Stricker Learning Span criterion validity: a remote self-administered multi-device compatible digital word list memory measure shows similar ability to differentiate amyloid and tau PET-defined biomarker groups as in-person Auditory Verbal Learning Test.

OBJECTIVE: The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey's Auditory Verbal Learning Test (AVLT). METHOD: Participants (N = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer's disease (AD) continuum (amyloid PET positive, A+, n = 125) or not (A-, n = 228), and those with biological AD (amyloid and tau PET positive, A+T+, n = 55) vs no evidence of AD pathology (A-T-, n = 195). Analyses were repeated among CU participants only. RESULTS: The SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p's > .05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education, and sex, including when limited to CU participants. Medium (A- vs A+) to large (A-T- vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups. CONCLUSIONS: Remotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.

Associations of reproductive factors and exogenous estrogens with global and domain-specific cognition in later life.

INTRODUCTION: Few studies have comprehensively examined the impact of reproductive factors (i.e., reproductive window, parity, hormonal contraception [HC], and menopausal hormone therapy [MHT]) on global and domain-specific cognition in later life. METHODS: We studied a population-based sample of 2458 women (median age 74.2 years) residing in Olmsted County, Minnesota; participants underwent a clinical evaluation and comprehensive cognitive testing. RESULTS: The length of a woman's reproductive window was not associated with cognition. Higher parity was associated with greater cognitive decline in all domains. Ever HC use was associated with less decline in all domains. Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial; results were driven by women who initiated MHT 5 or more years after menopause. Additional adjustments for APOE and vascular-related covariates did not attenuate the results. DISCUSSION: Multiple reproductive risk factors are associated with cognitive decline in later life. HIGHLIGHTS: The length of a woman's reproductive window was not associated with cognition longitudinally. Greater parity was associated with greater cognitive decline longitudinally. Ever HC use was associated with less decline in global cognition and all domain-specific z-scores longitudinally (all p < 0.01). Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial longitudinally (all p < 0.01). The greatest cognitive decline was among women who initiated MHT more than 5 years after menopause.

Characteristics and Outcomes of Critically Ill Patients With Pulmonary Hypertension Who Undergo Endotracheal Intubation and Mechanical Ventilation.

Background: Patients with pulmonary hypertension (PH) who undergo endotracheal intubation have an increased risk of adverse outcomes, but little is known regarding prognostic factors and there is limited evidence to guide management. We sought to define characteristics, prognostic factors, and outcomes of critically ill patients with PH who underwent intubation. Study Design: We performed a single-center retrospective cohort study of critically ill patients with group 1, 3 or 4 PH who underwent intubation. Results: Eighty-one patients were included. Patients had a median age of 56 years (interquartile range 44-65) and were predominantly female (n = 53, 65%) and Caucasian (n = 71, 88%). Forty-five (56%) had group 1 PH while 25 (31%) had group 3 PH and 11 (14%) had group 4 PH. Patients were admitted to the hospital for right ventricular failure (n = 21, 25.6%), sepsis (n = 18, 22.2%), and respiratory failure (n = 19, 23.1%). Hypoxemic respiratory failure (n = 54, 66.7%) was the most common indication for intubation. In-hospital mortality was 30.9% and 1-year mortality was 48.2%. All patients (11 of 11, 100%) intubated electively for intensive care unit procedures survived to hospital discharge while only 1 of 6 (16.7%) intubated in the setting of a cardiac arrest survived. After adjusting for right ventricular systolic pressure, pre-intubation PaO2 (odds ratio [OR] = 0.99, 95% confidence interval [CI] 0.97-1.00, P = .02) and postintubation PaO2 (OR = 0.97 per 1mm Hg, 95% CI 0.95 to 0.99, P = .003), pH (OR = 0.49 per 0.1 increase, 95% CI 0.29 to 0.80, P = .005) and PaCO2 (OR = 1.08 per 1mm Hg, 95% CI 1.02 to 1.14, P = .005) were significantly associated with in-hospital mortality. Results were similar when we excluded patients intubated electively or in the setting of cardiac arrest. Conclusions: Intubation in critically ill patients with PH is associated with significant in-hospital mortality and nearly 50% 1-year mortality. Potentially modifiable factors, such as peri-intubation gas exchange, are associated with an increased risk of death while other demographic and hemodynamic variables are not.

