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The emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages. Additionally, the in vivo safety and efficacy of the compounds were assessed using zebrafish embryo infection models. Our screen identified 11 hit compounds for Stm and 17 hit compounds for Mtb that were effective against intracellular bacteria and non-toxic for host cells. Further experiments were conducted to prioritize Stm hit compounds that were able to clear the intracellular infection in primary human macrophages. From these, two structurally related Stm hit compounds, GSK1379738A and GSK1379760A, exhibited significant activity against Stm in infected zebrafish embryos. In addition, we identified compounds that were active against intracellular Mtb, including morpholino-imidazo/triazolo-pyrimidinones that target PIK3CB, as well as 2-aminobenzimidazoles targeting ABL1. Overall, this study provided insights into kinase targets acting at the host–pathogen interface and identified several kinase inhibitors as potential HDTs. [ABSTRACT FROM AUTHOR]

Background: Evidence on long COVID symptom clustering patterns among patients with COVID-19 is limited. We summarized long COVID symptoms in clusters defined by number of symptoms co-occurring together, and we assessed Health-Related Quality of Life (HQRoL), Work Productivity and Activity Impairment (WPAI) outcomes across these clusters over time. We assessed associations between the clusters and BNT162b2 vaccination status., Methods: A prospective longitudinal patient-reported outcomes (PRO) study recruited laboratory-confirmed symptomatic COVID-19 patients seeking testing from a national retail pharmacy. Long COVID-19 symptoms were self-reported by participants at 4-week, 3-month and 6-month surveys. Patient classes identified via latent class analysis (LCA) with long COVID-19 symptoms were simplified into clusters based on number of symptoms. HRQoL and WPAI outcomes were collected using EQ-ED-5L and WPAI: GH questionnaires. Mixed models for repeated measures analyses were conducted to examine associations between exposure groups and outcomes., Results: The study included 328 participants that were segmented into three groups of long COVID-19 symptoms based on LCA and then simplified by the number of symptoms (Cluster 1 low, <2; Cluster 2 moderate, 2-6; and Cluster 3 high, >6 symptoms). The number of long COVID-19 symptoms was negatively associated with HRQoL and WPAI, whereby participants with high symptom burden (>6 symptoms) had the lowest HRQoL and WPAI scores assessed by absenteeism, presenteeism, work productivity loss, activity impairment, and hours worked metrics. Compared with those unvaccinated and not up-to-date with COVID-19 vaccination, subjects boosted with BNT162b2 consistently reported less symptom burden during the follow-up, regardless of their symptom-based cluster., Conclusion: Three distinct patient clusters based on frequency of long COVID symptoms experienced different HRQoL and WPAI outcomes over 6 months. The cluster with more concomitant symptoms experienced greater burden than the others. Participants up-to-date with BNT162b2 reported lower symptom burden across all clusters and timeframes., Clinical Trial Registration: Clinicaltrials.gov NCT05160636., (© 2024. The Author(s).)

