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Frank A Schumacher,1 Irene B Helenowski,1 Laura B Oswald,2 Brian D Gonzalez,2 James T Benning,1 Alicia K Morgans1 1Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 2Program of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL, USACorrespondence: Frank A SchumacherFeinberg School of Medicine, Northwestern University, 1835 W Thomas St, Apt 2F, Chicago, IL, 60622, USATel +1 314 640-2883Email frank.schumacher@northwestern.eduBackground: Multiple treatments for metastatic prostate cancer have similar efficacy, leaving patients with complicated treatment choices. Shared decision-making can facilitate difficult treatment decisions, but the extent to which this is used for metastatic prostate cancer is unknown. We assessed patient, caregiver, and physician perceptions of decision locus of control (shared decision-making vs physician- or patient-directed decisions) and the degree of agreement between groups.Methods: Triads of patients, caregivers, and physicians completed surveys of decision-making practices after a clinic visit in which a decision occurred. To evaluate the degree of agreement for decision locus of control, we used the quadratic-weighted kappa coefficient (κ). We used relative frequencies to evaluate which knowledge learned and treatment factors were most strongly endorsed by patients as informing and influencing their treatment decision-making, respectively.Results: Fifty triads participated, with median patient age of 72 years. A majority of patients, caregivers, and physicians reported shared decision-making (66%, 56%, and 52%, respectively). Patients and physicians demonstrated minimal agreement about decision locus of control (44%, κ=0.35 [SD = 0.52]), but caregiver reports were not statistically significantly associated with physician and patient reports (38%, κ=0.23, [SD = 0.28]), p=0.055; 44%, κ=0.34 [SD = 1.98], p=0.14). Treatment efficacy was the most common patient-reported factor influencing treatment decisions (44%).Conclusion: This study characterized metastatic prostate cancer patients’, caregivers’, and physicians’ experiences and communication preferences for treatment decision-making. Patients and physicians had greater agreement in decision locus of control compared with caregivers, yet patient-physician agreement was minimal. Metastatic prostate cancer patients report being influenced by information about treatment efficacy and clear next steps, and a desire for patient-friendly language and an invitation to be as involved in decision making at their preferred level. Emphasizing these may increase agreement in decision locus of control between all participants in the decision-making process.Keywords: prostate cancer, decision making, shared decision making, treatment decisions, cancer survivorship

Venetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real-world data published on HMAs plus VEN have been either single-center studies or using community-based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real-world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85-13.5), with OS significantly worse among patients with TP53-mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30-day and 60-day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE-A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Combination chemotherapy and immunotherapy regimens have significantly improved survival for patients with previously untreated advanced non-small cell lung cancer (NSCLC). Improvements in overall survival (OS) in two separate pembrolizumab trials have demonstrated survival improvements over chemotherapy alone, regardless of PD-L1 status. The optimal chemotherapy backbone for combination with immunotherapy is unknown. We hypothesized nab-paclitaxel may be a well-suited platinum partner to use in combination with checkpoint inhibitor therapy for both adenocarcinoma and squamous histology and conducted a phase I/II trial to assess the efficacy of this regimen in advanced NSCLC., Methods: Adult patients with previously untreated, stage IIIB/IV NSCLC (any histology) with an Eastern Cooperative Oncology Group performance status of 0-1, any PD-L1 expression, and no EGFR mutations or ALK translocations, received carboplatin area under the curve (AUC) 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3w. Co-primary endpoints were progression-free survival (PFS) and overall response rate (ORR)., Results: Forty-six evaluable patients enrolled, 14 in phase I and 32 in phase II, from June 2015 to July 2018 with a median duration of follow-up of 35.4 months. Median time from enrollment to data lock was 42 months. In the ITT population, the ORR was 35%, median PFS was 5.6 months (95% CI, 4.6-8.2), and median OS was 15.4 months (CI, 12.4-28.1). There were no statistical differences in PFS or OS by PD-L1 status. The 2- and 3-year landmark OS rates were 33% and 24%, respectively., Conclusion: Carboplatin, nab-paclitaxel, and pembrolizumab are a safe and effective regimen for patients with both squamous and nonsquamous NSCLC. Although this study did not meet the prespecified endpoints, the median and landmark OS results are consistent with durable benefit of this regimen as seen in phase III trials for first-line treatment of advanced NSCLC., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: To assess urologists' attitudes toward treating lesbian, gay, bisexual, transgender, or queer (LGBT) patients and counseling practices during diagnosis and treatment of prostate cancer., Methods: A 35-question survey was sent to program directors of U.S. urology residency programs., Results: 154 responses met the inclusion criteria. Respondents were primarily male, heterosexual, in academia, representing a range of ages and geography. 54.2% of respondents don't assume patients are heterosexual. While 88% of providers feel comfortable discussing sexual health with LGBTQ patients, 42.9% disagree that knowing sexual orientation is necessary to providing optimal care. 57.8% of respondents don't provide intake forms to indicate sexual orientation and 60.4% don't inquire about sexual orientation during history-taking. A majority (32.7%) reported 1-5 hours of LGBTQ health training. 74.3% believe more training is needed. 74.5% agreed to being listed as an LGBTQ-Friendly Provider currently, 65.8% felt they needed additional training. 63.6% agreed the prostate is a source of sexual pleasure. 55.9% believed it important to assess sexual satisfaction in patients who engage in receptive anal intercourse after prostate cancer treatment. Responses were mixed regarding the timing of resuming receptive anal intercourse after treatment and whether patients are counseled to refrain from anal stimulation before PSA testing. Answers to knowledge questions regarding anal cancer and communication were primarily correct; answers to questions regarding anejaculation and differences in health concerns were mixed., Conclusion: Ongoing education is necessary on specific differences between heterosexual and lesbian, gay, bisexual, transgender, or queer (LGBTQ) patient concerns and how to apply this knowledge in order to address the needs of a rapidly aging LGBTQ population., Competing Interests: Declaration of Competing Interest The authors report no financial disclosures or conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We previously reported activity of pelareorep, pembrolizumab and chemotherapy. Patients developed new T-cell clones and increased peripheral T-cell clonality, leading to an inflamed tumour. To evaluate a chemotherapy-free regimen, this study assesses if pelareorep and pembrolizumab has efficacy by inducing anti-tumour immunological changes (NCT03723915)., Methods: PDAC patients who progressed after first-line therapy, received iv pelareorep induction with pembrolizumab every 21-days. Primary objective is overall response rate. Secondary objectives included evaluation of immunological changes within tumour and blood., Results: Clinical benefit rate (CBR) was 42% amongst 12 patients. One patient achieved partial response (PR) and four stable disease (SD). Seven progressed, deemed non-responders (NR). VDAC1 expression in peripheral CD8 +  T cells was higher at baseline in CBR than NR but decreased in CBR upon treatment. On-treatment peripheral CD4 +  Treg levels decreased in CBR but not in NR. Analysis of tumour demonstrated PD-L1 +  cells touching CD8 +  T cells, and NK cells were more abundant post-treatment vs. baseline. A higher intensity of PD-L1 in tumour infiltrates at baseline, particularly in CBR vs. NR. Finally, higher levels of soluble (s)IDO, sLag3, sPD-1 observed at baseline among NR vs. CBR., Conclusion: Pelareorep and pembrolizumab showed modest efficacy in unselected patients, although potential immune and metabolic biomarkers were identified to warrant further evaluation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Iloprost, a prostacyclin analog, has lung cancerpreventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable. We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance., Methods: Participants self-administered nebulized iloprost (5ug) or placebo four (QID) or two (BID) times daily. As QID dose was well tolerated and due to expiration of the placebo, the BID dosing and placebo were eliminated early on in the trial. Bronchoscopy with biopsyat six standard sites was performed at treatment initiation and two months post-iloprost, with exploratory histological analysis. Bulk RNA sequencing, single cell RNA sequencing and an in vitro assay of epithelial progenitor cell iloprost response were performed on a subset of biopsies in an exploratory investigation of response mechanisms and predictive biomarkers., Results and Discussion: Thirty-four of a planned 48 participants were recruited to the trial.Inhaled iloprost was well tolerated with no adverse events > grade 2. Compliance was 67% in the QID group. The trial was not powered to detect histologic response and none was found. Bulk RNA sequencing of biopsies pre/post iloprost suggest that iloprost is immunomodulatory and downregulates cell proliferation pathways. Single cell RNA sequencing showed an increase in CD8-positive T cells with upregulation of genes in interferon γ signaling. In vitro iloprost response by epithelial progenitor cells correlated with histologic response with kappa coefficient of 0.81 (95% CI 0.47, 1.0). Inhaled iloprost was well tolerated with suboptimal compliance. Molecular analysis suggested that iloprosthas immunomodulatory and antiproliferative effects.The progenitor cell iloprost response assay may be a promising avenue to develop predictive biomarkers., Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02237183, identifier NCT02237183., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Miller, Ghosh, Merrick, Kubala, Szabo, Bengtson, Kocherginsky, Helenowski, Benante, Schering, Kim, Kim, Ha, Bergan, Khan and Keith.)

