Elevated Exposure to Air Pollutants Accelerates Primary Glomerular Disease Progression.

Introduction: Environmental contributors to kidney disease progression remain elusive. We explored how residential air pollution affects disease progression in patients with primary glomerulopathies. Methods: Nephrotic Syndrome Study Network (NEPTUNE) and CureGlomerulonephropathy (CureGN) participants with residential census tract data and ≥2 years of follow-up were included. Using Cox proportional hazards models, the associations per doubling in annual average baseline concentrations of total particulate matter with diameter ≤2.5 µm (PM2.5) and its components, black carbon (BC), and sulfate, with time to ≥40% decline in estimated glomerular filtration rate (eGFR) or kidney failure were estimated. Serum tumour necrosis factor levels and kidney tissue transcriptomic inflammatory pathway activation scores were used as molecular markers of disease progression. Results: PM2.5, BC, and sulfate exposures were comparable in NEPTUNE (n = 228) and CureGN (n = 697). In both cohorts, participants from areas with higher levels of pollutants had lower eGFR, were older and more likely self-reported racial and ethnic minorities. In a fully adjusted model combining both cohorts, kidney disease progression was associated with PM2.5 (adjusted hazard ratio 1.55 [95% confidence interval: 1.00-2.38], P = 0.0489) and BC (adjusted hazard ratio 1.43 [95% confidence interval: 0.98-2.07], P = 0.0608) exposure. Sulfate and PM2.5 exposure were positively correlated with serum tumour necrosis factor (TNF) (P = 0.003) and interleukin-1ß levels (P = 0.03), respectively. Sulfate exposure was also directly associated with transcriptional activation of the TNF and JAK-STAT signaling pathways in kidneys (r = 0.55-0.67, P-value <0.01). Conclusion: Elevated exposure to select air pollutants is associated with increased risk of disease progression and systemic inflammation in patients with primary.

Return to Sports Rates in Pediatric Patients After Bilateral Versus Unilateral Medial Patellofemoral Ligament Reconstruction.

BACKGROUND: Patellofemoral instability commonly occurs during sports activities. The return to sports (RTS) rate for pediatric patients after bilateral medial patellofemoral ligament reconstruction (MPFLR) is unknown. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate RTS outcomes for pediatric patients undergoing bilateral MPFLR. It was hypothesized that (1) fewer pediatric patients would RTS after bilateral MPFLR compared with unilateral MPFLR and that (2) for those in the bilateral cohort who were able to RTS, fewer patients would attain the same level of play as or higher level than the preinjury level. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We prospectively collected RTS data on retrospectively identified matched cohorts of patients aged ≤18 years who underwent unilateral and bilateral MPFLR. We matched each participant with bilateral MPFLR at a 1 to 2 ratio with a participant with unilateral MPFLR by concomitant procedure, age, and sex. Postoperative complications and preoperative imaging measurements were collected from medical records. Patient-reported outcomes were obtained using a current Single Assessment Numeric Evaluation score collected at the time of primary outcome data. RESULTS: We matched 16 participants (mean age, 14 years) who underwent bilateral MPFLR to 32 participants (mean age, 14.3 years) in a corresponding unilateral MPFLR cohort. We found a significant decrease in RTS rates for pediatric patients after bilateral MPFLR when compared with unilateral MPFLR (69% vs 94%; P = .03). Among those who returned to sports, there was no difference in the level of play achieved. For participants who did not RTS or returned at a lower level of play after bilateral MPFLR, 57% cited fear of reinjury as the primary reason. There were no differences in postoperative complications or current Single Assessment Numeric Evaluation scores between cohorts. The bilateral cohort had a significantly higher Caton-Deschamps index compared with the unilateral cohort, although the absolute difference was small (1.3 vs 1.2; P = .005). CONCLUSION: We found that pediatric patients have a lower RTS rate after bilateral MPFLR when compared with a matched unilateral MPFLR cohort. No differences in the level of play were achieved among those who returned to sports. Fear of reinjury was a commonly cited reason for not returning to sports.

MR Imaging-based Biomarker Development in Hemorrhagic Stroke Patients Including Brain Iron Quantification, Diffusion Tensor Imaging, and Phenomenon of Ultra-early Erythrolysis.

This review article discusses the role of MR imaging-based biomarkers in understanding and managing hemorrhagic strokes, focusing on intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage. ICH is a severe type of stroke with high mortality and morbidity rates, primarily caused by the rupture of small blood vessels in the brain, resulting in hematoma formation. MR imaging-based biomarkers, including brain iron quantification, ultra-early erythrolysis detection, and diffusion tensor imaging, offer valuable insights for hemorrhagic stroke management. These biomarkers could improve early diagnosis, risk stratification, treatment monitoring, and patient outcomes in the future, revolutionizing our approach to hemorrhagic strokes.