Background: the importance of sucking milk directly at the mother's breast is often underestimated and many aspects of direct breastfeeding of very preterm infants are not investigated., Aim: The primary endpoint of the study was to identify maternal and infant clinical predictors of direct breastfeeding in a cohort of infants born at <32 weeks of gestation or weighing <1500 g. The secondary endpoint was to evaluate the possible effects of direct breastfeeding on infant neurodevelopment., Study Design: Seventy-two infants born between July 2018 and December 2019 were divided into the subgroup that were directly breastfed (n = 42) and not directly breastfed (n = 30) at discharge. Maternal and infant characteristics were compared, and differences were analysed., Results: Logistic regression analysis demonstrated that the percentage of maternal milk taken during hospitalization, maternal age, and weight (z-score) at discharge were positively correlated with the likelihood of direct breastfeeding at discharge. Direct breastfeeding was not correlated with the cognitive score at 24 months corrected age., Conclusions: Direct breastfeeding at discharge is more probable in infants of older mothers who receive more breastmilk and who experience greater weight gain. Direct breastfeeding is not correlated with the cognitive score at 24 months corrected age., Competing Interests: Declaration of competing interest Authors declare no conflicts of interest relating to the work under submission., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Five-year net survival and conditional survival from vulvar squamous cell carcinoma (VSCC) patients in Italy have shown no progress during the past three decades. This study aims to estimate the complete prevalence and multiple indicators of cure., Methods: Observed prevalence was estimated using 31 Italian cancer registries covering 47 % of Italian women. A subset of 22 cancer registries was used to estimate model-based long-term survival and indicators of cure, i.e., complete prevalence, cure fraction (CF), time to cure (TTC), proportion of 'already cured' patients, and cure prevalence., Results: In 2018, VSCC patients alive in Italy (complete prevalence) were 6620 or 22 per 100,000 women. The cure fraction (the proportion of newly diagnosed patients who will not die of VSCC) did not change between 2000 and 2010 both for all patients (32 %) and in each age group. The time to cure (5-year conditional net survival >95 %) was 11 years for patients aged ≥44 years, but excess mortality remained for >15 years in the other age groups. This led to a negligible (5 %) proportion of 'already cured' patients (living longer than time to cure). The proportion of patients alive <2 years (21 %) was the same as that of patients surviving ≥15 years. The cure prevalence (patients who will not die of VSCC) was 64 %. A considerable proportion of patients will not be cured even among those who survived ≥5 years., Conclusion: There is an urgent need to reshape the current vulvar care model in Italy., Competing Interests: Declaration of competing interest Emanuele Crocetti declares an epidemiological advice for Astrazeneca, not related to this study. The author Gemma Gatta is a Guest Editor for the European Journal of Surgical Oncology and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: The COVID-19 pandemic triggered one of the largest global health and economic crises in recent history. COVID-19 vaccination (CV) has been the central tool for global health and macroeconomic recovery, yet estimates of CV's global health and macroeconomic value remain scarce., Methods: We used regression analyses to measure the impact of CV on gross domestic product (GDP), infections and deaths. We combined regression estimates of vaccine-averted infections and deaths with estimates of quality-adjusted life years (QALY) losses, and direct and indirect costs, to estimate three broad value components: (i) QALY gains, (ii) direct and indirect costs averted and (iii) GDP impacts. The global value is the sum of components over 148 countries between January 2020 and December 2021 for CV generally and for Pfizer-BioNTech specifically., Results: CV's global value was US$5.2 (95% CI US$4.1 to US$6.2) trillion, with Pfizer-BioNTech's vaccines contributing over US$1.9 (95% CI US$1.5 to US$2.3) trillion. Varying key parameters results in values 10%-20% higher or lower than the base-case value. The largest value component was GDP impacts, followed by QALY gains, then direct and indirect costs averted. CV provided US$740 of value per dose, while Pfizer-BioNTech specifically provided >US$1600 per dose. We estimated conservative benefit-cost ratios of 13.9 and 30.8 for CV and Pfizer-BioNTech, respectively., Conclusions: We provide the first estimates of the broad value of CV incorporating GDP, QALY and direct and indirect cost impacts. Through December 2021, CV produced significant health and economic value, represented strong value for money and produced significant macroeconomic benefits that should be considered in vaccine evaluation., Competing Interests: Competing interests: JPS, DB and JSK are employees of Data for Decisions (DfD) and worked on this study in that capacity. JPS and DB have worked on other studies funded by grants from Pfizer Inc. to DfD. DEB is an external consultant to DfD and in that capacity has worked on this and other studies funded by grants from Pfizer Inc. to DfD. JPS and DEB in their personal capacities have received compensation from Pfizer Inc. for providing consulting services and for speaking and participating in meetings and advisory boards. MDF, MK, JLN and JY are employees of Pfizer Inc. and each held Pfizer stock or stock options at the time of the study. Pfizer Inc. employs MDF, MK, JLN and JY, but otherwise played no role in study design, data collection and analysis, decision to publish or preparation of the article., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Influenza and influenza-like illness (ILI) pose significant clinical and economic burdens globally each year. This systematic literature review examined quantitative studies evaluating the impact of patients' influenza/ILI on their caregivers' well-being, focusing on health-related quality of life (HRQoL), work productivity, and activity impairment. A comprehensive search across six databases, including the Cochrane Database of Systematic Reviews, Embase, MEDLINE via PubMed, Ovid, PsycNet, and Web of Science, yielded 18,689 records, of which 13,156 abstracts were screened, and 662 full-text articles were reviewed from January 2007 to April 2024. Thirty-six studies [HRQoL: 2; productivity: 33; both: 1] covering 22 countries were included. Caregivers of 47,758 influenza or ILI patients across 123 study cohorts were assessed in the review. The mean workday loss among caregivers ranged from 0.5 to 10.7 days per episode, influenced by patients' influenza status (positive or negative), disease severity (mild or moderate-to-severe), age, viral type (influenza A or B), and vaccination/treatment usage. The HRQoL of caregivers, including their physical and emotional well-being, was affected by a patient's influenza or ILI, where the severity and duration of a patient's illness were associated with worse HRQoL. This review shows that the consequences of influenza or ILI significantly affect not only patients but also their caregivers.

