A Framework for the Administration of Anti-amyloid Monoclonal Antibody Treatments in Early-Stage Alzheimer's Disease.

The US Food and Drug Administration (FDA) approval of lecanemab for early-stage Alzheimer's disease (AD) represents an exciting new chapter in the management of neurodegenerative disease, but likewise presents numerous clinical, technical, and financial logistical challenges for both academic and non-academic medical institutions hoping to administer this drug. Minimal resources exist that provide guidance for establishing and maintaining a lecanemab treatment program at the institutional level. The current report aims to provide healthcare institutions a framework for the planning, onboarding, and longitudinal treatment of AD with anti-amyloid monoclonal antibody treatments. We present an implementation study involving three stages: (1) feasibility assessment, (2) operations and going live, and (3) monitoring assessment. We found that implementation of lecanemab in clinical practice was feasible due to the assignment of an enterprise-wide project manager to facilitate the planning phase, a cost analysis showing that lecanemab was financially sustainable, and the development of electronic medical record tools to support operational efficiency.

An Atypical Presentation of Gonococcal Endocarditis.

A 53-year-old male presented following cardiac arrest, followed by cardiopulmonary resuscitation. He was found to have myocardial infarction, bihemispheric cerebral embolization and mitral valve endocarditis. Mitral valve replacement was performed and Neisseria gonorrhoeae was detected on PCR. This case represents a valuable addition to the limited reports on gonococcal endocarditis.

Left dural carotid cavernous fistula mimicking an inflammatory process: A case report.

A female in her 70s presented with altered mental status, left eye pain, ophthalmalgia, and diplopia following a fall. Brain MRI demonstrated contrast-enhancing left peri-insular T2 hyperintense changes that was read as possible herpes simplex encephalitis by neuroradiology. Cerebral angiogram revealed a Barrow Type D left sided carotid cavernous fistula. The patient was subsequently treated with endovascular transvenous coil embolization of the left cavernous sinus resulting in complete occlusion of the fistula. The goal of this case is to present a unique case of a carotid cavernous fistula radiologically mimicking herpes simplex encephalitis. Early recognition of carotid cavernous fistula on neuroimaging is important for prompt treatment of symptoms.

Abnormal clinical presentation and surgical outcome of an intraventricular cavernoma of the third ventricle.

We present a unique case of a man presenting with progressive short-term memory deficits over 10+ years who was found to have a large intraventricular cavernoma in the anterior wall of the third ventricle with invasion of medial limbic structures. Identifying intraventricular cavernomas early is crucial to prevent substantial growth and to increase the chance of successful patient outcomes.

Implementation and review of the care ecosystem in an integrated healthcare system.

BACKGROUND AND OBJECTIVES: The University of California, San Francisco Memory and Aging Center (UCSF-MAC) led the development and tested a collaborative care model delivered by lay care team navigators (CTNs) with support from a multidisciplinary team known as the Care Ecosystem (CE). We evaluated outcomes related to the feasibility of the CE in a non-academic healthcare system, including acceptability, adoption, and fidelity to the original UCSF model. RESEARCH DESIGN AND METHODS: The CE team at HealthPartners consisted of two CTNs, a social worker, an RN, a program coordinator, and a behavioral neurologist. Intake forms were developed to collect demographic, baseline, and annual data at one year related to dementia severity and caregiver status. Experience surveys were completed at 6 and 12 months by participating caregivers. All data was entered into REDCap. RESULTS: A total of 570 PWD-caregiver dyads were recruited into the CE: 53% PWDs female, average age 75.2 ± 9.43, 19% living within rural communities. Of the 173 dyads assessed at one year, 30% responded to the annual intake forms and 58% of responded to experience surveys. At one year, PWDs progressed in disease severity and functional impairment, although caregiver burden and mood remained unchanged. We observed a significant reduction in caregiver reported emotional challenges associated with caregiving, sleep problems, and obtaining caregiver help at one year. 86% of caregivers reported feeling supported by their CTN nearly always or quite frequently, and 88% rated the CTN as highly responsive to what was important to them. DISCUSSION AND IMPLICATIONS: The CE was feasible and well-received within a non-academic healthcare system.

