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Background: Ventricular free-wall rupture (VFWR) is an infrequent but catastrophic complication of acute myocardial infarction (AMI). Most reports about outcome after surgical treatment are single-center experiences. We examined the early and mid-term outcomes after surgical repair of post-AMI VFWR using the Netherlands Heart Registration (NHR) database. Methods: We included data from NHR patients (>18 years old) who underwent surgery for post-AMI VFWR between 2014 and 2019. The primary end-point was in-hospital mortality. Secondary outcomes included postoperative complications and mid-term survival. Results: The study included 148 patients (54.7% male, mean age 66.5 +/- 11.1 years). Critical preoperative status was found in 62.6% of subjects. In-hospital mortality was 31.1% (46 of 148). Multivariable analysis identified female sex [odds ratio (OR), 5.49; 95% confidence interval (CI): 2.24-13.46] and critical preoperative status (OR, 4.06; 95% CI: 1.36-12.13) as independent predictors of in-hospital mortality. The overall median postoperative follow-up was 2.2 (interquartile range, 0.7-3.8) years. Overall survival rates at three and five years were 58.9% and 55.7%, respectively. Among hospital survivors, only 15 (14.7%) patients died during follow-up, with a five-year survival rate of 80.8%. Conclusions: In-hospital mortality after surgical repair of post-AMI VFWR is considerable. Female sex and preoperative critical status are independent predictors of early postoperative (in-hospital) death. Logistic EuroSCORE I can reliably predict in-hospital mortality (optimal cut-off >33%). Mid-term follow-up of patients surviving in-hospital course shows excellent results.

BACKGROUND: Aortic coarctation in the adult is usually associated with chronic systemic hypertension, which leads to the sequelae of congestive heart failure, vascular dysfunction and decreased lifespan. Open and endovascular treatment modalities both provide excellent procedural outcomes with minimal mortality and morbidity, but a structured algorithm for workup and periprocedural decision making is not well established. We outline our heart team decision making approach along with our institution’s experience treating this condition. METHODS: We retrospectively reviewed twenty-four consecutive adult patients treated for aortic coarctation since 2010 at a single center. Outcomes of interest included mortality, treatment approach, device used and post-procedure hypertension status. We describe our protocol for work-up and intervention decision making. We explain our rationale for recommending treatment and the approach, open or endovascular, using existing literature and our experience. RESULTS: Procedural success rate was 100%, and there were no 30-day, one-year or five-year mortalities, whether the approach was open or endovascular. At last contact, 32% of patients were normotensive and no longer taking blood pressure medications. Several patients presented with complex problems as a result of commonly described complications of prior open or endovascular repair, and we describe our approach to the management of these difficult cases. CONCLUSIONS: Even at a high-volume heart and vascular hospital, aortic coarctation is an uncommon presentation in adult patients. Our experience suggests that excellent outcomes are obtained by discussing each patient among a multidisciplinary heart team and developing a work-up and treatment protocol to guide selection of interventional modality.

The COVID‐19 pandemic prompted social distancing, workplace closures, and restrictions on mobility and trade that had cascading effects on economic activity, food prices, and employment in low‐ and middle‐income countries. Using longitudinal data from Bangladesh, Kenya, and Nigeria covering a period from October 2020 to April 2021, the paper assesses whether knowledge of a person infected with COVID‐19 is associated with food insecurity, job loss and business closures, and coping strategies to smooth consumption. The likelihood of households to experience food insecurity at the extensive and intensive margins increased among those who knew an infected person in Bangladesh and Kenya.

Background: Transcatheter tricuspid valve-in-valve (TViV) and valve in-ring (TViR) implantation have become a viable therapy for a failed tricuspid bioprosthesis. Here we report short (thirty days) and long (one-year) term clinical outcomes of ten patients who underwent TViV at our institution. Methods: The electronic databases of New York Presbyterian Columbia Medical Center were retrospectively reviewed for cases of transcatheter tricuspid valve replacement (TViV or TViR). Between 2012 and 2019, data from ten patients who underwent TViV were collected. The primary safety outcome was procedure-related adverse events, including clinically evident cardiac perforation, new pericardial effusion and sustained ventricular arrhythmia. The primary efficacy endpoint was defined as successful valve deployment with total (paravalvular or intravalvular) tricuspid regurgitation (TR) estimated as mild or less. Results are descriptive in nature. Results: A total of ten patients who underwent TViV were included in the study. Of them, 40% presented with isolated tricuspid bioprosthetic stenosis (TS), 20% with isolated TR and 40% with mixed TS and TR. All patients were treated with the SAPIEN valve (first generation, XT, or Sapien 3). The TViV procedure was successful in all patients, and no immediate post-replacement paravalvular leak (PVL) or intra-procedural complications were reported. The primary safety and efficacy endpoints were met in all patients. At thirty-days, all patients were alive and reported significant improvements in symptoms and functional status. Conclusions: Transcatheter tricuspid valve implantation is a safe and effective therapy for degenerative tricuspid bioprosthesis.

Multisystem inflammatory syndrome in children (MIS-C), which was first documented in the United Kingdom and later recognized in other countries, is a postinfectious immune response to coronavirus disease 2019 (COVID-19). Its clinical manifestation resembles that of other inflammatory processes. Differentiation can be accomplished through epidemiology, a positive temporal relationship to COVID-19, and multiorgan involvement. Health care providers should maintain a high level of suspicion for MIS-C during the COVID-19 pandemic. A consistent picture of this immune response is emerging and diagnostic and treatment approaches are evolving. Advances continue to be made in the knowledge attainment regarding MIS-C clinical presentation and management.

