Feasibility of Water Therapy for Slowing Autosomal Dominant Polycystic Kidney Disease Progression.

BACKGROUND: In animal models of ADPKD, high water intake (HWI) decreases vasopressin secretion and slows disease progression, but the efficacy of HWI in human ADPKD is uncertain. METHODS: This exploratory, prospective, crossover study of ADPKD subjects (n=7) evaluated the hypothesis that HWI slows the rate of increase in height-adjusted total kidney volume (ht-TKV; a biomarker for ADPKD progression) and reduces pain. Subjects at high risk of ADPKD progression (i.e., Mayo Imaging Classifications 1C/1D) were evaluated during 6 months of usual water intake (UWI), followed by 12 months of HWI calculated to reduce urine osmolality (Uosm) to < 285 mOsm/kg. Measurements of Uosm, serum copeptin (secreted in equimolar amounts with vasopressin), MRI measurements of htTKV, and pain survey responses were compared between HWI and UWI. RESULTS: During HWI, mean 24-hour Uosm decreased compared to UWI (428 [398-432] mOsm/kg vs. 209 [190-223] mOsm/kg; p=0.01), indicating adherence to the protocol. Decreases during HWI also occurred in levels of serum copeptin (5.8±2.0 pmol/L to 4.2±1.6 pmol/L; p=0.03), annualized rate of increase in ht-TKV (6.8% [5.9 - 8.5] to 4.4% [3.0 - 5.0]; p<0.02), pain occurrence and pain interference during sleep (p<0.01). HWI was well tolerated. CONCLUSIONS: HWI in patients at risk of rapid progression of ADPKD slowed the rate of ht-TKV growth and reduced pain. This suggests that suppressing vasopressin levels by HWI provides an effective non-pharmacologic treatment of ADPKD.

[Ga68] DOTATATE PET/MRI-Guided Radiosurgical Treatment Planning and Response Assessment in Meningiomas.

BACKGROUND: Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. METHODS: Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and PFS was evaluated using Cox regression. RESULTS: 27 patients with 64 tumors (26% WHO-1, 41% WHO-2, 26% WHO-3, 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) (mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (p < 0.0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. CONCLUSIONS: DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post radiosurgery. Lesion size decrease was statistically significant, however it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery.

CT-based diagnosis in patients presenting with throat pain: A single institutional review.

RATIONALE AND OBJECTIVE: To determine if patient demographic data, medical history, physical examination, and laboratory tests will help predict likelihood of imaging-based diagnosis using CT of the neck performed in the ED for a chief complaint of throat pain. MATERIAL AND METHODS: Single institutional, retrospective review of 367 CT scans of the neck performed for the evaluation of throat pain in the ED from August 2013 to September 2019. Patients' clinical history, physical exams, lab findings, and imaging results were recorded. RESULTS: A total of 367 CT scans of the neck performed for the evaluation of throat pain included a recorded exam and clinical history. Of these cases, we noted that the presence of cervical lymphadenopathy (OR = 2.69; 95% CI, 1.37-5.49), tonsillar findings (OR = 2.94; 95% CI, 1.4-6.57), increased white blood cell count (OR = 1.08; 95% CI, 1.02-1.15), and temperature (OR = 1.94; 95% CI, 1.1-3.6) were associated with increased likelihood of obtaining a diagnostic CT scan. CONCLUSION: Consideration of tonsillar abnormalities, lymphadenopathy, body temperature, and measured leukocyte count prior to ordering CT scans of the neck for throat pain may increase the diagnostic yield of such exams and decrease CT utilization in the ED.

Acceptability and usability of the Planning Advance Care Together (PACT) website for improving patients' engagement in advance care planning.

