Citations

Background Transvenous embolization is emerging as a promising treatment for cerebrospinal fluid-venous fistulas (CVF) associated with spontaneous intracranial hypotension (SIH). Objective To perform an independent validation of the efficacy and safety of the procedure and describe the procedural techniques used at our institution. Methods A retrospective review was performed including consecutive patients with SIH who had undergone CVF embolization with 3-month clinical and imaging follow-up. Clinical evaluation included the Patient Global Impression of Change (PGIC) Scale and six-item Headache Impact Test (HIT-6). Bern SIH score was used for imaging evaluation on brain MRI. Post-treatment changes in scores were assessed by Wilcoxon signed rank test. Procedural technical details, including use of upper-extremity access and dual-microcatheter pressure cooker technique, were recorded. Results 18 patients (13 female, median age 60 years) were included. 17 (94%) procedures were performed with upper-extremity access and 12 (67%) using dual-microcatheter pressure cooker technique. After embolization, 16 (89%) patients reported much or very much improved at follow-up PGIC; median (IQR) HIT-6 score improved from 68 (62–72) to 36 (36–38) and Bern SIH score improved from 8 (6–8) to 3 (1.5–3.5), p values <0.001. Side effects were transient embolization site back pain in 15 (83%) and rebound intracranial hypertension requiring medical management in 9 (50%) patients. HIT-6 and Bern SIH score changes were similar between conventional and pressure cooker techniques ( p values >0.05). Conclusion Transvenous embolization is independently validated as a highly effective and safe treatment for CVF and is feasible using upper-extremity venous access. Dual-microcatheter and balloon/coil pressure cooker techniques may be used to optimize distribution of embolic material and potentially, treatment efficacy.

Importance Little is known about the burden and outcomes of respiratory syncytial virus (RSV)–positive acute respiratory infection (ARI) in community-dwelling older adults. Objective To assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults. Design, Setting, and Participants This was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI. Exposure RSV-positive and -negative ARI. Main Outcomes and Measures RSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed. Results In this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, −16.7 [95% CI, −31.8 to −1.8]; fatigue, −8.4 [95% CI, −14.3 to −2.4]; and difficulty in social functioning, −11.9 [95% CI, −19.8 to −4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: −4.0 [95% CI, −8.5 to −1.3]; difficulty in social functioning, −5.8 [95% CI, −10.3 to −1.3]; and limitation due to emotional problem, −7.0 [95% CI, −12.7 to −1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, −4.4 [95% CI, −7.3 to −1.5]; difficulty in social functioning, −5.2 [95% CI, −8.7 to −1.7] and limitation due to emotional problem, −5.7 [95% CI, −10.7 to −0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities. Conclusions and Relevance In this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.

Background Mechanisms underlying bioprosthetic valve deterioration are multifactorial and incompletely elucidated. Reparative circulating progenitor cells, and conversely calcification‐associated osteocalcin expressing circulating progenitor cells, have been linked to native aortic valve deterioration. However, their role in bioprosthetic valve deterioration remains elusive. This study sought to evaluate the contribution of different subpopulations of circulating progenitor cells in bioprosthetic valve deterioration. Methods and Results This single‐center prospective study enrolled 121 patients who had peripheral blood mononuclear cells isolated before bioprosthetic aortic valve replacement and had an echocardiographic follow‐up ≥2 years after the procedure. Using flow cytometry, fresh peripheral blood mononuclear cells were analyzed for the surface markers CD34, CD133, and osteocalcin. Bioprosthetic valve deterioration was evaluated by hemodynamic valve deterioration (HVD) using echocardiography, which was defined as an elevated mean transprosthetic gradient ≥30 mm Hg or at least moderate intraprosthetic regurgitation. Sixteen patients (13.2%) developed HVD during follow‐up for a median of 5.9 years. Patients with HVD showed significantly lower levels of reparative CD34 + CD133 + cells and higher levels of osteocalcin‐positive cells than those without HVD (CD34 + CD133 + cells: 125 [80, 210] versus 270 [130, 420], P =0.002; osteocalcin‐positive cells: 3060 [523, 5528] versus 670 [180, 1930], P =0.005 respectively). Decreased level of CD34 + CD133 + cells was a significant predictor of HVD (hazard ratio, 0.995 [95% CI, 0.990%–0.999%]). Conclusions Circulating levels of CD34 + CD133 + cells and osteocalcin‐positive cells were significantly associated with the subsequent occurrence of HVD in patients undergoing bioprosthetic aortic valve replacement. Circulating progenitor cells might play a vital role in the mechanism, risk stratification, and a potential therapeutic target for patients with bioprosthetic valve deterioration.

