for any of the remaining variables measured by the activity monitors when comparing the preoperative to the 1-month postoperative time point. All variables from motion analysis testing showed statistically significant differences or a trend toward significance at 1 year after VPS placement. Among the significantly correlated variables at baseline, cadence was inversely correlated with percentage of gait cycle spent in the support phase (contact with ground vs swing phase). CONCLUSIONS: This pilot study suggests that activity monitoring provides an early objective measure of improvement in gait entropy after VPS placement among patients with iNPH, although a more significant improvement was noted on the detailed clinical gait assessments. Further long-term studies are needed to determine the utility of remote monitoring for assessing gait improvement following VPS placement.

Impact of cytomegalovirus immunodominant HLA-I donor-recipient matching on the incidence and features of virus DNAemia and virus-specific T-cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation.

BACKGROUND: We investigated whether donor-recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)-I alleles may impact on the degree of CMV pp65/immediate-early 1 (IE-1) T-cell reconstitution and the incidence of CMV DNAemia in patients undergoing unmanipulated haploidentical hematopoietic stem cell transplantation with high-dose posttransplant cyclophosphamide (PT/Cy-haplo). METHODS: Multicenter observational study including 106 consecutive adult PT/Cy-haplo patients (34 CMV ID HLA-I matched and 72 mismatched). A real-time PCR was used for plasma CMV DNA load monitoring. Enumeration of CMV-specific (pp65/IE-1) interferon (IFN)-γ-producing T cells from several patients was performed by flow cytometry by days +30, +60, +90 and +180 after transplantation. RESULTS: The cumulative incidence of CMV DNAemia, clinically significant CMV DNAemia episodes (cs-CMVi), and recurrent CMV DNAemia was comparable across CMV ID HLA-I matched and mismatched patients (71.8% vs. 80.9%, p = .95; 40.7% vs. 44.2%, p = .85; 16.4% vs. 28.1%; p = .43, respectively). The percentage of patients exhibiting detectable CMV-specific IFN-γ-producing T-cell responses (either CD8+ or CD4+ ) was similar across groups; nevertheless, significantly higher CMV-specific CD8+ T-cell counts were enumerated in the CMV ID HLA-I matched compared to mismatched patients by day +60 (p = .04) and +180 (p = .016) after transplantation. CONCLUSION: CMV ID HLA-I matching may impact on the magnitude of CMV-pp65/IE-1-specific CD8+ T-cell reconstitution; yet, this effect seemed not to have an impact on the incidence of initial, recurrent CMV DNAemia, or cs-CMVi.

Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality.

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. Low DNA methylation as well as high RNA expression of MYO1E are associated with a shorter median survival time and an increased risk of mortality for LUAD, but not for LUSC. This study suggests that changes in MYO1E methylation and expression in LUAD patients may have an essential role in lung cancer's pathogenesis. It shows the utility of MYO1E DNA methylation and RNA expression in predicting survival for LUAD patients. Also, given the low normal expression of MYO1E in blood cells MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.

Features of cytomegalovirus DNAemia and virus-specific T-cell responses in allogeneic hematopoietic stem-cell transplant recipients during prophylaxis with letermovir.

BACKGROUND: There is scarce information on the natural kinetics of cytomegalovirus (CMV) DNAemia and dynamics of CMV-specific T-cell reconstitution in allogeneic hematopoietic transplant recipients (allo-HSCT) undergoing letermovir (LMV) prophylaxis. METHODS: Twelve adult CMV-seropositive high-risk recipients (median age, 53 years; 9 males/3 females) undergoing LMV prophylaxis and 13 non-LMV allo-HSCT controls (median age, 58 years; 7 males/6 females) were included. CMV DNAemia in plasma was monitored by real-time polymerase chain reaction. Preemptive antiviral therapy (PET) was administered upon detection of ≥1500 IU/ml. CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T cells were enumerated by flow cytometry around days +30, +60, and +90 after allo-HSCT. Ex vivo experiments assessing of the potential effect of LMV on CMV-specific T-cell expansion in a single CMV-seropositive donor were also conducted. RESULTS: Five LMV patients (41.6%) developed CMV DNAemia that cleared spontaneously. Four patients (33.3%) developed CMV DNAemia after LMV cessation, of which two required PET. Nine non-LMV patients (69.2%) developed CMV DNAemia (five required PET). The percentage of LMV and non-LMV patients exhibiting detectable CMV-specific T-cell responses was comparable (7/10 vs. 10/13; p = .71). Nevertheless, median CMV-specific CD4+ and CD8+ T-cell counts were lower in LMV patients by days +60 (p = .006 and .02, respectively) and +90 (p = .08 and .02). Ex vivo, CMV-specific CD8+ T cells expanded to the same level either in the presence (19.8%) or in the absence of LMV (20.6%). CONCLUSIONS: In our series, episodes of CMV DNAemia in LMV patients cleared spontaneously. A diminished degree of CMV-specific T-cell reconstitution in LMV patients compared to non-LMV patients was observed.