Background: Open surgical repair of a failed valve-sparing aortic root replacement (VSARR) or stentless bioroot aortic root replacement (bio-ARR) entails significant operative risks. Whether valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) is feasible in patients with a previous VSARR or stentless bio-ARR remains unclear, given lingering concerns about the ill-defined aortic annulus in these patients and the potential for coronary obstruction. We present our experience with patients who had a previous VSARR or stentless bio-ARR and underwent ViV-TAVR to repair a degenerated aortic valve with combined valvular disease, aortic insufficiency and aortic stenosis. Methods: In this retrospective data review, we identified and analyzed consecutive patients with a previous VSARR or stentless bio-ARR who underwent ViV-TAVR between December 1, 2014 and August 31, 2019. Results: ViV-TAVR was performed in twelve high-risk patients with previous VSARR or bio-ARR during the study period. Of these, seven received Medtronic Freestyle porcine stentless bioprosthetic aortic roots, three received homograft aortic roots, one underwent a Ross procedure and one underwent VSARR. ViV-TAVR restored satisfactory valve function in all patients, and technical success was 100%. No patient had more than mild regurgitation after implantation. No thirty-day mortality was seen. One patient had major bleeding after transapical access, one patient had a transient ischemic stroke, and one patient needed permanent pacemaker implantation. At a median last follow-up of 21.5 months (interquartile range, 9.0–69.0 months), all patients remained alive and had satisfactory valve function. Conclusions: In this study, ViV-TAVR was a clinically effective option for treating patients with a failed stentless bio-ARR or previous VSARR. Short-term and intermediate-term results after these procedures were favorable. These findings may have important implications for treating high-risk patients with structural aortic root deterioration and call for better transcatheter heart valves that are suitable for treating aortic insufficiency.

Introduction Innovative patient engagement models are required to identify people with prodromal and mild Alzheimer's disease who are “hidden” in their communities and not normally found in a memory clinic setting. Methods A marketing campaign and a web‐based pre‐screening tool were used to identify individuals at risk of dementia in five European countries. Harmonized clinical evaluation of these patients was performed in participating memory clinics within the MOPEAD project. Results A total of 1487 individuals completed the pre‐screening, with 547 of them found to be at risk of dementia (36.8%). Among the subset of 91 patients with a positive pre‐screening result that underwent full clinical evaluation, 49 (53.8%) were diagnosed with either mild cognitive impairment or Alzheimer's disease. Conclusion This novel web‐based pre‐screening tool showed to be a valid strategy to identify undiagnosed people with cognitive impairment.

Introduction Cryoablation has evolved as a safe alternative to radiofrequency ablation in the treatment of several supraventricular arrhythmias and has potential advantages, yet is limited by the properties of the cryogen used. We investigated a novel ultralow temperature cryoablation (ULTCA) system using nitrogen near its liquid-vapor critical point as a freezing source, achieving temperatures as low as -196 degrees Celsius in a long linear catheter with a continuous energy release. Initial safety, procedural and efficacy outcomes of ULTCA are described in patients undergoing cavotricuspid isthmus (CTI) ablation. Methods and results The Cryocure studies (NCT02355106, NCT02839304) are prospective, single-arm, multi-center, first-in-human clinical studies in 17 patients with atrial flutter (AFL) and 13 patients with atrial fibrillation (AF). A total of 30 patients, mean age 65±8 years old and 67% male, were enrolled and underwent ablation of the CTI. Acute success, defined as the confirmation of stable bidirectional conduction block across the CTI, was achieved in all 30 patients. After 12 months of follow-up, 14 out of 17 AFL patients remained free from any AFL. One (3.3%) procedure-related but not device-related serious adverse event was reported, involving transient inferolateral ST-elevation associated with temporary AV conduction block. Conclusion In this first-in-human clinical study the safety and performance results demonstrate the capabilities of ultralow temperature near-critical nitrogen as an effective energy source for CTI ablation. Ongoing, larger, studies should confirm our findings and evaluate the capabilities to create linear and focal transmural lesions in other arrhythmias. This article is protected by copyright. All rights reserved.

The purpose of this study was to assess the impact of coronavirus disease 2019 on perceived stress experienced by nurse practitioners/nurses and their desire to remain employed as health care providers. A cross-sectional survey of 40 questions was administered between May and September 2020 to a convenience sample of 433 nurse practitioners and nurses in Missouri and Georgia through a Qualtrics (Provo, UT) link provided via their professional organization listserv. Anxiety-related symptoms and perceived helplessness were correlated with personal protective equipment concerns and management approachability. Problematic stress was associated with willingness to leave their current job or the nursing profession altogether.

Introduction Dementia has been associated with COVID-19 prevalence, but whether this reflects higher infection, older age of patients, or disease severity remains unclear Methods We investigated a cohort of 12,863 UK Biobank community-dwelling individuals > 65 years old (1814 individuals >= 80 years old) tested for COVID-19 Individuals were stratified by age to account for age as a confounder Risk factors were analyzed for COVID-19-positive diagnosis, hospitalization, and death Results All-cause dementia, Alzheimer's disease (AD), and Parkinson's disease (PD) were associated with COVID-19-positive diagnosis, and all-cause dementia and AD remained associated in individuals >= 80 years old All-cause dementia, AD, or PD were not risk factors for overall hospitalization, but increased the risk of hospitalization of COVID-19 patients All-cause dementia and AD increased the risk of COVID-19-related death, and all-cause dementia was uniquely associated with increased death in >= 80-year-old patients Discussion All-cause dementia and AD are age-independent risk factors for disease severity and death in COVID-19 (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Introduction Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed. Methods A total of 336 consecutive brain donors exposed to repetitive head impacts from contact sports, military service, and/or physical violence were included. Blinded to clinical information, neuropathologists applied National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering CTE criteria. Blinded to neuropathological information, clinicians interviewed informants and reviewed medical records. An expert panel adjudicated TES diagnoses. Results A total of 309 donors were diagnosed with TES; 244 donors had CTE pathology. TES criteria demonstrated sensitivity and specificity of 0.97 and 0.21, respectively. Cognitive (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 1.2–5.1), but not mood/behavior or motor symptoms, were significantly associated with CTE pathology. Having Alzheimer's disease (AD) pathology was significantly associated with reduced TES accuracy (OR = 0.27; 95% CI: 0.12–0.59). Discussion TES criteria provided good evidence to rule out, but limited evidence to rule in, CTE pathology. Requiring cognitive symptoms in revised criteria and using AD biomarkers may improve CTE pathology prediction.