The success of chemotherapy regimens in patients with non-small cell lung cancer (NSCLC) could be restricted at least in part by cancer stem cells (CSC) niches within the tumor microenvironment (TME). CSC express CD133, CD44, CD47, and SOX2, among other markers and factors. Analysis of public data revealed that high expression of hyaluronan (HA), the main glycosaminoglycan of TME, correlated positively with CSC phenotype and decreased disease-free interval in NSCLC patients. We aimed to cross-validate these findings on human and murine lung cancer cells and observed that CD133 + CSC differentially expressed higher levels of HA, HAS3, ABCC5, SOX2, and CD47 (p < 0.01). We modulated HA expression with 4-methylumbelliferone (4Mu) and detected an increase in sensitivity to paclitaxel (Pa). We evaluated the effect of 4Mu + chemotherapy on survival, HA metabolism, and CSC profile. The combination of 4Mu with Pa reduced the clonogenic and tumor-forming ability of CSC. Pa-induced HAS3, ABCC5, SOX2, and CD47 expression was mitigated by 4Mu. Pa + 4Mu combination significantly reduced in vivo tumor growth, enhancing animal survival and restoring the CSC profile in the TME to basal levels. Our results suggest that HA is involved in lung CSC phenotype and chemosensitivity, and its modulation by 4Mu improves treatment efficacy to inhibit tumor progression., (© 2024. The Author(s).)

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking., Materials and Methods: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis., Results: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%)., Conclusions: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: It has recently been reported that it is possible to monitor lung oxygenation (rSO 2 L) by near-infrared spectroscopy (NIRS) in preterm infants with respiratory distress syndrome (RDS). Thus, our aim was to assess the possibility of monitoring rSO 2 L in infants with evolving and established bronchopulmonary dysplasia (BPD) and to evaluate if rSO 2 L correlates with BPD severity and other oxygenation indices., Methods: We studied 40 preterm infants with gestational age ≤30 weeks at risk for BPD. Patients were continuously studied for 2 h by NIRS at 28 ± 7 days of life and 36 weeks ± 7 days of postmenstrual age., Results: rSO 2 L was similar at the first and second NIRS recordings (71.8 ± 7.2 vs. 71.4 ± 4.2%) in the overall population, but it was higher in infants with mild than in those with moderate-to-severe BPD at both the first (73.3 ± 3.1 vs. 71.2 ± 3.2%, p = .042) and second (72.3 ± 2.8 vs. 70.5 ± 2.8, p = .049) NIRS recording. A rSO 2 L cutoff value of 71.6% in the first recording was associated with a risk for moderate-to-severe BPD with a sensitivity of 66% and a specificity of 60%. Linear regression analysis demonstrated a significant positive relationship between rSO 2 L and SpO 2 /FiO 2 ratio (p = .013) and a/APO 2 (p = .004)., Conclusions: Monitoring of rSO 2 L by NIRS in preterm infants with evolving and established BPD is feasible and safe. rSO 2 L was found to be higher in infants with mild BPD, and predicts the risk for developing moderate-to-severe BPD and correlates with other indices of oxygenation., (© 2024 Wiley Periodicals LLC.)

