A phase II trial of apalutamide for intermediate-risk prostate cancer and molecular correlates.

OBJECTIVES: To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. PATIENTS AND METHODS: Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. RESULTS: A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. CONCLUSIONS: Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.

Descriptive Analysis of Amputation-Free Survival After First Time Infra-Inguinal Bypass Occlusion.

INTRODUCTION: Occlusion after infra-inguinal bypass surgery for peripheral artery disease is a major complication with potentially devastating consequences. In this descriptive analysis, we sought to describe the natural history and explore factors associated with long-term major amputation-free survival following occlusion of a first-time infra-inguinal bypass. METHODS: Using a prospective database from a tertiary care vascular center, we conducted a retrospective cohort study of all patients with peripheral artery disease who underwent a first-time infra-inguinal bypass and subsequently suffered a graft occlusion (1997-2021). The primary outcome was longitudinal rate of major amputation-free survival after bypass occlusion. Cox proportional hazard models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) to explore predictors of outcomes. RESULTS: Of the 1318 first-time infra-inguinal bypass surgeries performed over the study period, 255 bypasses occluded and were included in our analysis. Mean age was 66.7 (12.6) years, 40.4% were female, and indication for index bypass was chronic limb threatening ischemia (CLTI) in 89.8% (n = 229). 48.2% (n = 123) of index bypass conduits used great saphenous vein, 29.0% (n = 74) prosthetic graft, and 22.8% (n = 58) an alternative conduit. Median (interquartile range) time to bypass occlusion was 6.8 (2.3-19.0) months, and patients were followed for median of 4.3 (1.7-8.1) years after bypass occlusion. Following occlusion, 38.04% underwent no revascularization, 32.94% graft salvage procedure, 25.1% new bypass, and 3.92% native artery recanalization. Major amputation-free survival following occlusion was 56.9% (50.6%-62.8%) at 1 y, 37.1% (31%-43.3%) at 5 y, and 17.2% (11.9%-23.2%) at 10 y. In multivariable analysis, factors associated with lower amputation-free survival were older age, female sex, advanced cardiorenal comorbidities, CLTI at index procedure, CLTI at time of occlusion, and distal index bypass outflow. Initial treatment after occlusion with both a new surgical bypass (HR 0.44, CI: 0.29-0.67) or a graft salvage procedure (HR 0.56, CI: 0.38-0.82) showed improved amputation-free survival. One-year rate of major amputation or death were 59.8% (50.0%-69.6%) for those who underwent no revascularization, 37.9% (28.7%-49.0%) for graft salvage, and 26.7% (17.6%-39.5%) for new bypass. CONCLUSIONS: Long-term major amputation-free survival is low after occlusion of a first-time infra-inguinal bypass. While several nonmodifiable risk factors were associated with lower amputation-free survival, treatment after graft occlusion with either a new bypass or a graft salvage procedure may improve longitudinal outcomes.

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults.

INTRODUCTION: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. METHODS: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. RESULTS: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24-3.56) and 0.45 per 100 person-years (95% CI: 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62-4.84) and 0.75 per 100 person-years (95% CI: 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56-3.16) and 0.21 per 100 person-years (95% CI: 0.067-0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017). CONCLUSION: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

Autonomous Chest Radiograph Reporting Using AI: Estimation of Clinical Impact.