Introduction The etiology of sporadic Alzheimer's disease (AD) requires non‐genetically modified animal models. Methods The relationship of tau phosphorylation to calcium‐cyclic adenosine monophosphate (cAMP)‐protein kinase A (PKA) dysregulation was analyzed in aging rhesus macaque dorsolateral prefrontal cortex (dlPFC) and rat primary cortical neurons using biochemistry and immuno‐electron microscopy. The influence of calcium leak from ryanodine receptors (RyRs) on neuronal firing and cognitive performance was examined in aged macaques. Results Aged monkeys naturally develop hyperphosphorylated tau, including AD biomarkers (AT8 (pS202/pT205) and pT217) and early tau pathology markers (pS214 and pS356) that correlated with evidence of increased calcium leak (pS2808‐RyR2). Calcium also regulated early tau phosphorylation in vitro. Age‐related reductions in the calcium‐binding protein, calbindin, and in phosphodiesterase PDE4D were seen within dlPFC pyramidal cell dendrites. Blocking RyRs with S107 improved neuronal firing and cognitive performance in aged macaques. Discussion Dysregulated calcium signaling confers risk for tau pathology and provides a potential therapeutic target.

Introduction Alzheimer's disease (AD) is a devastating condition with no effective treatments, with promising findings in rodents failing to translate into successful therapies for patients. Methods Targeting the vulnerable entorhinal cortex (ERC), rhesus monkeys received two injections of an adeno‐associated virus expressing a double tau mutation (AAV‐P301L/S320F) in the left hemisphere, and control AAV‐green fluorescent protein in the right ERC. Noninjected aged‐matched monkeys served as additional controls. Results Within 3 months we observed evidence of misfolded tau propagation, similar to what is hypothesized to occur in humans. Viral delivery of human 4R‐tau also coaptates monkey 3R‐tau via permissive templating. Tau spreading is accompanied by robust neuroinflammatory response driven by TREM2+ microglia, with biomarkers of inflammation and neuronal loss in the cerebrospinal fluid and plasma. Discussion These results highlight the initial stages of tau seeding and propagation in a primate model, a more powerful translational approach for the development of new therapies for AD.

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H2S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H2S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H2S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H2S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H2S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H2S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention., Scheme for sulfide dysregulation in ADRD. In ADRD, increased accumulation of sulfides, measured in plasma, may reflect increased formation of H2S metabolites produced in the vascular compartment. Several sulfide species are known to impair blood brain barrier leading to persistent excitotoxic stress and subsequent destructive changes in brain microvascular structure and cognitive function seen in ADRD.

Introduction We examined the long‐term risk of dementia after coronary artery bypass grafting (CABG) in relation to age and sex. Methods All CABG patients in Sweden 1992–2015 (n = 111,335), and matched controls (n = 222,396) were included in a population‐based study. Adjusted hazard ratios (aHR) for all‐cause dementia, vascular dementia, and Alzheimer's disease were calculated. Results There was no difference in the risk for all‐cause dementia between CABG patients and control subjects (aHR 0.98 [95% confidence interval 0.95 to 1.02]). CABG patients

Introduction The association between cerebral amyloid‐β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages. Methods In 318 cognitively unimpaired participants, we assessed the association between amyloid‐β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiological pathways. Interactions by Alzheimer's disease risk factors (age, sex and APOE‐ε4), and the mediation effect of tau and neurodegeneration were also investigated. Results Centiloids were positively associated with CSF biomarkers of tau pathology (p‐tau), neurodegeneration (t‐tau, NfL), synaptic dysfunction (neurogranin) and neuroinflammation (YKL‐40, GFAP, sTREM2), presenting interactions with age (p‐tau, t‐tau, neurogranin) and sex (sTREM2, NfL). Most of these associations were mediated by p‐tau, except for NfL. The interaction between sex and amyloid‐β on sTREM2 and NfL was also tau‐independent. Discussion Early amyloid‐β accumulation has a tau‐independent effect on neurodegeneration and a tau‐dependent effect on neuroinflammation. Besides, sex has a modifier effect on these associations independent of tau.

Introduction The extent that cognitive measures are documented in electronic health records (EHR) is important for quality care and addressing disparities in timely diagnosis of dementia or Alzheimer's disease (AD). Methods Analysis of U.S. EHR data to describe the frequency and factors associated with cognitive measures prior to diagnosis of dementia (N = 111,125) or AD (N = 30,203). Results Only 11% of dementia patients and 24% of AD patients had a cognitive measure documented in the 5 years prior to diagnosis. Black race, older age, non‐commercial health insurance, lower mean neighborhood income, greater in‐patient stays, and fewer out‐patient visits were associated with lacking cognitive measures. Discussion Extensive missing cognitive data and differences in the availability of cognitive measures by race, age, and socioeconomic factors hinder patient care and limit utility of EHR for dementia research. Structured fields and prompts for cognitive data inputs at the point of care may help address these gaps.

Accessibility to health care is crucial to management of chronic and acute conditions. Although the severe acute respiratory syndrome coronavirus 2 pandemic significantly impacts the issue of access to health care, with the introduction of Waiver 1135, telehealth has become a positive strategy in increasing safe access to health care. This report addresses considerations to take into account when advanced practice registered nurses use telehealth to facilitate access to care., Highlights • Telehealth etiquette and Waiver 1135 supporting the need for swift expansion of telehealth during the pandemic. • As of February 2020, there are 290,000 licensed practicing advanced practice registered nurses, and 89.7% are certified primary care providers with the potential to use telehealth to provide safe, quality health care. • Using telehealth increases safe patient access to care amidst the pandemic.

