Early Clinical Benefit Research Articles

Favorable Early Outcomes and High Clinical Benefit Achievement Rate with Concomitant Hip Arthroscopy and Periacetabular Osteotomy for the Treatment of Developmental Dysplasia of the Hip

PurposeTo report minimum two-year follow-up patient-reported outcomes (PROs), clinical benefit, and survivorship in patients who underwent concomitant hip arthroscopy and periacetabular osteotomy (PAO) for the surgical treatment of the developmental dysplasia of the hip (DDH). MethodsProspectively collected data were retrospectively reviewed for patients who underwent hip arthroscopy with concomitant PAO between December 2015 and September 2022. Patients with baseline and minimum two-year PROs were included. Exclusion criteria included those who underwent an isolated PAO or had a history of ipsilateral prior surgery. The PROs collected were Hip Outcome Score-Activities of Daily Living (HOS-ADL) and Hip Outcome Score-Sport-Specific Subscale (HOS-SSS). The minimal clinically important difference (MCID) was reported. Survivorship was defined as non-conversion to total hip arthroplasty (THA). ResultsThirty patients were included (29 females and 1 male). The average age at time of surgery was 27.48 ± 8.57 years, and the average body mass index was 23.97 ± 4.05. Further, 86.67%, 73.33%, and 100% underwent labral treatment, femoroplasty, and capsular closure, respectively. The pre-operative lateral center-edge angle increased from 17.07° ± 4.40 to 33.24° ± 3.40 postoperatively (P < 0.001). At a minimum of two-years follow-up, all PROs significantly improved from baseline (P < 0.001): HOS-ADL improved from 62.68 ± 16.18 to 91.66 ± 15.13, HOS-SSS from 38.96 ± 21.39 to 86.82 ± 19.56. Moreover, 90% and 93.33% achieved MCID for the HOS-ADL and HOS-SSS, respectively. No conversions to THA were reported. ConclusionAt a minimum two-years follow-up, the surgical management of DDH with PAO and concomitant hip arthroscopy demonstrated significant improvement in all PROs collected, with a high achievement rate for the MCID, and survivorship of 100%. These results suggest that, at short-term follow-up, this surgical approach seems to be safe and effective. Level of EvidenceRetrospective case-series

Simultaneous bilateral open wedge high tibial osteotomy versus simultaneous bilateral unicompartmental knee arthroplasty in the treatment of bilateral medial knee osteoarthritis: a retrospective study of an average three-year follow-up

ObjectiveThere is growing evidence that simultaneous bilateral open wedge high tibial osteotomy(SBOWHTO) and simultaneous bilateral unicompartmental knee arthroplasty(SBUKA) is an effective surgical treatment for bilateral medial knee osteoarthritis (MKOA). However, which intervention is more beneficial for bilateral MKOA patients remains unknown. Therefore, the aim of this study was to compare the effectiveness of these two strategies through early clinical outcomes, complication rates, and prosthetic survival.MethodsThe clinical data of 60 patients with bilateral MKOA admitted to the Affiliated Hospital of Qingdao University from January 2018 to December 2022 were retrospectively analyzed, and they were divided into SBOWHTO group (n = 28) and SBUKA group (n = 32) according to different treatment methods. Clinical relevant indexes, Hospital for Special Surgery (HSS) score, Knee Society Knee (KSS) score, range of motion(ROM), postoperative complications and prosthetic survival rate were compared between the two groups.ResultsPatients in the SBOWHTO group were followed up for 27 to 50 months, with an average of (37.18 ± 6.84) months. Patients in the SBUKA group were followed up for 24 to 59 months, with an average of (39.38 ± 9.74) months. There were no significant differences in postoperative KSS, HSS and ROM between SBOWHTO group and SBUKA group (p > 0.05). There was no significant difference in complication rate between the two groups (p = 0.721). There was no significant difference in prosthetic survival rate (p = 0.622) and prosthetic survival curve (χ2 = 0.546, p = 0.46) between the two groups.ConclusionsThis study compared early clinical outcomes, complication rates, and prosthesis retention rates after SBOWHTO and SBUKA, and found that the early clinical benefits of SBOWHTO and SBUKA were comparable in patients with bilateral MKOA.

Lumen-apposing metal stents provide early and late clinical benefits for the management of benign gastrointestinal strictures: Is there a role for definitive therapy?