Physician attitudes toward sports medicine coverage of mixed martial arts.

BACKGROUND: The popularity of modern Mixed Martial Arts (MMA) has been increasing since 2000s. It has drawn the attention of the media due to higher injury rates compared to other sports, and it is possible that this may have led to a generally negative image of MMA among viewers, including but not limited to, physicians. Therefore, our study aimed to understand the attitudes of physicians toward MMA and being asked to cover MMA events. METHODS: A cross-sectional study with an online survey was answered by 410 physicians from four physician organizations throughout the USA. Demographic data, sports event-related, sports coverage experience, athleticism, and familiarity with MMA answers were analyzed. Wilcoxon, Fisher Exact, and χ2 tests were used to compare the data. The main outcomes was the association between characteristics of physicians and attitude toward MMA coverage. RESULTS: Physician characteristics influenced positive attitudes toward MMA coverage. Those who regularly followed MMA felt more strongly that combat sport events required physician coverage, mainly for boxing (92.4% vs. 73.4%; P<0.001), kickboxing (89.9% vs. 54.7%; P<0.001), and taekwondo (50.6% vs. 38.4%; P=0.046). Doctors who considered themselves athletic or who had covered MMA events in the past were more likely to think that all sporting events should be covered by physicians (97.4% vs. 65.9%; P<0.01; 98.4% vs. 72.8%, P<0.001, respectively). Family medicine (72/139 [51.8%]) and physical medicine and rehabilitation (7/11 [63.6%]) were the specialties more inclined to agree with physician coverage for these events. CONCLUSIONS: Physicians familiar with MMA, either as a previous ringside physician or as a spectator, are more inclined to believe these events should have physician coverage as are those more experienced with sports medicine, such as family medicine and physical medicine and rehabilitation specialists. Therefore, specialized sports medicine training should be provided to allow for appropriate MMA physician coverage. With additional training, MMA event organizers should feel comfortable asking physicians in any specialty to provide sports medicine coverage to improve care for MMA athletes.

Association of Hypertensive Disorders of Pregnancy With Cognition in Later Life.

BACKGROUND AND OBJECTIVES: Studies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GH/CH) and preeclampsia/eclampsia (PE/E), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later life. We examined the effects of any HDP, GH/CH, PE/E, and nulliparity on cognition in later life. METHODS: Participants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical record-abstracted pregnancy information. A cognitive battery of 9 tests was conducted every 15 months. Global cognitive and domain-specific z scores (memory, executive/attention, visuospatial, and language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype [GH/CH, PE/E], or nulliparous) and cognitive decline, adjusting for age and education. Additional models adjusted for APOE, smoking, hypertension, dyslipidemia, body mass index (BMI), diabetes, stroke, and heart disease. Interactions between pregnancy history and age or education on cognitive performance were examined. RESULTS: Of the 2,239 women, 1,854 (82.8%) had at least 1 pregnancy (1,607 all normotensive, 100 GH/CH, and 147 PE/E); 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E vs women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (all p < 0.05) in age- and education-adjusted models. There was an interaction (p = 0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = -0.42, p < 0.001) vs 12 + years (b = -0.11, p = 0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z scores compared with women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = -0.04, p < 0.001), language (beta = -0.03, p = 0.001), and attention (beta = -0.04, p < 0.001) z scores. Adjustment for vascular risk factors, BMI, smoking, and APOE did not attenuate results. DISCUSSION: Women with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.

Post-Transplant and In-Hospital Risk Factors for ARDS After Hematopoietic Stem Cell Transplantation.