Objectives: Most prior advance care planning (ACP) interventions lack integration of the social context of patients' ACP process, which patients indicate is critically important. The current study developed the Planning Advance Care Together (PACT) website to foster inclusion of loved ones in the ACP process. Methods: To provide feedback about the PACT website, patients with advanced cancer (N = 11), their caregivers (N = 11), and experts (N = 10) participated in semi-structured interviews. Patients and caregivers also completed standardized ratings of acceptability and usability. Results: Overall, patient (n = 11) and caregiver (n = 11) ratings of acceptability and usability of the website exceeded benchmark cut-offs (≥24 on the Acceptability E-Scale and ≥ 68 on the System Usability Scale). Patients, caregivers, and experts liked the topic of ACP but felt that it could be emotionally challenging. They recommended focusing more on planning and less on end of life. They appreciated being able to include loved ones and recommended adding resources for caregivers. Conclusions: Study findings support the preliminary usability and acceptability of the PACT website. Findings will be used to inform a modified prototype of the PACT website that is interactive and ready for field testing with patients with advanced cancer and their loved ones. Innovation: We utilized a novel application of the shared mind framework to support patients with advanced cancer in engaging their loved ones in the ACP process.

Supporting underrepresented minority students and advancing educational and health equity: Travelers Summer Research Fellowship (TSRF) program radiology panel.

OBJECTIVE: The COVID-19 pandemic has highlighted the racial disparities in health outcomes within our nation. This is especially relevant in the field of radiology where the lack of minority representation is particularly striking. The purpose of this paper is to describe a pipeline program designed to support underrepresented minority (URM) students and provide a model to bridge URMs to careers in medicine hence cultivating health equity. METHODS: We designed a radiology pipeline program within The Travelers Summer Research Fellowship Program (TSRF) to give underrepresented students an opportunity to engage with radiologists. Participants experience a rich inquiry-based curriculum and completed pre- and post-intervention surveys that measured motivational factors for medical education and interest level in medical careers. RESULTS: 29 undergraduate students participated in the 2021 TSRF Program. The data comparing the pre- and post-surveys demonstrated that the TSRF program played a positive role in sparking interest in radiology, debunking misperceptions about radiologists, and boosting participant confidence regarding medical school applications. DISCUSSION: We created an interactive curriculum for URM students to cultivate a new generation of radiologists that will reflect and better meet the needs of the populations they are serving thereby mitigating the current health disparities in our nation.

Association Between the Attention Network Test, Neuropsychological Measures, and Disability in Post-Acute Traumatic Brain Injury.

Cognitive impairment after traumatic brain injury (TBI) is persistent and disabling. Assessing cognitive function in a reliable and valid manner, using measures that are sensitive to the integrity of underlying neural substrates, is crucial in clinical research. The Attention Network Test (ANT) is one such assessment measure that has demonstrated associations with neural regions involved in attention; however, clinical utility of the ANT is limited because its relationship with neuropsychological measures of cognitive function (i.e., its construct validity) has not yet been established in TBI. We evaluated the association between the ANT and 1) a neuropsychological battery assessing executive function and memory and 2) global function assessed by the Glasgow Outcome Scale-Extended (GOSE). Forty-eight adults with complicated mild-severe TBI were evaluated ∼5 months post-injury. Using principal component analysis and multi-variate linear regression adjusted for age, gender, education, and cause of injury, we found that ANT reaction time and executive network scores predicted a principal component assessing processing speed and executive function. Conversely, the ANT did not predict a principal component assessing memory. The ANT was weakly associated with the GOSE. Among persons with TBI during the post-acute phase of recovery, the ANT has good construct validity as evidenced by its associations with neuropsychological measures of processing speed and executive function, but not memory. Given that ANT networks are known to relate to specific neuroanatomical regions, the ANT may be a useful outcome measure for evaluating novel therapeutics targeting attention and executive functions after TBI.