This study aimed to characterize the clinical outcomes, safety, and efficacy of lumen-apposing metal stents (LAMS) in treating benign gastrointestinal strictures. A single-center retrospective review of all patients who underwent LAMS placement for benign strictures from June 2017 to July 2023. Primary outcomes were technical success, early clinical success, late clinical success (LCS), and sustained post-LAMS clinical success (SPLCS). Secondary outcomes included stent dwell time, stenosis changes, adverse events, reintervention rates, and symptomatology evaluation. Thirty-five patients underwent placement of 42 LAMS (74% female, mean age: 54.2 ± 11.7 years). Anastomotic strictures accounted for 64% of cases (N=27, 45% at the gastrojejunal anastomosis). The median STD was 91.0 days (interquartile range [IQR]: 55.0-132.0). Technical success was obtained in all cases. Early clinical successand LCS were achieved in 80% of cases overall. SPLCS was achieved in 45% (n=15) of cases. The overall reintervention rate was 63%, with a median time to reintervention being 50.5 days (IQR: 24-105). adverse eventsoccurred in 28% (n=12) overall, with a 24% migration rate (n=10). Follow-up was completed in 83% of cases with a median duration of 629 days (range: 192.0-1297.0). Overall symptom improvement occurred in 79% (n=27) during indwelling LAMS versus 58% and 56% at 30- and 60-days post-removal, respectively. LAMS for benign gastrointestinal strictures are associated with high technical and early clinical success/LCS rates, positive quality-of-life metrics, and a tolerable adverse event rate. Overall, recurrence of symptoms and high reintervention rates post-LAMS removal reinforce the difficulty in managing benign gastrointestinal strictures but also argue for LAMS as a definitive therapy in select cases.

Effect of transcranial direct current stimulation in the initial weeks post-stroke: a pilot randomized study.

This study aimed at assessing the alterations in upper limb motor impairment and connectivity between motor areas following the post-stroke delivery of cathodal transcranial direct current stimulation sessions. Modifications in the Fugl-Meyer Assessment scores, connectivity between the primary motor cortex of the unaffected and affected hemispheres, and between the primary motor and premotor cortices of the unaffected hemisphere were compared prior to and following six sessions of cathodal transcranial direct current stimulation application in 13 patients (active = 6; sham = 7); this modality targets the primary motor cortex of the unaffected hemisphere early after a stroke. Clinically relevant distinctions in Fugl-Meyer Assessment scores (≥9 points) were observed more frequently in the Sham Group than in the Active Group. Between-group differences in the alterations in Fugl-Meyer Assessment scores were not statistically significant (Mann-Whitney test, p=0.133). ROI-to-ROI correlations between the primary motor cortices of the affected and unaffected hemispheres post-therapeutically increased in 5/6 and 2/7 participants in the Active and Sham Groups, respectively. Between-group differences in modifications in connectivity between the aforementioned areas were not statistically significant. Motor performance enhancements were more frequent in the Sham Group compared to the Active Group. The results of this hypothesis-generating investigation suggest that heightened connectivity may not translate into early clinical benefits following a stroke and will be crucial in designing larger cohort studies to explore mechanisms underlying the impacts of this intervention. ClinicalTrials.gov Identifier: NCT02455427.

Early clinical outcomes of bipolar hemiarthroplasty for femoral neck fractures in elderly patients using the OCM approach: a retrospective study.

This study aims to assess the early clinical outcomes of bipolar hemiarthroplasty for treating femoral neck fractures in elderly patients aged 75 and above using the Orthopädische Chirurgie München (OCM) approach. A retrospective analysis was conducted on a cohort of 95 elderly patients who underwent bipolar hemiarthroplasty for Garden Type III and IV femoral neck fractures between January 2020 and December 2022. The participants were categorized into two groups according to the surgical approach used: the OCM approach and the posterior-lateral approach (PLA). The average follow-up duration was 11.20 ± 2.80 months for the OCM group and 11.12 ± 2.95 months for the PLA group, with both groups ranging from 6 to 18 months. Clinical outcomes assessed included surgical duration, incision length, postoperative hospital stay, time to ambulation, hemoglobin levels, serum creatine kinase (CK) levels, C-reactive protein (CRP) levels, pain (assessed using the Visual Analogue Scale, VAS), and functional recovery (evaluated through Harris hip scores). Additionally, complications such as intraoperative and postoperative fractures, deep vein thrombosis, wound infection, nerve injury, postoperative dislocation, leg length discrepancy, and Trendelenburg gait were monitored. There was no significant difference in the surgical duration between the OCM and PLA groups. However, the OCM group exhibited shorter incision lengths, reduced postoperative hospital stays, and earlier ambulation times compared to the PLA group. Significantly lower intraoperative blood loss, smaller decreases in hemoglobin levels on postoperative days 1 and 3, lesser hidden blood loss, and decreased levels of CK and CRP were observed in the OCM group. Pain levels, measured by VAS scores, were lower, and Harris hip scores, indicating functional recovery, were higher at 2 and 6 weeks postoperatively in the OCM group than in the PLA group. The incidence of complications, such as periprosthetic fractures, intramuscular venous thrombosis, hip dislocations, Trendelenburg gait, and leg length discrepancies, showed no significant differences between the groups. The OCM approach for bipolar hemiarthroplasty in patients aged 75 and above with femoral neck fractures offers significant early clinical benefits over the traditional PLA, including faster recovery, reduced postoperative pain, and enhanced early functional recovery.