BACKGROUND: ARDS is a serious complication of hematopoietic stem cell transplant (HSCT). Pre-transplant risk factors for developing ARDS after HSCT have been recently identified. The objective of this study was to better understand post-transplant risk factors for developing ARDS after HSCT. METHODS: This was a nested case-control study. ARDS cases were matched to hospitalized non-ARDS controls by age, type of transplantation (allogeneic vs autologous), and time from transplantation. In a conditional logistic regression model, any potential risk factors were adjusted a priori for risk factors known to be associated with ARDS development. RESULTS: One hundred and seventy ARDS cases were matched 1:1 to non-ARDS hospitalized controls. Pre-admission, cases were more likely to be on steroids (odds ratio [OR] 1.90 [1.13-3.19], P = .02). At time of admission, cases had lower platelet count (OR 0.95 [0.91-0.99], P = .02), lower bicarbonate (OR 0.94 [0.88-0.99], P = .035), and higher creatinine (OR 1.91 [1.23-2.94], P = .004). During the first 24 h after admission, cases were more likely to have received transfusion (OR 2.41 [1.48-3.94], P < .001), opioids (OR 2.94 [1.67-5.18], P < .001), and have greater fluid administration (OR 1.52 [1.30-1.78], P < .001). During the hospitalization, ARDS cases had higher temperature (OR 1.77 [1.34-2.33], P < .001) and higher breathing frequency (OR 1.52 [1.33-1.74], P < .001). ARDS cases were more likely to have had sepsis (OR 68.0 [15.2-301.7], P < .001), bloodstream infection (OR 4.59 [2.46-8.57], P < .001), and pneumonia (OR 9.76 [5.01-19.00], P < .001). CONCLUSIONS: Several post-transplant predictors of ARDS development specific to the HSCT population were identified in the pre-hospital and early in-hospital domains. These findings can provide insights into causal mechanisms of ARDS development and be used to develop HSCT-specific risk prediction models.

Performance of plasma phosphorylated tau 181 and 217 in the community.

Plasma phosphorylated tau 181 (P-tau181) and 217 (P-tau217) are indicators of both amyloid and tau pathology in clinical settings, but their performance in heterogeneous community-based populations is unclear. We examined P-tau181 and P-tau217 (n = 1,329, aged 30-98 years), in the population-based Mayo Clinic Study of Aging. Continuous, unadjusted plasma P-tau181 and P-tau217 predicted abnormal amyloid positron-emission tomography (PET) (area under the receiver operating characteristic curve (AUROC) = 0.81-0.86) and tau PET entorhinal cortex (AUROC > 0.80), but was less predictive of a tau PET temporal region of interest (AUROC < 0.70). Multiple comorbidities were associated with higher plasma P-tau181 and P-tau217 levels; the difference between participants with and without chronic kidney disease (CKD) was similar to the difference between participants with and without elevated brain amyloid. The exclusion of participants with CKD and other comorbidities affected the establishment of a normal reference range and cutpoints. Understanding the effect of comorbidities on P-tau181 and P-tau217 levels is important for their future interpretation in the context of clinical screening, diagnosis or prognosis at the population level.

Body temperature trends of critically Ill patients on continuous renal replacement therapy: A single-center retrospective study.

BACKGROUND: Interpretation of human body temperature in patients on continuous renal replacement therapy (CRRT) is challenging. Clinicians currently use definitions of 'normal' temperature derived from healthy patients over a century ago and apply these definitions to patients on continuous renal replacement therapy (CRRT). There is a significant opportunity to refine temperature definitions to apply to the increasing population of critically ill patients on CRRT. METHODS: A total of 1361 critically ill patients admitted to the hospital between 12/1/2006 and 11/31/2015 and requiring CRRT were studied. Temperature data were summarized (median, IQR) and compared during time periods that patients were on CRRT and time periods that they were not on CRRT using paired comparisons. Additionally, analyses were performed to compare temperature dynamics between patients who died during their hospitalization with those who did not. RESULTS: The median body temperature change was -0.6 °C (95% CI -1.3, -0.6) from 12 h before CRRT to 12 h after CRRT (p < .001), and an increase of 0.6 °C (95% CI 0.2, 0.6) from 12 h before CRRT end to 12 h after CRRT end (p < .001). Temperature significantly increased by a median 0.3 °C from the start to the end of CRRT. CONCLUSIONS: There are significant body temperature changes in critically ill patients on CRRT with cooling at the time of CRRT initiation and warming at the time of CRRT cessation.