A Case of Minimally Progressive Prodromal Alzheimer's Disease.

Prodromal Alzheimer's disease (AD) is a neurodegenerative condition typically progressing to dementia within 3 years. We describe a case of a mild cognitive impairment (MCI) patient with biomarker evidence for amyloidosis, tau, and neurodegeneration who had minimal changes in clinical phenotype during an 11-year period. AD biomarkers were obtained with cerebrospinal fluid analysis and amyloid PET imaging, both of which supported a biological diagnosis of AD. However, the patient's neuropsychological profile remained stable over 11 years except for mild memory-retrieval changes. This case provides evidence that MCI with supportive AD biomarkers may have an atypically minimal progression.

Eight-year outcomes of aortic valve replacement with the Carpentier-Edwards PERIMOUNT Magna Ease valve.

INTRODUCTION: The Carpentier-Edwards PERIMOUNT Magna Ease valve is a third-generation bioprosthesis for aortic valve replacement (AVR). This is a postapproval study reporting on its 8-year outcomes. METHODS: Adults undergoing AVR with the Magna Ease valve between October 2007 and December 2012 were enrolled for this prospective, nonrandomized, single-arm, and multicenter study. Assessments occurred preoperatively, at hospital discharge, 6 months, 1 year, and annually thereafter for up to 8 years. Outcomes included safety endpoints, hemodynamic performance, and New York Heart Association (NYHA) functional class. RESULTS: Of the 258 study patients, 67.5% were in NYHA Class I or II, and 32.5% were in NYHA Class III or IV at baseline. Concomitant procedures were performed in 44.2%. Total follow-up was 1597.6 patient-years, and median follow-up was 7 years (interquartile range: 5.5-8.0 years). Eight years following AVR, the functional class remained improved from baseline with 93.9% in NYHA Class I/II and 6.1% in NYHA Class III; 38 deaths had occurred, 8 of which were valve related; freedom from all-cause mortality was 80.7% (95% confidence intervals: 74.9, 86.4); freedom from valve-related mortality was 95.8% (92.8, 98.8); freedom from reintervention, explant, major bleeding events, and structural valve deterioration was 89.8% (85.1, 94.6), 94.8% (91.7, 97.9), 85.1% (80.0, 90.1), and 90.1% (84.7, 95.4), respectively; effective orifice area was 1.5 ± 0.5 cm2 , the mean gradient was 14.8 ± 8.3 mmHg, and 88.6% of patients had no or trivial aortic regurgitation. CONCLUSIONS: This study demonstrated satisfactory safety and sustained hemodynamic and functional improvements at 8 years following AVR with the Magna Ease valve.

Brain Glucose Hypometabolism and Iron Accumulation in Different Brain Regions in Alzheimer's and Parkinson's Diseases.

The aim of this study was to examine the relationship between the presence of glucose hypometabolism (GHM) and brain iron accumulation (BIA), two potential pathological mechanisms in neurodegenerative disease, in different regions of the brain in people with late-onset Alzheimer's disease (AD) or Parkinson's disease (PD). Studies that conducted fluorodeoxyglucose positron emission tomography (FDG-PET) to map GHM or quantitative susceptibility mapping-magnetic resonance imaging (QSM-MRI) to map BIA in the brains of patients with AD or PD were reviewed. Regions of the brain where GHM or BIA were reported in each disease were compared. In AD, both GHM and BIA were reported in the hippocampus, temporal, and parietal lobes. GHM alone was reported in the cingulate gyrus, precuneus and occipital lobe. BIA alone was reported in the caudate nucleus, putamen and globus pallidus. In PD, both GHM and BIA were reported in thalamus, globus pallidus, putamen, hippocampus, and temporal and frontal lobes. GHM alone was reported in cingulate gyrus, caudate nucleus, cerebellum, and parietal and occipital lobes. BIA alone was reported in the substantia nigra and red nucleus. GHM and BIA are observed independent of one another in various brain regions in both AD and PD. This suggests that GHM is not always necessary or sufficient to cause BIA and vice versa. Hypothesis-driven FDG-PET and QSM-MRI imaging studies, where both are conducted on individuals with AD or PD, are needed to confirm or disprove the observations presented here about the potential relationship or lack thereof between GHM and BIA in AD and PD.