Background Automated interpretation of normal chest radiographs could alleviate the workload of radiologists. However, the performance of such an artificial intelligence (AI) tool compared with clinical radiology reports has not been established. Purpose To perform an external evaluation of a commercially available AI tool for (a) the number of chest radiographs autonomously reported, (b) the sensitivity for AI detection of abnormal chest radiographs, and (c) the performance of AI compared with that of the clinical radiology reports. Materials and Methods In this retrospective study, consecutive posteroanterior chest radiographs from adult patients in four hospitals in the capital region of Denmark were obtained in January 2020, including images from emergency department patients, in-hospital patients, and outpatients. Three thoracic radiologists labeled chest radiographs in a reference standard based on chest radiograph findings into the following categories: critical, other remarkable, unremarkable, or normal (no abnormalities). AI classified chest radiographs as high confidence normal (normal) or not high confidence normal (abnormal). Results A total of 1529 patients were included for analysis (median age, 69 years [IQR, 55-69 years]; 776 women), with 1100 (72%) classified by the reference standard as having abnormal radiographs, 617 (40%) as having critical abnormal radiographs, and 429 (28%) as having normal radiographs. For comparison, clinical radiology reports were classified based on the text and insufficient reports excluded (n = 22). The sensitivity of AI was 99.1% (95% CI: 98.3, 99.6; 1090 of 1100 patients) for abnormal radiographs and 99.8% (95% CI: 99.1, 99.9; 616 of 617 patients) for critical radiographs. Corresponding sensitivities for radiologist reports were 72.3% (95% CI: 69.5, 74.9; 779 of 1078 patients) and 93.5% (95% CI: 91.2, 95.3; 558 of 597 patients), respectively. Specificity of AI, and hence the potential autonomous reporting rate, was 28.0% of all normal posteroanterior chest radiographs (95% CI: 23.8, 32.5; 120 of 429 patients), or 7.8% (120 of 1529 patients) of all posteroanterior chest radiographs. Conclusion Of all normal posteroanterior chest radiographs, 28% were autonomously reported by AI with a sensitivity for any abnormalities higher than 99%. This corresponded to 7.8% of the entire posteroanterior chest radiograph production. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Park in this issue.

Contemporary indications for open abdominal aortic aneurysm repair in the endovascular era.

OBJECTIVE: Despite the emergence of endovascular aneurysm repair (EVAR) as the most common approach to abdominal aortic aneurysm repair, open aneurysm repair (OAR) remains an important option. This study seeks to define the indications for OAR in the EVAR era and how these indicatioxns effect outcomes. METHODS: A retrospective cohort study was performed of all OAR at a single institution from 2004 to 2019. Preoperative computed tomography scans and operative records were assessed to determine the indication for OAR. These reasons were categorized into anatomical contraindications, systemic factors (connective tissue disorders, contraindication to contrast dye), and patient or surgeon preference (patients who were candidates for both EVAR and OAR). Perioperative and long-term outcomes were compared between the groups. RESULTS: We included 370 patients in the analysis; 71.6% (265/370) had at least one anatomic contraindication to EVAR and 36% had two or more contraindications. The most common anatomic contraindications were short aortic neck length (51.6%), inadequate distal seal zone (19.2%), and inadequate access vessels (15.7%). The major perioperative complication rate was 18.1% and the 30-day mortality was 3.0%. No single anatomic factor was identified as a predictor of perioperative complications. Sixty-one patients (16.5%) underwent OAR based on patient or surgeon preference; these patients were younger, had lower incidences of coronary artery disease and chronic obstructive pulmonary disease, and were less likely to require suprarenal cross-clamping compared with patients who had anatomic and/or systemic contraindications to EVAR. The patient or surgeon preference group had a lower incidence of perioperative major complications (8.2% vs 20.1%; P = .034), shorter length of stay (6 days vs 8 days; P < .001) and no 30-day mortalities. The multivariable adjusted risk for 15-year mortality was lower for patient or surgeon preference patients (adjusted hazard ratio, 0.44; 95% confidence interval, 0.24-0.80; P = .007) compared with those anatomic or systemic contraindications. CONCLUSIONS: Within a population of patients who did not meet instruction for use criteria for EVAR, no single anatomic contraindication was a marker for worse outcomes with OAR. Patients who were candidates for both aortic repair approaches but elected to undergo OAR owing to patient or surgeon preference have very low 30-day mortality and morbidity, and superior long-term survival rates compared with those patients who underwent OAR owing to anatomic and/or systemic contraindications to EVAR.

Pharmacokinetics of levonorgestrel and etonogestrel in rat or minipig following intravenous, subcutaneous, or intradermal administration.