Background: Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood-brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma., Methods: We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m 2 , 80 mg/m 2 , 135 mg/m 2 , 175 mg/m 2 , 215 mg/m 2 , and 260 mg/m 2 ) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood-brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual., Findings: 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12-12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40-215 mg/m 2 ), and 12 patients were treated at dose level 6 (260 mg/m 2 ). A total of 68 cycles of LIPU-MB-based blood-brain barrier opening were done (median 3 cycles per patient [range 2-6]). At a dose of 260 mg/m 2 , encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m 2 in the case of the grade 3 encephalopathy, and to 215 mg/m 2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m 2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood-brain barrier opening was most commonly associated with immediate yet transient grade 1-2 headache (12 [71%] of 17 patients). The most common grade 3-4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood-brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 μM [95% CI 0·022-0·063] in non-sonicated brain to 0·139 μM [0·083-0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 μM [0·562-1·747] in non-sonicated brain to 5·878 μM [3·462-9·980] μM in sonicated brain [5·9-times increase], p=0·0001)., Interpretation: LIPU-MB using a skull-implantable ultrasound device transiently opens the blood-brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing., Funding: National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family., Competing Interests: Declaration of interests AMS and RS have received in-kind (drug) support from Bristol-Myers Squibb, in-kind (ultrasound devices) and research support from and Carthera, and in-kind (drug) and research support from Agenus. AMS, DYZ, VAA, and RS are co-authors of intellectual property filed by Northwestern University related to therapeutic ultrasound. RS has acted or is acting as a scientific advisor or has served on advisory boards for the following companies: Alpheus Medical, AstraZeneca, Boston Scientific, Carthera, Celularity, GT Medical, Insightec, Lockwood (BlackDiamond), Northwest Biotherapeutics, Novocure, Syneos Health (Boston Biomedical), TriAct Therapeutics, and Varian Medical Systems. RVL is on the scientific advisory board and speakers’ bureau for Merck and on the speakers’ bureau for Novocure; has obtained research support from Bristol-Myers Squibb; and has received honoraria for editing from EBSCO INFORMATION services, Medlink, Neurology, and Elsevier. PK participates in advisory boards for Novocure, Janssen, SDP Oncology, Affinia, Sintetica, Mirati; has done consulting for Biocept, Enclear Therapies, Affinia Therapeutics and Bioclinica; and has received research support from Genentech and Novocure. MC, CD, GB, and AC are employees of Carthera, inventors of patents related to the technology, or have stock ownership in Carthera. AC has received funding support from Horizon 2020 European Innovation Council; is a paid consultant of Carthera; and is part of the Board of Directors of Carthera. JB is vice chair of the Neuro Education Track Subcommittee from the American Society of Anesthesiologists., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Shared decision-making (SDM) for metastatic prostate cancer (mPC) engages patients in the decision-making process and may be associated with better outcomes relative to physician- or patient-directed decision-making. We assessed the association between decision locus of control (DLOC) and patient-reported quality of life (QOL), functional outcomes, and decision satisfaction among mPC patients., Methods: After a clinic visit in which a treatment decision was made (baseline), mPC patients completed DLOC and QOL surveys. QOL was re-assessed at 2- and 4-months post-baseline. Mean scores for each QOL dimension (physical, emotional, cognitive, social, and role functioning) were compared by DLOC group using mixed effects models. Patient preferences for DLOC and provider communication techniques were similarly collected via survey., Results: Median age of participants (N = 101) was 69 years (range: 49-92); most were White (80%) and married (82%). 62% reported using SDM. At baseline, there were no differences in QOL dimensions between DLOC groups. At 4 months, patient-directed (p = 0.01) and SDM (p = 0.03) were associated with better physical functioning than physician-directed decision-making, and there was an indication of potentially greater decision satisfaction among patients who reported patient-directed (p = 0.06) or SDM (p = 0.10). SDM was the most reported preferred DLOC., Conclusion: mPC patients reporting SDM had better physical functioning at 4 months than physician- or patient-directed decision-making, suggesting measurable benefit from patient involvement in decision-making. Future investigations of these associations in larger, more diverse populations can further clarify these previously unmeasured benefits of patient engagement in treatment decisions., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Sonographers performing venous duplex ultrasound (VDUS) of patients with coronavirus disease 2019 (COVID-19) have an increased risk of exposure owing to their close contact with these patients for an extended period. The objective of the present study was to evaluate the efficacy of a modified COVID-19 VDUS protocol to reduce sonographer exposure to COVID-19 patients., Methods: We performed a single-center retrospective review. Patients who had undergone VDUS under the modified COVID-19 protocol between March 1, 2020, and June 30, 2020, with a confirmed or presumed COVID-19 diagnosis at the VDUS were included. The modified COVID-19 protocol was defined as the ability of the sonographer to terminate the examination on detection of an acute deep vein thrombosis (DVT). The primary outcome measures were the number of anatomic deep venous segments recorded by the sonographer, which was used as a surrogate measure for sonographer exposure time, and the number of acute DVTs found on follow-up examinations in segments not visualized at the index VDUS., Results: A total of 160 lower extremity VDUS (LEVDUS) scans and 72 upper extremity VDUS (UEVDUS) scans were performed using the modified COVID-19 protocol. The index VDUS had found an acute DVT for 44 of 160 patients (27.5%) who had undergone LEVDUS and 26 of 72 (36.6%) who had undergone UEVDUS. On follow-up imaging, 7 of 38 LEVDUS scans (17.9%) and 1 of 10 UEVDUS scans (10%) had demonstrated a new acute DVT. Malignancy and surgery 30 days before imaging were significantly associated with acute lower extremity DVT, and mechanical ventilation and extracorporeal membrane oxygenation were associated with acute upper extremity DVT. On the index VDUS, the average was 10.6 of 12 total visualized segments on LEVDUS and 6.4 of 10 total segments on UEVDUS. Of the index VDUS scans, 35.6% of the LEVDUS and 78.6% of the UEVDUS scans had been abbreviated. The index VDUS scans that were positive for acute DVT had had significantly fewer visualized segments for both lower (8.4 vs 11.5; P < .0001) and upper (4.2 vs 7.6) extremities (P < .0001). On the follow-up examinations, only one of eight new acute DVTs had been found in a patient whose index VDUS had been abbreviated and the corresponding segment not assessed. These findings did not affect the patient's clinical course., Conclusions: The modified COVID-19 VDUS protocol reduced sonographers' potential exposure time to COVID-19. Additionally, the clinical efficacy was maintained, with no missed DVTs, despite the abbreviation of the VDUS examinations., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Optimal medical therapy for acute lower extremity deep venous thrombosis (DVT) remains an enigma. While clinical trials demonstrate non-inferiority with an oral anti-Xa inhibitor, or direct oral anticoagulant (DOAC), versus combined low-molecular weight heparin (LMWH) and oral vitamin K antagonist (VKA), the most effective regimen remains to be determined., Methods: This study is a single-center retrospective cohort study from October 2014 to December 2015 of patients with a diagnosis of acute DVT and subsequent serial lower extremity venous duplex. Demographics, medical history, medications, serial ultrasound findings, as well as the primary anticoagulant used for treatment were collected and analyzed by two independent data extractors. Treatment failure was defined as any new DVT or progression of an existing DVT within 3 months of diagnosis of the index clot. Risk factors for treatment failure were assessed using standard odds ratios and Fischer's exact test., Results: Among 496 patients with an acute lower extremity DVT, 54% ( n = 266) were men, mean age was 61 years, 35% ( n = 174) involved the popliteal or more proximal segments, and 442 had documentation of the primary treatment for DVT: 20% ( n = 90) received nothing; 20% ( n = 92) received an oral VKA; 34% ( n = 149) received a DOAC; 20% ( n = 90) received LMWH; and 5% ( n = 21) received another class of anticoagulant. Within 3 months, 21% ( n =89 out of 427) had treatment failure defined as any new DVT or progression of prior DVT. Patients treated with a DOAC were less likely to experience treatment failure when compared with any other treatment (odds ratio 0.43; 95% confidence intervals [0.23, 0.79]; p = 0.0069) and when compared with traditional oral VKA (OR 0.44; 95% CI [0.21, 0.92]; p = 0.029). None of prior history of DVT, pulmonary embolism, thrombophilia, renal insufficiency, hepatic insufficiency, cancer, or antiplatelet therapy correlated with treatment failure. Treatment outcome did not correlate with being on any anticoagulation versus none ( p = 0.74), nor did it correlate with the duration of treatment (<3 months versus ≥3 months) ( p = 0.42). Proximal and distal DVTs showed no difference in treatment failure (19% versus 22%, respectively; p = 0.43)., Conclusion: In summary, the use of a DOAC for acute lower extremity DVT yielded better overall outcomes and fewer treatment failures at 3 months as compared to traditional oral VKA therapy based on serial duplex imaging.

