Faculty Bibliography

BACKGROUND/UNASSIGNED:Loneliness has been declared an "epidemic" associated with negative physical, mental, and cognitive health outcomes such as increased dementia risk. Less is known about the relationship between loneliness and advanced neuroimaging correlates of Alzheimer's disease (AD). OBJECTIVE/UNASSIGNED:To assess whether loneliness was associated with advanced neuroimaging markers of AD using neuroimaging data from Framingham Heart Study (FHS) participants without dementia. METHODS/UNASSIGNED:In this cross-sectional observational analysis, we used functional connectivity MRI (fcMRI), amyloid-β (Aβ) PET, and tau PET imaging data collected between 2016 and 2019 on eligible FHS cohort participants. Loneliness was defined as feeling lonely at least one day in the past week. The primary fcMRI marker was Default Mode Network intra-network connectivity. The primary PET imaging markers were Aβ deposition in precuneal and FLR (frontal, lateral parietal and lateral temporal, retrosplenial) regions, and tau deposition in the amygdala, entorhinal, and rhinal regions. RESULTS/UNASSIGNED:Of 381 participants (mean age 58 [SD 10]) who met inclusion criteria for fcMRI analysis, 5% were classified as lonely (17/381). No association was observed between loneliness status and network changes. Of 424 participants (mean age 58 [SD = 10]) meeting inclusion criteria for PET analyses, 5% (21/424) were lonely; no associations were observed between loneliness and either Aβ or tau deposition in primary regions of interest. CONCLUSIONS/UNASSIGNED:In this cross-sectional study, there were no observable associations between loneliness and select fcMRI, Aβ PET, and tau PET neuroimaging markers of AD risk. These findings merit further investigation in prospective studies of community-based cohorts.

BACKGROUND/UNASSIGNED:The literature documents that laminoforaminotomy (CLF), whether performed open, minimally invasively, or microendoscopically, is safer than anterior cervical diskectomy/fusion (ACDF) for lateral cervical disease. METHODS/UNASSIGNED:ACDF for lateral cervical disc disease and/or spondylosis exposes patients to multiple major surgical risk factors not encountered with CLF. These include; carotid artery or jugular vein injuries, esophageal tears, dysphagia, recurrent laryngeal nerve injuries, tracheal injuries, and dysphagia. CLF also exposes patients to lower rates of vertebral artery injury, dural tears (DT)/cerebrospinal fluid fistulas, instability warranting fusion, adjacent segment disease (ASD), plus cord and/or nerve root injuries. RESULTS/UNASSIGNED:Further, CLF vs. ACDF for lateral cervical pathology offer reduced tissue damage, operative time, estimated blood loss (EBL), length of stay (LOS), and cost. CONCLUSION/UNASSIGNED:CLFs', whether performed open, minimally invasively, or microendoscopically, offer greater safety, major pros with few cons, and decreased costs vs. ACDF for lateral cervical disease.

BACKGROUND/UNASSIGNED:Morbid obesity (MO) is defined by the World Health Organization (WHO) as Class II (i.e. Body Mass Index (BMI) >/= 35 kg/M2 + 2 comorbidities) or Class III (i.e. BMI >/= 40 kg/M2). Here, we reviewed the rates for adverse event/s (AE)/morbidity/mortality for MO patients undergoing anterior cervical surgery as inpatients/in-hospitals, and asked whether this should be considered the standard of care? METHODS/UNASSIGNED:We reviewed multiple studies to document the AE/morbidity/mortality rates for performing anterior cervical surgery (i.e., largely ACDF) for MO patients as inpatients/in-hospitals. RESULTS/UNASSIGNED:MO patients undergoing anterior cervical surgery may develop perioperative/postoperative AE, including postoperative epidural hematomas (PEH), that can lead to acute/delayed cardiorespiratory arrests. MO patients in-hospitals have 24/7 availability of anesthesiologists (i.e. to intubate/run codes) and surgeons (i.e. to evacuate anterior acute hematomas) who can best handle typically witnessed cardiorespiratory arrests. Alternatively, after average 4-7.5 hr. postoperative care unit (PACU) observation, Ambulatory Surgical Center (ASC) patients are sent to unmonitored floors for the remainder of their 23-hour stays, while those in Outpatient SurgiCenters (OSC) are discharged home. Either for ASC or OSC patients, cardiorespiratory arrests are usually unwitnessed, and, therefore, are more likely to lead to greater morbidity/mortality. CONCLUSION/UNASSIGNED:Anterior cervical surgery for MO patients is best/most safely performed as inpatients/in-hospitals where significant postoperative AE, including cardiorespiratory arrests, are most likely to be witnessed events, and appropriately emergently treated with better outcomes. Alternatively, MO patients undergoing anterior cervical procedures in ASC/OSC will more probably have unwitnessed AE/cardiorespiratory arrests, resulting in poorer outcomes with higher mortality rates. Given these findings, isn't it safest for MO patients to undergo anterior cervical surgery as inpatients/in-hospitals, and shouldn't this be considered the standard of care?