Frailty Transitions One Year After Total Joint Arthroplasty: A Cohort Study.

BACKGROUND: Total joint arthroplasty (TJA) is prevalent and offered to patients regardless of frailty status experiencing pain, disability, and functional decline. This study aims to describe changes in levels of frailty 1 year after TJA. METHODS: We identified a retrospective cohort of adult patients undergoing primary TJA between 2005 and 2016 using an institutional total joint registry. Associations between categorized frailty deficit index (FI) and change in FI were analyzed using linear regression models. Mortality, deep periprosthetic joint infection, and reoperation were analyzed using time to event methods. RESULTS: In total, 5341 patients (37.6% non-frail, 39.4% vulnerable, and 23.0% frail) with items necessary to determine FI at 1 year after TJA were included. Preoperatively, 29% of vulnerable patients improved to non-frail 1 year later, compared to only 11% regressing to frail. Four in 10 frail patients improved to vulnerable/non-frail. Improvements in activities of daily living (ADL) were more evident in frail and vulnerable patients, with >30% reduction in the percentage of patients expressing difficulties with walking, climbing stairs, and requiring ADL assistance 1 year after TJA. Increases in frailty 1 year after TJA were associated with significantly increased rates of mortality (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.24-1.82, P < .001), deep periprosthetic joint infection (HR 3.98, 95% CI 1.85-8.58, P < .001), and reoperation (HR 1.80, 95% CI 1.19-2.72, P = .005). CONCLUSION: Frailty states are dynamic with patient frailty shown to be modifiable 1 year after TJA. Preoperative frailty measurement is an important step toward identifying those that may benefit most from TJA and for postoperative frailty surveillance.

Plasma, platelet and red blood cell transfusion ratios for life-threatening non-traumatic haemorrhage in medical and post-surgical patients: An observational study.

BACKGROUND AND OBJECTIVES: Despite the broad utilization of component-based transfusion strategies that aim to reconstitute whole blood during acute traumatic haemorrhage, data for haemorrhage occurring outside of trauma and surgery are limited. METHODS: This is an observational cohort study of adults experiencing critical non-traumatic, non-intraoperative haemorrhage during hospitalization at an academic medical centre from 2011 to 2015. The primary goal was to evaluate differences in plasma and platelet to red blood cell (RBC) transfusion ratios across patient demographic, clinical and laboratory characteristics. Secondarily, associations between transfusion ratios and clinical outcomes were assessed. RESULTS: Seven hundred nine patients were included: 498 (70.2%) medical and 211 (29.8%) post surgical. The gastrointestinal tract (36.7%) was the most common site of bleeding. Most patients received RBCs without plasma (35.5%) or platelets (54.2%). Among those receiving plasma, 82.3% received a plasma to RBC ratio < 1:1 at 24 h. For platelets, the most common ratio was 1-2:1 (52.9%). Transfusion ratios were generally consistent across comorbid disease severity, admission type and anatomic sites of bleeding. Higher plasma utilization was observed in the emergency department, while greater platelet utilization occurred in intensive care units. Higher transfusion ratios were observed in those with greater laboratory haemostatic abnormalities prior to the haemorrhagic event. Clinical outcome differences were limited, though greater platelet utilization in the first 24 h was associated with higher mortality and fewer hospital-free days. CONCLUSIONS: Transfusion ratios for critical non-traumatic haemorrhage were primarily related to laboratory abnormalities preceding the haemorrhagic event and practice environments. Clinical outcome differences across ratios were limited.

Spontaneous resolution rates in congenital nasolacrimal duct obstruction managed with massage or topical antibiotics compared with observation alone.