The objective of these studies was to determine the pharmacokinetics of levonorgestrel and etonogestrel in Sprague-Dawley rat or Göttingen minipig following various administration routes.Four sequential crossover studies were conducted: Study 1 administered levonorgestrel 30 µg intravenously and intradermally in four minipigs; Study 2 administered levonorgestrel 30 µg intravenously in 12 rats; Study 3 administered levonorgestrel 60 µg intravenously and subcutaneously in 12 rats; and Study 4 administered etonogestrel 30 µg intravenously in 12 rats. Samples were quantified using liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters were estimated via noncompartmental analysis.Cmax and AUCinf for etonogestrel and levonorgestrel were similar following 30 µg intravenous bolus in rats, suggesting comparable pharmacokinetics. Levonorgestrel exposure was dose-proportional in rats, based on two-fold higher AUCinf following levonorgestrel 60 versus 30 µg. The bioavailability of intradermal and subcutaneous levonorgestrel was 97.7% (Study 1) and 90.3% (Study 3), respectively. The minipig levonorgestrel clearance was 21.5 L/hr, which was about 20-fold higher than both the rat levonorgestrel (range: 0.985-1.45 L/hr) and etonogestrel clearance (range: 0.803-0.968 L/hr).These studies contribute to the gap in knowledge of nonclinical levonorgestrel and etonogestrel pharmacokinetics, which is necessary for the ongoing development of long-acting reversible contraceptives.

Early Results and Technical Tips of Combining Iliac Branch Endoprostheses with Fenestrated Aortic Stent Grafts during Endovascular Repair of Complex Abdominal and Thoracoabdominal Aortic Aneurysms.

BACKGROUND: Concomitant iliac artery aneurysms can pose challenges during repair of complex abdominal and thoracoabdominal aortic aneurysms. In fenestrated aortic aneurysm repairs (FEVAR), preservation of internal iliac perfusion is important to minimize risk of spinal cord ischemia. Currently, most commonly used fenestrated stent grafts and the only approved iliac branch devices are manufactured by different companies in the United States. We report our experience with combining Iliac Branch Endoprosthesis (IBE) (W.L. Gore and Associates, Flagstaff, AZ) and fenestrated stent grafts, using the Zenith platform (Cook Medical, Bloomington, IN). METHODS: Retrospective review of consecutive patients who underwent FEVAR at a single institution from September, 2015 to June, 2020 was performed. Patients were deemed high-risk for open repair. Fenestrated aortic components implanted were either physician-modified or custom manufactured. Cases in which IBEs were deployed during FEVAR were specifically reviewed. Anatomic details were obtained from preoperative CT scans. Postoperative outcomes such as mortality, technical success, major adverse events, limb patency, limb-related endoleaks and re-intervention rates were assessed. RESULTS: During the study period, 171 patients underwent FEVAR at our institution. Among those, 15 patients had unilateral IBE implantation during FEVAR, while one received bilateral IBE implantation. Fourteen cases involved physician-modified fenestrated endograft, and Zenith Fenestrated (Cook Medical, Bloomington, IN) in combination with Excluder bifurcated main body and IBE (W.L. Gore and Associates, Flagstaff, AZ). Mean operative, and fluoroscopy times were 340.2 minutes, and 65.4 minutes respectively. A total of 67 viscerorenal target vessels (mean = 3.9, range =_3-5) and 15 internal iliac arteries were incorporated, with a mean of 160 cc contrast used. Completion angiograms were free of type 1 and type 3 endoleaks. Technical success was 100%. There was no perioperative mortality. One patient developed spinal cord ischemia post-operative day two with neurological recovery. At mean follow-up of 430 days, overall survival was 100% with no aneurysm-related mortalities. Limb patency remained 100%. There were no type 3 endoleaks while one patient had a type 1B endoleak that is currently being monitored. There was one re-intervention for type 1C renal branch graft endoleak. CONCLUSION: Combining IBE with FEVAR allows internal iliac preservation during endovascular repair of complex abdominal aortic aneurysms, with encouraging early results.

Incremental peritoneal dialysis is a safe and feasible prescription in incident patients with preserved residual kidney function.

