Citations

Abstract Background Silicon (Si) is a possible sensor material for photon counting detectors (PCDs). A major drawback of Si is that roughly two‐thirds of x‐ray interactions in the diagnostic energy range are Compton scattering. Because Compton scattering is an energy‐insensitive process, it is commonly assumed that Compton events retain little spectral information. Purpose To quantify how much information can be recovered from Compton scattering events in models of Si PCDs. Methods We built a simplified model of Si interactions including two interaction mechanisms: photoelectric effect and Compton scattering. We considered three different binning options that represent strategies for handling Compton events: in Compton censoring, all events under 38 keV (the maximum energy possible from Compton scattering for a 120 keV incident photon) were discarded; in Compton counting, all events between 1 and 38 keV were placed into a single bin; in Compton binning, all events were placed into energy bins of uniform width. These were compared to the ideal detector, which always recorded the correct energy (i.e., 100% photoelectric effect). Every photon was assumed to interact once and only once with Si, and the energy bin width was 5 keV. In the primary analysis, the Si detector was irradiated with a 120 kV spectrum filtered by 30 cm of water, with 99.5% of the arriving spectrum above 38 keV so that there was good separation between photoelectric effect and Compton scattering, and the figures of merit were the Cramér – Rao lower bound (CRLB) of the variance of iodine and water basis material decomposition images, as well as the CRLB of virtual monoenergetic images (i.e., linear combinations of material images) that maximize iodine CNR or water CNR. We also constructed a local linear estimator that attains the CRLB. In secondary analyses, we applied other sources of spectral distortion: (1) a nonzero minimum energy threshold; (2) coarser, 10 keV energy bins; and (3) a model of charge sharing. Results With our chosen spectrum, 67% of the interactions were Compton scattering. Consistent with this, the material decomposition variance for the Compton censoring model, averaged over both basis materials, was 258% greater than the ideal detector. If Compton events carried no spectral information, the Compton counting model would show similar variance. Instead, its basis material variance was 103% greater than the ideal detector, implying that Compton counts indeed carry significant spectral information. The Compton binning model had a basis material variance 60% greater than the ideal detector. The Compton binning model was not affected by a 5 keV minimum energy threshold, but the variance increased from 60% to 107% when charge sharing was included and to 78% with coarser energy bins. For optimized CNR images, the average variance was 149%, 12%, and 10% higher than the ideal detector for the Compton censoring, counting, and binning models, reinforcing the hypothesis that Compton counts are useful for detection tasks and that precise energy assignments are not necessary. Conclusions Substantial spectral information remains after Compton scattering events in silicon PCDs.

AbstractBackgroundChronic wounds have been associated with an elevated burden of cellular senescence, a state of essentially irreversible cell cycle arrest, resistance to apoptosis, and a secretory phenotype. However, whether senescent cells contribute to wound chronicity in humans remains unclear. The objective of this article is to assess the role of clinicopathological characteristics and cellular senescence in the time‐to‐healing of chronic wounds.MethodsA cohort of 79 patients with chronic wounds was evaluated in a single‐center academic practice from February 1, 2005, to February 28, 2015, and followed for up to 36 months. Clinical characteristics and wound biopsies were obtained at baseline, and time‐to‐healing was assessed. Wound biopsies were analyzed histologically for pathological characteristics and molecularly for markers of cellular senescence. In addition, biopsy slides were stained for p16INK4a expression.ResultsNo clinical or pathological characteristics were found to have significant associations with time‐to‐healing. A Cox proportional hazard ratio model revealed increased CDKN1A (p21CIP1/WAF1) expression to predict longer time‐to‐healing, and a model adjusted for gender and epidermal hyperplasia revealed increased CDKN1A expression and decreased PAPPA expression to predict longer time‐to‐healing. Increased p16INK4a staining was observed in diabetic wounds compared to non‐diabetic wounds, and the same association was observed in the context of high dermal fibrosis.ConclusionsThe findings of this pilot study suggest that senescent cells contribute to wound chronicity in humans, especially in diabetic wounds.