Therapy-related myeloid neoplasms (t-MNs) are a complication of treatment with cytotoxic chemotherapy and/or radiation therapy. The majority of t-MNs show chromosomal abnormalities associated with myelodysplastic syndrome (MDS) or KMT2A rearrangements and are characterized by poor clinical outcomes. A small but substantial subset of patients have normal karyotype (NK) and their clinical characteristics and mutational profiles are not well studied. We retrospectively studied patients diagnosed with t-MN at three institutions and compared the mutational profile and survival data between t-MNs with NK and t-MNs with abnormal karyotype (AK). A total of 204 patients with t-MN were identified including 158 with AK and 46 with NK. NK t-MNs, compared to AK, were enriched for mutations in TET2 (p < 0.0001), NPM1 (p < 0.0001), ASXL1 (p = 0.0003), SRSF2 (p < 0.0001), RUNX1 (p = 0.0336) and STAG2 (p = 0.0099) and showed a significantly lower frequency of TP53 mutations (p < 0.0001). Overall survival (OS) was significantly lower in AK t-MNs as compared to NK cases (p = 0.0094). In our study, NK t-MNs showed a significantly better OS, a higher prevalence of MN-associated mutations and a lower frequency of TP53 mutations compared to their AK counterparts. The distinct clinical and mutational profile of NK t-MNs merits a separate classification., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The aim of this study is to assess the efficacy of the TRUE-Bolivia (Trauma Responders Unifying to Empower Communities Bolivia) trauma first responder course at improving participant confidence in first responder abilities and increasing knowledge of trauma response skills., Methods: Participants attended the 4-h TRUE-Bolivia course at the municipal department of urban transportation and universities and medical schools in Santa Cruz, Bolivia and completed a demographic survey and pre- and post-course knowledge assessments. All participants who attended the full course and completed both knowledge assessments were included in the study, with 453 people attending at least one portion of the course and 329 completing the full course and assessments., Results: A majority of participants were men, had completed high school or attended university, and worked or trained in the fields of transportation or medicine. Participant ratings of confidence on a 5-point Likert scale improved from a median of 3 (interquartile range [IQR] 2) before the course to 5 (IQR 1) after the course (P < 0.01). The median number of correct answers on the pre-course nine-question knowledge assessment was 3 (IQR 3), improving to 7 (IQR 3) on the post-course assessment (P < 0.01). All demographic groups demonstrated improvements in scores from the pre- to post-test. Female gender, higher education level, a background in medicine, and prior training in first aid were associated with higher pre- and post-test scores., Conclusions: The TRUE-Bolivia course increased knowledge of first responder skills and improved confidence in these abilities in participants from a variety of backgrounds. Further study is needed to determine the long-term skill utilization by participants and the course's impact on local trauma morbidity and mortality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To investigate the results of real-world application of non-myeloablative autologous HSCT for multiple sclerosis (MS)., Methods: Between July 2003 and October 2019 at a single center (Northwestern University), 414 patients with relapsing remitting MS (RRMS) and 93 patients with newly diagnosed secondary progressive MS (SPMS) underwent non-myeloablative HSCT., Results: There was one treatment-related death (0.19%) due to hospital-acquired legionella pneumonia, and one patient developed neutropenic bacteremia (Klebsiella pneumonia) without sepsis. Overall 5-year survival was 98.8%. Post HSCT secondary autoimmune diseases (2nd ADs) were idiopathic thrombocytopenia (ITP) and hypo or hyperthyroidism. ITP was highest with alemtuzumab (14%) and 0 to 2.8% for the non-alemtuzumab regimens. After HSCT, 16 patients developed hypothyroidism (3.5%) and 15 developed hyperthyroidism / Grave's disease (3.3%). Relapse free survival (RFS) at 5 years for RRMS and SPMS was 80.1% and 98.1%, respectively, while progression free survival (PFS) at 4 years for RRMS and SPMS was 95% versus 66%, respectively. For patients with RRMS, the EDSS significantly improved (p < 0.0001) at each follow-up from a pre-HSCT mean of 3.87 to 2.51, 2.50, 2.41, 2.33, and 2.19 at 1, 2, 3, 4, and 5 years, respectively. For SPMS, the EDSS improved significantly only at 1 year but not thereafter. For SPMS, the mean baseline EDSS of 5.09 changed post-HSCT to 4.85 (p = 0.04), 4.88 (p = 0.2), 4.92 (p = .27), 4.72 (p = 0.07), and 4.2 (p = 0.21) at 1, 2, 3, 4, 5 years, respectively., Conclusion: In patients with RRMS, autologous non-myeloablative HSCT is an effective one-time therapy, while HSCT appears of less benefit for newly diagnosed SPMS., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Remnant radioiodine ablation is discouraged in low-risk differentiated thyroid cancer because it confers no survival advantage. The impact of remnant radioiodine ablation on health-related quality of life in these patients is not well described. We hypothesized remnant radioiodine ablation is associated with lower health-related quality of life in early-stage differentiated thyroid cancer survivors., Methods: A retrospective matched-pair analysis was conducted in stage I differentiated thyroid cancer survivors recruited from a thyroid cancer support group. Respondents self-reported via online survey. Dysphonia and dysphagia were reported via Likert scale. Health-related quality of life was evaluated using Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile. Respondents who received remnant radioiodine ablation were matched for age, sex, race, and years since diagnosis with respondents who did not receive remnant radioiodine ablation. PROMIS t-scores were compared between remnant radioiodine ablation and nonremnant radioiodine ablation groups, and among those with or without surgical complications., Results: One hundred and twenty-two pairs were matched. There was no significant difference in incidence of self-reported hypocalcemia, infection, dysphonia, or dysphagia between remnant radioiodine ablation and no remnant radioiodine ablation groups. There was no significant difference in mean PROMIS t-scores. Of respondents reporting normal preoperative voice and swallowing, there were no significant differences in postprocedural outcomes or PROMIS scores. Regardless of remnant radioiodine ablation treatment, those with surgical complications of hypocalcemia, dysphonia, or dysphagia reported worse PROMIS scores across multiple domains. Remnant radioiodine ablation-associated xerostomia was associated with worse PROMIS scores across multiple domains., Conclusion: This is the first study to use PROMIS measures to evaluate the association between remnant radioiodine ablation and health-related quality of life in early-stage differentiated thyroid cancer survivors treated surgically. Surgical and remnant radioiodine ablation-associated complications were associated with significantly worse PROMIS scores across multiple domains., (Copyright © 2021. Published by Elsevier Inc.)

We compared three fludarabine-based regimens for systemic sclerosis patients with a high-risk cardiac phenotype that according to EBMT criteria would be a contraindication for a high-dose cyclophosphamide (200 mg/kg) transplant regimen. All three regimens included fludarabine, ATG, and cyclophosphamide (60 mg/kg), while two regimens also included rituximab with or without IVIG. Treatment related mortality (TRM) was 2.4%. The mean number of days of neutropenia (ANC < 500) was 5.2, the mean number of platelet and red blood cell transfusions was 0.3 and 1.85, respectively. Skin score, forced vital capacity (FVC), and total lung capacity (TLC) improved with all three regimens. For patients whose regimen did not include rituximab versus those that included rituximab, 1-year overall relapse rate was higher 36% (5/14) versus 3.6% (1 of 28) (p = 0.01), secondary autoimmune diseases were higher 21% (3/14) versus 0% (0/28) (p = 0.03), and upper respiratory tract infections were higher 28% (4/14) versus 3.6% (1/28) (p = 0.04). In this safety study, a fludarabine-based regimen was relatively safe with a TRM of 2.4% and a neutropenic interval of only 5.2 days in systemic sclerosis patients with a high-risk cardiac phenotype. The addition of rituximab decreased 1-year relapse rate, risk of late secondary autoimmune diseases, and upper-respiratory tract infections.

Background: The comorbidity-polypharmacy score (CPPS) was developed to quantify the severity of comorbidities of patients with geriatric trauma. CPPS is the sum of the number of medications and comorbidities, and is thus objective, user-friendly, and potentially adaptable to many clinical situations. We sought to understand if CPPS associates with outcomes and mortality after common vascular surgery procedures., Methods: This is a retrospective single-center study. A total of 466 patients who underwent carotid endarterectomy, infrainguinal bypass, percutaneous lower extremity revascularization, or endovascular abdominal aortic aneurysm repair at a single medical center were included. CPPS were classified as mild, moderate, severe, and morbid based on scores of 0-7, 8-15, 15-21, and ≥21, respectively. End points were reinterventions, 30-day readmission, and mortality. We used chi-squared tests to analyze differences in categorical variables; Kruskal-Wallis tests to analyze differences in continuous variables; Kaplan-Meier estimation and Cox proportional hazard modeling to examine survival data; and receiver operator characteristic (ROC) curve analyses to assess sensitivity and specificity., Results: The mean preoperative CPPS was 14.1 ± 6.1. Higher CPPS were associated with longer hospital and postoperative length of stay (P < 0.001). Severe and morbid CPPS categories had higher rates of ICU admission, reintervention, and 30-day readmission which did not reach statistical significance after correction for multiple comparisons. CPPS was independently associated with 1- and 5-year mortality in a multivariable Cox model (hazard ratio = 2.2, 95% confidence interval: 1.3-3.3). ROC analysis revealed C-statistics of 0.81 and 0.72 for 1-year and 5-year all-cause mortality, respectively (P < 0.001)., Conclusions: CPPS is a simple and pragmatic clinical tool for quantifying risk of postoperative outcomes and mortality after common vascular surgery procedures. Further investigation is needed to validate the use of CPPS in enhancing existing predictors of patient outcomes and in serving as an adjunctive tool for determining resource allocation and discharge planning in patients who underwent vascular surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Perioperative infarcts are a known complication that can occur during the resection of glioblastoma (GBM). Recent studies suggest that gross total and even "supra-total" resections may be associated with an increased survival but the rate of complications, including perioperative ischemia, may increase with these more aggressive resection strategies. However, little is known about the impact that perioperative infarcts have on survival, functional outcomes, and tumor recurrence patterns. Our study attempted to quantify and characterize the functional consequences of a perioperative infarct, as well as risk factors associated with occurrence. Methods: Seventy-three patients with a diagnosis of GBM and perioperative ischemia by MRI were identified from the electronic medical record system. We obtained demographic, prognostic, and stroke risk factor data. Infarct volumes were calculated from diffusion-weighted MRI scans, and subjects were segregated into an infarct cohort or a control cohort based on whether the identified lesion appeared to be an infarct in an arterial distribution or instead appeared to be expected postoperative changes. A multivariate statistical analysis was performed on the dataset. Results: Median age was 58.6 years, median post-op KPS (Karnofsky Performance Status) was 90, and median extent of resection (based on MRI) was 97.8%. Overall, perioperative arterial infarcts were uncommon (2.0%), did not have a statistically significant impact on survival (17.9 vs. 18.9 months), did not worsen neurologic function, and did not alter the pattern of recurrence. Conclusion: Perioperative arterial infarcts were uncommon in our patients despite aggressive resection and when present had no impact on survival or neurologic function. Given the clear benefit of maximal tumor resection, the risk of perioperative infarct should not deter maximal safe resection., (Copyright © 2020 Lupa, Raizer, Helenowski, Liu, Kesavabhotla and Tate.)

Purpose: Catheter-associated urinary tract infection (CAUTI) is a priority quality metric for hospitals. The impact of placement of indwelling urinary catheter (IUC) by medical students on CAUTI rates is not well known. This study examined the impact of a simulation-based medical student education curriculum on CAUTI rates at an academic medical center., Method: Patient characteristics, procedural data, and outcome data from all operating room IUC insertions from June 2011 through December 2016 at the Northwestern University Feinberg School of Medicine were analyzed using a multivariable model to evaluate associations between CAUTI and inserting provider. Infection data before and after implementation of a simulation-based IUC competency course for medical students were compared., Results: A total of 57,328 IUC insertions were recorded during the study period. Medical students inserted 12.6% (7,239) of IUCs. Medical students had the lowest overall rate of CAUTI among all providers during the study period (medical students: 0.05%, resident/fellows: 0.2%, attending physicians: 0.3%, advanced practice clinicians: 0.1%, nurses: 0.2%; P = .003). Further, medical student IUC placement was not associated with increased odds of CAUTI in multivariable analysis (odds ratio, 0.411; 95% confidence interval: 0.122, 1.382; P = .15). Implementation of a simulation-based curriculum for IUC insertion resulted in complete elimination of CAUTI in patients catheterized by medical students (0 in 3,471)., Conclusions: IUC insertion can be safely performed by medical students in the operating room. Simulation-based skills curricula for medical students can be effectively implemented and achieve clinically relevant improvements in patient outcomes.