Introduction Gait impairment is common in neurodegenerative disorders. Specifically, gait variability—the stride‐to‐stride fluctuations in distance and time—has been associated with neurodegeneration and cognitive impairment. However, quantitative comparisons of gait impairments across the cognitive spectrum of dementias have not been systematically investigated. Methods Older adults (N = 500) with subjective cognitive impairment, Parkinson disease (PD), mild cognitive impairment (MCI), PD‐MCI, Alzheimer's disease (AD), PD‐dementia, Lewy body dementia, and frontotemporal dementia, as well cognitive normal controls, who were assessed for their gait and cognitive performance. Results Factor analyses grouped 11 quantitative gait parameters and identified four independent gait domains: rhythm, pace, variability, and postural control, for group comparisons and classification analysis. Among these domains, only high gait variability was associated with lower cognitive performance and accurately discriminated AD from other neurodegenerative and cognitive conditions. Discussion Our findings indicate that high gait variability is a marker of cognitive‐cortical dysfunction, which can help to identify Alzheimer's disease dementia.

Introduction Blood‐based Alzheimer's disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington Heights‐Inwood Columbia Aging Project (WHICAP), a multi‐ethnic community study of aging and dementia. Methods We measured plasma amyloid beta (Aβ)40, Aβ42, total tau (t‐tau), phosphorylated tau (p‐tau)181, and p‐tau217, and neurofilament light chain (NfL) in 113 autopsied participants (29% with high AD neuropathological changes) and in 300 clinically evaluated individuals (42% with clinical AD). Receiver operating characteristics were used to evaluate each biomarker. We also investigated biomarkers as predictors of incident clinical AD. Results P‐tau181, p‐tau217, and NfL concentrations were elevated in pathologically and clinically diagnosed AD. Decreased Aβ42/Aβ40 ratio and increased p‐tau217 and p‐tau181 were associated with subsequent AD diagnosis. Discussion Blood‐based AD biomarker concentrations are associated with pathological and clinical diagnoses and can predict future development of clinical AD, providing evidence that they can be incorporated into multi‐ethnic, community‐based studies.

The purpose of this article is to inform nurse practitioners and other healthcare professionals regarding the utilization of CardioMEMs, a wireless pulmonary artery pressure monitoring device, in reducing heart failure-related hospital readmission rates. This article will briefly explain how CardioMEMs also helps to reduce the risk of Covid-19 in patients with heart failure.

The dual pandemics of coronavirus disease-19 (COVID-19) and diabetes among patients are associated with 2- to 3-times higher intensive care admissions and higher mortality rates. Whether sheltering at home, quarantined with a positive COVID-19 test, or hospitalized, the person living with diabetes needs special considerations for successful management. Having diabetes and being COVID-19–positive increases the risk of poor outcomes and death. Providers need to give anticipatory pharmacologic guidance to patients with diabetes during COVID-19 lockdown. Patients with diabetes need to be more observant than others and to use self-protective actions. This review (1) discusses the clinical observations of COVID-19, diabetes and underlying mechanisms, (2) describes special considerations in caring for patients with diabetes in a COVID-19 environment, and (3) reviews clinical implications for the health care provider. This review highlights current evidenced-based knowledge. Additional research regarding clinical management is warranted

Vaccination is an important step to avoid coronavirus disease 2019 infection and alleviate the disruption caused by the pandemic. Health care providers can improve outcomes by educating themselves and subsequently encouraging patients to vaccinate against the virus. This can be accomplished by understanding how the coronavirus disease 2019 vaccine works and what causes barriers and fear of vaccination.

Introduction Fornix deep brain stimulation (fx‐DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback phenomena that were reported previously during acute diencephalic stimulation. Methods Thirty‐nine patients with mild AD who took part in a prior fx‐DBS trial (NCT01608061) were studied. After localizing patients’ implanted electrodes and modeling the volume of tissue activated (VTA) by DBS during systematic stimulation testing, we performed (1) voxel‐wise VTA mapping to identify flashback‐associated zones; (2) machine learning–based prediction of flashback occurrence given VTA overlap with specific structures; (3) normative functional connectomics to define flashback‐associated brain‐wide networks. Results A distinct diencephalic region was associated with greater flashback likelihood. Fornix, bed nucleus of stria terminalis, and anterior commissure involvement predicted memory events with 72% accuracy. Flashback‐inducing stimulation exhibited greater functional connectivity to a network of memory‐evoking and autobiographical memory‐related sites. Discussion These results clarify the neuroanatomical substrates of stimulation‐evoked flashbacks.

Background: Trans-apical, echo-guided NeoChord mitral valve (MV) repair is an innovative procedure to treat degenerative mitral regurgitation (MR) without concomitant annuloplasty. Recently, leaflet-to-annulus index (LAI) has been identified as a positive prognostic predictor of outcomes at 1-year follow up. The aim of this study is to develop a pre-operative predictor tool to assess probability of success with NeoChord procedure utilizing multi-factor echocardiographic and anatomic variables. Methods: We included ninety-one consecutive patients with prolapse/flail of the posterior mitral leaflet, who subsequently underwent NeoChord MV repair between November 2013 and October 2016. All patients completed post-operative echocardiographic follow-up assessments for up to 2 years. A random forest regression algorithm identified and ranked the most relevant predictors of moderate-severe MR. A multi-variable Cox regression model was performed at follow-up intervals, to assess variables associated with residual MR that was classified as mild or less. Bootstrapping re-samples were used to validate an estimated survival model. Predictive accuracy was assessed using a discrimination index that corrected for over-optimism. Results: We developed a nomogram which used the results of a multi-variable model to predict the probability of mild or less residual MR at follow-up periods (discharge, 1, 3, 6 months, 1 and 2 years). Identified predictors included LAI, systolic pulmonary artery pressure, indexed left ventricle end-systolic volume (iLVESV), prolapse/flail width (FW), systolic antero-posterior (AP) annulus diameter, systolic latero-lateral (LL) annulus diameter and presence of calcification. Conclusions: A NeoChord MV repair prediction tool would be helpful in clinical decision-making and in the identification of patients who may benefit from a ringless mitral valve repair using the NeoChord procedure.