Aim: We developed the Promotion of Breastfeeding (PROBREAST) programme and evaluated what effect it had on the breastfeeding rate in infants born at less than 32 weeks of gestation or weighing ≤1500 grams., Methods: We compared the breastfeeding rate in two cohorts of patients who were born before (n = 72; January 2017 to June 2018) and after (n = 80; July 2018 to December 2019) the application of the programme. Moreover, we compared the correlation between type of feeding at discharge and post-discharge breastfeeding rate, between exclusive breastfeeding, postnatal growth and neurodevelopment., Results: Infants in the PROBREAST group had an exclusive breastfeeding rate at discharge higher (42 vs. 16%, p < 0.001) than that in the historical control group. Exclusive breastfeeding was negatively correlated with weight z-score at discharge, but not at 12 and 24 months corrected age, and was positively correlated with cognitive score at 24 months corrected age., Conclusion: The application of a structured programme for the promotion of breastfeeding improved the breastfeeding rate in very preterm infants. We demonstrated that exclusive breastfeeding at discharge improved their neurodevelopment without impairing growth., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV)., Objectives: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP., Materials and Methods: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25 +0 -31 +6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO 2 /FiO 2 ratio after LISA, and adverse effect rate., Results: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456-1.671; p = .681). We found that the SpO 2 /FiO 2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms., Conclusions: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA., (© 2024 Wiley Periodicals LLC.)

Background: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms., Methods: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates., Results: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue., Conclusions: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.

Background: Post-COVID conditions encompass a range of long-term symptoms after SARS-CoV-2 infection. The potential clinical and economic burden in the United States is unclear. We evaluated diagnoses, medications, healthcare use, and medical costs before and after acute COVID-19 illness in US patients at high risk of severe COVID-19., Methods: Eligible adults were diagnosed with COVID-19 from April 1 to May 31, 2020, had ≥ 1 condition placing them at risk of severe COVID-19, and were enrolled in Optum's de-identified Clinformatics ® Data Mart Database for ≥ 12 months before and ≥ 13 months after COVID-19 diagnosis. Percentages of diagnoses, medications, resource use, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified by age and COVID-19 severity., Results: The cohort included 19,558 patients (aged 18-64 y, n = 9381; aged ≥ 65 y, n = 10,177). Compared with baseline, patients during the post-acute phase had increased percentages of blood disorders (16.3%), nervous system disorders (11.1%), and mental and behavioral disorders (7.7%), along with increases in related prescriptions. Overall, there were substantial increases in inpatient and outpatient healthcare utilization, along with a 23.0% increase in medical costs. Changes were greatest among older patients and those admitted to the intensive care unit for acute COVID-19 but were also observed in younger patients and those who did not require COVID-19 hospitalization., Conclusions: There is a significant clinical and economic burden of post-COVID conditions among US individuals at high risk for severe COVID-19., (© 2024. The Author(s).)

Objective: Conduct a comprehensive analysis of the health and economic outcomes of patients with a COVID-19-associated hospitalization in the US during the predominance of the XBB and JN.1 Omicron lineages., Methods: This analysis used data from the PINC AI Healthcare Database (PHD) for all patients with a hospital admission date occurring between February 4, 2023, and February 29, 2024 with an ICD-10-CM code U07.1 "COVID-19" in any position. The data were used to estimate the mean and median length of stay (LOS), mean and median hospitalization cost, and proportion of patients that died in the hospital, by age and level of care (normal ward, intensive care [ICU], invasive mechanical ventilation [IMV])., Results: LOS, hospitalization costs, and inpatient mortality increased with both the level of care and age. Patients not receiving ICU care had the shortest LOS, lowest inpatient mortality, and lowest hospitalization costs. LOS, hospitalization costs, and inpatient mortality were higher for those receiving ICU care and highest for those receiving IMV in the ICU. Within each level of care (normal ward, ICU without IMV, and ICU with IMV), the LOS, inpatient mortality, and hospitalization cost generally increased with age, indicating that older adults with COVID-19 required a longer recovery period, have a higher likelihood of death, and accrue higher costs. However, the proportion of pediatric patients with an ICU admission and/or IMV usage remained high., Limitations: The PHD data may not be representative of all hospitalized patients in the US., Conclusions: These findings suggest that COVID-19 continues to have severe and costly consequences in all age groups, but particularly for older adults including long LOS, ICU admission, need for IMV, mortality, and high hospital costs.