Background: Survivors of cancer in the United States are often financially encumbered by expenses and lost wages from cancer treatment. The majority of patients with thyroid cancer are diagnosed before age 65, when they are not eligible for Medicare. We hypothesized that financial distress would be common among thyroid cancer survivors and would be associated with poor health-related quality of life., Methods: A financial distress questionnaire and Patient-Reported Outcomes Measurement Information System (29-item) were completed online by 1,743 adult thyroid cancer survivors living in the United States. Multivariable modeling was used to identify variables which independently predicted poor health-related quality of life. The magnitude of predicted change was estimated by β coefficients and 95% confidence intervals. A β ≥3 was considered clinically significant; α was set at 0.01., Results: Financial difficulties were reported by 43% of thyroid cancer survivors and were associated with worse anxiety (β = 5.07; P < .01) and depression (β = 5.47; P < .01). Living in poverty was associated with worse anxiety (β = 4.14; P < .01) and depression (β = 4.35; P < .01). Lost productivity at work was associated with worse fatigue (β = 5.99; P < .01) and social functioning (β = -4.07; P < .01). Inability to change jobs was associated with worse fatigue (β = 3.08; P < .01), pain interference (β = 3.56; P < .01), and social functioning (β = -3.09; P < .01). Receiving disability benefits was associated with worse pain interference (β = 3.93; P < .01). Impaired ability to obtain a job was associated with worse social functioning (β = -3.02; P < .01). Reported unemployment rate was 12.3%., Conclusion: Financial distress and negative financial events were common among thyroid cancer survivors and were associated with poorer health-related quality of life across 5 Patient-Reported Outcomes Measurement Information System health domains., (Copyright © 2019. Published by Elsevier Inc.)

Background: Predictive models that take race into account like the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPT RC) and the new Prostate Biopsy Collaborative Group (PBCG) RC have been developed to equitably mitigate the overdiagnosis of prostate specific antigen (PSA) screening. Few studies have compared the performance of both calculators across racial groups., Methods: From 1485 prospectively recruited participants, 954 men were identified undergoing initial prostate biopsy for abnormal PSA or digital rectal examination in five Chicago hospitals between 2009 and 2014. Discrimination, calibration, and frequency of avoided biopsies were calculated to assess the performance of both risk calculators., Results: Of 954 participants, 463 (48.5%) were Black, 355 (37.2%) were White, and 136 (14.2%) identified as Other. Biopsy results were as follows: 310 (32.5%) exhibited no cancer, 323 (33.9%) indolent prostate cancer, and 321 (33.6%) clinically significant prostate cancer (csPCa). Differences in area under the curve (AUC)s for the detection of csPCa between PCPT and PBCG were not statistically different across all racial groups. PBCG did not improve calibration plots in Blacks and Others, as it showed higher levels of overprediction at most risk thresholds. PCPT led to an increased number of avoidable biopsies in minorities compared to PBCG at the 30% threshold (68% vs. 28% of all patients) with roughly similar rates of missed csPCa (23% vs. 20%)., Conclusion: Significant improvements were noticed in PBCG's calibrations and net benefits in Whites compared to PCPT. Since PBCG's improvements in Blacks are disputable and potentially biases a greater number of low risk Black and Other men towards unnecessary biopsies, PCPT may lead to better biopsy decisions in racial minority groups. Further comparisons of commonly used risk calculators across racial groups is warranted to minimize excessive biopsies and overdiagnosis in ethnic minorities.

Background: Endovascular aneurysm repair (EVAR) is currently the most common treatment of abdominal aortic aneurysms. Potential predictors of long-term survival after EVAR include physiologic, functional, and cognitive status, but assessments of these conditions have been difficult to standardize. Objective radiographic findings, such as skeletal muscle atrophy, or sarcopenia, may provide an additional means for selection of patients. This study investigates sarcopenia as a method to predict 1-year survival in patients undergoing EVAR., Methods: A single-institution retrospective review was conducted of all patients who underwent elective EVAR from September 2002 to June 2014. Patients with an available periprocedural computed tomography (CT) scan and clinical data were included in the analysis. Normalized total psoas cross-sectional area (nTPA) was measured on axial CT images using the area of the bilateral psoas muscle at the third lumbar vertebral level normalized to the square of patient height. A threshold for optimal estimate of sarcopenia based on nTPA was determined using a receiver operating characteristic curve. Sarcopenia was evaluated as an independent risk predictor using univariate, multivariate, and survival analysis., Results: A total of 272 EVAR-treated patients were evaluated, including 237 men and 35 women with a median age of 72 years and mean body mass index of 28.6 kg/m 2 . There was a significant increase in overall mortality in patients in the lowest quartile of nTPA (Q1, 23.53%; Q2, 13.24%; Q3, 7.35%; Q4, 5.88%; P = .01). The estimated nTPA threshold for increased mortality after EVAR was 500 mm 2 /m 2 . Using this threshold, sarcopenia accounted for 57% of the risk effect in our 1-year survival model., Conclusions: Sarcopenia can assist in identifying EVAR candidates who are less likely to benefit from surgery. It can be readily evaluated from preoperative CT scans and may be a useful tool in evaluation of abdominal aortic aneurysm patients with applications in risk evaluation and telemedicine., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Lymphedema after regional nodal irradiation is a severe complication that could be minimized without significantly compromising nodal coverage if the anatomic region(s) associated with lymphedema were better defined. This study sought to correlate dose-volume relationships within subregions of the axilla with lymphedema outcomes to generate treatment planning guidelines for reducing lymphedema risk., Methods and Materials: Women with stage II-III breast cancer who underwent breast surgery with axillary assessment and regional nodal irradiation were identified. Nodal targets were prospectively contoured per Radiation Therapy Oncology Group guidelines for field design. The axilla was divided into 8 distinct subregions that were retrospectively contoured. Lymphedema outcomes were assessed by arm circumferences. Multivariate Cox proportional hazards regression assessed patient, surgical, and dosimetric predictors of lymphedema outcomes., Results: Treatment planning computed tomography scans for 265 women treated between 2013 and 2017 were identified. Median post-radiation therapy follow-up was 3 years (interquartile range [IQR], 1.9-3.6). Dose to the axillary-lateral thoracic vessel juncture (ALTJ; superior to level I) was most associated with lymphedema risk (maximally selected rank statistic = 6.3, P < .001). The optimal metric was ALTJ minimum dose (D min ) <38.6 Gy (3-year lymphedema rate 5.7% vs 37.4%, P <.001), although multiple parameters relating to sparing of the ALTJ were highly correlated. Multivariate analysis confirmed ALTJ D min <38.6 Gy (hazard ratio [HR], 0.13; P < .001), body mass index (HR, 1.06/unit; P = .002), and number of lymph nodes removed (HR, 1.08/node; P < .001) as significant predictors. Women with ALTJ D min <38.6 Gy maintained median V 45Gy of 99% in the supraclavicular (IQR, 94-100%), 100% in level III (IQR, 97%-100%), 98% in level II (IQR, 86%-100%), and 91% in level I (IQR, 75%-98%) nodal basins., Conclusions: Anatomic studies suggest the ALTJ region is typically traversed by arm lymphatics and appears to be an organ at risk in breast radiation therapy. Ideally, avoidance of the ALTJ may be feasible while simultaneously encompassing breast-draining nodal basins. Confirmation of this finding in future prospective studies is needed., (Copyright © 2019. Published by Elsevier Inc.)