Extracranial Carotid Plaque Calcification and Cerebrovascular Ischemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Although coronary calcification quantification is an established approach for cardiovascular risk assessment, the value of quantifying carotid calcification is less clear. As a result, we performed a systematic review and meta-analysis to evaluate the association between extracranial carotid artery plaque calcification burden and ipsilateral cerebrovascular ischemic events. METHODS: A comprehensive literature search was performed in the following databases: Ovid MEDLINE(R) 1946 to July 6, 2022; OVID Embase 1974 to July 6, 2022; and The Cochrane Library (Wiley). We performed meta-analyses including studies in which investigators performed a computed tomography assessment of calcification volume, percentage, or other total calcium burden summarizable in a single continuous imaging biomarker and determined the association of these features with the occurrence of ipsilateral stroke or transient ischemic attack. RESULTS: Our overall meta-analysis consisted of 2239 carotid arteries and 9 studies. The presence of calcification in carotid arteries ipsilateral to ischemic stroke or in stroke patients compared with asymptomatic patients did not demonstrate a significant association with ischemic cerebrovascular events (relative risk of 0.75 [95% CI, 0.44-1.28]; P=0.29). When restricted to studies of significant carotid artery stenosis (>50%), the presence of calcification was associated with a reduced risk of ischemic stroke (relative risk of 0.56 [95% CI, 0.38-0.85]; P=0.006). When the analysis was limited to studies of patients with mainly nonstenotic plaques, there was an increased relative risk of ipsilateral ischemic stroke of 1.72 ([95% CI, 1.01-2.91]; P=0.04). Subgroup meta-analyses of total calcium burden and morphological features of calcium showed wide variability in their strength of association with ischemic stroke and demonstrated significant heterogeneity. CONCLUSIONS: The presence of calcification in carotid plaque confers a reduced association with ipsilateral ischemic events, although these results seem to be limited among carotid arteries with higher degrees of stenosis. Adoption of carotid calcification measures in clinical decision-making will require additional studies providing more reproducible and standardized methods of calcium characterization and testing these imaging strategies in prospective studies.

Changes in eating patterns in response to chronic insufficient sleep and their associations with diet quality: a randomized trial.

STUDY OBJECTIVES: Insufficient sleep leads to overconsumption, but the factors contributing to this effect are poorly understood. Therefore, we assessed the influence of prolonged curtailment of sleep on free-living eating patterns linked with overconsumption and explored associations of these eating patterns with diet quality under different sleep conditions. METHODS: Sixty-five adults (47 females) participated in outpatient randomized crossover studies with two 6-week conditions: adequate sleep (7-9 h/night) and sleep restriction (-1.5 h/night relative to screening). Food records were collected over 3 nonconsecutive days, from which we ascertained data on eating frequency, midpoint, and window and intakes of energy and nutrients. Linear mixed models were used to assess the impact of sleep condition on change in eating pattern (sleep × week interaction) and the relation between eating patterns and dietary intakes (sleep × eating pattern interaction). RESULTS: Sleep condition impacted the change in eating frequency across weeks, with eating frequency increasing in sleep restriction relative to adequate sleep (ß = 0.3 ± 0.1; P = .046). Across conditions, eating more frequently tended to relate to higher energy intakes (ß = 60.5 ± 34.6; P = .082). Sleep also influenced the relation of variability in eating midpoint with intakes of saturated fat (ß = 6.0 ± 2.1; P = .005), polyunsaturated fat (ß = -3.9 ± 2.0; P = .051), and added sugar (ß = 17.3 ± 6.2; P = .006), with greater midpoint variability associated with more adverse changes in these diet quality components in sleep restriction vs adequate sleep. CONCLUSIONS: Chronic short sleep increases eating frequency and adversely influences associations of variability in meal timing with components of diet quality. These findings help to explain how short sleep leads to overconsumption and obesity. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Impact of Sleep Restriction in Women; URL: https://clinicaltrials.gov/ct2/show/NCT02835261; Identifier: NCT02835261 and Name: Impact of Sleep Restriction on Performance in Adults; URL: https://clinicaltrials.gov/ct2/show/NCT02960776; Identifier: NCT02960776. CITATION: Barragán R, Zuraikat FM, Tam V, RoyChoudhury A, St-Onge M-P. Changes in eating patterns in response to chronic insufficient sleep and their associations with diet quality: a randomized trial. J Clin Sleep Med. 2023;19(11):1867-1875.

Comparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging.

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18-86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

Distinct and joint effects of low and high levels of Aß and tau deposition on cortical thickness.

Alzheimer's disease (AD) is defined by the presence of Amyloid-ß (Aß),tau, and neurodegeneration (ATN framework) in the human cerebral cortex. Yet, prior studies have suggested that Aß deposition can be associated with both cortical thinning and thickening. These contradictory results are attributed to small sample sizes, the presence versus absence of tau, and limited detectability in the earliest phase of protein deposition, which may begin in young adulthood and cannot be captured in studies enrolling only older subjects. In this study, we aimed to find the distinct and joint effects of Aß andtau on neurodegeneration during the progression from normal to abnormal stages of pathologies that remain elusive. We used18F-MK6240 and 18F-Florbetaben/18F-Florbetapir positron emission tomography (PET) and magnetic resonance imaging (MRI) to quantify tau, Aß, and cortical thickness in 590 participants ranging in age from 20 to 90. We performed multiple regression analyses to assess the distinct and joint effects of Aß and tau on cortical thickness using 590 healthy control (HC) and mild cognitive impairment (MCI) participants (141 young, 394 HC elderlies, 52 MCI). We showed thatin participants with normal levels of global Aßdeposition, Aß uptakewassignificantly associated with increasedcortical thickness regardless of tau (e.g., left entorhinal cortex with t > 3.241, p < 0.0013). The relationship between tau deposition and neurodegeneration was more complex: in participants with abnormal levels of global tau, tau uptake was associated with cortical thinning in several regions of the brain (e.g., left entorhinal with t < -2.80, p < 0.0096 and left insula with t-value < -4.284, p < 0.0001), as reported on prior neuroimaging and neuropathological studies. Surprisingly, in participants with normal levels of global tau, tau was found to be associated with cortical thickening. Moreover, in participants with abnormal levels of global Aßandtau, theresonancebetween them, defined as their correlation throughout the cortex, wasassociated strongly with cortical thinning even when controlling for a direct linear effect. We confirm prior findings of an association between Aß deposition and cortical thickening and suggest this may also be the case in the earliest stages of deposition in normal aging. We also illustrate that resonance between high levels of Aß and tau uptake is strongly associated with cortical thinning, emphasizing the effects of Aß/tau synergy inAD pathogenesis.

Impact of acute TTE-evidenced cardiac dysfunction on in-hospital and outpatient mortality: A multicenter NYC COVID-19 registry study.

BACKGROUND: COVID-19 is associated with cardiac dysfunction. This study tested the relative prognostic role of left (LV), right and bi- (BiV) ventricular dysfunction on mortality in a large multicenter cohort of patients during and after acute COVID-19 hospitalization. METHODS/RESULTS: All hospitalized COVID-19 patients who underwent clinically indicated transthoracic echocardiography within 30 days of admission at four NYC hospitals between March 2020 and January 2021 were studied. Images were re-analyzed by a central core lab blinded to clinical data. Nine hundred patients were studied (28% Hispanic, 16% African-American), and LV, RV and BiV dysfunction were observed in 50%, 38% and 17%, respectively. Within the overall cohort, 194 patients had TTEs prior to COVID-19 diagnosis, among whom LV, RV, BiV dysfunction prevalence increased following acute infection (p<0.001). Cardiac dysfunction was linked to biomarker-evidenced myocardial injury, with higher prevalence of troponin elevation in patients with LV (14%), RV (16%) and BiV (21%) dysfunction compared to those with normal BiV function (8%, all p<0.05). During in- and out-patient follow-up, 290 patients died (32%), among whom 230 died in the hospital and 60 post-discharge. Unadjusted mortality risk was greatest among patients with BiV (41%), followed by RV (39%) and LV dysfunction (37%), compared to patients without dysfunction (27%, all p<0.01). In multivariable analysis, any RV dysfunction, but not LV dysfunction, was independently associated with increased mortality risk (p<0.01). CONCLUSIONS: LV, RV and BiV function declines during acute COVID-19 infection with each contributing to increased in- and out-patient mortality risk. RV dysfunction independently increases mortality risk.