BACKGROUND/AIMS: To determine if nasolacrimal massage or topical antibiotics are associated with higher rates of resolution compared with observation alone in a population-based cohort of infants with congenital nasolacrimal duct obstruction (CNLDO). METHODS: The medical records of all children <5 years diagnosed with CNLDO while residing in Olmsted County, Minnesota from 1 January 1995 through 31 December 2004 were retrospectively reviewed for type of management and non-surgical resolution of tearing. RESULTS: Among 1958 infants diagnosed and followed for CNLDO, 516 (26.4%) were merely observed, 506 (25.8%) were prescribed massage alone, 485 (24.8%) were prescribed at least one course of topical antibiotics, 397 (20.3%) were prescribed both topical antibiotics and massage, and 54 (2.8%) had no documented therapy. Non-surgical resolution, occurring in 1669 (85.2%) during a median follow-up of 3.1 months (range: 1 week-248 months), was 74.6% for the merely observed, 89.7% for those prescribed digital massage, 87.0% for those prescribed antibiotics and 90.7% for those treated with both. This comparison was significant in unadjusted (p<0.001) and multivariable comparisons (p<0.001). CONCLUSION: Prescribing topical antibiotics or digital massage for infants with CNLDO in this cohort, individually or in combination, was associated with a higher rate of spontaneous resolution than observation alone.

FIO2 Trajectory as a Pragmatic Intermediate Marker in Acute Hypoxic Respiratory Failure.

BACKGROUND: Several markers of oxygenation are used as prognostic markers in acute hypoxemic respiratory failure. Real-world use is limited by the need for invasive measurements and unreliable availability in the electronic health record. A pragmatic, reliable, and accurate marker of acute hypoxemic respiratory failure is needed to facilitate epidemiologic studies, clinical trials, and shared decision-making with patients. [Formula: see text] is easily obtained at the bedside and from the electronic health record. The [Formula: see text] trajectory may be a valuable marker of recovery in patients with acute hypoxemic respiratory failure. METHODS: This was a historical cohort study of adult subjects admitted to an ICU with acute hypoxemic respiratory failure secondary to community-acquired pneumonia and/or ARDS. RESULTS: Our study included 2,670 subjects. [Formula: see text] and [Formula: see text] were consistently more available than was [Formula: see text] in the electronic health record: ([Formula: see text] vs [Formula: see text] vs [Formula: see text] : 100 vs 100 vs 72.8% on day 1, and 100 vs 99 vs 21% on day 5). A worsening [Formula: see text] trajectory was associated with reduced ventilator-free days. From days 2 to 5, every increase in [Formula: see text] by 10% from the previous day was associated with fewer ventilator-free days (on day 2: adjusted mean -1.25 [95% CI -1.45 to -1.05] d, P < .001). The [Formula: see text] trajectory also provided prognostic information. On days 3 - 5, an increase in [Formula: see text] from the previous day was associated with increased ventilator-free days (on day 3: adjusted mean 2.09 (95% CI 1.44-2.74) d; P < .001). [Formula: see text] models did not add predictive information compared with models with [Formula: see text] alone (on day 2: adjusted [Formula: see text] vs [Formula: see text] R2 0.122 vs 0.119; and on day 3: 0.153 vs 0.163). CONCLUSIONS: [Formula: see text] and [Formula: see text] are pragmatic and readily available intermediate prognostic markers in acute hypoxic respiratory failure. The [Formula: see text] trajectory in the first 5 d of ICU admission provided important prognostic information (ventilator-free days). Although the [Formula: see text] trajectory was also associated with ventilator-free days, it did not provide more information than the [Formula: see text] trajectory alone.

The order of vasopressor discontinuation and incidence of hypotension: a retrospective cohort analysis.