Background: The relationship between preoperative hyperglycemia and complications after surgery is not well defined. We compared the relationship of preoperative versus postoperative hyperglycemia on clinical outcomes and assessed if preoperative hyperglycemia was a predictor for postoperative hyperglycemia in patients undergoing elective colorectal surgery., Methods: We performed a retrospective review of an institutional database for patients who underwent elective colorectal resection between July 2015 and June 2017. Data regarding patient characteristics, history of diabetes, preoperative and postoperative hyperglycemic events, and postoperative complications were collected. Bivariate and multivariate logistic analyses were used to assess relationships., Results: Of 755 surgical operations reviewed, preoperative hyperglycemia >180 mg/dL was not significantly associated with adverse outcomes in an adjusted model. Only postoperative hyperglycemia >180 mg/dL was significantly associated with complications, including acute kidney injury (odds ratio 2.58, P < 0.001), anastomotic leak (odds ratio 2.64, P = 0.01), arrhythmia (odds ratio 2.40, P = 0.009), and sepsis (odds ratio 3.86, P < 0.001). Preoperative hyperglycemia remained a significant predictor of postoperative hyperglycemia (odds ratio 4.91, P < 0.001)., Conclusion: Postoperative hyperglycemia was more significantly associated with adverse clinical outcomes after elective colorectal surgery than was preoperative hyperglycemia. However, preoperative hyperglycemia was associated with postoperative hyperglycemia, suggesting that improved glycemic management preoperatively may help reduce hyperglycemic events after surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Regional nodal irradiation for women with breast cancer is known to be an important risk factor for the development of upper extremity lymphedema, but tools to accurately predict lymphedema risks for individual patients are lacking. This study sought to develop and validate a nomogram to predict lymphedema risk after axillary surgery and radiation therapy in women with breast cancer., Methods and Materials: Data from 1832 women accrued on the MA.20 trial between March 2000 and February 2007 were used to create a prognostic model with National Cancer Institute Common Toxicity Criteria Version 2.0 grade 2 or higher lymphedema as the primary endpoint. Multivariable logistic regression estimated model performance. External validation was performed on data from a single large academic cancer center (N = 785)., Results: In the MA.20 trial cohort, 3 risk factors were predictive of lymphedema risk: body mass index (adjusted odds ratio, 1.05 per unit body mass index; 95% confidence interval [CI], 1.03-1.08, P < .001), extent of axillary surgery (adjusted odds radio for 8-11 lymph nodes removed, 3.28 [95% CI, 1.53-7.89] P = .004; 12-15 lymph nodes, 4.04 [95% CI, 1.76-10.26] P = .002; ≥16 nodes, 5.08 [95% CI, 2.26-12.70] P < .001), and extent of nodal irradiation (adjusted odds radio for limited, 1.66 [95% CI, 1.08-2.56] P = .02; for extensive, 2.31 [95% CI, 1.28-4.10] P = .004). A nomogram was created from these data that predicted lymphedema risk with reasonable accuracy confirmed by both internal (concordance index, 0.69; 95% CI, 0.64-0.74) and external validation (concordance index, 0.71; 95% CI, 0.66-0.76)., Conclusions: The nomogram created from the MA.20 randomized trial data using clinical information may be useful for lymphedema screening and risk stratification for therapeutic intervention trials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The use of pressure-offloading support surfaces is considered the standard of care for pressure ulcers (PUs) by most surgeons. The fluid immersion simulation system (FIS) has shown significant results in previous studies. We compared it, for the first time, with a representative air-fluidised bed (AFB) for outcomes related to post-surgical flap closures. This trial was performed over 25 months, in which 40 subjects between 18 and 85 years of age with ≤2 PUs and history of <3 surgical closures underwent reconstruction by one surgeon. Subjects were randomly assigned to either treatment group for 2 weeks after closure. The primary endpoint was success of closure after the study period. Secondary endpoints included incidence of complications and nursing and patient acceptability of the device. The FIS group included 19 subjects, and the AFB group included 21. Flap failure rate was similar between groups (15% vs 17%; P = .99). The Minor complications rate, particularly dehiscence, was higher in the FIS group (66.7% vs 15%; P = .02). Nurse and patient self-reported acceptability had better mean numeric scores in the FIS compared with AFB (nurse: 1.5 vs 1.9; P = .12; patient: 1.9 vs 2.2; P = .14). Further analysis will be conducted to gain better insight on the FIS as an alternative treatment for PUs., (© 2019 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Introduction: Thyroid cancer survivors are a rapidly growing population in the United States. The factors that drive health-related quality of life (HRQOL) in this population have not been well characterized. We hypothesized that more aggressive treatments and greater treatment-related adverse effects would be associated with worse HRQOL scores in thyroid cancer survivors., Methods: Thyroid cancer survivors (18-89 years of age) completed an online survey regarding their clinical history in addition to the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 instrument. Univariable and multivariable modeling were performed to evaluate factors associated with worse HRQOL scores. We generated β-values and 95% confidence intervals to quantify the effect of each independent variable in the model., Results: Thyroid cancer survivors (n = 1,743) reported a high incidence of complications related to surgery and radioactive iodine ablation. Postoperative dysphonia (ß 1.83-3.07) and dysphagia (ß 2.05-3.65) predicted worse HRQOL scores across multiple PROMIS domains. Younger patient age (age <45 years) and short- or long-term complications of radioactive iodine, including gastrointestinal symptoms (51.9%), appetite changes (71.2%), sialadenitis (58.1%), xerostomia (73.3%), and xerophthalmia (45.1%) were associated with worse HRQOL scores (P < .01)., Conclusion: The factors associated with significantly worse HRQOL scores across multiple PROMIS domains for thyroid cancer survivors included patient age <45 years, postoperative hypocalcemia, dysphonia, dysphagia, scar appearance, and complications from radioactive iodine. Methods of evaluation, management, and prevention of these factors might positively impact HRQOL., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There is a paucity of patient-reported data on thyroidectomy scar perception. The effect of neck scarring on quality of life is not known. We hypothesized that worse perception of neck appearance would be related to worse health-related quality of life and that perception improves with time., Methods: Survivors of thyroid cancer (n = 1,710) were surveyed online. Respondents were asked to score the appearance of their neck via a 5-point Likert scale. Quality of life was evaluated via the Patient-Reported Outcomes Measurement Information System 29. The relationships between neck appearance, patient characteristics, quality of life, and Patient-Reported Outcomes Measurement Information System domains were analyzed with multivariable models and Spearman partial correlations (r s )., Results: Older age was associated with better perception of neck appearance (odds ratio 0.975/year; 95% confidence interval 0.967-0.983; P < .001). Greater time since surgery was also associated with improved perception (odds ratio 0.962/year; 95% confidence interval 0.947-0.977; P < .0001). We observed no statistically significant difference between current and preoperative baseline perception >2 years after surgery. On multivariable analysis, age >45 years, >2 years since surgery, and higher self-reported quality of life were independent predictors of better self-reported neck appearance (P ≤ .0003). In patients ≤2 years after surgery (n = 568), the PROMIS domains of anxiety, depression, social function, and fatigue had weak but statistically significant correlations with worse perception of neck appearance (P < .0001)., Conclusion: Age >45, >2 years since surgery, and higher quality of life were independently associated with better self-reported neck appearance. Perception of neck appearance returned to preoperative baseline 2 years after surgery. PROMIS domains had a weak but significant association with neck appearance perception in patients ≤2 years after surgery. The impact of post-thyroidectomy neck appearance on quality of life appears to be mild and transient and returns to preoperative levels after 2 years., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Identification of an organism is the gold standard for the diagnosis of fungal infection; however, we have previously shown that invasive procedures infrequently lead to a change in management in children with cancer or who have undergone stem cell transplant with suspected respiratory tract invasive fungal infection (RT-IFI). There is also a paucity of data on the cost of RT-IFI in this population. We therefore compared the costs of RT-IFI diagnosed based on CT scan alone versus those who underwent a bronchoalveolar lavage (BAL) or respiratory tract biopsy (RTB)., Procedure: We collected cost data on patients at a single center undergoing chemotherapy or who were post-hematopoietic stem cell transplant (HSCT) and were suspected of having RT-IFI between 2007 and 2012. Cost data were included for 14 days from the day of their diagnostic CT scan or procedure., Results: Cost data were available for 76 patients. Thirty-six patients were diagnosed with suspected RT-IFI based on CT only, and 40 patients underwent BAL or RTB. Costs related to chest X-rays (CXRs), inpatient/intensive care unit (ICU) beds, anesthesia, operating room (OR) time, and procedures were significantly higher in the BAL/RTB group versus CT scan group (all P < 0.01). Costs related to CT scans were significantly higher in the CT scan group (P = 0.0002). Overall costs were significantly higher for patients who underwent BAL or RTB versus CT scan only (P < 0.0001)., Conclusion: Our previous data showed that BAL and RTB infrequently led to a change in management in this population. We now demonstrate that this strategy is costly as well., (© 2019 Wiley Periodicals, Inc.)

Importance: Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS)., Objective: To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression., Design, Setting, and Participants: Between September 20, 2005, and July 7, 2016, a total of 110 patients with relapsing-remitting MS, at least 2 relapses while receiving DMT in the prior year, and an Expanded Disability Status Scale (EDSS; score range, 0-10 [10 = worst neurologic disability]) score of 2.0 to 6.0 were randomized at 4 US, European, and South American centers. Final follow-up occurred in January 2018 and database lock in February 2018., Interventions: Patients were randomized to receive HSCT along with cyclophosphamide (200 mg/kg) and antithymocyte globulin (6 mg/kg) (n = 55) or DMT of higher efficacy or a different class than DMT taken during the previous year (n = 55)., Main Outcomes and Measures: The primary end point was disease progression, defined as an EDSS score increase after at least 1 year of 1.0 point or more (minimal clinically important difference, 0.5) on 2 evaluations 6 months apart, with differences in time to progression estimated as hazard ratios., Results: Among 110 randomized patients (73 [66%] women; mean age, 36 [SD, 8.6] years), 103 remained in the trial, with 98 evaluated at 1 year and 23 evaluated yearly for 5 years (median follow-up, 2 years; mean, 2.8 years). Disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMT group. Median time to progression could not be calculated in the HSCT group because of too few events; it was 24 months (interquartile range, 18-48 months) in the DMT group (hazard ratio, 0.07; 95% CI, 0.02-0.24; P < .001). During the first year, mean EDSS scores decreased (improved) from 3.38 to 2.36 in the HSCT group and increased (worsened) from 3.31 to 3.98 in the DMT group (between-group mean difference, -1.7; 95% CI, -2.03 to -1.29; P < .001). There were no deaths and no patients who received HSCT developed nonhematopoietic grade 4 toxicities (such as myocardial infarction, sepsis, or other disabling or potential life-threatening events)., Conclusions and Relevance: In this preliminary study of patients with relapsing-remitting MS, nonmyeloablative HSCT, compared with DMT, resulted in prolonged time to disease progression. Further research is needed to replicate these findings and to assess long-term outcomes and safety., Trial Registration: ClinicalTrials.gov Identifier: NCT00273364.

