Citations

Background: With the improvement in outcomes for acute coronary syndrome (ACS), the practice of routine admission to cardiac intensive care units (CICUs) is evolving. We aimed to describe the epidemiology of patients with ACS admitted to contemporary CICUs. Methods: Using the CCCTN (Critical Care Cardiology Trials Network) Registry for consecutive medical CICU admissions across 26 advanced CICUs in North America between 2017 and 2020, we identified patients with a primary diagnosis of ACS at CICU admission and compared patient characteristics, resource utilization, and outcomes to patients admitted with a non-ACS diagnosis and across sub-populations of patients with ACS, including by indication for CICU admission. Results: Of 10 118 CICU admissions, 29.4% (n=2978) were for a primary diagnosis of ACS, with significant interhospital variability (range, 13.4%–56.6%). Compared with patients admitted with a diagnosis other than ACS, patients with ACS had fewer comorbidities, lower acute severity of illness with less utilization of advanced CICU therapies (41.3% versus 66.1%, P <0.0001), and lower CICU mortality (5.4% versus 9.9%, P <0.0001). Monitoring alone, without another CICU indication at the time of admission, was the most frequent admission indication in patients with ACS (53.8%); less common indications in patients with ACS included respiratory insufficiency, shock, or the need for vasoactive therapy. Of patients with ACS admitted for monitoring alone, 94.8% did not subsequently require advanced intensive care unit therapies and had a low CICU length of stay (1.5 days [0.9–2.4] versus 2.6 [1.4–5.1], P <0.0001) and CICU mortality (0.6% versus 11.0%, P <0.0001), compared with patients with ACS with an admission indication beyond monitoring. Conclusions: In a registry of tertiary care CICUs, ACS represent ≈1/3 of all admissions with significant variability across hospitals. More than half of the ACS admissions to the CICU were for routine monitoring alone, with a low rate of complications and mortality. This observation highlights an opportunity for prospective studies to refine triage strategies for lower risk patients with ACS.

11507 Background: Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma and is associated with high risk of relapse and a poor prognosis for advanced disease. In preclinical LMS models, unesbulin, a microtubule polymerization inhibitor, potentiated the activity of dacarbazine (DTIC) (Jernigan F, et al. Mol Cancer Ther. 2021;20:1846–1857). Here, we report preliminary safety and efficacy results from a Phase 1b dose escalation study evaluating the combination of unesbulin with DTIC in patients with advanced LMS (NCT03761095). Methods: In this single-arm, open-label, Phase 1b clinical trial, patients with advanced LMS received unesbulin orally at 200, 300, or 400 mg twice weekly (BIW) in combination with intravenous DTIC at 1,000 mg/m2 once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of unesbulin in combination with DTIC and to characterize the safety profile of the combination. The time-to-event continual reassessment model (TITE-CRM) was used for dose finding. An expansion cohort with up to 12 additional patients is currently being enrolled. Results: As of the data cutoff on January 6, 2022, 29 LMS patients have been treated. Median prior lines of therapy were 3 (range 1–6). Of 27 evaluable patients, 12 had non-uterine and 15 had uterine LMS. The MTD/RP2D of unesbulin was determined to be 300 mg BIW with DTIC 1,000 mg/m2 every 21 days using the TITE-CRM. At the RP2D, the most common treatment-related adverse events included fatigue, diarrhea, neutropenia, and thrombocytopenia. In the intent-to-treat population, the overall response rate (ORR) was 17.2% (5/29) and the disease control rate (DCR) (DCR = complete response + partial response + stable disease at 12 weeks) was 58.6%. At the 300 mg dose level, the ORR was 19% (4/21) and the DCR was 57.1%. Patients received a median of four cycles (range 1–12). The study is ongoing, with patients continuing to receive treatment. Conclusions: Unesbulin 300 mg BIW in combination with DTIC 1,000 mg/m2 every 21 days was well tolerated and demonstrated promising efficacy in a heavily pre-treated patient population with advanced LMS; these results support further investigation. Updated clinical results will be presented as the data mature. A randomized, placebo-controlled, Phase 2/3 trial is planned. Clinical trial information: NCT03761095.