Impact of in-hospital initiation of sodium-glucose cotransporter-2 inhibitors in patients with heart failure and reduced ejection fraction

Abstract Introduction Safety and early clinical benefit make sodium-glucose cotransporter-2 inhibitor (SGLT-2i) therapy suitable for in-hospital initiation in patients with heart failure and reduced ejection fraction (HFrEF). Despite randomized controlled trials and guideline recommendations, they are underused and clinical inertia may play a role. Objectives Primary: To assess the impact of initiating SGLT-2i at discharge on 90-day prescription rates in patients with HFrEF during hospitalization for acute heart failure (AHF). Secondary: To evaluate the presence of contraindications at discharge and the independent factors associated with in-hospital prescription, and to assess clinical outcomes at 90 days. Methods Retrospective analysis of a consecutive prospective single-center cohort. Adult patients hospitalized between January 2021 and October 2022 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) &amp;lt;40% were included. Patients who underwent heart transplantation during hospitalization, used SGLT2i before admission, died or were referred during the index hospitalization were excluded. Those who started SGLT-2i before or at discharge were compared with those who did not. The primary outcome was SGLT-2i prescription rate at 90 days, and the exploratory secondary endpoints was the composite of hospitalization or urgent visit for AHF or all-cause mortality at 90 days. Independent factors associated with inpatient SGLT-2i prescription were analyzed using a logistic regression model. Results Among 378 patients with documented HFrEF, 240 (64%) met the inclusion criteria. Mean age was 76±11 years, 75.4% were male and the mean LVEF was 25±13%. SGLT-2i was indicated during hospitalization in 31.6% of patients. A total of 86% of the cohort had a 90-day follow-up, and the SGLT2i prescription rate was 94.2% in those with in-hospital initiation and 14.4% in those without (p&amp;lt;0.001). Among those without contraindications at discharge (n=141), the independent factor associated with inpatient prescription was lower age, OR 0.96 (0.93-0.99) for each year. There were no statistically significant differences between the two groups for the combined endpoint of all-cause death, HF rehospitalisation or unplanned HF visit at 90 days (p=0.3). Conclusions In-hospital initiation of SGLT-2-i was associated with significantly higher prescription rates 90 days after discharge, without differences in death from all causes and hospitalization or urgent visit for AHF at 90 days. This study reflects the presence of medical inertia, particularly in older patients. It also highlights the hospitalization period as an optimal time to start SGLT-2i and achieve the proven clinical benefits that accumulate rapidly over weeks, with solid safety and tolerability.

Abstract 13696: Sotagliflozin is Associated With Early Clinical Benefit for Heart Failure and Atherosclerotic Events

Background: SGLT inhibitors reduce cardiovascular (CV) death and heart failure (HF)-related outcomes in HF patients, with benefits observed within 1 month. Less data exist for the time to clinical benefit for reducing HF or major cardiovascular events (MACE; CV death, myocardial infarction, and stroke) with SGLT inhibitors in patients with chronic kidney disease at high CV risk. Objective: This analysis evaluates the time to clinical benefit for HF-related events and MACE with sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, in SCORED. Methods: SCORED was a randomized, double-blind study of 10,584 patients with type 2 diabetes, chronic kidney disease, and other CV risk factors, where patients were randomized 1:1 to sotagliflozin or placebo. The primary endpoint was total CV death, hospitalization for HF, or urgent visit for HF. A prespecified secondary endpoint was total MACE. The present post hoc analysis calculated the sotagliflozin:placebo hazard ratios (HR) and 95% confidence intervals (CI) for each of these outcomes and determined the day after randomization where the treatment effect reached statistical significance (p&lt;0.05) and remained statistically significant for the duration of follow-up. Results: The overall risk of the primary endpoint was reduced by 26% (HR (95% CI) = 0.74 (0.63, 0.88); p&lt;0.001) with sotagliflozin, with a sustained significant reduction 95 days after randomization (HR (95% CI) = 0.70 (0.50, 0.98) at 95 days; Figure A). For MACE, the overall risk reduction with sotagliflozin was 23% (HR (95% CI) = 0.77 (0.65, 0.91); p&lt;0.001), with a sustained significant reduction 94 days after randomization (HR (95% CI) = 0.69 (0.47, 0.99) at 94 days; Figure B). Conclusion: In this stable, outpatient population at high risk for CV events, the time to clinical benefit with sotagliflozin was very early at approximately three months for both HF- and MACE-related outcomes.

Extended treatment in cerebral ischemia score 2c or 3 as goal of successful endovascular treatment is associated with clinical benefit

Background and purposeSuccessful reperfusion, defined as a modified treatment in cerebral ischemia (mTICI) score 2b or 3, is an important goal for endovascular treatment (EVT) of stroke. Recently, an extension of the mTICI score with an additional grade 2c indicating near-complete reperfusion (expanded TICI, eTICI) and a revised definition of success as eTICI 2c or 3 were proposed. We evaluate whether eTICI 2c translates into improved clinical outcome compared to eTICI 2b. Material and methodsConsecutive patients with large vessel occlusion in the anterior circulation who underwent EVT between December 2013 and December 2020 were included. Clinical outcome measures were favorable functional outcome at 90 days (modified Rankin Scale [mRS] scores 0 to 2 or return to pre-stroke mRS) and early neurological improvement (National Institutes of Health Stroke Scale [NIHSS] improvement ≥4 points or a score of 0–1 at 24 h). ResultsOf 1282 included patients (median age 76, median NIHSS 16), reperfusion was classified as eTICI 2b in 410 (32%), eTICI 2c in 242 (19%) and eTICI 3 in 464 (36%). eTICI 2c differed significally from 2b with respect to early neurological improvement (aOR = 1.49, 95% CI = 1.01–2.19). No statistically significant difference in favorable functional outcome at 90 days was found (eTICI 2c vs 2b, aOR = 1.31, 95% CI = 0.88–2.00). ConclusionOur study indicates early clinical benefit at 24 h of achieving eTICI 2c compared to eTICI 2b, but no significant difference was seen in favorable functional outcome at 90 days. Our results support eTICI 2c and 3 as the goal of a successful thrombectomy but do not exclude eTICI 2b as an acceptable result.

