Citations

AbstractDual combination therapy with a phosphodiesterase‐5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate‐risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined. We developed an expert consensus statement on the transition to sGC and other treatment escalations and transitions in PAH using a modified Delphi process. The Delphi process used a panel of 20 physicians with expertise in PAH. Panelists answered three questionnaires on the management of treatment escalations and transitions in PAH. The initial questionnaire included open‐ended questions. Later questionnaires consolidated the responses into statements that panelists rated on a Likert scale from −5 (strongly disagree) to +5 (strongly agree) to determine consensus. The Delphi process produced several consensus recommendations. Escalation should be considered for patients who are at high risk or not achieving treatment goals, by adding an agent from a new class, switching from oral to parenteral prostacyclins, or increasing the dose. Switching to a new class or within a class should be considered if tolerability or other considerations unrelated to efficacy are affecting adherence. Switching from a PDE5i to an SGC activator may benefit patients with intermediate risk who are not improving on their present therapy. These consensus‐based recommendations may be helpful to clinicians and beneficial for patients when evidence‐based guidance is unavailable.

An 85-year-old male presented to the podiatry clinic following a 1st to 5th left toe amputation as a complication of severe peripheral arterial disease and nonhealing wound despite endovascular intervention with an angiogram. At the visit, cellulitis with gangrene of the surgical site was noted. The patient was admitted to the brick and mortar (BAM) hospital and taken to surgery for a transmetatarsal amputation of the left limb. In the immediate postoperative period, the incisional margins appeared dusky creating concern for flap viability. The medical team recommended a vascular bypass versus a below-knee amputation. However, given the age, comorbidities, and nutritional status, the family refused further surgical intervention. As such, Mayo Clinic’s home hospital program, Advanced Care at Home (ACH), was consulted for continued nonsurgical acute management at home. The patient was transferred to ACH and transported home three days after BAM admission to continue IV antibiotic therapy and wound care. Discharge from ACH occurred 11 days after admission to the BAM hospital. This case highlights the importance of developing health care alternatives to traditional hospitalization and demonstrates that ACH can manage highly complex, elder postoperative patients from the comfort of their homes.

AbstractExtramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1% of cases and can be differentiated from infectious etiologies based on fluid cytology.

AbstractBackgroundThough pathogenic variations in PSEN1 leading to Autosomal Dominant Alzheimer's disease (ADAD) are all highly penetrant, there is substantial inter‐individual variability in the rates of cognitive decline and biomarker change observed in ADAD. We hypothesized that this inter‐individual variability may be associated with the location of the pathogenic variant within PSEN1. We tested this hypothesis using biomarker and cognitive data from the Dominantly Inherited Alzheimer Network (DIAN) observational study.MethodPSEN1 pathogenic variant carriers [grouped based on whether their ADAD genotype affected transmembrane (PSEN1 TM; N = 125) or cytoplasmic (PSEN1 CY; N = 62) domains] and non‐carriers [NC; N = 176] enrolled in DIAN underwent clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection of cerebrospinal fluid (CSF). Linear mixed effects models with a restricted cubic spline were used to determine cross‐sectional differences in clinical and biomarker measures between NC, PSEN1 TM, and PSEN1 CY groups, across the disease course (estimated years to symptom onset; EYO).ResultBackground characteristics are reported in Table 1. PSEN1 CY and PSEN1 TM groups had elevated β‐amyloid (PiB‐PET) and phosphorylated‐tau levels (CSF pTauT181) compared to NC, but these biomarker measures were not different between PSEN1 TM and CY groups (Figure 1a‐b). Additionally, the PSEN1 TM group had decreased glucose metabolism compared to NC but was similar to the PSEN1 CY group (Figure 1c). However, we observed that PSEN1 TM carriers had significantly smaller hippocampal volume, greater lateral ventricle volume, and greater cognitive impairment (Figure 1d‐f) across EYO as compared to PSEN1 CY carriers.ConclusionDespite similar β‐amyloid PET and CSF pTauT181 levels across EYO, individuals with pathogenic variants affecting transmembrane domains in PSEN1 may have more rapid progression of disease as measured by cognitive function and neurodegeneration as compared to those with variants affecting cytoplasmic domains. These results have implications both for understanding the heterogeneity in ongoing ADAD clinical trials and for better understanding the pathobiology of ADAD.