BACKGROUND: Incremental peritoneal dialysis (PD) is recommended as a component of high-quality care by the international society for PD; however, its feasibility and clinical outcomes have not been widely reported. The aim of this study is to describe our experience with incremental PD. METHODS: This was a retrospective cohort study of incident PD patients at Eastern Health between 2015 and 2019. Patients who stopped PD within 30 days were excluded. Incremental PD was defined in CAPD as using <8 L/day of exchange volume and in automated PD as dialysing without a last fill. Dialysis modality accorded with patient and physician preferences. RESULTS: The 96 patients were included in this study; 54 with incremental PD. Compared to full-dose PD, incremental PD patients were more likely to be female, had less comorbid diabetes (28% vs. 52%) and higher residual kidney function (RKF) (Kt/V 2.0 ± 0.7 vs. 1.4 ± 0.7). Age, BMI and starting eGFR did not differ between groups. Incremental PD exposed patients to lower exchange volumes (4.4 ± 2.1 vs. 8.5 ± 1.1 L/day), glucose load (46 ± 41 g/day vs. 119 ± 46) and was associated with a longer peritonitis-free survival. PD technique survival, rates of peritonitis or hospitalization were comparable between groups. Predictors for longer incremental PD use included older age and higher starting eGFR. CONCLUSIONS: Incremental PD is a feasible, goal-directed initial prescription in patients with RKF with comparable peritonitis rates and technique survival. Validation of this prescription in prospective studies is warranted.

Myocarditis Following COVID-19 Vaccination: A Systematic Review (October 2020-October 2021).

INTRODUCTION: Reports of SARS-CoV-2 coronavirus (COVID-19) vaccine-related myocarditis, particularly after mRNA vaccines, have raised concerns amongst the general public. This review examined the literature regarding myocarditis post COVID-19 vaccination, drawing from vaccine safety surveillance databases and case reports. METHODS: Combinations of search terms were used in PubMed and COVID-19-specific repositories - LitCovid and the Cochrane COVID-19 Study Register - between 1 October 2020 and 31 October 2021. Manual searches of GoogleScholar and screening of article bibliographies were also performed. RESULTS: Information was obtained from five vaccine safety surveillance databases. Fifty-two (52) case reports totalling 200 cases of possible COVID-19 vaccine-related myocarditis were summarised. Vaccine surveillance databases differed in reporting formats and vaccination rates; however, gross estimates suggested low overall incidence rates of 2-5 per million mRNA vaccines. The incidence appeared to be higher in younger male populations, with onset of symptoms within a few days, usually after the second dose. Some with prior COVID-19 infections had onset after the first dose. Cases with prior unrelated myocarditis were also noted. Almost all presented with chest pain (98.0%). Troponin elevation was universally described and cardiac magnetic resonance imaging was commonly reported based on the updated Lake Louise criteria. Clinical course was mild in the majority, with response to anti-inflammatory treatment. CONCLUSION: COVID-19 vaccine-related myocarditis is an important but rare adverse event. More research is needed into its pathogenesis and reasons for its predominance in young males, while gaps in data exist in those aged <16 years, as well as those with prior COVID-19 infections and prior myocarditis.

Amino acid differences between diabetic older adults and non-diabetic older adults and their associations with cardiovascular function.

BACKGROUND: Ageing and insulin resistant states such as diabetes mellitus frequently coexist and increase the risk of cardiovascular disease development among older adults. Here we investigate metabolic differences in amino acid profiles between ageing and diabetes mellitus, and their associations with cardiovascular function. METHODS: In a group of community older adults we performed echocardiography, cardiac magnetic resonance imaging as well as cross sectional and longitudinal metabolomics profiling based on current and archived sera obtained fifteen years prior to examination. RESULTS: We studied a total of 515 participants (women 50%, n = 255) with a mean age 73 (SD = 4.3) years. Diabetics had higher alanine (562 vs 448, p < 0.0001), higher glutamate (107 vs 95, p = 0.016), higher proline (264 vs 231, p = 0.008) and lower arginine (107 vs 117, p = 0.043), lower citrulline (30 vs 38, p = 0.006) levels (µM) compared to non-diabetics. Over time, changes in amino acid profiles differentiated diabetic older adults from non-diabetic older adults, with greater accumulation of alanine (p = 0.002), proline (p = 0.008) and (non-significant) trend towards greater accumulation of glycine (p = 0.057) among the older diabetics compared to the older non-diabetics. However, independent of diabetes status, amino acids were associated with cardiovascular functions in ageing, [archived valine (p = 0.011), leucine (p = 0.011), archived isoleucine (p = 0.0006), archived serine (p = 0.008), archived glycine (p = 0.006) methionine (p = 0.003)] which were associated with impairments in E/A ratio. CONCLUSION: Markers of branched chain amino acids and one ­carbon metabolism pathways were associated with changes in cardiovascular function in older adults regardless of diabetes status. However, nitrogen handling pathways were specifically altered among older adults with diabetes. These findings broaden our understanding into specific amino acid pathways that may be altered between diabetic and non-diabetic older adults, and their relevance to cardiovascular function in ageing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02791139.