The technical development of photon-counting detector CT.

Since 1971 and Hounsfield's first CT system, clinical CT systems have used scintillating energy-integrating detectors (EIDs) that use a two-step detection process. First, the X-ray energy is converted into visible light, and second, the visible light is converted to electronic signals. An alternative, one-step, direct X-ray conversion process using energy-resolving, photon-counting detectors (PCDs) has been studied in detail and early clinical benefits reported using investigational PCD-CT systems. Subsequently, the first clinical PCD-CT system was commercially introduced in 2021. Relative to EIDs, PCDs offer better spatial resolution, higher contrast-to-noise ratio, elimination of electronic noise, improved dose efficiency, and routine multi-energy imaging. In this review article, we provide a technical introduction to the use of PCDs for CT imaging and describe their benefits, limitations, and potential technical improvements. We discuss different implementations of PCD-CT ranging from small-animal systems to whole-body clinical scanners and summarize the imaging benefits of PCDs reported using preclinical and clinical systems. KEY POINTS: • Energy-resolving, photon-counting-detector CT is an important advance in CT technology. • Relative to current energy-integrating scintillating detectors, energy-resolving, photon-counting-detector CT offers improved spatial resolution, improved contrast-to-noise ratio, elimination of electronic noise, increased radiation and iodine dose efficiency, and simultaneous multi-energy imaging. • High-spatial-resolution, multi-energy imaging using energy-resolving, photon-counting-detector CT has been used in investigations into new imaging approaches, including multi-contrast imaging.

Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group

Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis. Ruxolitinib (RUX) is approved for second-line therapy in high-risk PV pts with hydroxyurea intolerance or resistance. The RuxoBEAT trial (NCT02577926, registered on October 1, 2015, at clinicaltrials.gov) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 380 pts with PV or ET, randomized to receive RUX or best available therapy. This pre-specified futility analysis assesses the early clinical benefit and tolerability of RUX in previously untreated PV pts (6-week cytoreduction was allowed). Twenty-eight patients were randomly assigned to receive RUX. Compared to baseline, after 6 months of treatment, there was a significant reduction of median hematocrit (46 to 41%), the median number of phlebotomies per year (4.0 to 0), and median patient-reported pruritus scores (2 to 1), and a trend for reduced night sweat scores (1.5 to 0). JAK2V617F allele burden, as part of the scientific research program, also significantly decreased. One hundred nine adverse events (AEs) occurred in 24/28 patients (all grade 1 to 3), and no pt permanently discontinued treatment because of AEs. Thus, treatment with ruxolitinib in untreated PV pts is feasible, well-tolerated, and efficient regarding the above-mentioned endpoints.

Post-operative outcomes, including opioid utilization and length of stay, following total knee arthroplasty: A retrospective case matched series comparing conventional and robotic-assisted total knee arthroplasty

Keywords Total Knee Arthroplasty, robotic-assisted, opioid use&#x0D; Background With the rise of robotic arm-assisted total knee arthroplasty (TKA) cases, there is a need to determine if there are clinical benefits associated with this technology. The purpose of this study was to further evaluate if robotic-assisted TKAs result in improved inpatient post-operative outcomes compared to conventional TKAs.&#x0D; Materials and Methods After IRB approval, a retrospective chart review of 100 robotic-assisted primary TKAs and 100 matched controls undergoing conventional TKA was performed. Patients underwent primary TKA from 2016 to 2018 with minimum 6-month postoperative follow-up by a single fellowship-trained arthroplasty surgeon at a high-volume joint center. Exclusion criteria included &lt;6 month postoperative follow-up, incomplete chart information, inflammatory arthritis, and BMI &gt;40. Demographics and post-operative outcomes, including length of stay (LOS), opioid consumption, duration of opioid use, and discharge status, were recorded.&#x0D; Results There were no significant differences in pre-operative demographics between the two groups. A decrease in LOS (1.58 vs. 2.18 days, p &lt; 0.001) and morphine equivalents (73.52 vs. 102.50, p = 0.017) was reported for the robotic TKA group compared to the control group. The robotic group also reported fewer patients at six weeks postoperatively requiring opioids compared to the control group (37 vs. 61, p = 0.001). Average KOOS Jr at 6-months postoperatively was 81.73 for the control group and 78.22 in the robotic group (p = 0.039).&#x0D; Conclusion Robotic-assisted TKA patients experienced significantly decreased LOS, morphine equivalents, and opioid usage at 6-week postoperatively, indicating that there are early clinical benefits of robotic-assisted TKA. No significant differences between the robotic and control groups were reported in pre-operative KOOS Jr. Although average 6-month postoperative KOOS Jr was slightly higher for the control group, the difference was clinically insignificant. Our average KOOS Jr for both cohorts was higher than the national 1-year postoperative average, 76.8.