BACKGROUND:Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. OBJECTIVE:To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. METHODS:This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. RESULTS:332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized β = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized β = -0.14, p = 0.028) in a linear regression model. CONCLUSIONS:PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

OBJECTIVE/UNASSIGNED:A pilot study to preliminarily examine the effects of Prism EFP NeuroFeedback (NF) in adult ADHD. METHOD/UNASSIGNED:Prism EFP NF is a form of NF specifically designed to target emotional dysregulation (ED) through down regulation of amygdala activity. Prism EFP NF has been shown to improve other disorders with significant ED. Nine participants with adult ADHD received an open trial of Prism EFP NF consisting of fifteen sessions over 8 weeks; all completed at least 5 weeks of treatment with seven completing all 8 weeks. Outcomes were assessed by change in ADHD symptoms from baseline to End of Treatment. RESULTS/UNASSIGNED:About two-third reduction was seen in total DSM ADHD symptom scores (primary outcome measure) with improvement observed in all other clinical measures. No significant adverse events were seen. CONCLUSION/UNASSIGNED:This preliminary trial found substantial effects of Prism EFP NF on ADHD/ED symptoms and global impairment.

Migraine is a leading cause of disability worldwide. A minority of individuals with migraine develop resistant or refractory conditions characterised by ≥ 8 monthly days of debilitating headaches and inadequate response, intolerance, or contraindication to ≥3 or all preventive drug classes, respectively. Resistant and refractory migraine are emerging clinical definitions stemming from better knowledge of the pathophysiology of migraine and from the advent of migraine-specific preventive treatments. Resistant migraine mostly results from drug failures, while refractory migraine has complex and still unknown mechanisms that impair the efficacy of preventive treatments. Individuals with resistant migraine can be treated with migraine-specific preventive drugs. The management of refractory migraine is challenging and often unsuccessful, being based on combinations of different drugs and non-pharmacological treatment. Future research should aim to identify individuals at risk of developing treatment failures, prevent the condition, investigate the mechanisms of refractoriness to treatments, and find effective treatment strategies.

Correlating the structure and dynamics of proteins with biological function is critical to understanding normal and dysfunctional cellular mechanisms. We describe a quantitative method of hydroxyl radical generation via Fe(II)-ethylenediaminetetraacetic acid (EDTA)-catalyzed Fenton chemistry that provides ready access to protein oxidative footprinting using equipment commonly found in research and process control laboratories. Robust and reproducible dose-dependent oxidation of protein samples is observed and quantitated by mass spectrometry with as fine a single residue resolution. An oxidation analysis of lysozyme provides a readily accessible benchmark for our method. The efficacy of our oxidation method is demonstrated by mapping the interface of a RAS-monobody complex, the surface of the NIST mAb, and the interface between PRC2 complex components. These studies are executed using standard laboratory tools and a few pennies of reagents; the mass spectrometry analysis can be streamlined to map the protein structure with single amino acid residue resolution.

BACKGROUND:Patient-reported outcomes (PRO) are increasingly utilized as part of the routine clinical assessment in people with multiple sclerosis (pwMS). The long-term effect of disease modifying therapies (DMTs) and their discontinuation on PRO measures remains largely unknown. METHODS:Two pwMS groups treated with natalizumab were selected from the New York State MS Consortium (NYSMSC) database. The first group utilized long-term follow-up data of pwMS that either still continue natalizumab treatment or discontinued. Minimal requirement of three visits (before natalizumab initiation, during treatment and after discontinuation/latest follow-up) was implemented. The second group consisted of pwMS that completed PRO questionnaire on the day of the infusion and 7 days later PROs were assessed using the LIFEware System™ that assesses limitations in multiple physical and psychosocial domains. Additional physical disability was assessed using Expanded Disability Status Scale (EDSS) and Timed 25-ft walk test (T25FWT). PRO reports were Rasch-transformed, ranging from 0 to 100, with higher scores indicating a better outcome. Linear mixed-effect models and paired analyses were utilized. RESULTS:Within the prospective cohort, 242 pwMS were followed on average of 6.5 years. Greater number of PRO domains worsened in the 141 pwMS that discontinued natalizumab when compared to 101 pwMS that remained on the drug (10 vs. 2 PRO domains). PwMS that discontinued natalizumab had significant decline in PROs regarding lower extremities, bladder and bower control and psychosocial aspects (feeling lonesome). Contrarily, pwMS that continued natalizumab had significant improvement in bladder and bowel PRO measures. Seven days after the natalizumab infusion, the 67 pwMS from the prospective cohort reported improvement in PRO measures of fatigue (62.8 vs. 66.4, p = 0.019), bladder limitations (80.3 vs. 85.0, p = 0.012), and feelings of lonesomeness (81.2 vs. 88.0, p = 0.009). CONCLUSION/CONCLUSIONS:Continuous natalizumab treatment provides long-term stability or improvement in PRO measures. Natalizumab also provides short term improvements recorded after the infusion.