A Novel Proteomics-Based Strategy for the Investigation of Peptide Sequences in Extraterrestrial Samples.

Method development is one of the objectives of the astrophysical community for characterizing the organic matter in objects of the solar system. In this context, we report on the development of an enzyme-catalyzed stereoselective hydrolysis, inspired by the proteomics discipline, which has enabled the indirect detection of peptide sequences in extraterrestrial samples. A proof of concept has been performed on a Murchison extract. We show that our approach can successfully highlight l- and d-amino acids involved in peptide bonds. While we show that some d-amino acids must have been involved in peptide bonds, we cannot at this stage conclude on the indigenous or exogenous nature of these biopolymers. However, our strategy constitutes the first step toward direct UPLC-MS evidence of peptide sequences in extraterrestrial samples. It should thus contribute to deepening knowledge on the molecules available in the solar system, hence providing new clues about their chemical history, especially on Earth.

Empowering Surgeons, Anesthesiologists, and Obstetricians to Incorporate Environmental Sustainability in the Operating Room.

OBJECTIVE: We review the existing research on environmentally sustainable surgical practices to enable SAO to advocate for improved environmental sustainability in operating rooms across the country. SUMMARY OF BACKGROUND DATA: Climate change refers to the impact of greenhouse gases emitted as a byproduct of human activities, trapped within our atmosphere and resulting in hotter and more variable climate patterns.1 As of 2013, the US healthcare industry was responsible for 9.8% of the country's emissions2; if it were itself a nation, US healthcare would rank 13th globally in emissions.3 As one of the most energy-intensive and wasteful areas of the hospital, ORs drive this trend. ORs are 3 to 6 times more energy intensive than clinical wards.4 Further, ORs and labor/delivery suites produce 50%-70% of waste across the hospital.5,6 Due to the adverse health impacts of climate change, the Lancet Climate Change Commission (2009) declared climate change "the biggest global health threat of the 21st century" and predicted it would exacerbate existing health disparities for minority groups, children and low socioeconomic patients.7. METHODS/RESULTS: We provide a comprehensive narrative review of published efforts to improve environmental sustainability in the OR while simultaneously achieving cost-savings, and highlight resources for clinicians interested in pursuing this work. CONCLUSION: Climate change adversely impacts patient health, and disproportionately impacts the most vulnerable patients. SAO contribute to the problem through their resource-intensive work in the OR and are uniquely positioned to lead efforts to improve the environmental sustainability of the OR.

Prospective trial of regional (hockey-stick) prostate cryoablation: oncologic and quality of life outcomes.

PURPOSE: To report long-term follow-up of the efficacy of subtotal prostate ablation using a "hockey-stick" template, including oncologic control and quality of life (QoL) impact. METHODS: We performed a prospective controlled trial to evaluate the efficacy of subtotal prostate ablation in selected men with baseline and confirmatory biopsy showing grade group (GG) 1-2 prostate cancer. "Hockey-stick" cryoablation that included the ipsilateral hemi-gland and contralateral anterior prostate was performed. Prostate biopsies and QOL queries were performed at 6, 18 and 36 months following regional ablation, and follow-up was updated to include subsequent clinic visits. RESULTS: Between August 2009 and January 2012, 72 men were screened for eligibility and 47 opted to undergo confirmatory biopsy. Of these, 23 were deemed eligible and treated with regional cryoablation. Median age was 64 years. Median follow-up was 74 months. A single patient had < 1 mm of in-field viable tumor with therapy effect on 36-month biopsy. At time of last follow-up, a total of 12/23 (52%) patients did not have evidence of disease, all patients had preserved urinary control with no patients requiring pads for urinary incontinence. Sexual decline was significant at 3 and 6 months (P < 0.01 for both), though improvement was seen at subsequent time points. CONCLUSION: Subtotal (hockey-stick template) cryoablation of the prostate provides oncologic control to targeted tissue in a generally low-risk group with minimal impact on sexual and urinary function. Further studies are needed to evaluate this ablation template in the MRI-targeted era and higher risk populations.

