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Currently, the effect of aging on sympathetic baroreflex control is equivocal, with some studies finding that integrated sympathetic baroreflex threshold gain is not affected by age, and others finding that it is blunted in older compared to young adults. While these studies evaluated the effect of aging on baroreflex control of integrated sympathetic burst frequency, it remains unclear how aging modulates the baroreflex control of postganglionic action potentials (AP). In young adults, the arterial baroreflex exerts non‐uniform control over varying‐sized APs spontaneously firing within bursts of muscle sympathetic nerve activity (MSNA), with the strongest control over medium sized AP clusters, and less control over the smallest and largest APs. Therefore, we tested the hypothesis that resting baroreflex control of AP subpopulations and integrated sympathetic bursts would be blunted in older compared to young adults. Baroreflex threshold relationships for integrated MSNA bursts and the underlying subpopulations of AP clusters (obtained using microneurography and a continuous wavelet transform) were assessed during 5 minutes of supine rest in eleven older (45‐75 years, 5 females) and eleven young (21‐30 years, 5 females) adults. Baroreflex threshold was quantified as the slope of the linear regression between AP probability (%) and MSNA burst probability (%) versus diastolic blood pressure (DBP, mmHg; Finger plethysmography). AP discharge was greater in older compared to young adults (Older: 614 ± 327 spikes/100 beats vs. Young: 211 ± 107 spikes/100 beats, P < 0.001), and the baroreflex control of AP subpopulations was reset towards greater firing probabilities in older adults (group‐by‐cluster effect: P < 0.001). Specifically, the arterial baroreflex threshold gain of medium AP clusters was greater in older compared to young adults (e.g. Cluster 4, Older: ‐7.8 ± 3.1 %/mmHg vs. Young: ‐4.1 ± 2.9 %/mmHg, P = 0.010), whereas the baroreflex threshold gains for the smallest (e.g. Cluster 1, Older: ‐1.2 ± 1.1 %/mmHg vs. Young: ‐0.7 ± 0.4 %/mmHg, P = 0.197) and largest (e.g. Cluster 10, Older: ‐0.5 ± 0.4 %/mmHg vs. Young: ‐0.6 ± 0.6 %/mmHg, P = 0.673) AP clusters were not modified by aging. Additionally, integrated sympathetic burst threshold gain was greater in older compared to young adults (Older: ‐7.9 ± 3.8 %/mmHg vs. Young: ‐3.9 ± 1.8 %/mmHg, P = 0.005), and the operating point was shifted rightward towards a higher DBP (Older: 76 ± 8 mmHg vs. Young: 68 ± 7 mmHg, P = 0.021). Contrary to our hypothesis, the strength of baroreflex control over medium sized AP clusters as well as integrated sympathetic baroreflex threshold gain was greater in this group of older adults compared to young adults.

Spinal cord and dorsal root ganglion stimulation are minimally invasive surgical techniques used to treat an array of chronic pain disorders. There is a paucity of data related to defining best practices in these specific patient populations, and historically, providers have relied on consensus committees to opine on the best techniques for patient safety and experience. The most efficacious mechanism of surgical closure—specifically a running suture closure compared to a surgical staple closure—is debated. A retrospective review of 155 patients implanted with either a spinal cord or dorsal root ganglion stimulator between 2017 and 2019 was undertaken to determine if the type of surgical closure was related to degree of postoperative surgical site discomfort. The primary outcome showed no statistically significant difference on postoperative pain scores between the suture (6.0 (IQR 5.0–8.0)) and staple (7.0 (IQR 5.0–8.0)) cohorts at postoperative day (POD) #1 (adjusted β 0.17 (95% CI −0.61 to 0.95), P = 0.670 ). This finding held for postoperative pain scores at POD #10 as well (staples (1.0 (IQR 0.0–4.0)) and suture (2.0 (IQR 0.0–5.0), adjusted β −0.39 (95% CI −1.35 to 0.58), P = 0.432 )). A regression analysis was performed to identify secondary factors impacting postoperative pain scores. Higher preoperative pain score (β 0.50 (95% CI 0.09 to 0.92), P = 0.019 ) and female gender (β 1.09 (95% CI 0.15 to 2.02), P = 0.023 ) were predictive of higher incisional pain scores at POD#10. Increasing age was associated with decreased incisional pain scores at POD#10 (β −0.06 (95% CI −0.09 to −0.03), P < 0.001 ). These findings are of interest to the pain practitioner and may be valuable in preoperative discussions with prospective patients.