Background: Surgical site infection (SSI) poses a significant burden to patients and healthcare resources. Vascular Quality Initiative (VQI) data identify a higher rate of SSIs for lower extremity bypass than other vascular procedures. Bundled interventions have successfully reduced SSIs in other surgical procedures., Study Design: We evaluated our institution-specific VQI data for modifiable risk factors associated with index hospitalization SSI from January 2012 through October 2015. We implemented an evidence-based lower extremity bypass operation SSI reduction bundle (ie perioperative chlorhexidine showers and transverse groin incisions) and prospectively enrolled all patients who had lower extremity bypass procedures, with a target adherence rate of 50% per bundle component. Bundle adherence and SSI events were measured from March 2016 through August 2017. We carried out a pre-post evaluation of bundle effectiveness in reducing index hospitalization SSI., Results: In the pre-intervention period, 43 of 234 (18%) patients had SSI events. The only risk factors associated with SSI (ie female sex, diabetes, overweight BMI) were not readily modifiable. In an 18-month period after introduction of our intervention, adherence rates to preoperative chlorhexidine showers, a transverse incision, and a postoperative chlorhexidine shower were 71% (52 of 73), 48% (24 of 50), and 88% (64 of 73), respectively. Compliance with all applicable bundle components was 36% (26 of 73). The SSI rate post-intervention decreased from 18% to 4% (3 of 73). Intention-to-treat multivariable analysis showed a 97% SSI risk reduction with the bundle (p = 0.002). As-treated analysis identified 85% (p = 0.02) and 62% (p = 0.047) SSI risk reductions from the preoperative and postoperative chlorhexidine showers, respectively., Conclusions: In this evaluation study of the effectiveness of a quality improvement intervention, SSIs were markedly decreased after implementation of our evidence-based bundle for lower extremity vascular bypass procedures., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Carotid artery stenting remains an effective alternative to carotid endarterectomy for stroke prevention; however, the long-term durability of carotid artery stenting remains poorly defined. We performed a 10-year "real-world" comparative analysis of carotid endarterectomy and carotid artery stenting to help evaluate the success of these procedures in preventing late ischemic stroke events., Methods: This was a single-center retrospective review of 996 patients (symptomatic and asymptomatic) treated with carotid endarterectomy or carotid artery stenting from January 2001 through December 2011 at a tertiary academic medical center. All-cause death, stroke, and myocardial infarction event rates were analyzed using log-rank analysis., Results: Among the 996 patients treated with carotid endarterectomy (n = 787) or carotid artery stenting (n = 209), the 30-day, 1-year, 5-year, and 10-year survival rates for carotid endarterectomy patients were 99.1%, 95.3%, 77.9%, and 54.8%; carotid artery stenting rates were 99.5%, 96.2%, 67.8%, and 40.2%, respectively (P = .005, at 10 years). There was no significant difference in early stroke rates or myocardial infarction rates between the groups. Subgroup analysis comparing symptomatic status demonstrated no statistically significant differences in overall survival, stroke, or myocardial infarction rates at 10 years. In addition to reduced long-term overall survival, carotid artery stenting patients had a higher long-term restenosis rate as compared to carotid endarterectomy (6.3% vs 2.8%, P < .0001) and reduced restenosis-free survival (P = .01)., Conclusions: Early death, stroke, and myocardial infarction rates are comparable after carotid endarterectomy and carotid artery stenting. Carotid artery stenting is an effective means of preventing stroke among patients with carotid artery stenosis. Symptomatic status does not seem to affect rates of stroke, myocardial infarction, or death. Carotid endarterectomy continues to be the preferred long-term solution for extracranial carotid artery occlusive disease as it is associated with better long-term survival and lower restenosis rates., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Multiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis., Methods: Plasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia. The controls (n = 22) were age- and sex-matched participants who had no peripheral arterial disease or history of stroke or myocardial infarction. Patients with chronic kidney disease were excluded. Metabolites and internal standards were measured using high-performance liquid chromatography and tandem mass spectrometry., Results: Plasma metabolite concentrations differed significantly between the advanced atherosclerosis and control cohorts. After adjustment for traditional atherosclerosis risk factors, indole (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75-0.95; P = .004), tryptophan (OR, <0.001; 95% CI, <0.001-0.003; P < .001), indole-3-propionic acid (OR, 0.27; 95% CI, 0.019-0.91; P = .02), and indole-3-aldehyde (OR, 0.12; 95% CI, 0.014-0.92; P = .04) concentrations negatively associated with advanced atherosclerosis, whereas the kynurenine/tryptophan ratio (OR, 61.7; 95% CI, 1.9->999; P = .02) was positively associated. Furthermore, tryptophan and indole-3-propionic acid concentrations (Spearman coefficients of 0.63 and 0.56, respectively; P < .001) correlated with the ankle-brachial index, a surrogate for overall atherosclerotic disease burden. Fourteen patients experienced a major postoperative cardiac complication within 30 days in the advanced atherosclerosis cohort, which was associated with baseline kynurenine/tryptophan ratio (P = .001) and hippuric acid (P = .03). In a multivariate analysis, only the kynurenine/tryptophan ratio remained significantly associated with a postoperative cardiac complication (OR, 44.1; 95% CI, 3.3-587.1; P = .004). Twenty patients in the advanced atherosclerosis cohort experienced a major adverse cardiac event during the follow-up period, which was associated with hippuric acid (P = .002) and the kynurenine/tryptophan ratio (P < .001) at baseline. Both hippuric acid and the kynurenine/tryptophan ratio were independently associated with a major adverse cardiac event in multivariate analyses that included diabetes mellitus., Conclusions: Specific microbe-derived metabolite signatures associate with advanced human atherosclerosis and postoperative cardiac complications. We suggest that these metabolites are potential novel biomarkers for atherosclerotic disease burden and that further investigation into mechanistic links between defined microbial metabolic pathways and cardiovascular disease is warranted., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Prior studies have shown that sex bias exists with subject enrollment in clinical trials, with more men being enrolled than women. The objective of this study was to identify if sex bias continues to exist in present day clinical trials entered into ClinicalTrials.gov . We hypothesize that males and females are not equally represented in recent clinical trials., Materials and Methods: Data were abstracted from all interventional Phase I, II, and III clinical trials with adult subjects entered into ClinicalTrials.gov from January 1, 2011 to December 31, 2013 and completed by November 30, 2015. Number and sex of subjects, funding source, allocation, end point classification, interventional model, and purpose were recorded. Studies pertaining to diseases that were sex specific were excluded., Results: Of 1,668 studies included in the initial search, 167 were excluded due to sex-specific study topic. Of the remaining 1,501 studies, 177,656 (51.1%) male and 170,331 (49.0%) female subjects were included. There was a significant difference in the sex of the subjects included in Phase I (64.1% male/35.9% female), Phase II (48.4% male/51.6% female), and Phase III (51.0% male/49.1% female) clinical trials (p < 0.05). Similarly, there was a significant difference in the sex of the subjects included in industry (50.7% male/49.3% female), National Institutes of Health (NIH) (56.6% male/43.4% female), "Other US Federal" (62.5% male/37.5% female), and "Other" funded (53.4% male/46.6% female) clinical trials (p < 0.0001), as well as between randomized (50.5% male/49.6% female) and nonrandomized (54.8% male/45.2% female) clinical trials (p < 0.0001). Upon evaluating if the sex of the subjects included in the individual clinical trials was equally matched, we found that only 4.1% of clinical trials had 100% sex matching, 22.2% had 80% sex matching, and 56.5% had 50% sex matching. Using a liberal 50% sex-matching criteria, Phase III and II clinical trials matched the sex of the subjects more frequently compared to Phase I trials (60.8%, 57.8%, and 45.5%, respectively, p = 0.003)., Conclusion: These data reveal that sex bias is present in current day clinical trials. Despite legislation requiring NIH-funded clinical trials to include women, NIH-funded trials were not better than industry-funded trials at matching the inclusion of both sexes.

Purpose: Postoperative stereotactic radiosurgery (SRS) is increasingly utilized following resection of brain metastases (BM); however, there are no volumetric data guiding dose selection. We performed a volumetric analysis to guide cavity SRS dosing for resected BM., Methods: 83 consecutive patients with gross total resection who underwent postoperative SRS to 90 cavities were identified. The 12 Gy isodose lines (V12 total ) along with the volume of brain parenchyma receiving 12 Gy excluding cavity fluid, ventricular fluid, and calvarium (V12 parenchyma ) were contoured. Local recurrence (LR) and radionecrosis (RN) were calculated using cumulative incidence rates. Multivariate analysis (MVA) and cutpoint analysis were conducted., Results: Median follow-up was 12.3 months; median dose was 16 Gy. 1- and 2-year cumulative incidence rates of LR were 7.9% and 11.0%. Radiation dose [hazard ratio (HR) 2.04, p = 0.002] was significantly associated with time to LR on MVA. 1- and 2-year cumulative incidence rates of RN were 2.6% and 5.5% respectively. MVA demonstrated increased risk of RN with a larger V12 parenchyma (HR 1.46, p = 0.0496). Cavities ≤ 10 cc showed a low 2-year RN risk (4.3%), but had a modest LR risk (13.9%). A radiation dose ≥ 18 Gy significantly improved LC (HR 4.79, p = 0.01)., Conclusions: V12 parenchyma should be examined in postoperative SRS to assess RN risk. Cavities > 10 cc treated with 16 Gy achieved excellent LC and minimal RN at 2 years. Cavities ≤ 10 cc may be better treated with a dose ≥ 18 Gy to significantly improve LC given the low RN rate observed with 16 Gy.

Purpose: To improve the curability of older patients with newly diagnosed Hodgkin lymphoma., Patients and Methods: We conducted a multicenter phase II study that administered brentuximab vedotin (Bv) sequentially before and after standard doxorubicin, vinblastine, and dacarbazine (AVD) for untreated patients with Hodgkin lymphoma age 60 years or older. After two lead-in doses of single-agent Bv (1.8 mg/kg once every 3 weeks), patients received six cycles of AVD chemotherapy followed by four consolidative doses of Bv in responding patients., Results: Patient characteristics included median age of 69 years (range, 60 to 88 years), 63% male, median Eastern Cooperative Oncology Group performance status 1, 81% stage III to IV disease, 60% International Prognostic Score 3 to 7, median Cumulative Illness Rating Scale-Geriatric comorbidity score of 7 (52% grade 3 to 4); and 12% had loss of instrumental activities of daily living at diagnosis. Thirty-seven (77%) of 48 patients completed six cycles of AVD, and 35 patients (73%) received at least one Bv consolidation. Overall response and complete remission rates after initial Bv lead-in dose were 18 (82%) of 22 and 8 (36%) of 22, respectively, and 40 (95%) of 42 and 34 (90%) of 42, respectively, after six cycles of AVD among 42 response-evaluable patients. Twenty (42%) of 48 patients experienced a grade 3 to 4 adverse event, most commonly neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%); 33% had grade 2 peripheral neuropathy, which was reversible in a majority of patients. By intent-to-treat, the 2-year event-free survival, progression-free survival, and overall survival rates were 80%, 84%, and 93%, respectively. Furthermore, 2-year progression-free survival rates for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of ≥ 10 versus < 10 were 45% versus 100%, respectively ( P < .001), and with baseline loss versus no loss of instrumental activities of daily living were 25% versus 94% ( P < .001), respectively, the latter persisting on multivariable analyses., Conclusion: Altogether, sequential Bv-AVD was well tolerated and was associated with robust outcomes. Furthermore, geriatric-based measures were strongly associated with patient survival.