Introduction This study investigated the diagnostic and disease‐monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Methods Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants. Results Phosphorylated‐tau181 (P‐tau181), neurofilament light, amyloid‐β (Aβ42/40), Total‐tau and Glial fibrillary acidic protein were altered in AD dementia but P‐tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P‐tau181 was increased in MCI converters compared to non‐converters. Higher P‐tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P‐tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals. Discussion P‐tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P‐tau181 as a non‐invasive and cost‐effective diagnostic and prognostic biomarker in AD.

Although the COVID‐19 pandemic resulted in about a 24% decline in India's GDP during the April–June 2020 quarter, the nation's agricultural sector, somewhat surprisingly, seems to have done remarkably well. This paper examines whether the public transfer program Pradhan Mantri Garib Kalyan Yojana (PMGKY), announced immediately after the lockdown, benefited farmers in dealing with the COVID shock. Overall, 95% of the smallholders received support from at least one of PMGKY's four components. Direct cash transfers had significantly more impact than in‐kind transfer schemes. The result shows that farmers receiving cash transfers under PM‐KISAN, one component of PMGKY, were more likely to invest in buying seeds. In contrast, farmers receiving cash transfers under PM‐UY, another piece of PMGKY, were more likely to invest in fertilizer and pesticides. Finally, smallholders who received benefits from all four components of PMGKY were more likely to invest in purchasing seeds, fertilizer, and pesticides. Findings suggest the fungibility of public cash transfers from the recent PMGKY scheme is significant in alleviating credit constraints and increasing future investments in modern inputs.

BACKGROUND: Reductive annuloplasty repair of ischemic mitral regurgitation (IMR) is associated with high rates of recurrent MR, which may be improved with etiology-specific annuloplasty rings. METHODS: From October 2005 to May 2015, 128 consecutive patients underwent repair of IMR with the GeoForm ring. Clinical data was extracted from our local Society of Thoracic Surgeons database and electronic medical records. Mortality data was obtained from the Michigan State Social Security Death Index. RESULTS: The average age of patients was 65±11 years with mean pre-op left ventricular ejection fraction (LVEF) of 30%±10% and MR grade of 3.1±0.9 (0–4+). Thirty-day mortality was 4.7%, rate of renal failure 7.9%, rate of atrial fibrillation 27.3%, and no strokes were observed. Of the surviving patients, 89% (109/122) had a follow-up echocardiogram beyond 1 month with a mean echocardiographic follow-up of 59±39 months. LVEF improved from 30%±10% to 38%±14%, P

Introduction This study examines the utility of a multipanel of cerebrospinal fluid (CSF) biomarkers complementing Alzheimer's disease (AD) biomarkers in a clinical research sample. We compared biomarkers across groups defined by clinical diagnosis and pTau181 /Aβ42 status (+/-) and explored their value in predicting cognition. Methods CSF biomarkers amyloid beta (Aβ)42 , pTau181 , tTau, Aβ40 , neurogranin, neurofilament light (NfL), α-synuclein, glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL-40), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), S100 calcium binding protein B (S100B), and interleukin 6 (IL6), were measured with the NeuroToolKit (NTK) for 720 adults ages 40 to 93 years (mean age = 63.9 years, standard deviation [SD] = 9.0; 50 with dementia; 54 with mild cognitive impairment [MCI], 616 unimpaired). Results Neurodegeneration and glial activation biomarkers were elevated in pTau181 /Aβ42 + MCI/dementia participants relative to all pTau181 /Aβ42 - participants. Neurodegeneration biomarkers increased with clinical severity among pTau181 /Aβ42 + participants and predicted worse cognitive performance. Glial activation biomarkers were unrelated to cognitive performance. Discussion The NTK contains promising markers that improve the pathophysiological characterization of AD. Neurodegeneration biomarkers beyond tTau improved statistical prediction of cognition and disease stages.

© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Introduction: Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Methods: Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Results: Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Discussion: Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD., This work is co‐funded by the UK Medical Research Council (MR/M023664/1), the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant and the Bluefield Project, as well as a JPND grant “GENFI‐prox” (by DLR/BMBF to MS, joined with JDR, JvS, MO, BB and CG). MM is supported by the Cambridge Trust & Sidney Sussex College Scholarship. PSJ is supported by the Cambridge Centre for Parkinson Plus. KAT is supported by the British Academy Postdoctoral Fellowship (KAT: PF160048) and Guarantors of Brain (KAT: 101149). TR is supported by the Cambridge Centre for Parkinson Plus and Cambridge Biomedical Resource Centre. RAK is supported by Medical Research Council (RAK: SUAG/047/G101400). JBR reports grants from the NIHR Cambridge Biomedical research centre, Wellcome Trust (103838), and Medical Research Council (SUAG051/G101400; MR/T033371/1); personal fees from Asceneuron, WAVE, Astex, and Biogen; and grants from Janssen, AZ Medimmune, and Eli Lilly, outside the submitted work. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS‐JF‐19a‐004‐517), and by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK.

Introduction Phosphorylated tau (p‐tau) in cerebrospinal fluid (CSF) is an established Alzheimer's disease (AD) biomarker. Novel immunoassays targeting N‐terminal and mid‐region p‐tau181 and p‐tau217 fragments are available, but head‐to‐head comparison in clinical settings is lacking. Methods N‐terminal‐directed p‐tau217 (N‐p‐tau217), N‐terminal‐directed p‐tau181 (N‐p‐tau181), and standard mid‐region p‐tau181 (Mid‐p‐tau181) biomarkers in CSF were evaluated in three cohorts (n = 503) to assess diagnostic performance, concordance, and associations with amyloid beta (Aβ). Results CSF N‐p‐tau217 and N‐p‐tau181 had better concordance (88.2%) than either with Mid‐p‐tau181 (79.7%–82.7%). N‐p‐tau217 and N‐p‐tau181 were significantly increased in early mild cognitive impairment (MCI)‐AD (A+T–N–) without changes in Mid‐p‐tau181 until AD‐dementia. N‐p‐tau217 and N‐p‐tau181 identified Aβ pathophysiology (area under the curve [AUC] = 94.8%–97.1%) and distinguished MCI‐AD from non‐AD MCI (AUC = 82.6%–90.5%) signficantly better than Mid‐p‐tau181 (AUC = 91.2% and 70.6%, respectively). P‐tau biomarkers equally differentiated AD from non‐AD dementia (AUC = 99.1%–99.8%). Discussion N‐p‐tau217 and N‐p‐tau181 could improve diagnostic accuracy in prodromal‐AD and clinical trial recruitment as both identify Aβ pathophysiology and differentiate early MCI‐AD better than Mid‐p‐tau181.