The optimal order of vasopressor discontinuation during shock resolution remains unclear. We evaluated the incidence of hypotension in patients receiving concomitant vasopressin (VP) and norepinephrine (NE) based on the order of their discontinuation. In this retrospective cohort study, consecutive patients receiving concomitant VP and NE infusions for shock admitted to intensive care units were evaluated. The primary outcome was hypotension incidence following discontinuation of VP or NE (VP1 and NE1 groups, respectively). Secondary outcomes included the incidence of acute kidney injury (AKI) and arrhythmias. Subgroup analysis was conducted by examining outcomes based on the type of shock. Of the 2,035 included patients, 952 (46.8%) were VP1 and 1,083 (53.2%) were NE1. VP1 had a higher incidence of hypotension than NE1 (42.1% vs. 14.2%; P < 0.001), longer time to shock reversal (median: 2.5 vs. 2.2 days; P = .009), higher hospital [29% (278/952) vs. 24% (258/1083); P = .006], and 28-day mortality [37% (348/952) vs. 29% (317/1,083); P < 0.001] when compared with the NE1 group. There were no differences in ICU mortality, ICU and hospital length of stay, new-onset arrhythmia, or AKI incidence between the two groups. In subgroup analyses based on different types of shock, similar outcomes were observed. After adjustments, hypotension in the following 24 h and 28-day mortality were significantly higher in VP1 (Odds ratios (OR) 4.08(3.28, 5.07); p-value < .001 and 1.27(1.04, 1.55); p-value < .001, respectively). Besides, in a multivariable model, the need for renal replacement therapy (OR 1.68 (1.34, 2.12); p-value < .001) was significantly higher in VP1. Among patients with shock who received concomitant VP and NE, the VP1 group was associated with a higher incidence of hypotension in comparison with NE1. Future studies need to validate our findings and their impact on clinical outcomes.

Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes.

Importance: Cerebrospinal fluid phosphorylated tau (p-tau) 181, p-tau217, and p-tau231 are associated with neuropathological outcomes, but a comparison of these p-tau isoforms in blood samples is needed. Objective: To conduct a head-to-head comparison of plasma p-tau181 and p-tau231 measured on the single-molecule array (Simoa) platform and p-tau181 and p-tau217 measured on the Meso Scale Discovery (MSD) platform on amyloid and tau positron emission tomography (PET) measures, neurodegeneration, vascular pathology, and cognitive outcomes. Design, Setting, and Participants: This study included data from the Mayo Clinic Study on Aging collected from March 1, 2015, to September 30, 2017, and analyzed between December 15, 2020, and May 17, 2021. Associations between the 4 plasma p-tau measures and dichotomous amyloid PET, metaregion of interest tau PET, and entorhinal cortex tau PET were analyzed using logistic regression models; the predictive accuracy was summarized using area under the receiver operating characteristic curve (AUROC) statistic. Of 1329 participants without dementia and with p-tau181 and p-tau217 on MSD, 200 participants with plasma p-tau181 and p-tau231 on Simoa and magnetic resonance imaging and amyloid and tau PET data at the same study visit were eligible. Main Outcomes And Measures: Primary outcomes included amyloid (greater than 1.48 standardized uptake value ratio) and tau PET, white matter hyperintensities, white matter microstructural integrity (fractional anisotropy genu of corpus callosum and hippocampal cingulum bundle), and cognition. Results: Of 200 included participants, 101 (50.5%) were male, and the median (interquartile range [IQR]) age was 79.5 (71.1-84.1) years. A total of 177 were cognitively unimpaired (CU) and 23 had mild cognitive impairment. Compared with amyloid-negative CU participants, among amyloid-positive CU participants, the median (IQR) Simoa p-tau181 measure was 49% higher (2.58 [2.00-3.72] vs 1.73 [1.45-2.13] pg/mL), MSD p-tau181 measure was 53% higher (1.22 [0.91-1.56] vs 0.80 [0.66-0.97] pg/mL), MSD p-tau217 measure was 77% higher (0.23 [0.17-0.34] vs 0.13 [0.09-0.18] pg/mL), and Simoa p-tau231 measure was 49% higher (20.21 [15.60-25.41] vs 14.27 [11.27-18.10] pg/mL). There were no differences between the p-tau species for amyloid PET and tau PET metaregions of interest. However, among CU participants, both MSD p-tau181 and MSD p-tau217 more accurately predicted abnormal entorhinal cortex tau PET than Simoa p-tau181 (MSD p-tau181: AUROC, 0.80 vs 0.70; P = .046; MSD p-tau217: AUROC, 0.81 vs 0.70; P = .04). MSD p-tau181 and p-tau217 and Simoa p-tau181, but not p-tau231, were associated with greater white matter hyperintensity volume and lower white matter microstructural integrity. Conclusions and Relevance: In this largely presymptomatic population, these results suggest subtle differences across plasma p-tau species and platforms for the prediction of amyloid and tau PET and magnetic resonance imaging measures of cerebrovascular and Alzheimer-related pathology.