AbstractBackgroundCollagenase Clostridium histolyticum (CCH) has been proven effective in multiple subpopulations of PD men; however, no studies have evaluated its role with congenital penile curvature (CPC).AimTo evaluate the safety and efficacy of CCH in men with CPC.MethodsA prospective registry was queried of men undergoing CCH injections at our institution. Beginning in 2016, CCH was administered to CPC men using a similar protocol to PD. A comparative analysis was performed between cohorts to evaluate the safety and efficacy of therapy.OutcomesObjective measures included penile length and curvature, while subjective outcomes included standardized (International Index of Erectile Function and Peyronie’s Disease Questionnaire) and non-standardized assessments. Curvature outcomes were categorized as follows: 1 – included all men, with the most recent assessment considered final, and 2 – only men who had completed eight CCH injections or stopped early due to satisfaction.ResultsFrom 2014 to Oct 2021, a total of 453 men (408 PD, 45 CPC) underwent one or more CCH injections. In comparing cohorts, CPC men were younger (33 vs 58 years, p&lt;0.0001), had lesser baseline curvatures (52.5 vs 65°, p&lt;0.01), more ventral curves (25.7 vs 9.2%, p&lt;0.01), and longer penile lengths (12.5 vs 12.0 cm, p=0.04). Following treatment, both cohorts experienced similar curvature improvements. Specifically, PD men experienced 20-25° or 33-35% improvements depending on definition compared to 25-30° or 40-50% in CPC men (all p-values &gt;0.05). CPC and PD men also demonstrated similar changes on standardized questionnaires, with the exception of the Psychological and Physical subdomain, which was more improved in CPC men (-11 vs -4, p&lt;0.01). Baseline curvature was positively correlated with greater absolute (degree) and relative (percent) improvements. Adverse events were similar between groups after controlling for confounders.Clinical ImplicationsCCH may be safely and effectively administered in men with CPC. These data provide the first evidence for the efficacy of a non-surgical therapeutic option in this cohort.Strengths and LimitationsStrengths – large, prospective series with standardized assessments; Limitations - non-randomized study, short-term follow-up, and lack of standardized method to differentiate CPC from PD.ConclusionsCCH may be safely and effectively administered to men with CPC, with similar success rates compared to PD. Increasing curvature was associated with greater absolute (degree) and relative (percent) improvements, supporting the role for CCH in men with mild, moderate, or severe curvatures. External validation is warranted prior to routine implementation.

Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment–induced gonadotoxicity. Patients and Methods: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the “biological window” of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). Results: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33–42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56–2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45–2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01–0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. Conclusions: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.

AbstractClinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)‐based regimens before ASCT. Study endpoints included event‐free survival (EFS), progression‐free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI‐based regimens prior to ASCT. When adjusted for time to relapse, pre‐ASCT response and use of BV maintenance, patients receiving CPI‐based regimens had superior 2‐year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI‐based regimens were associated with superior 2‐year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03–0.5, p < .0001). OS did not differ by pre‐ASCT salvage regimen. In this large multicenter retrospective study, CPI‐based regimens improved EFS and PFS compared to other salvage regimens independent of pre‐ASCT response. These data support earlier sequencing of CPI‐based regimens in R/R cHL in the pre‐ASCT setting.

Abstract Background: Sub-Saharan African immigrants (SSAI) in the United States (US) constitute one of the fastest-growing segments of the immigrant population. Between 2010 and 2018, the SSAI population in the US increased by 53%, significantly outpacing the 12% growth rate for the overall foreign-born population in the US during that time frame. For the purposes of this study, we define SSAI as the 2 million individuals living in the US originally from the region of the African continent located south of the Saharan desert. Despite their growing numbers, little is published about the extent to which SSAI adapt to health behaviors more common in the US or remain immersed in the values, beliefs and practices reflective of their country of origin. Importantly, no study has comprehensively examined the social determinants of health factors among this population and its influence on health-seeking behaviors and decision-making regarding prostate cancer care and treatment options. This study employs the social determinant of migrant health framework to examine the impact of immigration on the health-seeking behaviors of SSAI including informed-decision making, psychosocial effects and coping mechanisms. This study will fill the void of research studies that link social determinant of health and immigration among SSAI. Methods: Grounded theory will guide the study design that include in-depth interviews to document the experiences of SSAI relative to health seeking behaviors, care, and treatment. We explore differences and similarities among participants based on country or region of origin in Africa. We employ the social determinants of migrant health framework to better understand the needs of SSAI prostate cancer survivors in the United States and how to effectively support these survivors. Results: We will present findings based on preliminary interviews conducted with SSAI prostate cancer survivors recruited from Florida or Minnesota. Additionally, we will report on the development of a SSAI social determinant of migration model that explains individual and structural factors that impact the health-seeking behaviors and coping mechanisms among this population. We will provide new understanding about specific social determinant of health factors that can be addressed in intervention studies among SSAI in the United States. Conclusion: This study examines the full range of racial, social, environmental, behavioral and structural factors that SSAI prostate cancer survivors experience. It will illuminate the decision-making process and overall quality of care among this understudied population. Citation Format: Ernie Kaninjing, Gladys Asiedu, Mary Ellen Young, Ebenezer Erefah, Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Solomon Rotimi, Che Ngufor, Arnold Merriweather, Jennifer Crook, Manisha Salinas, Parisa Fathi, Sha’Reff Rashad, John McCall, Ayinde Yahaya. The iCCARE consortium for prostate cancer in Black men: Grounded theory study of the social determinant of health factors among African immigrant men diagnosed with prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B050.