8022 Background: Maintenance therapy in multiple myeloma (MM) after first autologous hematopoietic cell transplantation (AHCT1) is considered standard of care. Data regarding maintenance therapy after a salvage AHCT (AHCT2) in the setting of relapsed MM are scarce. Therefore, we used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to examine the use of maintenance therapy after AHCT2 in MM patients and its effect on post-transplant patient outcomes. Methods: We included US adult MM patients who underwent AHCT2 after melphalan conditioning regimen from 2010-2018, and excluded patients who underwent tandem transplants. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Cox proportional hazards models were developed to study the main effect (maintenance use) with other covariates of interest including age, sex, race, performance status, HCT-comorbidity index, MM subtype, stage, creatinine, cytogenetic, conditioning melphalan dose, disease status at transplant, and time from AHCT1 to AHCT2. Results: Of 522 patients, 342 received maintenance therapy and 180 did not after AHCT2. Baseline characteristics were similar between the two groups. Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Common maintenance regimens included immunomodulatory drugs (IMID)-lenalidomide (N = 145, 42%) or pomalidomide (N = 46, 13%) and proteasome inhibitor, bortezomib (N = 45, 13%). Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, p < 0.001, REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)%, p 0.003, PFS 27.8% (22.4-33.5) vs. 9.8% (5.5-15.2), p < 0.001, and OS 54% (47.5-60.5) vs 30.9% (23.2-39.2) p < 0.001, respectively. IMID-containing maintenance regimens were associated with an improved 5-year PFS and OS compared to other maintenance regimens. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis, including NRM: hazard ratio (HR) 0.19 (0.08-0.44), p 0.0001, REL: HR 0.58 (0.47-0.72), p < 0.0001, PFS HR 0.52 (0.43-0.64), p < 0.0001, and OS HR 0.46 (0.36-0.60), p < 0.0001. We conducted additional analyses to investigate a possible selection bias in the maintenance group including landmark analysis at 100-days and 6-months post-AHCT2 as well as a subgroup analysis of patients who received melphalan 200mg/m2 as conditioning for AHCT2 (as a surrogate for fitness)- all these analyses also showed improved outcomes in the maintenance group. Second cancers were reported in 17 (5%) patients in the maintenance group and 6 (3%) patients and no-maintenance group (p 0.39). Conclusions: Maintenance therapy after AHCT2 is associated with superior outcomes in MM patients.

PURPOSE To present a summary of the recommendations for the treatment and follow-up for the biochemical recurrence of castration-resistant prostate cancer (PCa) as acquired through a questionnaire administered at the Prostate Cancer Consensus Conference for Developing Countries. METHODS A total of 27 questions were identified as relating to this topic. Responses from the clinician were tallied and are presented in percentage format. Topics included the use of imaging in staging, treatment recommendations across different patient scenarios of life expectancy and prostate-specific antigen (PSA) doubling time, and follow-up for nonmetastatic castration-resistant PCa. RESULTS A consensus agreed that in optimal conditions, positron emission tomography-computed tomography with prostate-specific membrane antigen would be used although in limited resource situations the combined use of CT of the abdomen and pelvic (or pelvic MRI), a bone scan, and a CT of the thorax or chest x-ray was recommended. In cases when PSA levels double in < 10 months, more than 90% of clinicians agreed on the use of apalutamide or enzalutamide, regardless of life expectancy. With a doubling time of more than 10 months, > 54% of experts recommended no treatment independent of life expectancy. More than half of the experts, regardless of resources, recommended follow-up with a physical examination and PSA levels every 3-6 months and imaging only in the case of symptoms. CONCLUSION The voting results and recommendations presented in this document can be used by physicians to support management for biochemical recurrence of castration-resistant PCa in areas of limited resources. Individual clinical decision making should be supported by available data.

Objective: Elastase-2 (ELA-2), a chymotrypsyn-serine protease elastase family member 2A, is expressed in several tissues such as the lungs, heart, liver, kidneys, brain, and vessels. ELA-2 was found to generate angiotensin II (AngII) in arteries and contribute to resistance arteries and vascular remodeling in animal models. It has also been shown that continuous infusion of AngII induces abdominal aortic aneurysm (AAA) in mice. Therefore, we sought to investigate the role of ELA-2 in an aortic dilation, which is a risk factor to AAA development, in a mouse model. Design and method: Male wild type (C57bl/6, WT) and ELA-2 knockout (CELA-2aTm1Bdr; ELA-2 KO) mice were treated with saline or angiotensin II (AngII, 2.28 g/g/min) for twenty-eight days by subcutaneously mini-pumps infusion. To evaluate the role of elastase-2 in a AAA development, mice were divided into four groups: WT treated with saline (WT+SAL), ELA-2KO treated with saline (ELA-2KO+SAL), WT treated with AngII (WT+AngII), and ELA-2KO treated with Ang II (ELA-2KO+AngII). The vascular ultrasound (US) was done before treatment and once a week during 28 days of treatment. The abdominal aorta measurements such as maximum aortic diameter, aortic para-renal diameter, aortic infra-renal diameter, and aortic supra-renal diameter were collected. A dilated aorta is a risk factor aortic rupture/aneurysm. Statistical analyses were performed by the Shapiro Wilk Normality test, two-way ANOVA with Sidak's multiple comparisons test. This study is approved by the Ethics Committee (CEUA-131/2019). Results: The most dilated aorta as measured by the maximum aorta diameter was detected in WT+AngII group and was 60% higher than in the WT+Saline (p = 0.01). There was no significant difference in the maximum aorta diameter between ELA-KO+SAL vs. ELA-2KO+AngII (p = 0.8). The measurement of dilation in aortic para-renal and aortic infra-renal showed that AngII induced a dilation in WT+AngII (p < 0.05), while not modified these parameters in ELA-2KO+AngII group. The aortic supra-renal diameter parameters and weight showed no differences between groups. Conclusions: These results suggest that ELA-2KO mice might be less susceptible to develop an aorta dilation. Therefore, Elastase-2 is a candidate factor that contributes to the formation and/or development of abdominal aortic aneurysm.