Responding to the Needs of Persons Living With Dementia and Their Caregivers During the COVID-19 Pandemic: Lessons From the Care Ecosystem.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic created challenges for persons with dementia, their caregivers, and programs that support them. The Care Ecosystem (CE) is a model of dementia care designed to support people with dementia and their family caregiver dyads through ongoing contact with a care team navigator (CTN) and an expert clinical team. CTNs provide support, education, and resources and help dyads manage dementia-related concerns as they evolve over the course of the disease. We aimed to understand how the CE responded to the needs of dyads during the initial 3 months of the COVID-19 pandemic. Research Design and Methods: We conducted a survey and qualitative interviews with staff members from 4 established CE programs located in 4 different states to explore (a) challenges dyads voiced during the pandemic, (b) CE staff approaches to addressing the needs of dyads, and (c) programmatic challenges faced and lessons learned. Findings: Nine staff members from 4 CE programs with an active collective caseload of 379 dyads were interviewed. Themes were identified that included dyad concerns regarding fear of illness, changing attitudes toward long-term care, decreased availability of services and resources, and impacts on patient and caregiver health and well-being. Programmatic challenges included maintaining effective communication with dyads and program staff, technological readiness, workflow restructuring, and program sustainability. Discussion and Implications: Approaches in supporting people with dementia and their caregivers should demonstrate flexibility, responsivity, and creativity, and these findings provide insight for understanding how dementia care programs can be positioned to offer continuous support for this vulnerable population.

Prodromal Dementia With Lewy Bodies: Evolution of Symptoms and Predictors of Dementia Onset.

BACKGROUND: Research criteria for prodromal dementia with Lewy bodies (DLB) were published in 2020, but little is known regarding prodromal DLB in clinical settings. METHODS: We identified non-demented participants without neurodegenerative disease from the National Alzheimer's Coordinating Center Uniform Data Set who converted to DLB at a subsequent visit. Prevalence of neuropsychiatric and motor symptoms were examined up to 5 years prior to DLB diagnosis. RESULTS: The sample included 116 participants clinically diagnosed with DLB and 348 age and sex-matched (1:3) Healthy Controls. Motor slowing was present in approximately 70% of participants 3 years prior to DLB diagnosis. In the prodromal phase, 50% of DLB participants demonstrated gait disorder, 70% had rigidity, 20% endorsed visual hallucinations, and over 50% of participants endorsed REM sleep behavior disorder. Apathy, depression, and anxiety were common prodromal neuropsychiatric symptoms. The presence of 1+ core clinical features of DLB in combination with apathy, depression, or anxiety resulted in the greatest AUC (0.815; 95% CI: 0.767, 0.865) for distinguishing HC from prodromal DLB 1 year prior to diagnosis. The presence of 2+ core clinical features was also accurate in differentiating between groups (AUC = 0.806; 95% CI: 0.756, 0.855). CONCLUSION: A wide range of motor, neuropsychiatric and other core clinical symptoms are common in prodromal DLB. A combination of core clinical features, neuropsychiatric symptoms and cognitive impairment can accurately differentiate DLB from normal aging prior to dementia onset.

Rapid Development and Deployment of an Intensivist-Led Venovenous Extracorporeal Membrane Oxygenation Cannulation Program.