Effect of Extent of Resection on Survival of Patients with Glioblastoma, IDH-Wild-Type, WHO Grade 4 (WHO 2021): Systematic Review and Meta-Analysis.

BACKGROUND: In light of the recently updated World Health Organization (WHO) 2021 central nervous system tumor classifications, the aim of the present study was to establish the effect of the resection extent on overall survival (OS) and progression-free survival (PFS) for patients who met the current diagnostic criteria for glioblastoma, isocitrate dehydrogenase (IDH)-wild-type (WT), WHO grade 4. METHODS: A systematic literature search was performed using the following databases: PubMed, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews and ClinicalTrials.gov to identify studies that had compared OS and PFS after gross total resection (GTR) versus subtotal resection (STR) or biopsy for glioblastoma IDH-WT. RESULTS: We identified 1439 studies, of which 9 met the inclusion and/or exclusion criteria. Of the 2023 patients, 788 had undergone GTR. The meta-analysis showed a significant increase in the OS and PFS duration after GTR for glioblastoma IDH-WT, with a median OS of 20 months (95% confidence interval [CI], 17-25) after GTR versus 12 months (95% CI, 9-15) after STR (P < 0.0001). The median PFS was 11 months (95% CI, 9-12) after GTR versus 7 months (95% CI, 5-7) after STR (P < 0.0001). GTR was associated with a 51% reduction in the mortality risk (hazard ratio, 0.49; 95% CI, 0.36-0.65) and a 42% reduction in the progression risk (hazard ratio, 0.58; 95% CI, 0.39-0.88) compared with STR. CONCLUSIONS: The results from our systematic review suggest that GTR is associated with improved OS and PFS compared with STR for glioblastoma, IDH-WT, WHO grade 4 (WHO 2021). However, our findings were limited by the various study designs and significant clinical and methodologic heterogeneity among the studies.

Treatment of tegmen dehiscence using a middle fossa approach and autologous temporalis fascia graft: Outcomes from a single center.

INTRODUCTION: Although bony defects of the tegmen surface are relatively common, the majority of dehiscences are asymptomatic. For those who experience symptoms, there is a wide spectrum of relatively benign manifestations such as hearing loss and otorrhea to potentially more serious but rare sequelae such as epilepsy and meningitis. Surgical management of tegmen dehiscences (TDs) can help prevent these symptoms. In this manuscript, we present one of the largest reported single team experiences of using a temporal craniotomy with middle cranial fossa approach and temporalis fascia graft in the treatment of tegmen defects. METHODS: We retrospectively reviewed every case of a TD surgically repaired by the same neurosurgeon/otolaryngologist team at Loyola University Medical Center from May 2015 to January 2022. In our chart review, we identified 44 patients with 48 cases of tegmen defect repair. We analyzed patient characteristics, operative details, and postoperative outcomes. RESULTS: 44 patients met inclusion criteria for the presence of TD (mean age 55 years, 55% male, and average body mass index 35.6). 89% of these patients had no clear etiology for the dehiscence. Commonly reported symptoms were hearing loss (89%) and CSF otorrhea (82%). The least reported presenting signs and symptoms were seizures (5%) and meningitis (2%). Most defects were repaired with both temporalis fascial and calvarial bone grafts (63%), while a minority were treated with temporalis fascia only (33%), temporalis fascia with muscle (2%), or fascia lata (2%). Every patient in our sample experienced resolution of CSF otorrhea after tegmen repair and 81% of the sample reported subjective hearing improvements after surgery. 6% of our sample had post-operative infections and 8% of patients underwent repeat unilateral surgery for a surgical complication. CONCLUSION: Craniotomy for middle fossa approach using autologous temporalis fascial grafts is a safe and effective method for the treatment of TD. These procedures should be performed by experienced and multidisciplinary teams.

SARS-CoV-2 Omicron BA.1 variant breakthrough infections in nursing home residents after an homologous third dose of the Comirnaty® COVID-19 vaccine: Looking for correlates of protection.

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.

Survival benefit of concomitant chemoradiation in adult supratentorial primary glioblastoma. A propensity score weighted population-based analysis.

BACKGROUND: This population study aims to assess the impact of the implementation of the original Stupp protocol on overall survival in patients with new-diagnosed supratentorial primary GBM. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to study the survival of histologically confirmed adult supratentorial GBM patients diagnosed between 1998 and 2016. Kaplan-Meier, and a univariate and propensity-score weighted multivariate Cox proportional hazard model adjusted for age at diagnosis, sex, race, marital status and extent of resection was used to assess the survival of patients prior to implementation of the Stupp protocol in 2005 (Pre-Stupp) and following implementation of the Stupp Protocol until 2016 (Post Stupp). RESULTS: Overall, 6390 patients satisfied inclusion exclusion criteria. Median survival times were 13 months for the Pre-Stupp and 15 months for Post-Stupp groups (P<0.001). The 1-, 2-, 5- and 10-year survival rates for the Pre-Stupp group were 51%, 18%, 5% and 2% respectively compared to 59%, 27%, 8% and 4% on the Post-Stupp group. Propensity-score weighted analysis showed a lower mortality risk for patients who underwent concomitant chemoradiation during the Post-Stupp era (HR=0.77, 95% CI 0.62-0.94). There was a 42% relative reduction in the risk of death for patients treated during the Post-Stupp era. CONCLUSIONS: This population-based propensity-score study with long-term follow-up suggests that the implementation of the Stupp protocol in 2005 had a positive impact on the survival of patients with supratentorial GBM. This "real-world" analysis validates the results of the original randomized control trial on which this protocol is based.