BACKGROUND: A 56 US hospital collaborative, Improving Pediatric Sepsis Outcomes, has developed variables, metrics and a data analysis plan to track quality improvement (QI)–based patient outcomes over time. Improving Pediatric Sepsis Outcomes expands on previous pediatric sepsis QI efforts by improving electronic data capture and uniformity across sites. METHODS: An expert panel developed metrics and corresponding variables to assess improvements across the care delivery spectrum, including the emergency department, acute care units, hematology and oncology, and the ICU. Outcome, process, and balancing measures were represented. Variables and statistical process control charts were mapped to each metric, elucidating progress over time and informing plan-do-study-act cycles. Electronic health record (EHR) abstraction feasibility was prioritized. Time 0 was defined as time of earliest sepsis recognition (determined electronically), or as a clinically derived time 0 (manually abstracted), identifying earliest physiologic onset of sepsis. RESULTS: Twenty-four evidence-based metrics reflected timely and appropriate interventions for a uniformly defined sepsis cohort. Metrics mapped to statistical process control charts with 44 final variables; 40 could be abstracted automatically from multiple EHRs. Variables, including high-risk conditions and bedside huddle time, were challenging to abstract (reported in &lt;80% of encounters). Size or type of hospital, method of data abstraction, and previous QI collaboration participation did not influence hospitals’ abilities to contribute data. To date, 90% of data have been submitted, representing 200 007 sepsis episodes. CONCLUSIONS: A comprehensive data dictionary was developed for the largest pediatric sepsis QI collaborative, optimizing automation and ensuring sustainable reporting. These approaches can be used in other large-scale sepsis QI projects in which researchers seek to leverage EHR data abstraction.

AbstractBackgroundMucopolysaccharidoses (MPS) is a group of hereditary multisystemic lysosomal disorders. Most neuroimaging studies in MPS have focused on the supratentorial compartment and craniocervical junction abnormalities, and data regarding posterior fossa findings are scarce in the literature. Thus, our purpose is to describe posterior fossa findings on magnetic resonance imaging (MRI) of MPS patients.MethodsWe reviewed routine MRI scans of MPS patients being followed up at our institution (types I, II, III, IV, and VI), focusing on posterior fossa structures.ResultsForty‐seven MPS patients were included. MRI‐visible perivascular spaces were commonly found in the midbrain and adjacent to the dentate nuclei (85% and 55% of patients, respectively). White‐matter lesion was not identified in most cases. Its most frequent localizations were in the pons and cerebellum (34% and 30% of patients, respectively). Enlargement of cerebrospinal fluid (CSF) spaces in the posterior fossa was present in 55% of individuals and was more frequent in neuronopathic patients (73% vs 40%; P = .02). Cerebellar volume was classified as normal, apparent macrocerebellum, atrophic, and hypoplastic in 38%, 38%, 21%, and 3% of patients, respectively. A depression of the posterior fossa floor in the midline sagittal plane was found in 22 patients (47%), which was statistical significantly associated with enlargement of CSF spaces (P = .02) and with apparent macrocerebellum (P = .03).ConclusionThe present study compiled the main posterior fossa findings in MPS patients. Classically described in the supratentorial compartment, MRI‐visible perivascular spaces, white matter lesions, and enlarged perivascular spaces were also found in the posterior fossa. However, atrophy, which commonly affects cerebral hemispheres, was not the most frequent cerebellar morphology found in our study. Moreover, potential findings for future research were described.

Abstract Background Light chain (AL) amyloidosis is a plasma cell neoplasm associated with high early mortality and severe morbidity that can cause severe disability. We explored the impact of AL amyloidosis on symptoms and well-being from the perspectives of patients and health care providers who regularly care for AL patients. We intended to develop a conceptual understanding of patient-reported outcomes in AL amyloidosis to identify the context of use and concept of interest for a clinical outcome assessments tool in this disease.Method Twenty patients and 10 professionals were interviewed. Patient interviews captured the spectrum of amyloidosis experience including time from diagnosis, type of organ involvement, and presence and type of treatment received. Interviews with professionals included physicians, advanced practice providers, registered nurse, and a patient advocate; these interviews covered similar topics. Results The impact of AL amyloidosis on patients’ life was multidimensional, with highly subjective perceptions of normality and meaning. Four major themes from patients and experts included diagnosis of AL amyloidosis, living with AL amyloidosis, symptom burden, and social roles. Barriers to patient-reported outcomes data collection in patients were additionally explored from experts. The themes provide a comprehensive understanding of the important experiences of symptom burden and its impact on daily life from AL amyloidosis patients’ and from the perspectives of professionals who care for patients with AL amyloidosis. Conclusion These findings further the conceptual understanding and identification of a preliminary model of concept of interest for development of a clinical outcome assessments tool for AL amyloidosis.