Association between CFTR modulators and changes in iron deficiency markers in cystic fibrosis.

BACKGROUND: Iron deficiency (ID) is a common extrapulmonary manifestation in cystic fibrosis (CF). CF transmembrane conductance regulator (CFTR) modulator therapies, particularly highly-effective modulator therapy (HEMT), have drastically improved health status in a majority of people with CF. We hypothesize that CFTR modulator use is associated with improved markers of ID. METHODS: In a multicenter retrospective cohort study across 4 United States CF centers 2012-2022, the association between modulator therapies and ID laboratory outcomes was estimated using multivariable linear mixed effects models overall and by key subgroups. Summary statistics describe the prevalence and trends of ID, defined a priori as transferrin saturation (TSAT) <20 % or serum iron <60 µg/dL (<10.7 µmol/L). RESULTS: A total of 568 patients with 2571 person-years of follow-up were included in analyses. Compared to off modulator therapy, HEMT was associated with +8.4 % TSAT (95 % confidence interval [CI], +6.3-10.6 %; p < 0.0001) and +34.4 µg/dL serum iron (95 % CI, +26.7-42.1 µg/dL; p < 0.0001) overall; +5.4 % TSAT (95 % CI, +2.8-8.0 %; p = 0.0001) and +22.1 µg/dL serum iron (95 % CI, +13.5-30.8 µg/dL; p < 0.0001) in females; and +11.4 % TSAT (95 % CI, +7.9-14.8 %; p < 0.0001) and +46.0 µg/dL serum iron (95 % CI, +33.3-58.8 µg/dL; p < 0.0001) in males. Ferritin was not different in those taking modulator therapy relative to off modulator therapy. Hemoglobin was overall higher with use of modulator therapy. The prevalence of ID was high throughout the study period (32.8 % in those treated with HEMT). CONCLUSIONS: ID remains a prevalent comorbidity in CF, despite availability of HEMT. Modulator use, particularly of HEMT, is associated with improved markers for ID (TSAT, serum iron) and anemia (hemoglobin).

Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease.

RATIONALE & OBJECTIVE: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD). STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy). PREDICTORS: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model. OUTCOME: Progression to ESKD. ANALYTICAL APPROACH: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log2 transformed to approximate normal distribution and normalized to urinary creatinine (Log2uPlasminogen/cr, Log2 urinary protein/cr [UPCR]). Expected plasmin(ogen) was calculated by multiple linear regression. RESULTS: Adjusted Log2uPlasminogen/cr was significantly associated with ESKD (HR per doubling Log2 uPlasminogen/cr 1.31 [95% CI, 1.22-1.40], P<0.001). Comparison of the predictive performance of the models including Log2 uPlasminogen/cr, Log2 UPCR, or both markers showed the plasmin(ogen) model superiority. The ratio of measured/expected urine plasmin(ogen) was independently associated with ESKD: HR, 0.41 (95% CI, 0.22-0.77) if ratio<0.8 and HR 2.42 (95% CI, 1.54-3.78) if ratio>1.1 (compared with ratio between 0.8 and 1.1). LIMITATIONS: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis. CONCLUSIONS: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease. PLAIN-LANGUAGE SUMMARY: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease.

Radiologists predict differential resource utilization but not clinical outcome in emergency department patients imaged with ultrasound for right upper quadrant pain.

PURPOSE: Radiologists with diverse training, specialization, and habits interpret imaging in the Emergency Department. It is necessary to understand if their variation predicts differential value. The purpose of this study was to determine whether attending radiologist variation predicts major clinical outcomes in adult Emergency Department patients imaged with ultrasound for right upper quadrant pain. METHODS: Consecutive ED patients imaged with ultrasound for RUQ pain from 10/8/2016 to 8/10/2022 were included (N = 7097). The primary outcome was prediction of hospital admission by signing attending radiologist. Secondary outcomes included: ED and hospital length of stay (LOS), 30-day mortality, 30-day re-presentation rate, subspecialty consultation, advanced imaging follow up (HIDA, MRI, CT), and intervention (ERCP, drainage or surgery). Sample size was determined a priori (detectable effect size: w = 0.06). Data were adjusted for demographic data, Elixhauser comorbidities, number of ED visits in prior year, clinical data, and system factors (38 covariates). P-values were corrected for multiple comparisons (false discovery rate-adjusted p-values). RESULTS: The included ultrasounds were read by 35 radiologists (median exams/radiologist: 145 [74.5-241.5]). Signing radiologist did not predict hospitalization (p = 0.85), abdominopelvic surgery or intervention within 30 days, re-presentation to the Emergency Department within 30 days, or subspecialty consultation. Radiologist did predict difference in Emergency Department length of stay (p < 0.001) although this difference was small and imprecise. HIDA was mentioned variably by radiologists (range 0-19%, p < 0.001), and mention of HIDA in the ultrasound report increased 10-fold the odds of HIDA being performed in the next 72 h (odds ratio 10.4 [8.0-13.4], p < 0.001). CONCLUSION: Radiologist variability did not predict meaningful outcome differences for patients with right upper quadrant pain undergoing ultrasound in the Emergency Department, but when radiologists mention HIDA in their reports, it predicts a 10-fold increase in the odds a HIDA is performed. Radiologists are relied on for interpretation that shapes subsequent patient care, and it is important to consider how radiologist variability can influence both outcome and resource utilization.