The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints.

Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt proper clinical endpoints to assess the extent of treatment benefit. While overall survival (OS) is the most accepted endpoint for phase III randomised controlled trials (RCTs) and drug approval, it is affected by many limitations. To overcome these limits, several clinical and radiological outcomes have been used. For instance, progression-free survival (PFS) is a useful endpoint to evaluate the benefit of sequential treatments, since it is not influenced by post-progression treatments, unlike OS. Moreover, radiological endpoints such as time to progression (TTP) and objective response rate (ORR) are frequently adopted. Nevertheless, the surrogacy between these endpoints and OS in the setting of unresectable HCC (uHCC) remains uncertain. Since most of the surrogate endpoints are radiology-based (e.g., PFS, TTP, ORR), the use of standardised tools is crucial for the evaluation of radiological response. The optimal way to assess the radiological response has been widely debated, and many criteria have been proposed over the years. Furthermore, none of the criteria have been validated for immunotherapy in advanced HCC. The coexistence of the underlying chronic liver disease and the access to several lines of treatments highlight the urgent need to capture early clinical benefit and the need for standardised radiological criteria to assess cancer response when using ICIs in mono- or combination therapies. Here, we review the most commonly used clinical and radiological endpoints for trial design, as well as their surrogacy with OS. We also review the criteria for radiological response to treatments for HCC, analysing the major issues and the potential future perspectives.

Abstract 1370: Targeting LSD1 rescues MHC-I antigen presentation in small cell lung cancer

Abstract Purpose: Small cell lung cancer (SCLC) is a highly aggressive cancer with early primary resistance and modest clinical benefit to immune checkpoint blockade (ICB). Mutation or transcriptional repression of the major histocompatibility complex class I (MHC-I) is a key mechanism driving resistance to T cell-based therapies. Lysine Demethylase 1 (LSD1) regulates gene expression through modulating mono- and di- methylated lysine 4 and 9 of histone H3. LSD1 is a therapeutic target of interests in SCLC due to its oncogenic requirement for tumor growth, and there has been growing evidence pointing to LSD1 as a repressor of tumor-intrinsic immunogenicity. Here investigated the role of LSD1 as a transcriptional regulator of antigen presentation in SCLC. Method: To perturb LSD1 function, we employed the pharmacological inhibitor ORY-1001 and shRNA-mediated knockdown. We then assessed changes in MHC-I expression on SCLC cell lines by flow cytometry and western blot. To analyze transcriptional changes following LSD1 inhibition, we performed RNA-seq on SCLC cells pre- and post-treatment with ORY-1001. To observe for antigen-specific T cell killing, we engineered SCLC cells to express endogenous antigens and co-cultured these cells with primary cognate CD8+ T cells. Finally, we treated genetically engineered mouse model (GEMM)-derived tumors on immunocompetent syngeneic mice with ORY-1001 with or without anti-PD-L1 blockade to assess for anti-tumor effects. Results: We discovered a significant and strong negative correlation between expression of LSD1 and genes encoding the MHC-I antigen presentation pathway. Inhibition of LSD1 induces expression of MHC-I genes and restores expression of genes encoding the antigen presentation machinery. Perturbation of LSD1 further activates interferon signaling and interferon-inducible expression of NLRC5, a well-characterized transcriptional activator of MHC-I genes. We further showed that targeting LSD1 sensitizes SCLC cells to MHC-I-restricted T cell-dependent cytolysis and enhances ICB efficacy in refractory SCLC tumors. Conclusion: Our data define a role for LSD1 as a potent negative regulator of MHC-I-mediated antigen presentation and provide rationale for the use of LSD1 inhibitors to augment response to immunotherapy in SCLC. Citation Format: Minh N. Nguyen, Hirokazu Taniguchi, Andrew Chow, Yingqian A. Zhan, Triparna Sen, Charles M. Rudin. Targeting LSD1 rescues MHC-I antigen presentation in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1370.

The impact of neoadjuvant treatment (NAT) on surgery in early breast cancer (EBC): A real-world data study.