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient’s condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.

ABSTRACT Introduction Peyronie's Disease (PD) is characterized by a fibrous scar of the tunica albuginea. PD is typically imaged with 2D ultrasound. We propose a classification system of these ultrasound findings in the evaluation of PD. Objective The purpose of this study is to establish a functional, reproducible sonographic classification system for evaluating PD and to examine the relationship between PD grading and curvature, duration of PD, and vascular erectile status. Methods In our study, 395 patients with PD underwent intracavernous injection with an erectile agent (ICI) followed by Color Doppler Duplex Ultrasound (CDDU). All CDDU studies were performed by a single examiner and all PD grading was done by two independent reviewers using saved images. CCDU findings including peak systolic velocities (PSV) and resistive indices (RIs) were recorded. PD grades of 2D images were classified into three grades: Grade 1 acoustic shadowing without calcification; Grade 2 focal microcalcifications of the tunica, pillars, or septal fibers; Grade 3 confluent calcification of the dorsal, septal, ventral tunica albuginea. Results There were 250 patients classified with Grade 1 (63%) sonographic changes, 75 with Grade 2 (19%), and 70 with Grade 3 (18%). Neither median age nor body mass index (BMI) of the cohorts were significantly different: Grade 1 (59.3 yr), Grade 2 (59 yr) and Grade 3 (60.3 yr), p = 0.711; BMI 27.6, 28.2, 27.7, p = 0.813. Medical risk factors for erectile dysfunction, including hypertension, heart disease, diabetes mellitus, hyperlipidemia, smoking history, and history of prostate surgery were not statistically different for the three cohorts. Most patients had previously used PDE5-Inhibitors (293/395). History and or physical findings of Dupuytren's palmar contracture was noted in 30/395 (7.6%) of men. The median duration of PD was not significantly different in the three cohorts (12, 12, 14 months p = 0.639). Neither CDDU diagnoses (Table 1) nor curvature varied by sonographic grades (Table 2). Conclusions The scar resulting from PD seals together the outer longitudinal and inner circular layers of the tunica albuginea causing deformity of the erect shaft. PD plaques are usually palpable and associated with focal thickening of the tunica. On 2D ultrasound, the typical appearance is an acoustic shadow. Most of our patients presented with Grade I acoustic shadowing and no calcifications 250/395 (63%); on the other hand, 19% had acoustic plaque shadowing and additional findings of focal tunica or deep microcalcifications and 18% had confluent calcification of the dorsal, septal or ventral tunica. We propose a unique and reproducible classification system. This grading system based on grayscale ultrasound of Peyronie's plaques may serve as a paradigm for diagnosis, didactics and integrated research. Disclosure Work supported by industry: no, by N/A.

ABSTRACT Introduction Intracavernosal injections (ICI) are a well-established treatment option with great success rates for men with erectile dysfunction. Unfortunately, the anticipation of pain with injections remains a significant barrier to the use of ICI. Objective This study aims to utilize a standardized verbal pain scale to examine the perception of pre- and post-injection pain in men who are undergoing their first injection with an intracavernosal erectile agent. Thus, inclusion criteria required no previous penile injection of any type, including but not limited to erectile medications and collagenase. Methods We determined a prospective pre-post observational study would be best to examine men undergoing their first ICI. Men who had no previous history of intracavernosal injection of any kind were asked to predict the pain associated with their first ICI with a score of zero to ten. Patients then received a 10 microgram (mcg) injection of prostaglandin E1 (PGE1). Immediately after they received their injection, they were asked to rate the pain they perceived with the injection on the same scale (0-10). The same physician administered pre- and post-injection scales in a standardized fashion. Results A total of 17 of men were asked to rate their pain as discussed in the Methods Section. The average age of men sampled was 61.8 years of age. On review of history, 64.7% of men were found to have used some type of PDE-5 inhibitor before visiting our clinic. The majority of men we saw had erectile dysfunction (70.6%) and/or Peyronie's Disease (58.8%). The average pre-injection prediction pain score was 5.29 +/- 1.90; the average post-injection perceived pain score was 1.21 +/- 0.81. Thus, there was an average decrease of over 4 points in predicted pain versus perceived pain. A two-sample t-test was performed; in addition, a Wilcoxson Signed Rank Test was performed. Both tests showed statistical significance in the difference between pre- and post-injection pain scores (p &lt;0.001). Conclusions We found that patients who are undergoing ICI for their first time have a significantly higher prediction of pain versus perception of pain after the injection. We have utilized this data in our clinic to explain to patients that while the majority of patients predict high pain scores associated with injection, the vast majority of patients report very minimal pain associated with the injection. Patients can be more open-minded to ICI therapy which could help aid them with their erectile status; this can particularly be helpful in patients who want to avoid surgery and in patients who are not good surgical candidates. Disclosure Work supported by industry: no, by N/A.