The Dosing of Mobile-Based Just-in-Time Adaptive Self-Management Prompts for Caregivers: Preliminary Findings From a Pilot Microrandomized Study.

BACKGROUND: Caregivers of people with chronic illnesses often face negative stress-related health outcomes and are unavailable for traditional face-to-face interventions due to the intensity and constraints of their caregiver role. Just-in-time adaptive interventions (JITAIs) have emerged as a design framework that is particularly suited for interventional mobile health studies that deliver in-the-moment prompts that aim to promote healthy behavioral and psychological changes while minimizing user burden and expense. While JITAIs have the potential to improve caregivers' health-related quality of life (HRQOL), their effectiveness for caregivers remains poorly understood. OBJECTIVE: The primary objective of this study is to evaluate the dose-response relationship of a fully automated JITAI-based self-management intervention involving personalized mobile app notifications targeted at decreasing the level of caregiver strain, anxiety, and depression. The secondary objective is to investigate whether the effectiveness of this mobile health intervention was moderated by the caregiver group. We also explored whether the effectiveness of this intervention was moderated by (1) previous HRQOL measures, (2) the number of weeks in the study, (3) step count, and (4) minutes of sleep. METHODS: We examined 36 caregivers from 3 disease groups (10 from spinal cord injury, 11 from Huntington disease, and 25 from allogeneic hematopoietic cell transplantation) in the intervention arm of a larger randomized controlled trial (subjects in the other arm received no prompts from the mobile app) designed to examine the acceptability and feasibility of this intensive type of trial design. A series of multivariate linear models implementing a weighted and centered least squares estimator were used to assess the JITAI efficacy and effect. RESULTS: We found preliminary support for a positive dose-response relationship between the number of administered JITAI messages and JITAI efficacy in improving caregiver strain, anxiety, and depression; while most of these associations did not meet conventional levels of significance, there was a significant association between high-frequency JITAI and caregiver strain. Specifically, administering 5-6 messages per week as opposed to no messages resulted in a significant decrease in the HRQOL score of caregiver strain with an estimate of -6.31 (95% CI -11.76 to -0.12; P=.046). In addition, we found that the caregiver groups and the participants' levels of depression in the previous week moderated JITAI efficacy. CONCLUSIONS: This study provides preliminary evidence to support the effectiveness of the self-management JITAI and offers practical guidance for designing future personalized JITAI strategies for diverse caregiver groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT04556591; https://clinicaltrials.gov/ct2/show/NCT04556591.

Does thePenicillin Allergy Label Affect Outcomes of Complicated Odontogenic Infections?

PURPOSE: Penicillins are a potent antibiotic in managing odontogenic infections, but 10% of the population is labelled as allergic to these drugs. This has limited their use and resulted in increased utilization of health care resources as well as complications associated with alternative antibiotics. The purpose of the study was to measure the association between patients labeled as penicillin allergic and treatment outcomes in a sample of patients treated for complicated odontogenic infections. Additionally, we sought to investigate antibiotic resistance patterns in these patients. MATERIALS AND METHODS: A retrospective cohort study was performed at the Michigan Medicine health care system to include patients who were treated for complicated odontogenic infections by oral and maxillofacial surgery between 2016 and 2020. Complicated odontogenic infection was defined as any odontogenic infection requiring admission and surgical management in the operating room. The primary predictor variable was the penicillin allergy label, which was determined by chart review and not confirmed with formal testing. Outcomes were measures of disease severity. The primary outcome variable was hospital length of stay. Secondary outcome variables were ICU admission (yes/no), repeat computed tomography scan(s), repeat surgery (yes/no), and re-admission (yes/no). Co-variates included were age, sex (male/female), tobacco use status, diabetes, immunocompromised state, number of spaces involved, white blood cell count upon admission and insurance status. For our secondary aim, the primary predictor variable was again penicillin allergy and outcome variable was antibiotic resistance as determined by wound culture results following surgical intervention. Negative binomial regression and logistic regression analyses were performed. P < .05 was considered significant. RESULTS: A total of 150 patients met the inclusion criteria and of those 17.3% reported as penicillin allergic. Patients labelled as penicillin allergic did not differ significantly from patients without penicillin allergy label in terms of treatment outcomes. Age, diabetes, and immunosuppression were associated with an increased length of stay. Patients labelled as penicillin allergic were at significantly higher risk for antibiotic resistance (relative risk = 2.34; 95% confidence interval, 1.66 to 3.32; P < .001), specifically clindamycin resistance (relative risk = 3.17; 95% confidence interval, 1.93 to 5.18; P < .001). CONCLUSIONS: Penicillin allergy was significantly associated with clindamycin resistance. There were similar outcomes amongst patients with and without a penicillin allergy label despite antibiotic differences. Delabeling efforts for patients with a reported penicillin allergy must be considered and local nomograms for antibiotic selection should be used by providers when seeking alternative antibiotics.