e12609 Background: NAT is being used with increasing frequency in the multimodal treatment of EBC. Oncologically, NAT provides an opportunity to assess response to early systemic therapy and tailor adjuvant treatment. The surgical objective of NAT is down staging the tumor, which may lead to improved chances of breast conservation surgery; potentially decreasing surgical morbidity. Down staging of axillary disease may also lead to minimizing the need for complete axillary lymph node dissection (ALND) and its associated surgical morbidity. We aimed to describe the potential impact of NAT on surgical de-escalation in the primary breast tumor and axilla in patients (pts) with HER2-positive, node-positive EBC treated in the community setting. Methods: We conducted a retrospective cohort study using a nationwide US electronic health record-derived de-identified database (Flatiron Health). Pts were diagnosed from Jan 1, 2011 to Sep 30, 2021, had reported clinical staging cN≥1, underwent primary breast surgery (index date), and had records indicating initiation of systemic treatment before surgery. Early clinical benefit includes, post-NAT: a) nodal pathologic complete response (pCR; pN=0); b) pCR (absence of residual invasive disease in the breast and axillary lymph nodes at NAT completion, subsequently confirmed at primary surgery); c) down staging (lowered T or N stage). Surgical operations recorded at index date were ALND and sentinel node excision (SNE), mastectomy (MT), and lumpectomy (LT). Results: 174 pts were included. At diagnosis, median age was 55 years, 162 pts (93%) presented with invasive ductal carcinoma, and &lt;5 had bilateral BC. 124 pts (71%) were treated with dual HER2 blockade. As for early clinical benefit, nodal pCR was achieved in 106 pts (61%), pCR in 90 (52%), and down staging in 137 (79%). Types of surgical procedure for the axilla were SNE only for 62 pts (36%), ALND only for 84 (48%), and SNE and ALND for 26 (15%). Surgical procedures for the breast were MT for 118 pts (68%), of which 59 were bilateral, and LT for 55 (32%). Compared with not achieving nodal pCR, achieving nodal pCR was associated with increased odds of SNE only (odds ratio [OR] 2.59 [95% confidence interval (CI) 1.28, 5.53]), decreased odds of ALND (OR 0.47 [95% CI 0.23, 0.93]), increased odds of LT (OR 2.05 [95% CI 1.00, 4.39]), and decreased odds of MT (OR 0.47 [95% CI 0.22, 0.96]). Conclusions: In a real-world population of pts with HER2-positive EBC, NAT use was associated with early clinical benefit, potentially leading to less invasive primary surgery of the breast and axilla. The high use of MT and bilateral MT despite a high pCR rate demonstrates the multiple factors at play behind surgical and pt decision making. These data illustrate how NAT use can benefit pts by de-escalating surgical treatment options. Limitations include the modest sample size and lack of association between early and long-term clinical benefit.

New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease.

The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach the recommended treatment goal of <55 mg/dL (<1.4 mmol/L). Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of “the lower, the better”, we also discuss the concept of “the earlier, the better”, which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event.

Subacromial Balloon Spacer: Indications, Rationale, and Technique.

First, a diagnostic arthroscopy is performed. In addition to evaluating the rotator cuff, care is taken to evaluate the tendinous insertion of the subscapularis as well as the long head of the biceps tendon, the labrum, and the articular cartilage of the joint. Synovectomy, bursectomy, and biceps tenodesis or tenotomy are performed as appropriate. For cases with an intact or repairable subscapularis, an acromioplasty is performed. The balloon size is determined with use of a probe through the lateral portal, measured from 1 cm medial to the superior glenoid rim to the lateral border of the acromion. The balloon-insertion device is advanced through the lateral portal, and the balloon is inflated with sterile saline solution after appropriate subacromial positioning. The balloon is then sealed and detached from the insertional device. Most treatment algorithms attempt to reduce pain and dysfunction with initial nonoperative treatment options4. For cases in which nonoperative treatment has failed, several surgical techniques have been described. These include partial rotator cuff repair, graft interposition, graft augmentation, superior capsular reconstruction, tendon transfers, and reverse total shoulder arthroplasty5. Ideal candidates for this procedure are patients with irreparable symptomatic rotator cuff tears. These patients should primarily complain of pain and have a preserved range of motion. Alternatively, if they have reduced range of motion because of pain, then their range of motion should improve after a corticosteroid injection. It is also important that the patient has an intact or repairable subscapularis. The balloon is beneficial in patients with medical comorbidities that would limit the use of other techniques dependent on biologic tissue healing or that would limit the use of arthroplasty. Poor candidates would be patients with pseudoparalysis, axillary nerve palsy, irreparable subscapularis tears, or severe glenohumeral arthritis (Hamada grade ≥3). A recent randomized clinical trial demonstrated the 2-year efficacy, safety, and benefits of the InSpace subacromial balloon spacer6. The authors reported significant early clinical benefit that was maintained over 2 years. Additionally, this benefit was equivalent or superior to the partial-repair control group at all included time points. The multiyear clinical efficacy of the subacromial balloon spacer in that study was similar to that reported by Familiari et al. and Senekovic et al. at 3 and 5 years postoperative, respectively1,7. Together, these studies would suggest that the initial benefit of the subacromial balloon spacer lasts beyond its biodegradation at 12 months postoperatively. Proper placement of the lateral portal should be made parallel to the supraglenoid tubercle. Such placement allows easy insertion and orientation of the balloon at the midpoint of the supraglenoid tubercle.Arthroscopic evaluation of the subscapularis must be performed. For cases with a torn subscapularis, partial or complete repair is recommended to maximize anteroposterior coupling forces that are critical to the function of the balloon.Preservation of the medial bursa and coracoacromial ligament will provide structural constraints against medial migration of the balloon into the supraspinatus fossa.Acromioplasty can be performed to create a smooth articulating surface and minimize friction on the implant, but should only be done in cases in which there is an intact or repairable subscapularis to minimize the risk of anterior escape.Adequate debridement, with acromioplasty as needed, will provide full visualization of the subacromial space to allow proper sizing of the spacer. Proper implant sizing will reduce the risk of subsequent balloon displacement postoperatively.If the measurement of the balloon is between 2 sizes, the larger spacer can be selected to limit displacement.Overinflation of the balloon can cause excessive tension on the deltoid. Underinflation increases the risk of escape. To optimize inflation of the balloon, the senior author prefers to fill the balloon to the recommended maximum volume and then remove saline solution until the balloon reaches the recommended final volume.If there is partial tearing of the long head of the biceps, a tenotomy or tenodesis is recommended. ROM = range of motionRCT = randomized clinical trialTSA = total shoulder arthroplastySCR = superior capsular reconstructionRC = rotator cuffISP = infraspinatusSSP = supraspinatusSSC = subscapularisRI = rotator intervalCAL = coracoacromial ligamentCA = coracoacromialC = coracoidMRI = magnetic resonance imagingSAD = subacromial decompressionPRO = patient-reported outcomeFDA = U.S. Food and Drug Administration.