Inclusion of Albumin in the Initial Resuscitation of Adult Patients with Medical Sepsis or Septic Shock: a Propensity Score-Matched Analysis.

INTRODUCTION: The impact of albumin resuscitation on sepsis outcomes is debated, particularly in the initial phase of resuscitation. We aimed to investigate the association between albumin use in the initial 6 h of resuscitation and subsequent outcomes in adult septic patients. METHODS: This single-center, retrospective, propensity score-matched cohort study included adult patients admitted to intensive care units (ICUs) with sepsis or septic shock from January 1, 2006, to May 4, 2018, at a tertiary referral hospital. We compared two groups based on albumin receipt within the initial six resuscitation hours (albumin group vs. non-albumin group). We performed a 1:2 propensity score matching to assess shock-free time in ICU as the primary outcome. RESULTS: Of 2,732 patients with medical sepsis, 286 cases in the albumin group were matched with 549 individuals in the non-albumin group. Compared to the non-albumin group, the albumin group required more intravenous fluids and had higher net fluid balance, lower mean arterial pressure, and lower serum base excess level in the initial 6 and 24 h of resuscitation. Shock-free time, ICU and hospital length of stay, and 28-day mortality were not different between albumin and non-albumin groups (56 vs. 66 h, P = 0.18; 3.5 days vs. 3.7 days, P = 0.61; 9.1 days vs. 9.5 days, P = 0.27; 36% vs. 32%, P = 0.25, respectively). CONCLUSIONS: Using albumin during the initial 6 h of resuscitation was not associated with benefits in clinical outcomes of patients with medical sepsis.

Association Between Antifibrinolytic Therapy and Perioperative Outcomes in Patients With Coronary Artery Stents Undergoing Noncardiac Surgery.

BACKGROUND: Patients with existing coronary artery stents are at an increased risk for major adverse cardiac events (MACEs) when undergoing noncardiac surgery (NCS). Although the use of antifibrinolytic (AF) therapy in NCS has significantly increased in the past decade, the relationship between perioperative AF use and its association with MACEs among patients with existing coronary artery stents has yet to be assessed. In this study, we aim to evaluate the association of MACEs in patients with existing coronary artery stents who receive perioperative AF therapy during orthopedic surgery. METHODS: A single-center retrospective cohort study was conducted in adult patients with existing coronary artery stents who underwent orthopedic surgery from 2008 to 2018. Two cohorts were established: patients with existing coronary artery stents who did not receive perioperative AF and patients with coronary artery stents who received perioperative AF. Associations between AF use and the primary outcome of MACEs within 30 days postoperatively and the secondary outcomes of thrombotic complications, excessive surgical bleeding, and intensive care unit (ICU) admissions were analyzed using logistic regression models. Inverse probability of treatment weighting was used to control for confounding. Secondary analyses examining the association between coronary stent type/timing and the outcomes of interest were performed using unadjusted logistic regression models. RESULTS: A total of 473 patients met study criteria, including 294 who did not receive AF and 179 patients who received AF. MACEs occurred in 15 (5.1%) patients who did not receive AF and 1 (0.6%) who received AF (P = .007). In weighted analyses, no significant difference was found in patients who received AF with regard to MACEs (odds ratio [OR] = 0.13, 95% confidence interval [CI], 0.01-1.74, P = .12), thrombotic complications (OR = 1.19, 95% CI, 0.53-2.68, P = .68), or excessive surgical bleeding (OR = 0.13, 95% CI, 0.01-2.23, P = .16) compared to patients who did not receive AF. CONCLUSIONS: The results of this study are inconclusive whether an association exists between perioperative AF use in patients with coronary artery stents and the outcome of MACEs compared to patients who did not receive perioperative AF therapy. The authors acknowledge that the imprecise CI hinders the ability to definitively determine whether an association exists in the study population. Further large prospective studies, powered to detect differences in MACEs, are needed to assess the safety of perioperative AF in patients with existing coronary artery stents and to clarify the mechanism of perioperative MACEs in this high-risk population.