The reliability and validity of the TBI-CareQOL system in four diverse caregiver groups.

PURPOSE: Establishing the psychometric reliability and validity of new measures is an ongoing process. More work is needed in to confirm the clinical utility of the TBI-CareQOL measurement development system in both an independent cohort of caregivers of traumatic brain injury (TBI), as well as in additional caregiver groups. METHODS: An independent cohort of caregivers of people with TBI (n = 139), as well as three new diverse caregiver cohorts (n = 19 caregivers of persons with spinal cord injury, n = 21 caregivers for persons with Huntington disease, and n = 30 caregivers for persons with cancer), completed 11 TBI-CareQOL measures (caregiver strain; caregiver-specific anxiety; anxiety; depression; anger; self-efficacy; positive affect and well-being; perceived stress; satisfaction with social roles and activities; fatigue; sleep-related impairment), as well as two additional measures to examine convergent and discriminant validity (PROMIS Global Health; the Caregiver Appraisal Scale). RESULTS: Findings support the internal consistency reliability (all alphas > 0.70 with the vast majority being > 0.80 across the different cohorts) of the TBI-CareQOL measures. All measures were free of ceiling effects, and the vast majority were also free of floor effects. Convergent validity was supported by moderate to high correlations between the TBI-CareQOL and related measures, while discriminant validity was supported by low correlations between the TBI-CareQOL measures and unrelated constructs. CONCLUSION: Findings indicate that the TBI-CareQOL measures have clinical utility in caregivers of people with TBI, as well as in other caregiver groups. As such, these measures should be considered as important outcome measures for clinical trials aiming to improve caregiver outcomes.

Diagnostic Accuracy of Unenhanced Computed Tomography for Evaluation of Acute Abdominal Pain in the Emergency Department.

Importance: Intravenous (IV) contrast medium is sometimes withheld due to risk of complication or lack of availability in patients undergoing computed tomography (CT) for abdominal pain. The risk from withholding contrast medium is understudied. Objective: To determine the diagnostic accuracy of unenhanced abdominopelvic CT using contemporaneous contrast-enhanced CT as the reference standard in emergency department (ED) patients with acute abdominal pain. Design, Setting, and Participants: This was an institutional review board-approved, multicenter retrospective diagnostic accuracy study of 201 consecutive adult ED patients who underwent dual-energy contrast-enhanced CT for the evaluation of acute abdominal pain from April 1, 2017, through April 22, 2017. Three blinded radiologists interpreted these scans to establish the reference standard by majority rule. IV and oral contrast media were then digitally subtracted using dual-energy techniques. Six different blinded radiologists from 3 institutions (3 specialist faculty and 3 residents) interpreted the resulting unenhanced CT examinations. Participants included a consecutive sample of ED patients with abdominal pain who underwent dual-energy CT. Exposure: Contrast-enhanced and virtual unenhanced CT derived from dual-energy CT. Main outcome: Diagnostic accuracy of unenhanced CT for primary (ie, principal cause[s] of pain) and actionable secondary (ie, incidental findings requiring management) diagnoses. The Gwet interrater agreement coefficient was calculated. Results: There were 201 included patients (female, 108; male, 93) with a mean age of 50.1 (SD, 20.9) years and mean BMI of 25.5 (SD, 5.4). Overall accuracy of unenhanced CT was 70% (faculty, 68% to 74%; residents, 69% to 70%). Faculty had higher accuracy than residents for primary diagnoses (82% vs 76%; adjusted odds ratio [OR], 1.83; 95% CI, 1.26-2.67; P = .002) but lower accuracy for actionable secondary diagnoses (87% vs 90%; OR, 0.57; 95% CI, 0.35-0.93; P < .001). This was because faculty made fewer false-negative primary diagnoses (38% vs 62%; OR, 0.23; 95% CI, 0.13-0.41; P < .001) but more false-positive actionable secondary diagnoses (63% vs 37%; OR, 2.11, 95% CI, 1.26-3.54; P = .01). False-negative (19%) and false-positive (14%) results were common. Interrater agreement for overall accuracy was moderate (Gwet agreement coefficient, 0.58). Conclusion: Unenhanced CT was approximately 30% less accurate than contrast-enhanced CT for evaluating abdominal pain in the ED. This should be balanced with the risk of administering contrast material to patients with risk factors for kidney injury or hypersensitivity reaction.