Abstract P3-02-03: Quantitative molecular breast imaging for early prediction of neoadjuvant systemic therapy response in locally advanced breast cancer patients

Abstract BACKGROUND: Increasing use of neoadjuvant systemic therapy (NAT) for early and locally advanced breast cancer led to critical need for development of tools capable of early treatment response assessment after NAT. Tc-99m sestamibi Molecular breast Imaging (MBI) as a functional imaging modality has a promise to detect changes in the tumor prior to anatomical changes detected by mammogram or ultrasound. PURPOSE: To evaluate the ability of quantitative MBI parameters to predict pathologic complete response (pCR) after completion of NAT in breast cancer patients. MATERIALS AND METHODS: Patients with invasive breast cancer (T1-T4, N0-N3, M0) planned for NAT followed by surgery were enrolled in a prospective IRB approved trial. MBI was performed at baseline and after two cycles of NAT. Patient demographic and tumor biology information (Ki-67, HER2, ER/PR) was collected. MBI images were quantified using a novel approach with corrections for scatter and attenuation and regions of interest (ROI) were drawn over tumors to compute three quantitative MBI uptake metrics for correlation with pathologic response: MBI-specific standardized uptake value (SUV), tumor to background ratio (TBR), and tumor volume. Pathologic complete response was determined based on final histopathology report at the time of surgery as absence of the invasive disease in the breast and axillary lymph nodes. MBI metrics at baseline, after 2 cycles of NAT and interval change were correlated with pCR and tumor biology using the Wilcoxon Rank Sum test, Kruskal-Wallis test or Fisher’s exact test. Statistical analysis was carried out using R (version 3.6.3, R Development Core Team). RESULTS: A total of 70 patients with median age 47.5 years (range 30-77) were included in the analysis. Breast cancer subtypes were: HER2 negative (ER/PR+) 35.7% (25/70), HER2 positive (ER/PR +/-) 35.7% (25/70), and triple negative (HER2-, ER/PR-) 28.6% (20/70). Change in SUV after 2 cycles of NAT was higher in patients with pCR compared to those who did not achieve pCR (mean decrease in SUV of 15.57 and 4.83 respectively, p&amp;lt;0.001). Additionally, change in TBR in patients with pCR was also higher compared to patients who did not achieve pCR (mean decreases of 1.14 and 0.56, respectively, p&amp;lt;0.001). No correlation was found between baseline SUV, baseline TBR, change in volume, and pCR. CONCLUSION: MBI-specific SUV and TBR changes after two cycles of NAT correlate and may predict pCR in patients with locally advanced breast cancer. Quantitative MBI parameters are novel promising imaging tools that may help to detect early clinical benefit and optimize management in patients receiving NAT. Citation Format: Miral M Patel, Beatriz E Adrada, Benjamin Lopez, Rosalind P Candelaria, Jia Sun, Medine Boge, Rania M Mohamed, Nabil Elshafeey, Gary Whitman, MD, Huong T Le-Petross, Lumarie Santiago, Marion E Scoggins, Deanna Lane, Tanya Moseley, Galit Zylberman, Jerica Saddler, Jessica WT Leung, Wei T Yang, Vincente Valero, S Cheenu Kappadath, Gaiane M Rauch. Quantitative molecular breast imaging for early prediction of neoadjuvant systemic therapy response in locally advanced breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-03.

PD22-07 INCIDENCE, RISK FACTORS, AND COMPLICATIONS OF TRAUMATIC URETHRAL CATHETERIZATION IN A SINGLE ACADEMIC CENTER: A PROSPECTIVE MULTIDISCIPLINARY QUALITY IMPROVEMENT PILOT STUDY

