Citations

The study included 1,738 Mayo Clinic Study of Aging participants (≥50 years old; 1,460 cognitively unimpaired and 278 with mild cognitive impairment (MCI)) and examined the cross-sectional association between cerebrovascular (CVD) imaging biomarkers (e.g., white matter hyperintensities (WMH), infarctions) and Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) scores, as well as their association with MCI. High (abnormal) WMH burden was significantly associated with having BDI-II>13 and BAI > 7 scores, and both (CVD imaging biomarkers and depression/anxiety) were significantly associated with MCI when included simultaneously in the model, suggesting that both were independently associated with the odds of MCI.

AbstractBackgroundProstate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes.MethodsWe retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan–Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups.ResultsAt the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate‐specific antigen (PSA) was 2.2 (0.1–26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6–100.9). The median (IQR) primary Gleason score was 8 (7–9) and over a median (IQR) follow‐up time of 2.2 (1.2–16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log‐rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16–0.86, p = 0.022).ConclusionsIn our single‐institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

370 Background: Mounting evidence suggests tailored preparation targeting geriatric vulnerabilities can improve functional outcomes after major surgery in older adults. Although many surgeons express interest in surgical optimization of older patients, few practices have the time or expertise to deliver geriatric prehabilitation before surgery. This study investigated the effectiveness of OPTI-Surg, a frailty prehabilitation toolkit, for improving surgical outcomes. In this abstract, we report adherence to the OPTI-Surg toolkit in the intervention arm. Methods: Thoracic (T), gastrointestinal (GI), and urologic (GU) oncological surgery practices affiliated with NCI’s Community Oncology Research Program (NCORP) were randomized 1:1:1, stratified by practice type, to usual care (control), OPTI-Surg toolkit, or OPTI-Surg with an implementation coach. The toolkit was implemented at the practice level and consisted of the 12-item Edmonton Frail Scale (EFS) and guided recommendations for interventions including referrals directed at identified vulnerabilities. Eligible patients were ≥70 years old and undergoing curative intent surgery for T, Gl, or GU cancers. Results: From July 2019 to October 2021, 155 patients were enrolled in the OPTI-Surg intervention arm. The EFS was administered to 153 (98.7%) of the enrolled patients, 143 of whom went on to have surgery. Overall, 134 (93.7%) surgical patients had at least one deficit identified on the EFS assessment and 55 (41.0%) of these patients received a recommended referral intended to optimize surgical outcomes. Among the 55 patients who received referrals, 44 (80.0%) followed through on the referral. Individual deficit rates were highest for medication use, general health status, and functional performance, and referrals were most frequently made for deficits in continence and functional independence (Table). Conclusions: In the OPTI-Surg geriatric surgical optimization trial, implementation of the frailty screening with the EFS assessment was successful. Rates of recommended referrals for patients with identified deficits, however, were low. When referred, most patients followed through for targeted prehabilitation. Clinical trial information: NCT03857620 .[Table: see text]

AbstractBackgroundFor men with prostate cancer, radiographic progression may occur without a concordant rise in prostate‐specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C‐11 choline positron emission tomography (PET) imaging in patients achieving ultra‐low PSA values and to evaluate clinical outcomes in this patient population.MethodsIn a single institution study, we reviewed the prospectively maintained Mayo Clinic C‐11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C‐11 choline PET scan while the PSA value was less than 0.5 ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan–Meier method. Intergroup differences were assessed using the log‐rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP.ResultsA total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7–106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration‐resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small‐cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow‐up of 49.4 (21.3–95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value <0.05). Visceral metastases were associated with decreased overall survival (p = 0.009 by log‐rank) as compared with other sites of rDP.ConclusionsMen with prostate cancer commonly experience metastatic progression at very low or even undetectable PSA levels. Periodic imaging, even at low absolute PSA values, may result in more timely identification of disease progression.

Background We performed an assessment of patient response rates and clinical outcomes to the global recall for textured breast implants and to our institution's letters informing them of their risk of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). Methods A retrospective review of patients who had textured implants placed at our institution was completed. Outcome measures included patient response rates to either the global recall or our institution's letters, rate of textured implant removal, and type of subsequent revision surgery. Results A total of 1176 patients with textured implants were reviewed for this study. In total, 374 patients (31.8%) reached out to discuss their risk of BIA-ALCL, and 297 (25.3%) eventually presented to the clinic. One hundred twenty eight patients (34.2%) responded after the letter but before the US Food and Drug Administration (FDA) ban of macrotextured BIOCELL implants, 186 (49.7%) after the FDA ban, and 48 (12.8%) after the manufacturer's multichannel campaign. One hundred eighteen patients with textured implants (11.6%) proceeded with surgery. Most underwent exchange with smooth implants (76 patients [64.4%]) after textured implant removal. Conclusions A significant portion of patients (31.8%) responded to our letters, the FDA ban, and the manufacturer's campaign. Despite the low incidence of BIA-ALCL and the ongoing recommendation for observation in the setting of no symptoms, 11.6% of our patients still elected to proceed with implant removal. Exchange to smooth implants was the most popular surgical option at 64.4%.