A pilot intervention of using a mobile health app (ONC Roadmap) to enhance health-related quality of life in family caregivers of pediatric patients with cancer.

Background: The Roadmap mobile health (mHealth) app was developed to provide health-related quality of life (HRQOL) support for family caregivers of patients with cancer. Methods: Eligibility included: family caregivers (age ≥18 years) who self-reported as the primary caregiver of their pediatric patient with cancer; patients (age ≥5 years) who were receiving cancer care at the University of Michigan. Feasibility was calculated as the percentage of caregivers who logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the 120-day study duration. Feasibility and acceptability was also assessed through a Feasibility and Acceptability questionnaire and the Mobile App Rating Scale to specifically assess app-quality. Exploratory analyses were also conducted to assess HRQOL self- or parent proxy assessments and physiological data capture. Results: Between September 2020-September 2021, 100 participants (or 50 caregiver-patient dyads) consented and enrolled in the ONC Roadmap study for 120-days. Feasibility of the study was met, wherein the majority of caregivers (N=32; 65%) logged into ONC Roadmap and engaged with it at least twice weekly for at least 50% of the study duration (defined a priori in the Protocol). The Feasibility and Acceptability questionnaire responses indicated that the study was feasible and acceptable with the majority (>50%) reporting Agree or Strongly Agree with positive Net Favorability [(Agree + Strongly Agree) - (Disagree + Totally Disagree)] in each of the domains (e.g., Fitbit use, ONC Roadmap use, completing longitudinal assessments, engaging in similar future study, study expectations). Improvements were seen across the majority of the mental HRQOL domains across all groups; even though underpowered, there were significant improvements in caregiver-specific aspects of HRQOL and anxiety and in depression and fatigue for children (ages 8-17 years), and a trend toward improvement in depression for children ages 8-17 years and in fatigue for adult patients. Conclusions: This study supports that mHealth technology may be a promising platform to provide HRQOL support for caregivers of pediatric patients with cancer. Importantly, the findings suggest that the study protocol was feasible, and participants were favorable to participate in future studies of this intervention alongside routine cancer care delivery.

Death Anxiety in Huntington Disease: Longitudinal Heath-Related Quality-of-Life Outcomes.

Objective: Death anxiety, represented by the HDQLIFE™ Concern with Death and Dying (CwDD) patient-reported outcome (PRO) questionnaire, captures a person's worry about the death and dying process. Previous work suggests that death anxiety remains an unremitting burden throughout all stages of Huntington disease (HD). Although palliative interventions have lessened death anxiety among people with advanced cancer, none has yet to undergo testing in the HD population. An account of how death anxiety is associated with longitudinal changes to aspects of health-related quality of life (HRQoL) would help optimize neuropalliative interventions for people with HD. Methods: HDQLIFE collected PROs concerning physical, mental, social, and cognitive HRQoL domains and clinician-rated assessments from people with HD at baseline and 12 and 24 months. Linear mixed-effects models were created to determine how baseline death anxiety was associated with follow-up changes in HRQoL PROs after controlling for baseline death anxiety and other disease and sociodemographic covariates. Results: Higher baseline HDQLIFE CwDD is associated with 12- and 24-month declines in HDQLIFE Speech Difficulties, neurology quality of life (NeuroQoL) Depression, Suicidality, HDQLIFE Meaning and Purpose, and NeuroQoL Positive Affect and Well-being. Interpretation: Death anxiety may be a risk factor for worsening mental health and speech difficulty. A further prospective study is required to evaluate whether interventions on death anxiety or mental health generally can reduce declines in HRQoL for people with HD over time.

An app-based just-in-time-adaptive self-management intervention for care partners: The CareQOL feasibility pilot study.