ABSTRACT Introduction The prevalence of erectile complaints in the US is estimated to be more than 50%. Most of the time ED complaints are evaluated and treated in the primary care setting. However, when first line measures are not efficient, patients are referred to general Urologists or to a specialized center. Objective The primary aim of this study is to describe the characteristics of patients referred to a tertiary center for evaluation of erectile complaints not responding to traditional first line therapies and, or patients with an associated complaint of penile deformity (rule out Peyronie's Disease/PD). Methods We retrospectively analyzed a cohort of patients between 2005 and 2019, detailing primary complaints, sexual histories, self-assessment scores, medical history and results of in office intracavernous injection followed by Color Doppler Duplex Ultrasound (CDDU). CDDU findings were recorded following injection of low dose alprostadil (10-20 mcg) and again after a period of privacy and visual sexual stimulation. CDDU findings including peak systolic velocities (PSV), and resistive indices (RIs) were recorded. Arterial insufficiency (AI) was defined as either a post-stimulation PSV &lt; 25 (severe) or a PSV 25-34.9 with RI ≥ 0.9 (moderate). Cavernous venous occlusion disease (CVOD) was defined as post-stimulation PSV ≥35 with RI &lt; 0.9. Vascular normal was defined as post-stim PSV ≥ 35 with RI ≥ 0.9. Results A total of 1490 patients with a median age of 60 (range, 18 – 88), median BMI of 28.4 (range, 15.9 – 56.8) and median Sexual Health Inventory for Men (SHIM) score of 10 (range, 0-25). In our cohort, 257/1489 (17.3%) patients had heart disease, 656/1489 (44.1%) patients had hypertension, 520/1489 (34.9%) patients had diabetes, and 203/1488 (13.6%) patients had a past medical history of hypertriglyceridemia. Smoking history was present in 853/1478 (57.7%) of patients and complaint of PDE-5 failure was made by 945/1201 (78.7%) patients who reported using it. 900 patients (60.4%) had a complaint of penile deformities and ED, 461 (30.9%) had a complaint of ED only, and 129 (8.7%) had a complaint of PD only. Prostate surgery history was noted in 316 men: radical retropubic prostatectomy 108, robotic assisted prostatectomy 134 and endoscopic resection or enucleation 74. Following CDDU we confirmed 767 (51.5%) patients with both ED and PD, 351 (23.6%) with ED only, and 310 (20.8%) PD only. We found 62 men (4.2%) had normal vascular erectile response to low dosage PGE1 (diagnosed as psychogenic ED vs. post-prostatectomy neurogenic ED). Among the 351 patients with ED only on Doppler, 132 (37.6%) had AI, 124 (35.3%) had CVOD, and 95 (27.1%) had a mixed vascular diagnosis. Among patients with vascular ED on diagnoses by CDDU, 73/351 (20.8%) had heart disease, 192/349 (55.0%) had smoking history, 273/311 (87.8%) complained of PDE5-inhibitor failure, 130/351 (37.0%) had diabetes, and median SHIM score was 7 (range 1-25). Conclusions This summary describes the characteristics in 1490 men who presented for evaluation of erectile complaints and or complaints of penile deformity to a tertiary care center. Patients referred to Urologists have complex ED, defined as refractory to PDE5-Inhibitors, associated with penile deformities, and multiple medical / surgical risk factors. Disclosure No