Use of Inner Branches During Physician-Modified Endografting for Complex Abdominal and Thoracoabdominal Aortic Aneurysms.

OBJECTIVES: Endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms have been performed widely in an increasing number of centers, utilizing custom-manufactured or physician-modified stent grafts containing fenestrations and side-arm branches for visceral and renal artery incorporation. Alternatively, inner branch configurations may be useful in complex anatomy, where application of fenestrations or side-arm branches can be challenging. Our study aims to evaluate the incidence of target vessel instability when incorporated with inner branch configurations, and report clinical outcomes of patients who underwent fenestrated/branched endovascular aortic repairs (F-BEVAR) containing one or more inner branches. METHODS: We reviewed patients who underwent F-BEVAR with at least one inner branch configuration for complex abdominal or thoracoabdominal aortic aneurysms at Keck Hospital of University of Southern California from 2014 to 2020. Endpoints were mortality, major adverse events (MAE), technical success, and target vessel instability. Target vessel instability was assessed using follow-up computed tomography (CT) and duplex imaging. RESULTS: Out of the 175 patients who underwent F-BEVAR for complex abdominal and TAAA during the study period, 17 patients had at least one inner branch configuration. All were deemed high-risk for open repair with multiple cardiovascular and/or pulmonary comorbidities. Eight (47%) patients had extent I, II, III thoracoabdominal aortic aneurysms, and 10 (59%) had prior aortic repairs. A total of 68 target vessels were incorporated (mean = 4 vessels/patient, range=1~6), of which 40% were inner branch configurations, most commonly for renal arteries. Technical success was 94.1%. There was one perioperative mortality due to massive myocardial infarction, as well as one patient who needed temporary hemodialysis. No device-related mortalities were observed. At 30 days, primary inner branch patency was 100% with no target vessel instability or reintervention. At mean follow-up of 5.8 months, the overall survival was 94% with one patient who expired from unknown cause. Overall primary inner branch patency was 96.3%, due to occlusion of a long lumbar artery branch with no clinical sequelae. CONCLUSION: Inner branch configurations can provide a safe alternative technique of branch incorporation during complex endovascular aortic repair.

Patient perspectives on the need for implanted device information: Implications for a post-procedural communication framework.

BACKGROUND: Shared decision making and patient-centred communication have become part of pre-procedural decisions and perioperative care across medical specialties. However, gaps exist in patient communication about the implanted device received and the benefits in sharing information about their procedure and device. OBJECTIVE: To understand the patients' knowledge of identifying information for their implanted devices and perspectives on sharing their implanted device information. METHODS: Four focus groups were conducted with patients who had received a cardiac or vascular implanted device from one of the study sites within the previous 6 months. Data were transcribed and thematically analysed. RESULTS: Five themes emerged: lack of awareness of identifying information on implanted devices; value of information on implanted devices; varying trust with sharing device information; perceived risk with sharing device information; and lack of consensus on a systematic process for tracking implanted devices. DISCUSSION: Patients desire post-procedural information on their implanted device and a designated plan for longitudinal follow-up, but lack trust and perceive risk with broadly sharing their implanted device information. CONCLUSION: After receiving an implanted device, post-procedural patient communication needs to be expanded to include identifying information on the device including the unique device identifier, how long-term tracking will be supported and the process for notification in case of a problem with the device. This communication should also include education on how sharing device information supports patients' long-term health care, post-market safety surveillance and research. PATIENT OR PUBLIC CONTRIBUTION: The research team included members who were also patients with implanted devices.

Patterns of metastases of prostatic ductal adenocarcinoma.