An international study to develop the EAR-Q patient-reported outcome measure for children and young adults with ear conditions.

BACKGROUND: There is currently a lack of patient-reported outcome measures for ear reconstruction. We developed the EAR-Q to measure ear appearance and post-operative adverse effects from the patient perspective. METHODS: Field-test data were collected from children and young adults in eight countries between 13 May 2016 and 12 December 2019. Rasch measurement theory (RMT) analysis was used to refine the scales and to examine their psychometric properties. RESULTS: Participants had microtia (n = 607), prominent ears (n = 145) or another ear condition (n = 111), and provided 960 assessments for the Appearance scale (e.g., size, shape, photos), and 137 assessments for the Adverse Effects scale (e.g., itchy, painful, numb). RMT analysis led to the reduction of each scale to 10-items. Data fit the Rasch model for the Appearance (X2(80) = 90.9, p = 0.19) and Adverse Effects (X2(20) = 24.5, p = 0.22) scales. All items in each scale had ordered thresholds and good item fit. There was no evidence of differential item function for the Appearance scale by age, gender, language, or type of ear condition. Reliability was high for the Appearance scale, with person separation index (PSI) and Cronbach alpha values with and without extremes ≥0.92. Reliability for the Adverse Effects scale was adequate (i.e., PSI and Cronbach alpha values ≥0.71). Higher scores (liked appearance more) correlated with higher scores (better) on Psychological, Social and School scales. INTERPRETATION: The EAR-Q can be used in those 8-29 years of age to understand the patient perspective in clinical practice and research, and in addition, can be used to benchmark outcomes for ear reconstruction internationally.

Utilization of radiation therapy in multiple myeloma: trends and changes in practice.

Plasma cell disorders including plasmacytomas and multiple myeloma (MM) are exquisitely radiosensitive, and thus, radiation therapy (XRT) is used effectively in their management. The role of XRT in the setting of novel MM therapeutics has not been explored. The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004 and 2013 was studied. Association between utilization of XRT as part of initial therapy and patient, disease, or treating facility characteristics was studied. A total of 111,281 cases with 91.6% MM, 7% osseous plasmacytoma (PLA-O), and 1.4% extramedullary plasmacytoma (PLA-E) were identified. XRT was utilized as part of initial therapy in 25.4% cases, including 69.3% of PLA-O, 60% of PLA-E, and 21.5% of MM patients. Patients with PLA-E and MM were significantly less likely to receive XRT as compared to PLA-O (p < 0.001). A significantly decreased use of XRT was noted over time (p < 0.001), and for advancing patient age (p < 0.001), women (p < 0.001), and blacks (p < 0.001), and with increasing income (p = 0.015). Patients with Medicare were less likely to receive XRT (OR 0.86, 95% CI 0.78, 0.94) as compared to uninsured as were those with initial treatment at academic or high-volume facilities and facilities performing stem cell transplant. There was overall decreased utilization of XRT in recent years, possibly due to advent of efficacious systemic agents for MM therapy, with a higher XRT utilization for plasmacytomas. Patterns of XRT use need to be explored prospectively, so that uniform standards of healthcare delivery can be maintained and treatment heterogeneity can be minimized.