Altres ajuts: This work was also supported by the National Institutes of Health (R21AG056974 and R01AG061566 to JF); Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (SLT002/16/00408 to AL); Fundació La Marató de TV3 (20141210 to JF, 044412 to RB). Fundació Catalana Síndrome de Down and Fundació Víctor Grífols i Lucas partially supported this work. This work was also supported by Generalitat de Catalunya (SLT006/17/00119 to JF) and a grant from the Fundació Bancaria La Caixa to RB. The discovery that nerve growth factor (NGF) metabolism is altered in Down syndrome (DS) and Alzheimer's disease (AD) brains offered a framework for the identification of novel biomarkers signalling NGF deregulation in AD pathology. We examined levels of NGF pathway proteins (proNGF, neuroserpin, tissue plasminogen activator [tPA], and metalloproteases [MMP]) in matched cerebrospinal fluid (CSF)/plasma samples from AD-symptomatic (DSAD) and AD-asymptomatic (aDS) individuals with DS, as well as controls (HC). ProNGF and MMP-3 were elevated while tPA was decreased in plasma from individuals with DS. CSF from individuals with DS showed elevated proNGF, neuroserpin, MMP-3, and MMP-9. ProNGF and MMP-9 in CSF differentiated DSAD from aDS (area under the curve = 0.86, 0.87). NGF pathway markers associated with CSF amyloid beta and tau and differed by sex. Brain NGF metabolism changes can be monitored in plasma and CSF, supporting relevance in AD pathology. These markers could assist staging, subtyping, or precision medicine for AD in DS.

Telemedicine has been effective at bridging the gap among patients, providers, and health systems. Authors from a large academic medical center in Baltimore, MD, anecdotally found that digital tools were beneficial in supporting substance use disorder recovery during a global pandemic. Audiovisual tools like Zoom (Zoom Video Communications, Inc, San Jose, CA) and Doximity (Doximity, Inc, San Francisco, CA), as well as increased frequency of communication with patients, have been most helpful to supporting recovery. The barriers noted were related to patient privacy and increased tendency of patients to avoid treatment, similar barriers as when treatment is provided in the clinic. The intent of this narrative is to discuss provider perspectives of benefits and barriers to telemedicine for substance use disorder treatment during the coronavirus disease 2019 pandemic.

Introduction Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI). Methods Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyceride [kMCT]; 15 g twice/day; n = 39) or placebo (n = 44). Results Free and cued recall (Trial 1; P = .047), verbal fluency (categories; P = .024), Boston Naming Test (total correct answers; P = .033), and the Trail‐Making Test (total errors; P = .017) improved significantly in the kMCT group compared to placebo (analysis of covariance; pre‐intervention score, sex, age, education, and apolipoprotein E4 as covariates). Some cognitive outcomes also correlated positively with plasma ketones. Plasma metabolic profile and ketone response were unchanged. Conclusions This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression to Alzheimer's disease.

As lockdown and school closure policies were implemented in response to the coronavirus, the federal government provided funding and relaxed its rules to support emergency food provision, but not guidance on best practices for effectiveness. Accordingly, cities developed a diverse patchwork of emergency feeding programs. This article uses qualitative data to provide insight into emergency food provision developed in five cities to serve children and families. Based on our qualitative analysis, we find that the effectiveness of local approaches appears to depend on: (i) cross‐sector collaboration, (ii) supply chains, and (iii) addressing gaps in service to increased risk populations.

COVID‐19 has had unprecedented effects on the US economy, in large part because of its effects on workers. Within food and agriculture, these effects pose the greatest threat to the production of labor‐intensive commodities—in particular, fruits and vegetables, the production of which tends to require large numbers of workers for harvesting and packing. We econometrically estimate the effects of COVID‐19 on fruit and vegetable production as the US agricultural labor supply is adversely affected by this pandemic. The major crop losses include $16 million in lettuce, $5 million in apples, and $4 million in grapes.

The digital divide limits opportunities for those without ready access to Internet. Movement online of essential activities during COVID‐19 took inadequate Internet service from inconvenient to emergency/crisis for many households. A negative correlation between rurality and Internet speed was found at the county level, highlighting the struggle for rural areas. Schools tackle challenges of providing equitable educational access by attempting to provide access for students, while even households with service available struggle to maintain sufficient speeds and/or can afford it. Essential activities moved online, yet sufficient Internet is an essential public service that remains unattainable for many US households.

Introduction Conventional risk factors targeted by prevention (e.g., low education, smoking, and obesity) are associated with a 1.2‐ to 2‐fold increased risk of dementia. It is unclear whether having a physical disease is an equally important risk factor for dementia. Methods In this exploratory multicohort study of 283,414 community‐dwelling participants, we examined 22 common hospital‐treated physical diseases as risk factors for dementia. Results During a median follow‐up of 19 years, a total of 3416 participants developed dementia. Those who had erysipelas (hazard ratio = 1.82; 95% confidence interval = 1.53 to 2.17), hypothyroidism (1.94; 1.59 to 2.38), myocardial infarction (1.41; 1.20 to 1.64), ischemic heart disease (1.32; 1.18 to 1.49), cerebral infarction (2.44; 2.14 to 2.77), duodenal ulcers (1.88; 1.42 to 2.49), gastritis and duodenitis (1.82; 1.46 to 2.27), or osteoporosis (2.38; 1.75 to 3.23) were at a significantly increased risk of dementia. These associations were not explained by conventional risk factors or reverse causation. Discussion In addition to conventional risk factors, several physical diseases may increase the long‐term risk of dementia.