PURPOSE/OBJECTIVE: The primary objective of this study was to establish the feasibility and acceptability of an intensive data collection protocol that involves the delivery of a personalized just-in-time adaptive intervention (JITAI) in three distinct groups of care partners (care partners of persons with spinal cord injury [SCI], Huntington's disease [HD], or hematopoietic cell transplantation [HCT]). RESEARCH METHOD/DESIGN: Seventy care partners were enrolled in this study (n = 19 SCI; n = 21 HD, n = 30 HCT). This three-month (90 day) randomized control trial involved wearing a Fitbit to track sleep and steps, providing daily reports of health-related quality of life (HRQOL), and completing end of month HRQOL surveys. Care partners in the JITAI group also received personalized pushes (i.e., text-based phone notifications that include brief tips or suggestions for improving self-care). At the end of three-months, care partners in both groups completed a feasibility and acceptability questionnaire. RESULTS: Most (98.6%) care partners completed the study, average compliance was 88% for daily HRQOL surveys, 96% for daily steps, and 85% for daily sleep (from wearing the Fitbit), and all monthly surveys were completed with the exception of one missed 3-month assessment. The acceptability of the protocol was high; ratings exceeded 80% agreement for the different elements of the study. Improvements were seen for the majority of the HRQOL measures. There was no evidence of measurement reactivity. CONCLUSIONS/IMPLICATIONS: Findings provide strong support for the acceptability and feasibility of an intensive data collection protocol that involved the administration of a JITAI. Although this trial was not powered to establish efficacy, findings indicated improvements across a variety of different HRQOL measures (~1/3 of which were statistically significant). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Extent of Extranodal Extension in Oral Cavity Squamous Cell Carcinoma is Not Independently Associated With Overall or Disease-Free Survival at a 2.0-mm Threshold.

PURPOSE: The presence of extranodal extension (ENE) conveys a poor prognosis in oral cavity squamous cell carcinoma (OSCC); however, there is no consensus regarding whether the histopathologic extent of ENE (e-ENE) may be a more discriminating prognostic indicator. The purpose of this study was to assess the impact of minor ENE (<2.0 mm) versus major ENE (≥ 2.0 mm) on overall survival (OS) and disease-free survival (DFS) in OSCC. MATERIALS AND METHODS: A single-institution, retrospective cohort study was designed using an electronic medical record review. Inclusion criteria included patients with OSCC and cervical node metastasis. All subjects were treated between the years 2009 and 2017 in the Michigan Medicine Department of Oral and Maxillofacial Surgery (Ann Arbor, Michigan). The primary predictor variable was e-ENE, measured as the maximum distance of tumor invasion into extranodal tissue from the outer aspect of the nodal capsule. Primary outcome variables were OS and DFS. Other covariates included demographic data, tumor staging, and histopathologic data. Descriptive statistics were performed. Kaplan-Meier survival plots for OS and DFS were performed. The data were mined for an alternative threshold at which e-ENE may impact survival using Cox proportional hazards models. RESULTS: One hundred sixty eight subjects were included (91 ENE-negative, 48 minor ENE, and 29 major ENE). Most subjects were male (62%) and the mean age was 62.9 years. Mean follow-up time was 2.97 +/- 2.76 years. There was no statistically significant difference in OS or DFS between minor and major ENE. Five-year OS for minor ENE was 30.4% versus 20.7% for major ENE (P = .28). Five-year DFS for minor ENE was 26.7% versus 18.1% for major ENE (P = .30). Five-year OS and DFS was worse for subjects with ENE-positive disease versus ENE-negative disease (OS: 26.9% vs 63.1%, hazard ratio [HR]: 2.70, 95% confidence interval [CI]: [1.77, 4.10], P < .001; DFS: 23.7% vs 59.7%, HR = 2.55, 95% CI [1.71, 3.79], P < .001). At an alternative threshold of 0.9 mm e-ENE, there was greater DFS in subjects with e-ENE 0.1-0.9 mm versus e-ENE > 0.9 (40.6% vs 18.9%, respectively) (HR = 0.49, 95% CI [0.24, 0.99], P = .047). CONCLUSION: There was no independent association between survival and e-ENE at a 2.0-mm threshold.

Comparing Kidney Health Outcomes in Children, Adolescents, and Adults With Focal Segmental Glomerulosclerosis.

Importance: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials. Objective: To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS. Design, Setting, and Participants: This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record-based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022. Exposures: Age: children (age <13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration, APOL1 genotype, urine protein-to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy. Main Outcomes and Measures: ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria. Results: The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio [HR], 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50). Conclusions and Relevance: In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.

Validation of Tabletop Microscopes for Microsurgery Simulation and Training.