Abstract Introduction: Although prostate cancer (CaP) mortality rates are low, higher morbidity rates have been reported in Black men. In addition, the transition from treatment to survivorship can be burdensome and negatively impact quality of life (QoL). However, informal and formal support networks and resources, particularly spousal support, help enhance the sense of self and patient’s activities of daily living. Community, family involvement, and interaction with other survivors have also been found to be beneficial to survivors during diagnosis and treatment. Thus, we convened a town hall event for CaP survivors and those who care for and love them to explore the multidimensional impact of CaP and better understand the clinical and psychosocial needs of ethnically diverse Black CaP survivors. Methods: The virtual inaugural town hall meeting, organized by the University of Oklahoma (OU) Health and Stephenson Cancer Center, was held on April 28, 2022. The panelists included ethnically diverse CaP survivors, a radiation oncologist and urologist, and the spouse of a survivor. The town hall also served as a means to provide informational resources to attendees. A post-town hall survey was made available to all attendees to evaluate the town hall session and collect clinical and sociodemographic variables. Quantitative data were analyzed using SPSS v27. The event was audio recorded, and the transcript was content-analyzed to identify emergent themes. Results: Twenty-one out of the 43 attendees completed the survey (response rate of 49%). The respondents were aged 31-74 years old (mean±SD, 58±13), mostly males (67%), married (68%), CaP survivors (52%), and college graduates (43%). More than 80% rated the town hall to be very good/excellent and educational in light of varied approaches, perspectives, stories, and experiences shared by all the panelists. Participants appreciated updated information conveyed on anatomy, screening, signs and symptoms, diagnosis, stages of CaP, treatment, and short-term and long-term side effects shared by the oncologist. Results highlighted the physical and psychosocial impacts and stresses of CaP diagnosis on a family as a unit, especially intergenerational communication of perceived susceptibility and risk. Panelists also highlighted the burden of CaP survivorship on relationships, especially with their partners/spouses with impending functional distress. Results also underscored the positive influence CaP survivors can have on other survivors via peer advocacy and support. Finally, giving more time to panelists, extending the Q&A session, including other caregivers as panelists, and having more town hall events were top recommendations offered by participants. Conclusion: The town hall format allowed panelists, especially CaP survivors, to freely express their experiences with CaP. Overall, more awareness was raised about the importance of CaP prevention, treatment decision-making, survivorship, and advocacy: invaluable discussions needed to engage this hard-to-reach population regarding CaP prevention and care. Citation Format: Motolani E. Ogunsanya, Ernie Kaninjing, Maleeha Shahid, Darla Kendzor, Kathleen Dwyer, Mary Ellen Young, Folakemi T. Odedina. Prostate cancer survivorship and advocacy in ethnically diverse Black men: Findings from a town hall event [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A041.

Abstract Primary sclerosing cholangitis (PSC) is a complex bile duct disorder. Its etiology is incompletely understood, but environmental chemicals likely contribute to risk. Patients with PSC have an altered bile metabolome, which may be influenced by environmental chemicals. This novel study utilized state-of-the-art high-resolution mass spectrometry (HRMS) with bile samples to provide the first characterization of environmental chemicals and metabolomics (collectively, the exposome) in PSC patients located in the United States of America (USA) (n = 24) and Norway (n = 30). First, environmental chemical- and metabolome-wide association studies were conducted to assess geographic-based similarities and differences in the bile of PSC patients. Nine environmental chemicals (false discovery rate, FDR &lt; 0.20) and 3143 metabolic features (FDR &lt; 0.05) differed by site. Next, pathway analysis was performed to identify metabolomic pathways that were similarly and differentially enriched by the site. Fifteen pathways were differentially enriched (P &lt; .05) in the categories of amino acid, glycan, carbohydrate, energy, and vitamin/cofactor metabolism. Finally, chemicals and pathways were integrated to derive exposure–effect correlation networks by site. These networks demonstrate the shared and differential chemical–metabolome associations by site and highlight important pathways that are likely relevant to PSC. The USA patients demonstrated higher environmental chemical bile content and increased associations between chemicals and metabolic pathways than those in Norway. Polychlorinated biphenyl (PCB)-118 and PCB-101 were identified as chemicals of interest for additional investigation in PSC given broad associations with metabolomic pathways in both the USA and Norway patients. Associated pathways include glycan degradation pathways, which play a key role in microbiome regulation and thus may be implicated in PSC pathophysiology.