Introduction The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population. Methods In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE ε4 were analyzed across groups. Results The prevalence of the APOE ε4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57–5.45, P < .001). Discussion APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.

The novel coronavirus SARS‐CoV‐2 first appeared in Wuhan, China, in December 2019 and led to the Coronavirus Disease 2019 (COVID‐19), which quickly spread globally. Protocols for surgical patients with COVID‐19 were lacking, particularly for pregnant women undergoing cesarean deliveries. Perioperative nurses at Tongji Hospital in Wuhan retrospectively analyzed the perioperative nursing process, including OR preparation, intraoperative care, and OR cleanup, for women with COVID‐19 undergoing cesarean deliveries. Preparation involved altering the layout of the surgical suite, educating staff members, providing personal protective equipment, and creating new in‐house guidelines to help protect personnel and patients. This article describes how perioperative personnel strategized to prevent the transmission of COVID‐19 in the OR and presents a multiple‐case summary of six pregnant patients with COVID‐19 who underwent cesarean deliveries at Tongji Hospital in January and February 2020.

Introduction Few studies have examined memory decline among patients with type 2 diabetes using different oral hypoglycemic drugs. Methods Participants with normal cognition (NC) or Alzheimer's disease (AD) dementia using a hypoglycemic medication (2005 to 2019) were identified from the National Alzheimer's Coordinating Center database. Delayed memory was assessed using the Wechsler Memory Scale Revised–Logical Memory test. Associations between oral drug classes and memory over time were examined using mixed‐effects models with inverse probability treatment weights. Results In NC (n = 1192), metformin use was associated with better memory performance over time, whereas in AD (n = 807), dipeptidyl peptidase‐4 (DPP4) inhibitor use was associated with a slower rate of memory decline. Interaction effects suggested greater benefit associated with DPP4 inhibitor use among APOE ε4 carriers. Discussion Associations between different oral hypoglycemic drugs and memory change were not consistent between cognitively normal elderly and those with AD dementia. APOE ε4 genotype modified some relationships.

Introduction: The mechanism behind the strong association between the ɛ2/ɛ3/ɛ4 apolipoprotein E gene (APOE) polymorphism and Alzheimer's disease is not well-characterized. Because low plasma levels of apoE associate with risk of dementia, genetic variants altering apoE levels in general may also associate with dementia. Methods: The APOE gene was sequenced in 10,369 individuals, and nine amino acid–changing variants with frequencies ≥2/10,000 were further genotyped in 95,228 individuals. Plasma apoE levels were measured directly. Results: Risk of all dementia and Alzheimer's disease (AD) increased with decreasing genetically determined apoE levels (P = 5 × 10−4 and P = 1 × 10−4 after APOE ɛ2/ɛ3/ɛ4 adjustment). Hazard ratios (95% confidence intervals) for all dementia and AD were 2.76 (1.39 to 5.47) and 4.92 (2.36 to 10.29) for the group with the genetically lowest apoE versus ɛ33. Discussion: We found that genetically low apoE levels increase and genetically high levels decrease risk, beyond ɛ2/ɛ3/ɛ4. This underscores that dementia risk more likely relates to variants affecting levels of apoE.

Introduction This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild‐to‐moderate Alzheimer's disease (AD). Methods Three hundred forty‐seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6‐week period of weekly conventional PE followed by a 12‐month period of monthly low‐volume PE), and placebo (sham). Results PE‐treated patients performed significantly better than placebo for the co‐primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS‐ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; P = .06; 66% less decline) scores at month 14. Moderate‐AD patients (baseline Mini‐Mental State Examination [MMSE] 18‐21) scored better on ADCS‐ADL (P = .002) and ADAS‐Cog (P = .05), 61% less decline both. There were no changes in mild‐AD patients (MMSE 22‐26). PE‐treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR‐sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC) (P

Introduction Neuronal extracellular vesicle (nEV) tau and insulin signaling biomarkers may detect preclinical Alzheimer's disease and age‐associated cognitive decline. Methods This case‐control study used repeated serum samples from 73 cognitively declining and 73 stable Wisconsin Registry for Alzheimer's Prevention participants (62.4 ± 6.3 years old). We immunocaptured nEVs; measured tau and insulin signaling biomarkers; and examined biomarker differences by group, their performance in group classification in training and test datasets (97, 49 individuals, respectively), and whether they predict cognitive performance change. Results Declining compared to stable individuals showed higher baseline total, p231‐, and p181‐tau with older age and higher annualized change for p‐IR and p‐IGF‐1R. Combining biomarkers classified decliners with 94% area under the curve (AUC), 86.0% sensitivity and 86.7% specificity, in training data, and 75% AUC, 71.4% sensitivity, and 77.3% specificity, in test data. Insulin biomarkers predicted cognitive performance change prospectively. Discussion Combining nEV biomarkers can identify individuals with age‐associated cognitive decline.

Introduction Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density. Methods We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [11C]UCB‐J PET and a cerebellar reference region for calculation of the distribution volume ratio. Results We observed widespread reductions of SV2A binding in medial temporal and neocortical brain regions in early AD compared to CN participants. These reductions were largely maintained after correction for volume loss and were more extensive than decreases in gray matter volume. Conclusion We were able to measure widespread synaptic loss due to AD using [11C]UCB‐J PET. Future studies will continue to evaluate the utility of SV2A PET for tracking AD progression and for monitoring potential therapies.

INTRODUCTION: Loss to follow-up in dementia studies is common and related to cognition, which worsens over time. We aimed to (1) describe dropout and missing cognitive data in the Swedish dementia registry, SveDem; (2) identify factors associated with dropout; and (3) estimate propensity scores and use them to adjust for dropout.METHODS: Longitudinal cognitive data were obtained from 53,880 persons from the SveDem national quality dementia registry. Inverse probability of censoring weights (IPCWs) were estimated using a logistic regression model on dropout.RESULTS: The mean annualized rate of change in Mini-Mental State Examination (MMSE) in those with a low MMSE (0 to 10) was likely underestimated in the complete case analysis (+1.5 points/year) versus the IPCW analysis (-0.3 points/year).DISCUSSION: Handling dropout by IPCWs resulted in plausible estimates of cognitive decline. This method is likely of value to adjust for biased dropout in longitudinal cohorts of dementia.