Summary: Lymphaticovenous anastomosis (LVA) surgery is an effective surgery for the treatment of lymphedema in the extremities. Indocyanine green lymphography is the reference standard for visualizing lymphatics for LVA surgery, but it has several limitations; most notably, superficial dermal congestion can mask deeper lymphatic vessels. To overcome the limitations, we add contrast-enhanced ultrasound (CEUS) lymphography. We have previously reported that CEUS lymphography can identify lymphatic vessels for LVA surgery that indocyanine green lymphography does not. Here, we describe how we perform CEUS lymphography, including workflow, technique, and documentation. Before informed consent, the patient must be screened for possible adverse reactions to microbubbles. The procedure involves multiple intradermal injections of the microbubble agent at various sites along the extremity. After each injection, imaging for microbubble uptake by lymphatic vessels is performed using an ultrasound scanner with contrast-specific software. We use sulfur hexafluoride lipid-type A microspheres (Lumason/SonoVue; Bracco Suisse SA), but we are investigating the performance of other Food & Drug Administration–approved microbubble agents for CEUS lymphography. Having a systematic approach to marking the skin can mitigate the hindrance of marking over ultrasound coupling gel. Another benefit of CEUS lymphography is the rapid identification of neighboring veins compatible in size and location for anastomosis. We hold regular scheduled multidisciplinary meetings for coordination of care, discussion of outcomes, quality assurance, and ongoing innovation.

Introduction: As interest in metastasis-directed therapy (MDT) for prostate cancer (PCa) grows, exploring indications and patient selection is increasingly more important. Thus far, few studies have described long-term outcomes after surgical MDT in those with disease recurrence involving the lung. The objective of our study was to compare the cumulative incidence of cancer-related death by treatment modality in men with metachronous pulmonary metastases from PCa. Methods: In a single-institution retrospective study, we identified 75 men from the prospectively maintained Mayo Clinic C-11 Positron Emission Tomography Choline PCa registry with recurrent prostate cancer involving the lung but no other visceral organs. Patients were categorized into 3 groups based on treatment modalities: wedge resection ± hormonal therapy, chemohormonal therapy, and hormonal therapy alone. The risk of cancer-related death after treatment at the time of lung metastases was reported as cumulative incidence estimates. Non–cancer-related deaths were treated as a competing risk of death. A univariate Cox regression model was conducted to assess the impact of treatment modality on the risk of cancer-related death. Results: At the time of lung metastasis, the median age was 69.5 years, and the median (IQR) prostate-specific antigen was 4 (1.3-8.6) ng/ml. Forty-seven patients (62.7%) had hormone-sensitive disease, and 28 patients (37.3%) had hormone-resistant disease. A total of 26 patients (34.7%) were treated with wedge resection ± hormonal therapy, 27 (36%) with chemohormonal therapy, and 22 (29.3%) with hormonal therapy alone. The median (IQR) follow-up time was 50.3 (31.1-78.4) months, and 21 patients (28%) died. Patients who were treated with wedge resection ± hormonal therapy had lower rated of cancer-related death compared with those who received chemohormonal therapy (Hazard Ratio [HR]: 4.14, 95% CI: 1.01-16.96, P = .048) or hormonal therapy alone (HR: 6.37, 95% CI: 1.72-23.54, P = .005). Conclusion: This exploratory analysis supports the safety and feasibility of surgical metastasis-directed therapy in select patients with recurrent prostate cancer involving the lung. Favorable long-term survival provides justification for further evaluation of this approach.

ABSTRACT Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49–67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo ( 4 – 14 ), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

Importance Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR ( NCT01737398 ; March 2013–November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo (“placebo”) group. Interventions Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, –22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, –4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was −81.7% with eplontersen and −11.2% with placebo (difference, −70.4% [95% CI, −75.2% to −65.7%]; P &amp;lt; .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, −24.8 [95% CI, −31.0 to −18.6; P &amp;lt; .001) and for Norfolk QoL-DN (−5.5 vs 14.2; difference, −19.7 [95% CI, −25.6 to −13.8]; P &amp;lt; .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration ClinicalTrials.gov Identifier: NCT04136184 ; EU Clinical Trials Register: EudraCT 2019-001698-10

Purpose We reviewed all 64 articles ever published by The Congenital Heart Surgeons’ Society (CHSS) Data Center to estimate the academic impact of these peer-reviewed articles. Materials and Methods The Congenital Heart Surgeons’ Society has performed research based on 12 Diagnostic Inception Cohorts. The first cohort (Transposition) began enrolling patients on January 1, 1985. We queried PubMed to determine the number of publications that referenced each of the 64 journal articles generated by the datasets of the 12 Diagnostic Inception Cohorts that comprise the CHSS Database. Descriptive summaries of the data were tabulated using mean with standard deviation and median with range. Results Sixty-four peer-reviewed papers have been published based on the CHSS Database. Fifty-nine peer-reviewed articles have been published based on the 12 Diagnostic Inception Cohorts, and five additional articles have been published based on Data Science. Excluding the recently established Diagnostic Inception Cohort for patients with Ebstein malformation of tricuspid valve, the number of papers published per cohort ranged from 1 for coarctation to 11 for transposition of the great arteries. The 11 articles generated from the CHSS Transposition Cohort were referenced by a total of 111 articles (median number of references per journal article = 9 [range = 0-22, mean = 10.1]). Overall, individual articles were cited by an average of 11 (mean), and a maximum of 41 PubMed-listed publications. Overall, these 64 peer-reviewed articles based on the CHSS Database were cited 692 times in PubMed-listed publications. The first CHSS peer-reviewed article was published in 1987, and during the 35 years from 1987 to 2022, inclusive, the annual number of CHSS publications has ranged from 0 to 7, with a mean of 1.8 publications per year (median = 1, mode = 1). Conclusion Congenital Heart Surgeons’ Society studies are widely referenced in the pediatric cardiac surgical literature, with over 10 citations per published article. These cohorts provide unique information unavailable in other sources of data. A tool to access this analysis is available at: [ https://data-center.chss.org/multimedia/files/2022/CAI.pdf ].