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) II (PD22)1 Sep 2021PD22-07 INCIDENCE, RISK FACTORS, AND COMPLICATIONS OF TRAUMATIC URETHRAL CATHETERIZATION IN A SINGLE ACADEMIC CENTER: A PROSPECTIVE MULTIDISCIPLINARY QUALITY IMPROVEMENT PILOT STUDY Andrew Chen, Hanson Zhao, Patricia Hain, Steven Simons, Jonathan Grein, and Maurice Garcia Andrew ChenAndrew Chen More articles by this author , Hanson ZhaoHanson Zhao More articles by this author , Patricia HainPatricia Hain More articles by this author , Steven SimonsSteven Simons More articles by this author , Jonathan GreinJonathan Grein More articles by this author , and Maurice GarciaMaurice Garcia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002011.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: An estimated 25% of inpatients require urethral catheterization during their hospital stay. Complications from iatrogenic traumatic urethral catheterization (TUC) are not uncommon and can result in significant morbidity. We aimed to identify the incidence and risk factors for TUC at our institution, describe short-term sequelae, and reduce incidence through a multi-disciplinary intervention. METHODS: Data on TUC was prospectively collected at our tertiary care institution from 9/2019 to 5/2020. TUC was defined as: request for urologic consult in patients with hematuria following catheterization, pain with a non-draining catheter, or cystoscopic findings of trauma. Cases of traumatic self-removal and pre-existing hematuria were excluded. A pilot intervention was performed by providing standardized in-service (use of Coudé catheters & insertion technique) to all nurses in cardiac surgery operating rooms. Anonymous pre- and post-didactic questionnaires were collected. All cardiac surgery patients were then standardized to routine Coudé placement. RESULTS: Over 9 months we recorded 79 cases of TUC. Incidence was 18.9 per 1,000 catheterizations in males. Management of cases is shown in Figure 1A. Two patients (6%) required complex operative interventions (1 required 3 operations and suffered a PE). Intubated patients were significantly more likely to require more invasive management, defined as any endoscopic or operative intervention (p=0.023).After teaching in-service, nurse comfort with Coudé insertion increased from 5.1 to 9.5/10. TUC decreased from 1.2% (5/430) to 0% (0/133) (p=0.24).Legal costs associated with TUC were estimated and found to be substantial (Figure 1B). CONCLUSIONS: TUC is not common- but is known to occur regularly. It can be associated with very significant morbidity and legal costs. While reduction in TUC was statistically insignificant in our early pilot data, clinical and financial benefits were recognized and supported hospital-wide use of Coudé catheters and regular teaching in-service by urology. The associated increased hospital cost is $34,500/year for our 900-bed hospital. Improvements to catheter design and teaching interventions to prevent such injuries is warranted. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e382-e382 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Chen More articles by this author Hanson Zhao More articles by this author Patricia Hain More articles by this author Steven Simons More articles by this author Jonathan Grein More articles by this author Maurice Garcia More articles by this author Expand All Advertisement Loading ...

Relative Clinical Outcomes Comparing Manual and Robotic-Assisted Total Knee Arthroplasty at Minimum 1-Year Follow-up.

Background: Total knee arthroplasty (TKA) demonstrates excellent durability using jig-based manual techniques (manual TKA [mTKA]), but significant rates of dissatisfaction remain. Modifications of mTKA techniques and TKA implant designs to improve outcomes have had minimal success. Studies comparing relative outcomes of mTKA and robotic-assisted TKA (raTKA) are limited. Purpose: This study sought to compare outcomes of mTKA and raTKA in patients at a single institution. Methods: We retrospectively reviewed all primary TKAs performed by 1 surgeon from 2015 to 2017. In all, 139 consecutive mTKAs (2015–2016) and 148 consecutive raTKAs (2016–2017) were included. No cases were excluded. Patient demographics, complications, readmission rates, and clinical and patient-reported outcomes were compared at a minimum of 1-year follow-up. A post hoc student t test and Pearson χ2 test were used for continuous and categorical data. Results: We found that mTKA patients compared with raTKA patients required significantly longer length of stay (LOS) (1.73 vs 1.18 days, respectively), greater morphine milligram equivalents consumption (89.6 vs 65.2, respectively), and increased physical therapy (PT) visits (13.0 vs 11.0, respectively) with increased 30-day readmission rates (4.3 vs 0.7%, respectively) that approached significance. Knee Injury and Osteoarthritis Outcome Score for Joint Replacement and the University of California at Los Angeles activity score did not differ significantly comparing raTKA with mTKA patients at 1 year. There were no differences in complication rates. Conclusion: Significant early clinical benefits were noted with raTKA, including lower opioid requirements, shorter LOS, and fewer PT visits when compared with mTKA. A reduction in 30-day readmission rates was noted with raTKA that was not significant. Excellent clinical results with similar patient-reported outcomes were noted in both groups at 1-year follow-up. Further prospective investigations at longer follow-up intervals comparing these techniques are warranted.

Evaluation of Dual Versus Triple Therapy by Landmark Analysis in the RE-DUAL PCITrial.

The aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial. Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events. A total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y12 inhibitor (and no aspirin), or warfarin plus a P2Y12 inhibitor plus aspirin. Landmark analysis was performed at 30 and 90days. There was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30days (110mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p<0.0001; 150mg: HR: 0.46; 95%CI: 0.30 to 0.72; p=0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110mg: HR: 0.65; 95%CI: 0.47 to 0.88; p=0.0062; 150mg: HR: 0.54; 95%CI: 0.37 to 0.79; p=0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110mg and bleeding reduction without increased thrombotic risk for dabigatran 150mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110mg and was similar with dabigatran 150mg versus warfarin. In RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an averageofonly 1.6days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase inthrombotic events with dabigatran 150mg. This could be helpful in the subset of patients with elevated riskforbothbleeding and thrombotic events.