Socioeconomic Disparities in Non-Small Cell Lung Cancer With Brain Metastases at Presentation: A Population-Based Study.

OBJECTIVE/BACKGROUND: The purpose of this study was to characterize the impact of household income disparities in the survival of patients with non-small cell lung cancer (NSCLC) presenting with brain metastasis on a population-based level. METHODS: This is a population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2016 including 15,808 NSCLC patients presenting with brain metastasis. RESULTS: This study comprises 15,808 adult patients with NSCLC presenting with brain metastases having an age range 64 ± 10 years with 51% male, 76% white, 52% married, 61% insured, and with 85% of lung adenocarcinoma histopathology. The 1-, 2- and 5-year survival rates for living in the lower household income quartile were 21%, 10%, and 3%, respectively, for the second quartile 24%, 10%, and 3%; for the third quartile 28%, 14%, and 4%; and for the top quartile 31%, 17%, and 4%, respectively. Multivariate Cox proportional hazard analysis showed that living in a higher quartile household income county is associated with increased survival (P < 0.0001), hazard ratio 0.87, 95% confidence interval (0.82-0.92). CONCLUSIONS: This population-based study suggests that living in higher median household income counties is associated with increased survival time and reduced risk of mortality for patients with NSCLC who have brain metastases present at diagnosis, independent of other factors. These findings underscore the importance of ensuring adequate and easy access to care for all patients, irrespective of their economic background.

Effectiveness of a Standardized External Ventricular Drain Placement Protocol for Infection Control.

INTRODUCTION: Placement of an external ventricular drain (EVD) is a common procedure routinely completed at bedside by neurosurgical residents. A standardized protocol for placement and maintenance of an EVD is potentially useful. METHODS: This single-institution retrospective review analyzed all patients who underwent placement of an EVD over a 5-year span using a standardized protocol. RESULTS: A total of 428 EVDs in 381 patients were placed as per this protocol. Overall compliance with the practice protocol was 98.7%. Overall, our infection rate was 1.86% (8 external ventricular drain-related infection [ERIs] over 428 EVDs). There was no difference in age for the ERI cases (median 55, range (50.5-60.5), compared with the non-ERI cases (median of 53, range [38-65]) (P = 0.512). Indications for placement of EVD were hemorrhage (51.9%, n = 198), tumor (16.2%, n = 62), trauma (12.8%, n = 49), hydrocephalus (11.5%, n = 44), cerebellar stroke (2.8%, n = 11), infection (3.1%, n = 12), unknown (1.3%, n = 5). Most EVDs (77.6%, n = 296) were placed bedside by second-year residents (median PGY level 2, interquartile range 1-2.75). Computed tomography confirmed placement in the ipsilateral frontal horn in 72% (n = 277) of EVDs. EVD-related complications were noted in 8.3% of EVDs (n = 32, with 8 infections and 24 tract hemorrhages). The median EVD duration was 10 days; duration of EVD had no statistically significant impact on the risk of an ERI (P = 1). Only replacement of an EVD was associated with an increased risk of infection. CONCLUSIONS: Adherence to a standard EVD placement protocol is useful in maintaining a low risk of ERI regardless of the duration of catheter utilization. Replacement of the catheter through the same access hole as the original catheter is associated with an increased risk of ERI.

Dandy's hemispherectomies: historical vignette.

To better understand Walter Dandy's intentions and the historical context of his work on hemispherectomy, the authors reviewed his original 1928 publication. Gliomas were considered incurable at that time. Presuming that the loss of motor function denoted a lack of useful tissue in that hemisphere, he pioneered radical removal of the involved cerebral hemisphere. Of the 5 patients operated on by Dandy, 1 died within 48 hours of hemorrhage because of a displaced vascular clip; 1 died of pneumonia in 2 weeks; 2 died of tumor recurrence, at 3 months and 3.5 years, respectively; and a fifth patient was lost to follow-up beyond the 2nd postoperative week. The authors queried the Thomson Reuters Web of Science and Scopus. A total of 88 papers fulfilled inclusion criteria. Half of these papers (44/88) were published after 2012. Only 11% of papers (10/88) quoted Dandy's paper accurately; half of them were published before 1997. Most publications (76% [67/88]) quoted Dandy incorrectly, all of them from 1997 and later. In the remaining 11 papers (13%), the accuracy of the quotes was unclear. The authors found a trend toward more accurate citation in earlier papers. Critically reviewing Dandy's report, with an understanding of the historical context, allows a better understanding of his intentions and the value of his contribution.