OBJECTIVES: To determine the safety and efficacy of a rapidly deployed intensivist-led venovenous extracorporeal membrane oxygenation cannulation program in a preexisting extracorporeal membrane oxygenation program. DESIGN: A retrospective observational before-and-after study of 40 patients undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation in an established cannulation program by cardiothoracic surgeons versus a rapidly deployed medical intensivist cannulation program. SETTING: An adult ICU in a tertiary academic medical center in Camden, NJ. PATIENTS: Critically ill adult subjects with severe respiratory failure undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation. INTERVENTIONS: Percutaneous cannulation for venovenous extracorporeal membrane oxygenation performed by cardiothoracic surgeons compared with cannulations performed by medical intensivists. MEASUREMENTS AND MAIN RESULTS: Venovenous extracorporeal membrane oxygenation cannulation site attempts were retrospectively reviewed. Subject demographics, specialty of physician performing cannulation, type of support, cannulation configuration, cannula size, imaging guidance, success rate, and complications were recorded and summarized. Twenty-two cannulations were performed by three cardiothoracic surgeons in 11 subjects between September 2019 and February 2020. The cannulation program rapidly transitioned to an intensivist-led and performed program in March 2020. Fifty-seven cannulations were performed by eight intensivists in 29 subjects between March 2020 and December 2020. Mean body mass index for subjects did not differ between groups (33.86 vs 35.89; p = 0.775). There was no difference in days on mechanical ventilation prior to cannulation, configuration, cannula size, or discharge condition. There was no difference in success rate of cannulation on first attempt per cannulation site (95.5 vs 96.7; p = 0.483) or major complication rate per cannulation site (4.5 vs 3.5; p = 1). CONCLUSIONS: There is no difference between success and complication rates of percutaneous venovenous extracorporeal membrane oxygenation canulation when performed by cardiothoracic surgeons versus medical intensivist in an already established extracorporeal membrane oxygenation program. A rapidly deployed cannulation program by intensivists for venovenous extracorporeal membrane oxygenation can be performed with high success and low complication rates.

Inferior Vena Cava Obstruction Following Surgical Repair of a Secundum Atrial Septal Defect.

Obstruction of the inferior vena cava (IVC) following surgical repair of an atrial septal defect (ASD) is a rare complication. We present the case of a patient who developed IVC obstruction following surgical repair of a large secundum ASD. The diagnostic and management approaches used to care for this patient are discussed. (Level of Difficulty: Intermediate.).

A Phase II, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Therapeutic Efficacy of Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease.

BACKGROUND: Intranasal insulin is a potential treatment for neurodegenerative disease shown to increase cerebral glucose uptake, reduce amyloid plaques, and improve verbal memory in cognitively impaired as well as healthy adults. Investigations have suggested rapid-acting insulins such as glulisine may result in superior cognitive benefits compared with regular insulin. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of rapid-acting intranasal glulisine in subjects with amnestic mild cognitive impairment (MCI) or mild probable Alzheimer's disease (AD). METHODS: We performed a single-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy of intranasal glulisine 20 IU twice daily versus saline placebo in 35 memory-impaired (MCI/AD) subjects using the Impel NeuroPharma I109 Precision Olfactory Delivery (POD®) device. The 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), Clinical Dementia Rating (CDR) global score, and Functional Assessment Questionnaire (FAQ) were measured at baseline and 3 and 6 months. Secondary outcome measures included digit span forward/backwards, Trail Making Test Parts A/B, Controlled Oral Word Association Test (COWAT), and Weschler Memory Scale (WMS)-IV logical memory. Adverse effects (AEs) and serious adverse effects (SAEs) were measured along with blood glucose/insulin levels. RESULTS: No significant difference in ADAS-Cog13, CDR Sum of Boxes (CDR-SOB), or FAQ scores were found between treatment groups at 3 and 6 months. Subjects in the saline group were significantly older than those in the glulisine group (p = 0.022). No significant differences in sex, education, apolipoprotein E4 (ApoE4) status, and Montreal Cognitive Assessment (MoCA) score existed between treatment groups. Overall, the number of adverse events per person was similar between groups (2.32 vs. 2.24; p = 0.824), although subjects receiving intranasal glulisine had higher rates of nasal irritation (25.0% vs. 13.9%) and respiratory symptoms (15.9% vs. 8.3%) compared with placebo. There were no differences in blood sugar or rate of hypoglycemia between the treatment and placebo groups. CONCLUSIONS: Intranasal glulisine was relatively safe and well-tolerated and did not consistently impact peripheral glucose or insulin levels. There were no enhancing effects of intranasal glulisine on cognition, function, or mood, but the ability to detect significance was limited by the number of subjects successfully enrolled and the study duration. CLINICALTRIALS. GOV REGISTRATION: NCT02503501.