BACKGROUND: The current study was conducted to investigate the patterns of metastases in men with metastatic prostatic ductal adenocarcinoma (DAC) and recurrence patterns after therapy. METHODS: All patients with a new diagnosis of DAC with de novo metastases and those with localized disease who developed metastases after treatment and were treated at the study institution from January 2005 to November 2018 were included. All patient and tumor characteristics and outcome data were collected. RESULTS: A total of 164 patients (37.7%) had metastatic DAC, including 112 with de novo metastases and 52 who developed metastases after treatment. Men with de novo metastases were found to have a significantly higher median prostate-specific antigen level and International Society of Urological Pathology grade but a lower cT3 and/or T4 classification compared with those with metastases that developed after treatment (all P < .05). Approximately 87% of men with de novo metastases progressed despite multiple systemic therapies, 37.6% required intervention for the palliation of symptoms, and 10.1% responded to systemic therapy and underwent treatment of the primary tumor. Men with de novo metastatic DAC and those who developed metastases after treatment had multiple metastatic sites (including bone and viscera), with higher rates of lung metastases noted in the posttreatment group (23.2% vs 44.2%; P = .01). A total of 45 patients who were treated with curative intent developed metastases at a median of 22 months (range, 0.9-74.8 months) after treatment, at low prostate-specific antigen levels (median, 4.4 ng/mL [interquartile range, 1.7-11.1 ng/mL]). CONCLUSIONS: The current study described the metastatic patterns of DAC in both patients with de novo metastatic disease and those who later progress to metastases. Men receiving treatment for DAC with curative intent require stringent long-term follow-up with imaging modalities, including chest imaging given the predilection toward lung metastases noted among these patients.

Intraoperative and early postoperative complications in postchemotherapy retroperitoneal lymphadenectomy among patients with germ cell tumors using validated grading classifications.

BACKGROUND: Postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an essential, yet potentially morbid, therapy for the management of patients with advanced germ cell tumors. In the current study, the authors sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAEs) and early postoperative complications. METHODS: Between 2000 and 2018, all patients who underwent PC-RPLND were analyzed for iAEs and early postoperative complications using the Kaafarani and Clavien-Dindo classifications, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. RESULTS: Of the 453 patients identified, 115 patients (25%) and 252 patients (56%), respectively, experienced an iAE and postoperative complication. Major iAEs (grade ≥3) were observed in 15 patients (3%) and major postoperative complications (grade ≥3) were noted in 80 patients (18%). The most common iAE was vascular injury (112 of 132 events; 85%), which occurred in 92 patients (20%), and the most frequent postoperative complication was ileus, which occurred in 121 patients (27%). Original and postchemotherapy retroperitoneal mass size, nonretroperitoneal metastases, intermediate and/or poor International Germ Cell Cancer Collaborative Group classification, previous RPLND, elevated tumor markers at the time of RPLND, and anticipated adjuvant surgical procedures increased the risk of both iAEs and postoperative complications. Patients who experienced an iAE were significantly more likely to experience a postoperative complication (odds ratio, 2.50; 95% confidence interval, 1.58-3.97 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the first analysis of PC-RPLND using validated classifications for both iAEs and postoperative complications, advanced disease and surgical complexity significantly increased the risks of major iAEs and postoperative complications. Standardized reporting of adverse perioperative events allows providers and patients to appreciate the consequences of PC-RPLND during counseling and decision making.

Signal inhibitory receptor on leukocytes (SIRL)-1 and leukocyte- associated immunoglobulin-like receptor (LAIR)-1 regulate neutrophil function in infants.

During severe respiratory syncytial virus (RSV) bronchiolitis there is a massive influx of activated neutrophils to the lungs. An exaggerated immune response contributes to lung damage and disease severity during RSV infection. We have previously shown that normal adult neutrophil function can be modulated by agonists of SIRL-1. Here we aimed to measure the potential of two immune checkpoints: SIRL-1 and LAIR-1, to regulate the function of fresh blood and sputum neutrophils from infants with and without severe RSV bronchiolitis. We show a modest inhibition of the oxidative burst through SIRL-1 and LAIR-1, in control and RSV-infected infants. In addition, SIRL-1 and LAIR-1 inhibited neutrophil extracellular traps (NET) formation by sputum neutrophils of RSV patients. Altogether our data show that inhibitory receptors LAIR-1 and SIRL-1 can be used to regulate neutrophil function.

Non-clinical Drivers of Variation in Preoperative MRI Utilization for Breast Cancer.