Objective: Describe the economic burden of COVID-19 on employers and employees in the United States (US)., Methods: A targeted literature review was conducted to evaluate the impact of COVID-19 on US-based employers and employees in terms of healthcare resource utilization (HCRU), medical costs, and costs associated with work-loss. Searches were conducted in MEDLINE, Embase, and EconLit using a combination of disease terms, populations, and outcomes to identify articles published from January 2021 to November 4, 2022. As data from the employer perspective were lacking, additional literature related to influenza were included to contextualize the impact of COVID-19, as it shifts into an endemic state, within the existing respiratory illness landscape., Results: A total of 41 articles were included in the literature review. Employer and employee perspectives were not well represented in the literature, and very few articles overlapped on any given outcome. HCRU, costs, and work impairment vary by community transmission levels, industry type, population demographics, telework ability, mitigation implementation measures, and company policies. Work-loss among COVID-19 cases were higher among the unvaccinated and in the week following diagnosis and for some, these continued for 6 months. HCRU is increased in those with COVID-19 and COVID-19-related HCRU can also continue for 6 months., Conclusions: COVID-19 continues to be a considerable burden to employers. The majority of COVID-19 cases impact working age adults. HCRU is mainly driven by outpatient visits, while direct costs are driven by hospitalization. Productivity loss is higher for unvaccinated individuals. An increased focus to support mitigation measures may minimize hospitalizations and work-loss. A data-driven approach to implementation of workplace policies, targeted communications, and access to timely and appropriate therapies for prevention and treatment may reduce health-related work-loss and associated cost burden.

Background: Dementia is the fourth leading cause of death in people >  65 years old in western countries., Objective: This cross-sectional assisted survey aimed to evaluate a multidisciplinary team approach of specialists of the Associazione Geriatri Extraospedalieri a favore di Anziani Svantaggiati and pharmacists to facilitate progress in the early identification and management of cognitive decline in patients >  60 years., Methods: A multidisciplinary team conducted this cross-sectional assisted survey. Patients (>60 years) with independent and/or assisted walking, subjective memory impairment, mild cognitive impairment or mild Alzheimer's disease (AD) who regularly attended pharmacies underwent the survey. An internal medical examination, a cardiovascular visit, and a short neuropsychological evaluation were conducted for each patient. Demographic, anamnestic, and clinical data were collected anonymously., Results: 279 eligible patients underwent the screening phase. 44% were overweight, 23% obese and 29% hypertensive. 62% of cases showed alterations of supra-aortic trunk with different percentages of stenosis. The neuropsychological evaluation highlighted that 67% of cases were normal according to age and education level, while 18% were in a state condition of cognitive frailty. Mild/moderate cognitive decline, or probably AD, was identified in 14% of cases., Conclusions: A multidisciplinary collaboration between pharmacists and specialist medical doctors is essential in early identification of prodromal symptoms of cognitive impairment and AD. The Prompt detection of the condition in this group of patients allowed the specialists to recommend in-depth diagnostic tests and follow-up procedures to slow the course of the disease. This would give time to carry out adequate caregiver training.

Background and Purpose: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy., Methods: We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm, repetition time = 2000 ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n = 53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p < .05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories., Results: In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p ≤ .01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population., Conclusions: Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress., (© 2023 American Society of Neuroimaging.)