Purpose: The occurrence of upper extremity lymphedema after regional nodal irradiation (RNI) for breast cancer treatment varies significantly based on patient and treatment factors. The relationship between the radiation therapy (RT) field design and lymphedema risk is not well-characterized. The present study sought to correlate the variations in RT field design with lymphedema outcomes., Methods and Materials: Women with stage II-IV breast cancer receiving RNI after breast surgery that included sentinel lymph node biopsy or axillary dissection were identified. Their arm circumference was measured before RT and at each follow-up visit to assess for lymphedema. Nodal RT fields were defined using a trifurcated system. Group 1 excluded the upper level I and II axilla, defined by the lateral border of the nodal field encompassing less than one-third of the humeral head. Group 2 included the upper level I and II axilla, defined by the lateral border of the nodal field encompassing more than one-third of the humoral head treated with an anterior oblique beam. Group 3 included the upper level I and II axilla the same as for group 2 but with parallel-opposed beams delivering a significant dose to the musculature posterior to the axilla., Results: From 1999 to 2013, 526 women received RNI. The median post-RT follow-up was 5.5 years. For the 492 women meeting the inclusion criteria, the cumulative incidence of lymphedema was 23.5% at 2 years and 31.8% at 5 years. On univariate analysis, the patients in group 1 had a lower 5-year lymphedema rate (7.7%) than those in group 2 (37.1%) and group 3 (36.7%; P < .0001). On multivariate analysis, inclusion of the upper level I and II axilla (groups 2 and 3) remained significantly associated with increased lymphedema risk., Conclusions: Variations in the RT field design significantly affect the development of lymphedema after RNI. In particular, the upper level I and II axilla appear to be important regions for lymphedema risk after axillary dissection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Physical activity ameliorates fatigue in systemic lupus erythematosus (SLE) patients by an unknown mechanism. Adipokines, which are influenced by adiposity and physical activity, may be associated with patient-reported fatigue. We describe cross-sectional associations between adipokines and fatigue, physical activity, and SLE disease activity. We measured adipokines, self-reported fatigue, and objective physical activity in 129 SLE patients. Fatigue was assessed with the Fatigue Severity Scale (FSS) and Patient Reported Outcomes Measurement Information System ® (PROMIS ® ) Fatigue score. Disease activity was measured with the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI). Participants wore an accelerometer for 7 days to measure physical activity. Leptin, adiponectin, and resistin were measured in stored serum with a Luminex bead-based assay. Multivariable regression models assessed relationships between fatigue and adipokines, and Spearman correlation coefficients summarized associations between adipokines, physical activity, and SELENA-SLEDAI. Median adipokine levels were: leptin 30.5 ng/ml (Interquartile Range 14.0, 56.6), adiponectin 11.6 μg/ml (7.2, 16.8) and resistin 1.4 ng/ml (1.0, 2.2). Associations between adipokines and FSS or PROMIS fatigue were not significant. Body mass index (BMI) ≥ 30 kg/m 2 was associated with FSS and PROMIS fatigue in regression analyses (p < 0.05). Weak correlations between leptin, adiponectin, leptin/adiponectin (L/A) ratio, and physical activity and between adiponectin and SELENA-SLEDAI score were not significant after adjusting for BMI. Adipokines were not associated with fatigue in SLE. Adipokines were correlated with physical activity (leptin, adiponectin, L/A ratio) and SLE disease activity (adiponectin), but most of these associations were explained by BMI.