ABSTRACT Introduction Intracavernosal injections (ICI) are a well-established treatment option with great success rates for men with erectile dysfunction. Unfortunately, the anticipation of pain with injections remains a significant barrier to the use of ICI. Objective This study aims to utilize a standardized verbal pain scale to examine the perception of pre- and post-injection pain in men who are undergoing their first injection with an intracavernosal erectile agent. Thus, inclusion criteria required no previous penile injection of any type, including but not limited to erectile medications and collagenase. Methods We determined a prospective pre-post observational study would be best to examine men undergoing their first ICI. Men who had no previous history of intracavernosal injection of any kind were asked to predict the pain associated with their first ICI with a score of zero to ten. Patients then received a 10 microgram (mcg) injection of prostaglandin E1 (PGE1). Immediately after they received their injection, they were asked to rate the pain they perceived with the injection on the same scale (0-10). The same physician administered pre- and post-injection scales in a standardized fashion. Results A total of 17 of men were asked to rate their pain as discussed in the Methods Section. The average age of men sampled was 61.8 years of age. On review of history, 64.7% of men were found to have used some type of PDE-5 inhibitor before visiting our clinic. The majority of men we saw had erectile dysfunction (70.6%) and/or Peyronie's Disease (58.8%). The average pre-injection prediction pain score was 5.29 +/- 1.90; the average post-injection perceived pain score was 1.21 +/- 0.81. Thus, there was an average decrease of over 4 points in predicted pain versus perceived pain. A two-sample t-test was performed; in addition, a Wilcoxson Signed Rank Test was performed. Both of these tests showed statistical significance in the difference between pre- and post-injection pain scores (p &lt;0.001). Conclusions We found that patients who are undergoing ICI for their first time have a significantly higher prediction of pain versus perception of pain after the injection. We have utilized this data in our clinic to explain to patients that while the majority of patients predict high pain scores associated with injection, the vast majority of patients report very minimal pain associated with the injection. Patients can be more open-minded to ICI therapy which could help aid them with their erectile status; this can particularly be helpful in patients who want to avoid surgery and in patients who are not good surgical candidates. Disclosure No

ABSTRACT Introduction Peyronie's Disease (PD) is a well described pathology affecting up to 5-10% of men. The presence and extent of penile calcifications is an important determinant in disease management. Calcifications have a variety of clinical presentations ranging from microcalcifications to calcified plaques. Calcified plaques were excluded from past Xiaflex clinical trials. Calcified plaques may necessitate plaque excision and grafting (E&G) sometimes combined with inflatable penile prosthesis (IPP) placement, which is more complex than plaque incision and grafting. Peyronie's Disease guidelines recommend color duplex Doppler ultrasound (CDDU) primarily to rule out Erectile Dysfunction. PD pathology such as corporal septal involvement, multifocal calcifications, and circumferential corporal calcification can be difficult to assess on penile ultrasound (PUS) due to acoustic shadowing and device limitations. We describe a series of patients in whom non-contrast CT scan was used to further define calcified or complicated pathology. Objective To describe the role of non-contrast CT scan of the penis for anatomic evaluation and surgical planning in patients with complicated calcified Peyronie's disease. Methods 23 male patients with a diagnosis of PD were evaluated by a single surgeon at a single academic institution between 2017 and 2021. All patients underwent color doppler ultrasound (CDDU) examination with artificial erection via intracavernosal alprostadil injection and were evaluated based on erectile function, plaque dimension, hourglass deformity, plaque septal involvement, and suspected calcification status. Patients with CDDU examination concerning for significant calcification or complexity proceeded to non-contrast CT scan for calcific confirmation and for 3-dimensional evaluation of their PD plaque prior to surgical discussion. Complexity was defined as concern for multifocal calcified plaques (&gt;2), partial/complete circumferential corpus cavernosum involvement, or septal involvement. Results All 23 patients had concerning findings on initial examination for calcified plaque. 9 of 23 (39.1%) patients had exam findings of an hourglass deformity. On CT evaluation, calcification was confirmed in 22 of 23 patients (95.7%). Plaque dimensions on CT scan ranged from 0.4 × 0.2 × 0.5 cm to 4.0 × 2.0 × 1.7 cm. Many of these measurements were approximations due to circumferential calcified plaque. This classic “gull-wing” appearance (Figure 1) was noted in 6 of 23 (26%) patients. 12 of 23 (52.2%) of patients had septal involvement on CT (Figure 2). 8 of 23 patients (34.8%) had significant multifocal disease (Figure 3). 8 of 23 patients (34.8%) decided to proceed with surgical correction via E&G (n = 3), IPP with E&G (n =1), or via IPP with manual remodeling via the Wilson technique (n = 4). Conclusions Non-contrast penile CT scan for evaluation of calcified Peyronie's disease allows for increased accuracy of surgical planning especially when evaluating for multifocal disease, circumferential plaque and/or septal involvement. These elements are critical in being able to provide accurate surgical recommendations and post operative discussions. Disclosure No