Physician Management Companies and Neonatology Prices, Utilization, and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: Physician management companies (PMCs) acquire physician practices and contract with hospitals to provide physician management services. We evaluated the association between PMC-NICU affiliations and prices, spending, utilization, and clinical outcomes. METHODS: We linked commercial claims to PMC-NICU affiliations and conducted difference- in-differences analyses comparing changes in prices paid for physician services per critical or intensive care NICU day, length of the NICU stay, physician spending (total paid amount for physician services during stay), spending on hospital services (total paid amount for hospital services during stay), and clinical outcomes in PMC-affiliated versus non-PMC-affiliated NICUs. The study included 2858 infants admitted to 34 PMC-affiliated NICUs and 92 461 infants admitted to 2348 NICUs without an affiliation. RESULTS: PMC affiliation was associated with a differential increase in the mean price of the 5 most common types of critical and intensive care days in NICU admissions by $313 per day (95% confidence interval, $207-$419) for PMC-affiliated versus non- PMC-affiliated NICUs. This represents a 70.4% increase in prices, relative to the preaffiliation period PMC and non- PMC-affiliated NICU means. PMC-NICU affiliation was also associated with a differential increase in physician spending by $5161 per NICU stay (95% confidence interval, $3062-$7260), a 56.4% increase. There was no significant association between PMC-NICU affiliation and changes in length of stay, clinical outcomes, or hospital spending. CONCLUSIONS: PMC affiliation was associated with large increases in prices and total spending for NICU services, but not with changes in length of stay or adverse clinical outcomes.

Cranial MRgFUS intraprocedural diffusion and T2 imaging and comparison with postablation lesion size and location.

OBJECTIVE: The ability to predict final lesion characteristics during magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for the treatment of essential tremor remains technically challenging, yet it is essential in order to avoid off-target ablation and to ensure adequate treatment. The authors sought to evaluate the technical feasibility and utility of intraprocedural diffusion-weighted imaging (DWI) in the prediction of final lesion size and location. METHODS: Lesion diameter and distance from the midline were measured on both intraprocedural and immediate postprocedural diffusion and T2-weighted sequences. Bland-Altman analysis was utilized to determine differences in measurement between intraprocedural and immediate postprocedural images with both sequences. RESULTS: Lesion size increased on both the postprocedural diffusion and T2-weighted sequences, although the difference was smaller on the T2-weighted sequence. There was only a small difference in intraprocedural and postprocedural lesion distance from the midline on both the diffusion and T2-weighted sequences. CONCLUSIONS: Intraprocedural DWI is both feasible and useful with regard to predicting final lesion size and providing an early indication of lesion location. Further research should determine the value of intraprocedural DWI in predicting delayed clinical outcomes.

Implementation and Evaluation of a Comprehensive Simulation Curriculum for the IR/DR Integrated Residency.

RATIONALE AND OBJECTIVES: Endovascular simulation is a validated training method, allowing residents to improve technical skills with interventional equipment in a risk-free environment. The purpose of this study was to assess the utility and efficacy of supplementing the IR/DR Integrated Residency training program with a dedicated 2-year endovascular simulation curriculum. MATERIALS AND METHODS: Trainees participated in a 2-year curriculum that included the completion of 8 modules using a high-fidelity endovascular simulator (Mentice AB, Gothenberg, Sweden). Procedural modules included IVC filter placement, transarterial chemoembolization, trauma embolization, uterine artery embolization, prostate artery embolization, and peripheral arterial disease interventions. Each quarter, two trainees were filmed while completing an assigned module. Sessions led by IR faculty were held with film footage review and didactics on the assigned topic. Pre- and postcase surveys were collected to evaluate trainee comfort and confidence and assess the validity of the simulation. At the conclusion of the 2-year period, a postcurriculum survey was sent to all trainees to determine how residents viewed the utility of the simulation sessions. RESULTS: Eight residents participated in the pre- and postcase surveys. The simulation curriculum significantly increased trainee confidence for these 8 residents. A separate postcurriculum survey was completed by all 16 IR/DR residents. All 16 residents felt that simulation was a helpful addition to their education. A total of 87.5% of all residents felt that the sessions improved their confidence in the IR procedure room. A total of 75% of all residents believe that the simulation curriculum should be incorporated into the IR residency program. CONCLUSION: Adoption of a 2-year simulation curriculum can be considered for existing IR/DR training programs with access to high-fidelity endovascular simulators using the described approach.