Purpose: Mehta casting is a potentially curative intervention for early-onset scoliosis (EOS) that typically requires multiple anesthetics. The Food and Drug Administration (FDA) reported that >3 hours of anesthesia under the age of 3 years old may alter brain development; however, no standard exists for the duration of anesthesia during casting. The purpose of this study is to quantify the variability in anesthesia during Mehta casting. We hypothesize that significant institutional variability exists and may be attributed to modifiable factors. Methods: An EOS registry was used to identify patients who underwent at least one Mehta casting procedure. Anesthesia exposure was quantified, and site variability was assessed by patient characteristics, cast placement, procedure type, and equipment used. Results: Our cohort consisted of 208 patients from 5 institutions (age 2.6±1.4 y). There were 1097 Mehta casting procedures, with 5.4±3.6 castings per patient. Of these patients, 106 (51%) were female, with an average age of 2.11±1.29 years old at the time casting was initiated. Patient etiologies included 154 idiopathic (74.0%), 22 syndromic (10.6%), 18 congenital (8.7%), 11 neuromuscular (5.3%), and 3 unknown (1.4%). Anesthesia time was 69±31 minutes and varied significantly between sites (59±14 to 117±46 min; P<0.001). Cumulative anesthesia time for patients under 3 years was 320±197 minutes with 120/161 (74.5%) patients exceeding 3 hours. Anesthesia time was lower after the FDA warning in 2016 compared with pre-2016 (71±30 vs. 66±32, P=0.008). Conclusions: Patients undergoing Mehta casting are at significant risk of exceeding 3 hours of anesthesia, which the FDA has stated may be harmful for children <3 years. Significant site variability indicates that standardization protocols should be developed to encourage best practices and minimize anesthetic times. Level of Evidence: Prognostic Level II.

The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4 + T cell compartment into older age. Here, we describe that naive CD4 + T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age. PREX1 promotes nuclear translocation of phosphorylated STAT5, thereby supporting homeostatic proliferation in response to IL-7. Through the same mechanism, increased expression of PREX1 also biases naive cells to differentiate into effector T cells. These findings are consistent with the concept that primarily beneficial adaptations during aging, i.e., improved homeostasis, account for unfavorable functions of the aged immune system, in this case biased differentiation.

Abstract We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3–10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6–22 and HR: 3.6, 95% CI: 1.1–12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2–6), trouble swallowing (HR 2.5, 95% CI: 1.4–4.5) and changes in speech (HR:2.4, 95% CI:1.1–4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1–5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2–38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6–46), preserved olfaction (HR: 8.7, 95% CI: 1.7–45), anhidrosis (HR: 1.8, 95% CI: 1–3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1–2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4–26). Patients with PAF have an estimated 12% (95% CI: 9–15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.

Purpose: To investigate patterns in oculoplastic surgery telemedicine visits at our institution during the pandemic period. Methods: Retrospective chart review of all patients who had a virtual consultation with the oculoplastic surgery service at Mayo Clinic Rochester between March 1, 2020, and March 1, 2021. Results: There were a total of 148 patients. Mean age was 65 years (95% confidence interval [CI]: 62–68). The mean driving distance to the medical center was 468 kilometers (95% CI: 352–586) and 15 (10%) patients came from states with no practicing American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) members. Out of the 205 virtual visits, 35 (17%) were new, 45 (22%) were return, and 125 (61%) were postoperative. Conversion rate to surgery was 60%. A comparison between type of virtual visits (new vs. return vs. postoperative) revealed that a diagnosis of eyelid malposition was most frequent in postoperative visits ( p = < 0.001), skin malignancy was most frequent in new visits ( p = 0.009), and orbital tumors ( p = 0.018) and thyroid eye disease ( p = < 0.001) were most frequent in return visits. Most virtual encounters had supportive media attached including external photographs in 127 (62%) visits and other imaging or testing in 18 (9%) visits. The average virtual visit lasted 18 min (95% CI: 14–22) with technical difficulties noted in 9 (4%) visits. Unanticipated conversion to in-person visits was noted in three (1%) cases. Conclusions: A wide range of oculoplastic surgery conditions was managed virtually during the COVID-19 pandemic. Utilization of initial virtual visit versus follow-up care varied by diagnosis. Virtual visits may improve access to oculoplastic subspecialty care for patients from underserved areas.