ABSTRACT Introduction Peyronie's Disease (PD) is characterized by a fibrous scar of the tunica albuginea. PD is typically imaged with 2D ultrasound. We propose a classification system of these ultrasound findings in the evaluation of PD. Objective The purpose of this study is to establish a functional, reproducible sonographic classification system for evaluating PD and to examine the relationship between PD grading and curvature, duration of PD, and vascular erectile status. Methods In our study, 395 patients with PD underwent intracavernous injection with an erectile agent (ICI) followed by Color Doppler Duplex Ultrasound (CDDU). All CDDU studies were performed by a single examiner and all PD grading was done by two independent reviewers using saved images. CCDU findings including peak systolic velocities (PSV) and resistive indices (RIs) were recorded. PD grades of 2D images were classified into three grades: Grade 1 acoustic shadowing without calcification; Grade 2 focal microcalcifications of the tunica, pillars, or septal fibers; Grade 3 confluent calcification of the dorsal, septal, ventral tunica albuginea. Results There were 250 patients classified with Grade 1 (63%) sonographic changes, 75 with Grade 2 (19%), and 70 with Grade 3 (18%). Neither median age nor body mass index (BMI) of the cohorts were significantly different: Grade 1 (59.3 yr), Grade 2 (59 yr) and Grade 3 (60.3 yr), p = 0.711; BMI 27.6, 28.2, 27.7, p = 0.813. Medical risk factors for erectile dysfunction, including hypertension, heart disease, diabetes mellitus, hyperlipidemia, smoking history, and history of prostate surgery were not statistically different for the three cohorts. Most patients had previously used PDE5-Inhibitors (293/395). History and or physical findings of Dupuytren's palmar contracture was noted in 30/395 (7.6%) of men. The median duration of PD was not significantly different in the three cohorts (12, 12, 14 months p = 0.639). Neither CDDU diagnoses (Table 1) nor curvature varied by sonographic grades (Table 2). Conclusions The scar resulting from PD seals together the outer longitudinal and inner circular layers of the tunica albuginea causing deformity of the erect shaft. PD plaques are usually palpable and associated with focal thickening of the tunica. On 2D ultrasound, the typical appearance is an acoustic shadow. Most of our patients presented with Grade I acoustic shadowing and no calcifications 250/395 (63%); on the other hand, 19% had acoustic plaque shadowing and additional findings of focal tunica or deep microcalcifications and 18% had confluent calcification of the dorsal, septal or ventral tunica. We propose a unique and reproducible classification system. This grading system based on grayscale ultrasound of Peyronie's plaques may serve as a paradigm for diagnosis, didactics and integrated research. Disclosure No