A Pilot Study Comparing Aortic Valve Area Estimates Derived from Fick Cardiac Output with Estimates Based on Cheetah-NICOM Cardiac Output.

Cardiac output during cardiac catheterization is often estimated using the modified Fick method (COFick). In this proof-of-concept, prospective non-randomized study carried out in a single academic healthcare centre, we examined whether replacing COFick in the Gorlin formula with Cheetah-NICOM monitor cardiac output (COCheetah) could produce an accurate and precise estimate of aortic valve area in patients with severe aortic stenosis. In twenty-six subjects, COFick and COCheetah were obtained concurrently. A spot and 3-minute running average of COCheetah was used. Bland and Altman analysis was used to derive bias, 95% limits of agreement (LOA) and confidence intervals (CI). The mean difference (bias) between AVACheetah (average) and AVAFick was 0.11 cm2 and the 95% LOA were ±0.42 cm2. The 95% CI of the bias was 0.02-0.2 cm2. The bias and 95% LOA of AVACheetah (spot value) were 0.14 ± 0.42cm2, with a 95% CI of 0.06-0.23 cm2. No proportional bias was present. AVACheetah thus appears to be a reasonably accurate measure of AVA in patients with severe aortic stenosis compared to AVAFick measured using a modified Fick CO. However, the limits of agreement were not narrow enough to consider AVACheetah and AVAFick interchangeable.

Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome.

BACKGROUND: Individuals with Down syndrome are likely to develop clinical and neuropathological brain changes resembling Alzheimer's disease dementia by the ages of 35-40 years. Intranasal insulin is a potential treatment for neurodegenerative disease that has been shown to reduce amyloid plaque burden and improve verbal memory performance in normal as well as memory-impaired adults. Investigations have shown that rapid-acting insulins may result in superior cognitive benefits compared with regular insulin. OBJECTIVES: The primary objective of this study was to measure the safety and feasibility of intranasal rapid-acting glulisine in subjects with Down syndrome. Secondarily, we estimated the effects of intranasal glulisine on cognition and memory in Down syndrome. METHODS: A single-center, single-dose, randomized, double-blind, placebo-controlled, cross-over pilot study was performed to test the safety of intranasal glulisine vs placebo in 12 subjects with Down syndrome aged ≥ 35 years. Intranasal administration utilized the Impel NeuroPharma I109 Precision Olfactory Delivery (POD®) device. The primary outcomes were the occurrence of any or related adverse and serious adverse events. Secondary post-treatment cognitive outcome measures included performance on the Fuld Object-Memory Evaluation and Rivermead Behavioral Memory Test. RESULTS: Intranasal glulisine was safe and well tolerated in the Down syndrome population. No adverse or serious adverse events were observed. CONCLUSIONS: Further investigations are necessary to better evaluate the potential cognitive-enhancing role of intranasal insulin in the Down syndrome population. CLINICALTRIALS. GOV ID: NCT02432716.

Asanguinous Del Nido Cardioplegia for an Aortic Valve Replacement Patient with Cold Agglutinins.

A patient with known cold agglutinins requiring an aortic valve replacement was referred for surgery. Asanguinous, Del Nido cardioplegia was used for myocardial protection. Warm induction followed by cold infusion prevented any agglutination and eliminated the need for subsequent cardioplegia doses. Following the cross-clamp period, the heart returned to normal sinus rhythm without need for defibrillation. Postoperative ejection fraction and systolic function were normal.