Introduction The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo‐controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60‐year‐old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non‐carriers who receive placebo. Methods Of the 252 enrolled, we present data on a total of 242 mutation carriers and non‐carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. Results We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non‐carriers, 30 to 53 years of age. Carriers were significantly younger than non‐carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. Discussion Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non‐carriers. Their demographic characteristics are representative of the local population.

Introduction We examined differences in cortical thickness in empirically derived mild cognitive impairment (MCI) subtypes in the Mayo Clinic Study of Aging. Methods We compared cortical thickness of four incident MCI subtypes (n = 192) to 1257 cognitive unimpaired individuals. Results The subtle cognitive impairment cluster had atrophy in the entorhinal and parahippocampal cortex. The amnestic, dysnomic, and dysexecutive clusters also demonstrated entorhinal cortex atrophy as well as thinning in temporal, parietal, and frontal isocortex in somewhat different patterns. Discussion We found patterns of atrophy in each of the incident MCI clusters that corresponded to their patterns of cognitive impairment. The identification of MCI subtypes based on cognitive and structural features may allow for more efficient trial and study designs. Given individuals in the subtle cognitive impairment cluster have less structural changes and cognitive decline and may represent the earliest group, this could be a unique group to target with early interventions.

Background: Chronic type A aortic dissection (cTAAD) in Marfan syndrome (MFS) is rare. Surgical experience is limited and the role of frozen elephant trunk (FET) technique remains undefined. We seek to evaluate the safety and efficacy of the total arch replacement (TAR) and FET technique for cTAAD in MFS. Methods: The clinical data of sixty-eight patients with MFS undergoing FET and TAR for cTAAD were analyzed. Results: Mean age was 35.8±9.7 years and thirty-nine were male (57.4%). Operative mortality was 10.3% (7/68). Stroke occurred in one (1.5%), re-exploration for bleeding in five (7.3%), low cardiac output in four (5.9%), and acute renal failure in two (2.9%). Follow-up was complete in 100% (61/61) at mean 7.3±4.0 years. The false lumen was obliterated in 73.5% across FET and 50.0% in unstented descending aorta (DAo). Distal dilation occurred in twenty patients, six of whom underwent thoracoabdominal aortic replacement, one abdominal aortic replacement and one thoracic endovascular aortic repair (TEVAR). Late death occurred in five. At ten years, 59.8% were free from distal aortic dilation, and the incidences were 23.2% for death, 14.4% for distal reoperation, and 62.4% for reoperation-free survival. Predictors for operative mortality were extra-anatomic bypass [odds ratio (OR), 229.592; P=0.036], preoperative maximal size (DMax) of aortic sinuses (mm) (OR, 1.134; P=0.032) and cardiopulmonary bypass (CPB) time (minute) (OR, 1.061; P=0.041). Risk factors for aortic dilatation included patent false lumen at diaphragmatic hiatus [hazard ratio (HR), 5.374; P=0.008], preoperative DMax (mm) of proximal DAo (HR, 1.068; P=0.001) and renal arteries (HR, 1.102; P=0.005) which also predicted distal reoperation (HR, 1.149; P=0.001). The time from onset to operation (day) (HR, 1.002; P=0.004) and CPB time (minute) (HR, 1.032; P=0.036) predicted late death. Conclusions: This study shows that the TAR and FET technique is a safe and durable approach to cTAAD in patients with MFS. The operation should be performed as early as possible to optimize clinical outcomes.

Objective The present work evaluates the relationship between postoperative immune and neurovascular changes and the pathogenesis of surgery-induced delirium superimposed on dementia. Background and rationale Postoperative delirium is a common complication in many older adults and in patients with dementia including Alzheimer's disease (AD). The course of delirium can be particularly debilitating, while its pathophysiology remains poorly defined. Historical evolution As of 2019, an estimated 5.8 million people of all ages have been diagnosed with AD, 97% of whom are >65 years of age. Each year, many of these patients require surgery. However, anesthesia and surgery can increase the risk for further cognitive decline. Surgery triggers neuroinflammation both in animal models and in humans, and a failure to resolve this inflammatory state may contribute to perioperative neurocognitive disorders as well as neurodegenerative pathology. Updated hypothesis We propose an immunovascular hypothesis whereby dysregulated innate immunity negatively affects the blood-brain interface, which triggers delirium and thereby exacerbates AD neuropathology. Early experimental data We have developed a translational model to study delirium superimposed on dementia in APPSwDI/mNos2-/- AD mice (CVN-AD) after orthopedic surgery. At 12 months of age, CVN-AD showed distinct neuroimmune and vascular impairments after surgery, including acute microgliosis and amyloid-β deposition. These changes correlated with attention deficits, a core feature of delirium-like behavior. Future experiments and validation studies Future research should determine the extent to which prevention of surgery-induced microgliosis and/or neurovascular unit dysfunction can prevent or ameliorate postoperative memory and attention deficits in animal models. Translational human studies should evaluate perioperative indices of innate immunity and neurovascular integrity and assess their potential link to perioperative neurocognitive disorders. Major challenges for the hypothesis Understanding the complex relationships between delirium and dementia will require mechanistic studies aimed at evaluating the role of postoperative neuroinflammation and blood-brain barrier changes in the setting of pre-existing neurodegenerative and/or aging-related pathology. Linkage to other major theories Non-resolving inflammation with vascular disease that leads to cognitive impairments and dementia is increasingly important in risk stratification for AD in the aging population. The interdependence of these factors with surgery-induced neuroinflammation and cognitive dysfunction is also becoming apparent, providing a strong platform for assessing the relationship between postoperative delirium and longer term cognitive dysfunction in older adults.