Indications for Hospitalization in Children with SARS-CoV-2 Infection during the Omicron Wave in New York City.

The emergence of the Omicron variant was accompanied by an acute increase in COVID-19 cases and hospitalizations in New York City. An increased incidence of COVID-19-associated croup in children during the Omicron wave has been recognized, suggesting that there may be other changes in clinical symptoms and severity. To better understand clinical outcomes and health care utilization in children infected with SARS-CoV-2 during the Omicron wave, we performed a cross-sectional study in pediatric patients aged ≤18 years who were tested for SARS-CoV-2 in pediatric emergency departments within a large medical system in New York City from 2 December 2021 to 23 January 2022. We described the clinical characteristics and outcomes of pediatric patients who presented to the pediatric emergency department and were hospitalized with SARS-CoV-2 infection during the Omicron wave in New York City. There were 2515 children tested in the ED for SARS-CoV-2 of whom 794 (31.6%) tested positive. Fifty-eight children were hospitalized for a COVID-19-related indication, representing 7.3% of all COVID-19-positive children and 72% of hospitalized COVID-19-positive children. Most (64%) children hospitalized for a COVID-19-related indication were less than 5 years old. Indications for hospitalization included respiratory symptoms, clinical monitoring of patients with comorbid conditions, and exacerbations of underlying disease. Eleven (19%) hospitalized children were admitted to the ICU and six (10%) required mechanical ventilation. Children infected with COVID-19 during the Omicron wave, particularly those less than 5 years old, were at risk for hospitalization. A majority of hospitalizations were directly related to COVID-19 infection although clinical indications varied with less than a half being admitted for respiratory diseases including croup. Our findings underscore the need for an effective COVID-19 vaccine in those less than 5 years old, continued monitoring for changes in clinical outcomes and health care utilization in children as more SARS-CoV-2 variants emerge, and understanding that children are often admitted for non-respiratory diseases with COVID-19.

Incomplete circle of Willis variants and stroke outcome.

BACKGROUND: There is considerable variation in circle of Willis morphology among the general population, and these variations have been correlated with risk of aneurysms, cerebral ischemia, and other clinical events. PURPOSE: To investigate the relationship between circle of Willis variants and stroke outcome. MATERIALS AND METHODS: We performed a retrospective study involving 297 patients from our institution's acute stroke academic registry. All received MRA examinations of the head upon admission for acute strokes. All imaging was reviewed to assess for circle of Willis variants (particularly A1 and P1 aplasia or hypoplasia) along with vertebral artery aplasia or hypoplasia. Stroke outcome was defined as good (walking independently at the time of discharge) or poor (inability to walk at discharge, assistance needed to walk at discharge, or death). Severity of stroke was assessed using the National Institute of Health Stroke Scale. RESULTS: An incomplete circle of Willis was seen in 34% of subjects. There was no significant association between age, gender, hypertension, or presence of arterial stenosis and circle of Willis completeness. Using logistic regression, we found that the presence of an incomplete circle of Willis decreased the odds of a stroke patient having a good outcome by 47% (p = 0.046, OR 0.53, 95% CI 0.281-0.988), after adjusting for age and severity of stroke at admission. CONCLUSION: This study suggests that an incomplete circle of Willis may be associated with a poorer prognosis for stroke patients.

Statistical Parametric Mapping in Amyloid Positron Emission Tomography.