Background: Historically, patients with chronic mesenteric ischemia (CMI) are underweight with a low body mass index (BMI). However, with the recent obesity epidemic many of these patients now are overweight with a high BMI. We evaluated the impact of BMI on outcomes after mesenteric revascularization for CMI., Methods: A retrospective chart review of patients undergoing open or endovascular mesenteric revascularization for CMI between January 2000 and June 2015 was performed. Demographics, comorbidities, BMI, Society for Vascular Surgery-combined comorbidity score, treatment modality, postoperative complications, reintervention, and all-cause mortality were analyzed. The primary end point for the study was all-cause mortality at 5 years. Patients were stratified using the World Health Organization BMI criteria. Univariate, Kaplan-Meier survival, and multivariate analyses were performed., Results: In the study period, 104 unique patients underwent mesenteric revascularization for CMI, for 77 of whom BMI information was available. Of these 77, 30 patients were treated by endovascular revascularization, and 47 patients were treated by open revascularization. Overall, 27 (35.1%) were overweight or obese with a BMI ≥25. Median follow-up time was 41 months. High BMI patients were less likely to have weight loss at the time of surgery (P = 0.004). Stratified by BMI <25 versus BMI ≥25, 5-year survival for patients treated by open revascularization was 90% versus 50% (P = 0.02); survival for patients treated by endovascular revascularization was 27% vs. 53% (P = 0.37). Multivariate survival analysis identified active smoking, hypertensive chronic kidney disease, open repair with the use of venous conduit instead of prosthetic conduit (P < 0.001), and history of peripheral arterial disease (PAD) (P = 0.002), as independent predictors of increased all-cause mortality., Conclusions: BMI needs to be considered in assessing and counseling patients on outcomes of mesenteric revascularization for CMI, as a BMI over 25 is associated with poorer long-term survival after open revascularization. Smoking, hypertensive chronic kidney disease, PAD, and open repair with the use of venous conduit are independent predictors of long-term mortality after mesenteric revascularization independent of BMI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Postoperative stereotactic radiosurgery (SRS) to the cavity after resection of brain metastases improves local control. We hypothesized that significant cavity constriction would occur from the immediate postoperative period to the time of SRS and aimed to elucidate optimal treatment timing., Methods: We retrospectively reviewed 79 consecutive patients with 85 resection cavities treated with SRS after gross total resection of a brain metastasis. Preoperative lesion, immediate postoperative cavity, and cavity at the time of SRS were contoured for each patient. Factors influencing cavity size and interval cavity change were analyzed., Results: Median immediate postoperative cavity volume was 7.5 cm 3 , and median SRS cavity volume was 8.7 cm 3 . Median time from surgery to SRS was 20 days. Median volumetric cavity change was an increase of 28%. Of cavities, 34 (40%) increased in size >2 cm 3 , whereas only 8 cavities (9%) decreased in size >2 cm 3 ; 43 cavities (51%) had ≤2 cm 3 change. The largest postoperative cavities experienced the smallest percentage cavity change in the time interval to SRS (Spearman correlation -0.32, P = 0.003)., Conclusions: Cavity size after brain metastasis resection increased a median of 28% from immediate postoperative scan to time of SRS. Greater than 90% of postoperative cavities either increased >2 cm 3 or remained within 2 cm 3 of their immediate postoperative cavity volume. Early postoperative SRS within 2-3 weeks may be appropriate to minimize cavity growth. Delaying postoperative SRS beyond 3 weeks in hopes of significant cavity contraction is not warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Severe aorto-iliac occlusive disease (AIOD) is traditionally treated with aorto-bifemoral bypass (ABF) or aorto-unifemoral bypass (AUF). However, cross-femoral bypass (CFB) and hybrid femoral endarterectomy and patch angioplasty with iliac stenting (EPS) have gained popularity as less invasive options. We sought to compare 1-year survival, primary patency, and major amputation rates between open surgical (ABF and AUF) and 2 less invasive reconstruction techniques (CFB and EPS) using a large, multicenter cohort., Study Design: This is a retrospective cohort study of patients who underwent either ABF/AUF or CFB/EPS for AIOD between 2006 and 2013 in the Society for Vascular Surgery Vascular Quality Initiative registry. Baseline patient and periprocedural variables were compared. Propensity score matching (PSM) was performed to predict the likelihood of more invasive repair. Kaplan-Meier analysis and Cox models were performed for 1-year survival, primary patency, and major amputation., Results: 1872 patients underwent procedures for AIOD, including 1,133 ABF/AUF and 739 CFB/EPS, during the study period. Indication was critical limb ischemia in 47.3% (n = 886). Median follow-up time was 305 days (range, 10-406). After PSM, the matched cohort included 1,094 ABF/AUF and 711 CFB/EPS patients. Multivariate analysis revealed that patient factors and procedure indication were significant predictors of 1-year mortality and major amputation, but not procedure type. ABF/AUF was associated with improved primary patency over CFB/EPS at 1 year (94.1% ± 1.1% vs. 92.3% ± 1.5%, hazard ratio 0.65, 95% confidence interval 0.45-0.94; P = 0.02)., Conclusions: In a propensity-matched cohort from a multicenter vascular surgery registry, a direct approach to AIOD (ABF/AUF) demonstrated better 1-year primary patency than commonly used less invasive strategies. However, treatment approach was not a predictor of 1-year survival or limb salvage, suggesting that patient factors and procedure indication have a greater impact on outcome., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Diminished pelvic arterial flow as a result of intentional coverage/embolization of internal iliac arteries (IIA) during isolated endovascular common iliac artery aneurysm (CIAA) repair or endovascular repair of abdominal aortic aneurysms (EVAR) may result in symptomatic pelvic ischemia. Although generally well tolerated, in severe cases, pelvic ischemia may manifest as recalcitrant buttock claudication, vasculogenic impotence, or perineal, vesicle, rectal, and/or spinal cord ischemia. Branched graft technology has recently become available; however, many patients are not candidates for endovascular repair with these devices. Therefore, techniques to preserve pelvic arterial flow are needed. We reviewed our outcomes of isolated endovascular CIAA repair or EVAR in conjunction with unilateral external-internal iliac artery bypass., Methods: Single-center, retrospective review of 10 consecutive patients who underwent hybrid endovascular abdominal aortic aneurysm (AAA) or CIAA repair with concomitant external-internal iliac artery bypass between 2006 and 2015. Demographics, index procedural details, postoperative symptoms, hospital length of stay (LOS), follow-up imaging, and bypass patency were recorded., Results: The cohort of 10 patients was all men with a mean age of 71 years (range: 56-84). Hybrid repair consisted of contralateral IIA coil embolization followed by EVAR with external iliac artery-internal iliac artery (EIA-IIA) bypass. All EIA-IIA bypasses were performed via a standard lower quadrant retroperitoneal approach with a prosthetic bypass graft. Technical success was 100%, and there were no perioperative deaths. One patient developed transient paraplegia, 1 patient had buttock claudication on the side of his hypogastric embolization contralateral to his iliac bypass, and 1 developed postoperative impotence. 20% of patients sustained long-term complications (buttock claudication and postoperative impotence). Mean LOS was 2.8 days (range: 1-9 days). Postoperative imaging was obtained in 90% of patients, and mean follow-up was 10.8 months (range: 0.5-36 months). All bypasses remained patent., Conclusions: Although branched graft technology continues to evolve, strategies to maintain adequate pelvic circulation are necessary to avoid the devastating complications of pelvic ischemia. We have demonstrated that a hybrid approach combining EVAR or isolated endovascular common iliac artery exclusion with a unilateral external-internal iliac bypass via a retroperitoneal approach is well tolerated with a short LOS and excellent patency rates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Carotid endarterectomy (CEA) reduces stroke risk in selected patients. However, CEA risk profile may be different in older patients. We compared characteristics and outcomes of octogenarians and nonagenarians with those of younger patients., Methods: Deidentified data from CEA patients were obtained from the Society for Vascular Surgery Vascular Quality Initiative (VQI) database. Prior CEA, carotid artery stent, or combined CEA and coronary artery bypass were excluded, yielding 7390 CEAs in octogenarians and nonagenarians (≥80 years of age) and 35,303 CEAs in younger patients (<80 years of age). We compared post-CEA outcomes, including periprocedural cerebral ischemic events and death, and details such as operative time, bleeding, and return to surgery., Results: Octogenarians and nonagenarians were more likely to have pre-CEA neurologic symptoms (51.4% vs 45.6%; P < .001) and to have never smoked (37.8% vs 22.0%; P < .001), and they were slightly more likely to have required urgent CEA (16.1% vs 13.4%; P < .001). Stenosis ≥70% was similar (octogenarians and nonagenarians, 94.2%; younger patients, 94.4%; P = .45). Perioperative ipsilateral neurologic events and ipsilateral stroke were slightly more common among octogenarians and nonagenarians (1.6% vs 1.1% [P < .001] and 1.2% vs 0.8% [P = .002]). Multivariate modeling (logistic regression) showed that pre-CEA neurologic symptoms (odds ratios, 1.35 [P = .005] and 1.42 [P = .007]), pre-CEA ipsilateral cortical ischemic event (odds ratios, 1.18 [P < .001] and 1.20 [P < .001]), and urgency (odds ratios, 1.75 [P < .001] and 1.67 [P < .001]) remained strong predictors of any ipsilateral neurologic event and any ipsilateral stroke, respectively. However, age ≥80 years remained a significant predictor of these outcomes (odds ratios, 1.37 [P = .003] and 1.44 [P = .004]). Kaplan-Meier estimated survival was lower for octogenarians and nonagenarians at 30 days and 1 year (98.6% vs 99.4% and 93.7% vs 97.0%; log-rank, P < .001). Age ≥80 years was also associated with a greater rate of discharge to other than home after CEA, a difference that was only partially explained by comorbidities in multivariate modeling., Conclusions: CEA was performed with low rates of perioperative neurologic events and mortality. Multivariate testing showed that the higher rate of neurologic complications in octogenarians and nonagenarians appeared partially related to symptomatic status and urgent surgery; but after adjusting for these factors, age ≥80 years still predicted a slightly higher rate. Periprocedural CEA outcomes appear similar in comparing older and younger patients, although longer term survival is lower for older patients, and older patients are at greater risk of discharge to other than home. CEA was associated with slightly higher risk of neurologic complications in older patients but may be considered appropriate for selected octogenarians and nonagenarians., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Inferior vena cava repair after planned and unplanned venotomy is performed by either interposition bypass, patch venopasty, or lateral venorrhaphy and primary repair. Primary repair of the inferior vena cava avoids the use of foreign material and allows an all-autologous repair in an expeditious fashion. The purpose of this study was to demonstrate the utility of inferior vena cava repair, determine the degree of inferior vena cava stenosis, and examine clinical outcomes after primary repair., Methods: We conducted a single-center retrospective review of patients who underwent primary inferior vena cava repairs between January 2002 and January 2014 at a tertiary care center. Primary repair followed lateral venorrhaphy for tumor extraction or for repair of an iatrogenic inferior vena cava injury. Patient demographics, cross-sectional vena cava dimensions, and patient outcomes were tabulated., Results: In total, 47 (30 men and 17 women) patients underwent primary inferior vena cava repair (median age 58 years, range 31-83 years). Twenty-six patients (15 men and 11 women) underwent en bloc radical nephrectomy, inferior vena cava tumor thrombus extraction, and primary lateral venorrhaphy (median age 61 years, range 39-83 years). The majority, 92% of these patients, had renal cell carcinoma on final pathology, with a median follow-up period of 39 months (range 1-108 months). Twenty-one patients (15 men and 6 women) underwent primary repair for iatrogenic inferior vena cava injury (median age 54 years, range 31-82 years). The median follow-up period was 18.5 months (3-110 months). Clinic follow-up with postoperative imaging was obtained in 76.9% of those undergoing tumor thrombus extraction (n = 20) and 76.2% of those undergoing repair of an iatrogenic injury (n = 16). Overall, there was a 13% infrarenal inferior vena cava diameter loss, 17% inferior vena cava diameter loss at the level of the renal veins, and 10% suprarenal inferior vena cava diameter loss when comparing postoperative with preoperative imaging. All patients remained asymptomatic; therefore, inferior vena cava narrowing associated with primary repair was clinically insignificant., Conclusion: Primary inferior vena cava repair is associated with less than 20% inferior vena cava diameter loss and does not compromise venous outflow from the extremities. Primary inferior vena cava repair is a safe and expeditious technique that provides excellent clinical outcomes and long-term patency., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Scaling up surgical and trauma care in low- and middle-income countries could prevent nearly 2 million annual deaths. Various survey instruments exist to measure surgical and trauma capacity, including Personnel, Infrastructure, Procedures, Equipment, and Supplies (PIPES) and International Assessment of Capacity for Trauma (INTACT)., Objective: We sought to evaluate surgical and trauma capacity in the Bolivian department of Potosí using a combined PIPES and INTACT tool, with additional questions to further inform intervention targets., Methods: In June and July 2014 a combined PIPES and INTACT survey was administered to 20 government facilities in Potosí with a minimum of 1 operating room: 2 third-level, 10 second-level, and 8 first-level facilities. A surgeon, head physician, director, or obstetrician-gynecologist completed the survey. Additional personnel responded to 4 short-answer questions. Survey items were divided into subsections, and PIPES and INTACT indices calculated. Medians were compared via Wilcoxon rank sum and Kruskal-Wallis tests., Findings: Six of 20 facilities were located in the capital city and designated urban. Urban establishments had higher median PIPES (8.5 vs 6.7, P = .11) and INTACT (8.5 vs 6.9, P = .16) indices compared with rural. More than half of surgeons and anesthesiologists worked in urban hospitals. Urban facilities had higher median infrastructure and procedure scores compared with rural. Fifty-three individuals completed short-answer questions. Training was most desired in laparoscopic surgery and trauma management; less than half of establishments reported staff with trauma training., Conclusions: Surgical and trauma capacity in Potosí was most limited in personnel, infrastructure, and procedures at rural facilities, with greater personnel deficiencies than previously reported. Interventions should focus on increasing the number of surgical and anesthesia personnel in rural areas, with a particular focus on the reported desire for trauma management training. Results have been made available to key stakeholders in Potosí to inform targeted quality improvement interventions., (Copyright © 2017 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.)

Objective: A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy., Design: We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints., Results: At 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=-0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention., Conclusions: We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice., Trial Number: NCT00468910., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Current practice for selecting donor units for umbilical cord blood transplant (UCBT) involves matching at HLA-A and HLA-B by low-resolution typing and the HLA-DRB1 allele by high-resolution (HR) typing. We retrospectively studied the impact of HR allele matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1 on transplant-related outcomes in 60 single-unit UCBTs in pediatric patients with malignant and nonmalignant conditions. Five-year overall survival of our cohort was 71% (95% confidence interval, 58-81); 27% experienced primary graft failure. Applying HR typing, donor-recipient mismatch variability increased ranging from 1/8 to 8/8, however, no impact on primary graft failure, graft-versus-host disease or posttransplant infection was observed. UCBTs with ≥6/8 HR matches did have a better overall survival (P=0.04) and decreased transplant-related mortality (P=0.02) compared with <6/8 HR matches. Using standard HLA typing, we showed an increased incidence of acute graft-versus-host disease (grade II to IV) and decreased transplant-related mortality in comparing the matched (6/6) versus ≤5/6 group (P=0.05 and 0.05, respectively). These data support the use of current guidelines for umbilical cord blood selection and encourage utilization of HR typing to select umbilical cord blood units matched at ≥6/8 especially when appropriate ≥5/6 units are available.