PURPOSE: Oral and maxillofacial surgery residency programs are increasingly adopting microsurgery as a core element of training; however, many barriers exist that limit trainees' proficiency. The purpose of this study was to perform a validation of 2 tabletop microscope simulations for their use as a training tool, which could serve as an affordable, alternative method to traditional microsurgery training methods. METHODS: A prospective, single-institution, multidepartmental validation study was performed. Two microscopes (monocular digital [DM] and binocular stereo [SM]) were used to perform anastomoses on simulation vessels including a silastic tube and a chicken thigh femoral artery. A microsurgeon panel was selected from a population of microsurgery faculty and fellows at Michigan Medicine (Ann Arbor, MI) to perform the anastomoses. The surgeons each performed 4 anastomoses, using each microscope with each vessel, and subsequently completed a survey evaluating the simulation. Predictor variables were the microscope and the vessel. Primary outcome variable was readiness for use, which was defined as the simulation's ability to incorporate into a microsurgical training curriculum in its current state. Secondary outcome variables included realism, value, usefulness, relevance, difficulty, and cost. Paired t tests were used to compare responses. Alpha was set to 0.05. RESULTS: Seven microsurgeons performed the simulation from the departments of oral and maxillofacial surgery (n = 5), plastic and reconstructive surgery (n = 1), and otolaryngology (n = 1). For readiness, the SM simulation required either no modification (n = 4) prior to implementation into a microsurgery curriculum or minimal modification (n = 3), compared to the DM simulation which required significant modification (n = 4) or extensive modification and re-evaluation (n = 3) (P = .002). The SM demonstrated a greater mean realism score than the DM for depth perception (5.00 vs 1.57, P < .001), field of view (4.57 vs 3.57, P = .038), lighting (5.00 vs 4.00, P = .038), and clarity (5.00 vs 3.86, P = .030). There was no statistically significant difference between SM and DM in value, usefulness, relevance, difficulty, or cost. CONCLUSIONS: Tabletop microscopes demonstrate considerable promise in the future of microsurgical education. The SM simulation was a realistic simulation that may be ready for use in a microsurgical curriculum. Future studies are required to demonstrate the efficacy of this simulation on microsurgical trainees.

Asthma and coronavirus disease 2019-related outcomes in hospitalized patients: A single-center experience.

BACKGROUND: Several chronic conditions have been associated with a higher risk of severe coronavirus disease 2019 (COVID-19), including asthma. However, there are conflicting conclusions regarding risk of severe disease in this population. OBJECTIVE: To understand the impact of asthma on COVID-19 outcomes in a cohort of hospitalized patients and whether there is any association between asthma severity and worse outcomes. METHODS: We identified hospitalized patients with COVID-19 with confirmatory polymerase chain reaction testing with (n = 183) and without asthma (n = 1319) using International Classification of Diseases, Tenth Revision, codes between March 1 and December 30, 2020. We determined asthma maintenance medications, pulmonary function tests, highest historical absolute eosinophil count, and immunoglobulin E. Primary outcomes included death, mechanical ventilation, intensive care unit (ICU) admission, and ICU and hospital length of stay. Analysis was adjusted for demographics, comorbidities, smoking status, and timing of illness in the pandemic. RESULTS: In unadjusted analyses, we found no difference in our primary outcomes between patients with asthma and patients without asthma. However, in adjusted analyses, patients with asthma were more likely to have mechanical ventilation (odds ratio, 1.58; 95% confidence interval [CI], 1.02-2.44; P = .04), ICU admission (odds ratio, 1.58; 95% CI, 1.09-2.29; P = .02), longer hospital length of stay (risk ratio, 1.30; 95% CI, 1.09-1.55; P < .003), and higher mortality (hazard ratio, 1.53; 95% CI, 1.01-2.33; P = .04) compared with the non-asthma cohort. Inhaled corticosteroid use and eosinophilic phenotype were not associated with considerabledifferences. Interestingly, patients with moderate asthma had worse outcomes whereas patients with severe asthma did not. CONCLUSION: Asthma was associated with severe COVID-19 after controlling for other factors.

Are Outcomes of Temporomandibular Joint Arthroscopy Influenced by Central Sensitization?

PURPOSE: A proportion of subjects with internal derangements of the temporomandibular joint (TMJ) may have a central sensitization disorder that may affect pain perception after surgery. This study aims to estimate the association between fibromyalgianess (FMness) score, a summed score of the Widespread Pain Index (WPI) and Symptom Severity Sore (SSS), and outcomes following TMJ arthroscopy. METHODS: A retrospective cohort study including individuals who received arthroscopy for TMJ internal derangement at Michigan Medicine between 2011 and 2020 was performed. A predictor variable, FMness score, was assigned via the sum of WPI and SSS. Univariate and bivariate analyses were performed. Linear-mixed effects models were used to analyze 6 different outcomes, each in their own model: pain, jaw functional limitation scale (JFLS), JFLS-mobility domain, pain-related disability, comfortable maximum interincisal opening, and active maximum interincisal opening. Covariance structure was selected based on null model fit separately for each outcome. RESULTS: Thirty-one subjects were included in the study sample. Twenty-eight subjects were female. Average age was 45.9 years. Bivariate analysis demonstrated that subject's FMness score was not correlated with pain (b = 0.03 [-0.10, 0.17] P = .59) or JFLS score (b = 1.00 [-.80, 2.81] P = .27). However, subject's FMness score was significant for predicting JFLS-mobility domain score (b = .61, [0.05, 1.18] P = .04). CONCLUSION: A greater extent of central sensitization was associated with lower comfortable mouth opening after surgery, greater limitations in opening wide enough to eat various foods (higher JFLS-mobility scores), and higher pain-related disability. Future studies with larger sample sizes and reconstructive TMJ operations such as total TMJ arthroplasty may help clarify the impact of SSS and WPI scores on outcomes of TMJ surgery.