BACKGROUND: Preoperative magnetic resonance imaging (MRI) utilization in breast cancer treatment has increased significantly over the past 2 decades, but its use continues to have interprovider variability and disputed clinical indications. OBJECTIVE: The aim of this study was to evaluate non-clinical factors associated with preoperative breast MRI utilization. METHODS: This study utilized TRICARE claims data from 2006 to 2015. TRICARE provides health benefits for active duty service members, retirees, and their dependents at both military (direct care with salaried physicians) and civilian (purchased care under fee-for-service structure) facilities. We studied patients aged 25-64 years with a breast cancer diagnosis who had undergone mammogram/ultrasound (MMG/US) alone or with subsequent breast MRI prior to surgery. Facility characteristics included urban-rural location according to the National Center for Health Statistics classification. Adjusted multivariable logistic regression tests were used to identify independent factors associated with preoperative breast MRI utilization. RESULTS: Of the 25,392 identified patients, 64.7% (n = 16,428) received preoperative MMG/US alone, while 35.3% (n = 8964) underwent additional MRI. Younger age, Charlson Comorbidity Index score ≥ 2, active duty or retired beneficiary category, officer rank (surrogate for socioeconomic status), Air Force service branch, metropolitan location, and purchased care were associated with an increased likelihood of preoperative MRI utilization. Non-metropolitan location and Navy service branch were associated with decreased MRI use. CONCLUSION: After controlling for expected clinical risk factors, patients were more likely to receive additional MRI when treated at metropolitan facilities or through the fee-for-service system. Both associations may point toward non-clinical incentives to perform MRI in the treatment of breast cancer.

The impact of combined iliac occlusive disease and aortic aneurysm on open surgical repair.

OBJECTIVE: Severe aortoiliac occlusive disease is a relative contraindication for endovascular aneurysm repair, owing to an association with high stent graft-related complication and reintervention rates in this population. Open AAA repair requiring aortofemoral bypass (AFB), however, may represent a unique population with differing outcomes from standard open repair. We sought to compare the demographic and procedural characteristics, as well as outcomes of patients undergoing standard intra-abdominal repairs (STD) versus those requiring AFB. METHODS: Using a prospectively maintained database, we retrospectively identified patients who underwent open AAA repair from 1994 to 2017. A total of 1087 consecutive cases were performed consisting of 981 STD (681 tube graft, 300 aortoiliac) and 106 AFB cases. Demographics, procedural data, postoperative complications, and long-term survival were analyzed. RESULTS: The AFB cohort had more women (39.0 vs 22.8%; P = .001) and higher rates of hypertension (81.1 vs 69.8%; P = .015), chronic obstructive pulmonary disease (28.3 vs 17.4%; P = .006), and smoking (50.9 vs 36%; P = .002). The AFB group had smaller mean aortic (5.22 vs 5.77 cm; P = .001) and graft (17.08 vs 18.2 mm; P = .001) diameters. Proximal clamp position and blood loss were equivalent, although total anesthesia time was longer (295 vs 234 minutes; P = .001) in the AFB cohort. Overall 30-day postoperative morbidity (38.7 vs 24.8%; P = .002) was higher in the AFB group. Specifically, postoperative renal insufficiency (8.2 vs 3.4%; P = .032), wound infection (5.7 vs 1.2%; P = .005), and hematoma/seroma (5.7 vs 1.2%; P = .003) were more likely. Hospital length of stay was longer for AFB (11.9 vs 9.9 days; P = .007). The 30-day mortality (0.9% AFB vs 1.8% STD; P = .50) and major morbidity (17 vs 11.5%; P = .10) did not differ. Reintervention rate within 30 days of the initial surgery (12.3 vs 4.6; P = .001) and overall (33 vs 18.9%; P = .001) was higher in the AFB group. Long-term survival was lower in the AFB group (5-year survival: 63.1% AFB vs 71.9% STD; hazard ratio 0.76, log-rank P = .047). Multivariate regression analysis identified age, comorbid conditions, and aneurysm characteristics-rather than repair type-as independent predictors of 30-day reintervention and mortality at 5 years. CONCLUSIONS: Patients requiring AFB for AAA owing to associated iliac occlusive disease have more preoperative comorbidities, postoperative complications, a longer length of stay, reintervention rates and shorter 5-year survival. Patient and aneurysm characteristics rather than surgical repair type appear to be responsible for these differences. Nevertheless, 30-day mortality and major morbidity were comparable, making AFB an attractive alternative to endovascular aneurysm repair in patients with advanced iliac occlusive disease.