Objective: To implement use of obstetric (OB) hospitalist telemedicine services (TeleOB) to support clinicians facing OB emergencies in low-resource hospital settings. Methods: TeleOB was staffed by OB hospitalists working at a tertiary maternity center. The service was available via real-time high-definition audio/video technology for providers at 17 outlying hospitals across a health system spanning two states. The initial 25 service activations are described. Results: TeleOB supported 17 deliveries, two postpartum emergency department (ED) consultations, and four antenatal ED consultations. In 10 of 17 (59%) deliveries, teleneonatology was jointly activated to support neonatal resuscitation. Sixteen (94%) deliveries occurred in multiparas, and five (29%) resulted from spontaneous preterm labor. Eighty percent (20/25) of activations occurred in facilities without maternity services. Conclusions: A TeleOB service staffed by OB hospitalists successfully supports hospitals in an integrated health care system. TeleOB is feasible for support of hospitals with no delivery facilities or with limited maternity care resources.

Abstract Aims In patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), a rare inherited arrhythmia syndrome, arrhythmic events can be prevented by medication and lifestyle recommendations. In patients who experience breakthrough arrhythmic events, non-adherence plays an essential role. We aimed to investigate the incidence and potential reasons for non-adherence to medication and lifestyle recommendations in a large, international cohort of patients with CPVT. Methods and results An online multilingual survey was shared with CPVT patients worldwide by their cardiologists, through peer-recruitment, and on social media from November 2022 until July 2023. Self-reported non-adherence was measured using the validated Medication Adherence Rating Scale (MARS) and a newly developed questionnaire about lifestyle. Additionally, validated questionnaires were used to assess potential reasons for medication non-adherence. Two-hundred-and-eighteen patients completed the survey, of whom 200 (92%) were prescribed medication [122 (61%) female; median age 33.5 years (interquartile range: 22–50)]. One-hundred-and-three (52%) were prescribed beta-blocker and flecainide, 85 (43%) beta-blocker, and 11 (6%) flecainide. Thirty-four (17%) patients experienced a syncope, aborted cardiac arrest or appropriate implantable cardioverter defibrillator shock after diagnosis. Nineteen (13.4%) patients were exercising more than recommended. Thirty (15%) patients were non-adherent to medication. Female sex [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.3–12.0, P = 0.019], flecainide monotherapy compared to combination therapy (OR 6.8, 95% CI 1.6–31.0, P = 0.010), and a higher agreement with statements regarding concerns about CPVT medication (OR 1.2, 95% CI 1.1–1.3, P &lt; 0.001) were independently associated with non-adherence. Conclusion The significant rate of non-adherence associated with concerns regarding CPVT-related medication, emphasizes the potential for improving therapy adherence by targeted patient education.

ABSTRACT Rhodococcus equi is an opportunistic pathogen known to cause pulmonary and extrapulmonary disease among immunocompromised patients. Treatment is frequently challenging due to intrinsic resistance to multiple antibiotic classes. While non- equi Rhodococcus spp. are prevalent, their clinical significance is poorly defined. There is also limited data on antibiotic susceptibility testing (AST) of Rhodococcus infection in humans. We conducted a single-center, retrospective cohort study evaluating clinical characteristics, microbiologic profile, and AST of Rhodococcus infections between June 2012 and 2022 at our tertiary academic medical center. Identification of Rhodococcus spp. was performed by Sanger 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry, and AST was performed by agar dilution. Three hundred twenty-two isolates of Rhodococcus spp. were identified from blood (50%), pulmonary (26%), and bone/joint (12%) sources. R. equi/hoagii, R. corynebacterioides , and R. erythropolis were the most frequently isolated species, with 19% of isolates identified only to genus level. One hundred ninety-nine isolates evaluated for AST demonstrated high-level resistance to amoxicillin/clavulanate, cephalosporins, and aminoglycosides. More than 95% susceptibility to imipenem, vancomycin, linezolid, rifampin, and clarithromycin was observed. Non- equi species showed a significantly more favorable AST profile relative to R. equi . Clinically significant Rhodococcus infection was rare with 10 cases diagnosed (majority due to R. equi ) and managed. The majority of patients received 2- or 3-drug combination therapy for 2–6 months, with favorable clinical response. Significant differences in AST were observed between R. equi and non- equi species. Despite high antimicrobial resistance to several antibiotic classes, imipenem and vancomycin remain appropriate empiric treatment options for R. equi . Future research evaluating mechanisms underlying antimicrobial resistance is warranted.