Effect of Prostate MRI Interpretation Experience on PPV Using PI-RADS Version 2: A 6-Year Assessment Among Eight Fellowship-Trained Radiologists.

BACKGROUND. Understanding the effect of specific experience in prostate MRI interpretation on diagnostic performance would help inform the minimum interpretation volume to establish proficiency. OBJECTIVE. The purpose of this article is to assess for an association between increasing experience in prostate MRI interpretation and change in radiologist-level PPVs for PI-RADS version 2 (v2) categories 3, 4, and 5. METHODS. This retrospective study included prostate MRI examinations performed between July 1, 2015, and August 13, 2021, that were assigned a PI-RADS v2 category of 3, 4, or 5 and with an MRI-ultrasound fusion biopsy available as the reference standard. All examinations were among the first 100-200 prostate MRI examinations interpreted using PI-RADS v2 by fellowship-trained abdominal radiologists. Radiologists received feedback through a quality assurance program. Radiologists' experience levels were classified using progressive subsets of 50 interpreted examinations. Change with increasing experience in distribution of individual radiologists' whole-gland PPVs for Gleason sum score 7 or greater prostate cancer, stratified by PI-RADS category, was assessed by hierarchic linear mixed models. RESULTS. The study included 1300 prostate MRI examinations in 1037 patients (mean age, 66 ± 7 [SD] years), interpreted by eight radiologists (median, 13 years of postfellow-ship experience; range, 5-22 years). Aggregate PPVs were 20% (68/340) for PI-RADS category 3, 49% (318/652) for category 4, and 71% (220/308) for category 5. Interquartile ranges (IQRs) of PPVs overlapped for category 4 (51%; IQR, 42-60%) and category 5 (70%; IQR, 54-75%) for radiologists' first 50 examinations. IQRs of PPVs did not overlap between categories of greater experience; for example, at the 101-150 examination level, PPV for category 3 was 24% (IQR, 20-29%), category 4 was 55% (IQR, 54-63%), and category 5 was 81% (IQR, 77-82%). Hierarchic modeling showed no change in radiologists' absolute PPV with increasing experience (category 3, p = .27; category 4, p = .71; category 5, p = .38). CONCLUSION. Absolute PPVs at specific PI-RADS categories did not change during radiologists' first 200 included examinations. However, resolution of initial overlap in IQRs indicates improved precision of PPVs after the first 50 examinations. CLINICAL IMPACT. If implementing a minimum training threshold for fellowship-trained abdominal radiologists, 50 prostate MRI examinations may be sufficient in the context of a quality assurance program with feedback.

Interrater Agreement of Bosniak Classification Version 2019 and Version 2005 for Cystic Renal Masses at CT and MRI.

Background The Bosniak classification system for cystic renal masses was updated in 2019 in part to improve agreement compared with the 2005 version. Purpose To compare and investigate interrater agreement of Bosniak version 2019 and Bosniak version 2005 at CT and MRI. Materials and Methods In this retrospective single-center study, a blinded eight-reader assessment was performed in which 195 renal masses prospectively considered Bosniak IIF-IV (95 at CT, 100 at MRI, from 2006 to 2019 with version 2005) were re-evaluated with Bosniak versions 2019 and 2005. Radiologists (four faculty members, four residents) who were blinded to the initial clinical reading and histopathologic findings assessed all feature components and reported the overall Bosniak class for each system independently. Agreement was assessed with Gwet agreement coefficients. Uni- and multivariable linear regression models were developed to identify predictors of dispersion in the final Bosniak class assignment that could inform system refinement. Results A total of 185 patients were included (mean age, 63 years ± 13 [standard deviation]; 118 men). Overall interrater agreement was similar between Bosniak version 2019 and version 2005 (Gwet agreement coefficient: 0.51 [95% CI: 0.45, 0.57] vs 0.46 [95% CI: 0.42, 0.51]). This was true for experts (0.54 vs 0.49) and novices (0.50 vs 0.47) and at CT (0.56 vs 0.51) and MRI (0.52 vs 0.43). Nine percent of masses prospectively considered cystic using Bosniak version 2005 criteria were considered solid using version 2019 criteria. In general, masses were more commonly classified in lower categories when radiologists used Bosniak version 2019 criteria compared with version 2005 criteria. The sole predictor of dispersion in Bosniak version 2019 class assignment was dispersion in septa or wall quality (ie, smooth vs irregular thickening vs nodule; 72% [MRI] and 60% [CT] overall model variance explained; multivariable P < .001). Conclusion Overall interrater agreement was similar between Bosniak version 2019 and version 2005; disagreements in septa or wall quality were common and strongly predictive of variation in Bosniak class assignment. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Eberhardt in this issue.