Alzheimer's disease (AD), the most common cause of dementia, has limited treatment options. Emerging disease modifying therapies are targeted at clearing amyloid-ß (Aß) aggregates and slowing the rate of amyloid deposition. However, amyloid burden is not routinely evaluated quantitatively for purposes of disease progression and treatment response assessment. Statistical Parametric Mapping (SPM) is a technique comparing single-subject Positron Emission Tomography (PET) to a healthy cohort that may improve quantification of amyloid burden and diagnostic performance. While primarily used in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, SPM's utility in amyloid PET for AD diagnosis is less established and uncertainty remains regarding optimal normal database construction. Using commercially available SPM software, we created a database of 34 non-APOE ε4 carriers with normal cognitive testing (MMSE > 25) and negative cerebrospinal fluid (CSF) AD biomarkers. We compared this database to 115 cognitively normal subjects with variable AD risk factors. We hypothesized that SPM based on our database would identify more positive scans in the test cohort than the qualitatively rated [11C]-PiB PET (QR-PiB), that SPM-based interpretation would correlate better with CSF Aß42 levels than QR-PiB, and that regional z-scores of specific brain regions known to be involved early in AD would be predictive of CSF Aß42 levels. Fisher's exact test and the kappa coefficient assessed the agreement between SPM, QR-PiB PET, and CSF biomarkers. Logistic regression determined if the regional z-scores predicted CSF Aß42 levels. An optimal z-score cutoff was calculated using Youden's index. We found SPM identified more positive scans than QR-PiB PET (19.1 vs. 9.6%) and that SPM correlated more closely with CSF Aß42 levels than QR-PiB PET (kappa 0.13 vs. 0.06) indicating that SPM may have higher sensitivity than standard QR-PiB PET images. Regional analysis demonstrated the z-scores of the precuneus, anterior cingulate and posterior cingulate were predictive of CSF Aß42 levels [OR (95% CI) 2.4 (1.1, 5.1) p = 0.024; 1.8 (1.1, 2.8) p = 0.020; 1.6 (1.1, 2.5) p = 0.026]. This study demonstrates the utility of using SPM with a "true normal" database and suggests that SPM enhances diagnostic performance in AD in the clinical setting through its quantitative approach, which will be increasingly important with future disease-modifying therapies.

Cost comparison of intra-detrusor injection of botulinum toxin versus augmentation cystoplasty for refractory neurogenic detrusor overactivity in children.

INTRODUCTION: Treatment options for refractory neurogenic detrusor overactivity (NDO) in children include botulinum toxin type A (BTX-A) and augmentation cystoplasty (AC). Although BTX-A is accepted in contemporary pediatric urologic practice, cost and long-term outcomes data for BTX-A are limited relative to the gold standard, AC. The purpose of this study was to compare the projected 10-year costs of AC versus BTX-A. METHODS: We performed a cost analysis from the payer perspective by computationally modeling treatment sequences by a Markov model. In the model, we used probabilities derived from published sources, and costs obtained at a tertiary medical center. The base case was a pediatric patient with refractory NDO. In the model, we assumed biannual BTX-A treatments. Treatment costs over 10 years were compared between immediate AC versus bridging therapy with BTX-A. Using the computational model, we simulated 100,000 instances of 10-year treatment cost for each of the two treatment modalities. The costs for the two treatment approaches were then compared using t-test and Wilcoxon test. RESULTS: The projected median and mean 10-year cost of immediately AC were $51,798.72 (95% CI [$51,798.72, $327,483.80]) and $123,473.4 (SD: $98,085.23) respectfully, while the projected median and mean 10-year cost of bridging therapy with BTX-A prior to proceeding to AC as needed were $74,552.46 (95% CI [$53,188.56, $309,913.07]) and $124,858.80 (SD: $84,495.35) (p < 0.001). CONCLUSIONS: For a typical index pediatric patient with NDO, bridging therapy with intravesical BTX-A is associated with an increased cost compared to immediate AC over a ten-year period.