Screening Positive for Cognitive Impairment: Impact on Healthcare Utilization and Provider Action in Primary and Specialty Care Practices.

BACKGROUND: Alzheimer's disease, the most common cause of dementia, goes unrecognized in half of patients presenting to healthcare providers and is associated with increased acute care utilization. Routine cognitive screening of older adults in healthcare settings could improve rates of dementia diagnosis and patterns of healthcare utilization. OBJECTIVE: To evaluate the impact of screening positive for cognitive impairment on provider action in primary and specialty care practices and patient healthcare utilization. DESIGN: Individuals asymptomatic for cognitive impairment completed cognitive screening with the Mini-Cog (MC). Outcomes included MC screen-positive rates, provider follow-up actions, and healthcare utilization for all participants over a period of 36 months (18 months prior to and following MC screening). Data were extracted from the electronic medical record (EMR). Healthcare provider interventions and healthcare utilization for screen-positive and -negative groups, before and after screening, were compared. PARTICIPANTS: Primary and specialty care patients (n = 787) aged ≥ 65 without history of cognitive impairment seen in HealthPartners, an integrated healthcare system in Minnesota and Western Wisconsin. KEY RESULTS: In primary care and neurology practices combined, over the entire 36-month study window, individuals screening positive showed 32% higher rates of ED visits (p < 0.05) pre and post-screening compared to those screening negative. Screen positive also showed 39% higher rates of hospitalizations pre-screening (p < 0.05) and 58% higher rates post-screening (p < 0.01). While screen-detected cognitive impairment was associated with some relevant provider follow-up action in 32% of individuals, subsequent healthcare utilization did not change between the 18-month pre- and post-screening periods. CONCLUSION: Despite being associated with higher rates of healthcare utilization, screening positive on the MC led to a change in provider action in a minority of cases and did not reduce post-screening healthcare utilization. Screening for cognitive impairment alone is not sufficient to alter patterns of provider practice or patient healthcare utilization.

Unexpected Left Atrial Thrombus After Aortic Valve Replacement and Left Atrial Ligation With AtriClip Device: A Case Report.

We report the unexpected transesophageal echocardiography (TEE) finding of a left atrial (LA) thrombus near the end of cardiopulmonary bypass and after deployment of an AtriClip (Atricure, Inc, Westchester, OH) in an 84-year-old man with atrial fibrillation and aortic stenosis undergoing aortic valve replacement and LA appendage ligation. TEE examination before cardiopulmonary bypass and deployment of the AtriClip had not shown a thrombus in the LA appendage. The heart was rearrested and thrombus was successfully removed through a left atriotomy. This case emphasizes the importance of careful TEE examination for dislodged thrombi after surgical manipulation of the LA appendage.

Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report.

BACKGROUND: Susac syndrome (retinocochleocerebral vasculopathy) is an autoimmune endotheliopathy affecting the precapillary arterioles of the brain, retina, and inner ear. It presents with encephalopathy, branch retinal artery occlusions, and hearing loss. The condition is often under recognized because the clinical symptoms may present at different times and physicians may be unfamiliar with the syndrome. Peripheral findings would be helpful in early diagnosis. There are numerous treatment regimens proposed with varying effectiveness. CASE PRESENTATION: We report the case of a 22-year-old Caucasian man in whom there were prominent skin findings, including livedo reticularis and a micropapular eruption which responded promptly to treatment suggesting that skin involvement may facilitate earlier diagnosis. Rituximab has occasionally been used in more refractory disease. We observed a prompt response to the combination of intravenous immunoglobulin, corticosteroids, and rituximab instituted immediately after diagnosis. CONCLUSIONS: A careful search for dermatological manifestations may help with earlier diagnosis. Skin findings may be another marker of endothelial cell involvement. Early use of rituximab as part of the therapeutic regimen may be warranted.