AbstractPurposeTo report the longitudinal lung growth and prognosis of fetuses with severe left sided congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO) in a single institution.MethodsFetal lung size (observed‐to‐expected lung area to head circumference [o/e‐LHR]) was measured in seven consecutive fetuses with isolated severe left‐sided CDH who underwent FETO. Fetal lung growth was used to prognosticate survival and need for ECMO.ResultsSeven consecutive fetuses had a FETO procedure in the timeframe of this study. A total of 44 longitudinal ultrasound were performed to evaluate lung development. FETO was performed at GA 28.5 ± 0.5 weeks. Five (71.4%) infants survived to one‐year follow‐up and ECMO was needed in three patients (42.8%). Fetal lung response was observed in all fetuses; mean o/e‐LHR increased from 22.5% ± 1.4 before FETO to 44.4% ± 9.8 before delivery. Infants who survived had a higher percentage of fetal lung growth (21.8%) than those who died (8.25%).ConclusionOur study supports the hypothesis that FETO promotes fetal lung growth in fetuses with severe left‐sided CDH, and the fetal pulmonary response seems to be associated with improved outcomes after the procedure.

Abstract Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially the underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity as well and the issue should be addressed in conjunction with each other. Methods: Food and Drug Administration (FDA) drug approvals from 7/2007-6/2019 were reviewed to identify oncology approvals, and trials with age details were selected. The primary outcome was the weighted mean difference in age between the clinical trial population and realworld population for various cancers. The secondary outcomes were the prevalence of race reporting and association of age and race reporting with each other. Group comparisons for proportions were performed using the χ2 test while continuous variables were compared using multiple analysis of variance (MANOVA) test or students t-test as appropriate. P values < .05 were considered significant. Results: Of the 261 trials, the race was reported in 223 (85.4%) of the trials while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time – 29 (85.3%) in 2007-2010 vs. 49 (80.3%) in 2011-2014 vs. 145 (85.4%) during 2015-2019 (p-value=0.41). No significant association between type of cancer and race reporting was noted – 147 (86.5%) of solid cancer trials vs. 76 (83.5%) of hematological cancer trials reported race (p-value=0.52). Age discrepancy between the clinical trial population and the real-world population was present for several cancer types. The discrepancy was higher for studies that did not report race, mean difference - 8.8 years 4 (95% CI -12.6 to -5.0 years) vs. studies that did report the race, mean difference -5.1 years, (95% CI -6.4 to -3.7 years), p-value=0.04. Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations. In the meantime, reporting these characteristics for these crucial trials should be mandated. Citation Format: Thejus Jayakrishnan, Sonikpreet Aulakh, Mizba Baksh, Kianna Nguyen, Meghna Ailawadhi, Ayesha Samreen, Ricardo Parrondo, Taimur Sher, Vivek Roy, Rami Manochakian, Aneel Paulus, Asher Chanan-Khan, Sikander Ailawadhi. Disparity in race and age reporting in landmark cancer clinical trials: Underrepresentation of the traditionally underserved U.S. population [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-104.

AbstractBackgroundDue to duty hour regulations, patient safety and inadequate operative time simulation have become a necessary part of surgical education and training in residency. Currently, there is no formal adoption of simulators for the use of surgical education or assessment in hand surgery. This literature review analyzes that the simulation techniques established thus far in hand surgery.MethodsA comprehensive literature search was performed on PubMed. Search results were filtered by title and abstract to isolate articles that were relevant to simulation in hand surgery. Articles that were nonspecific to the hand, non‐English and cadaveric were excluded. Additional articles were identified through references from the initial search.ResultsA total of 1192 articles were yielded from the initial query. After the application of the inclusion criteria, this was narrowed down to 28 articles. Another 8 additional articles were excluded as they did not pertain to the hand although the simulators could be adapted for hand surgery. A total of 20 articles were included in this study.ConclusionsSurgical simulation is a growing and essential field of surgical education. Simulators in hand surgery are limited and require further research and validation. Like other surgical subspecialties, hand surgery may benefit from the adoption of an official simulation curriculum for the assessment of residents and enhancement of technical skills.