Early Clinical Outcomes In Patients Research Articles

CTNI-66. IDH-MUTANT GLIOMA PATIENTS TREATED WITH VORASIDENIB: ONGOING DATA FROM THE VORASIDENIB EXPANDED ACCESS PROGRAM

Abstract BACKGROUND Vorasidenib (VOR) is an oral, brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1/2 (mIDH1/2) demonstrating clinical efficacy and safety in patients with mIDH1/2 glioma in the phase 3 INDIGO study (NCT04164901). Servier launched an expanded access program (EAP, NCT05592743) in November 2022 designed to provide access to VOR for patients with mIDH1/2 glioma. Early clinical outcomes of patients treated in this EAP are presented. METHODS Eligible participants were aged ≥12 years with mIDH1/2 glioma and, in the opinion of the treating oncologist, would potentially benefit from treatment with VOR. Safety assessments occur every two weeks for the first two 28-day cycles, then monthly for the duration of treatment. RESULTS As of the March 31, 2024 data cutoff, 71 participants have initiated treatment with VOR. Mean (SD) age was 42.7 (14.8) years; 39 (55%) were male; and 34 (48%) with astrocytoma. mIDH mutation status was 46 (65%) mIDH1. One participant had separate tumors with either mIDH1 or mIDH2 identified. The majority of participants had grade 2 gliomas (n=51 [72%]) and non-contrast–enhancing disease (n=49 [69%]). As of the data cutoff, 62 (87%) participants remain on treatment, with the majority initiating treatment within the past 6 months (n=49 [69%]). Nine (13%) participants have discontinued treatment due to: radiographic progressive disease (n=3); clinical progressive disease (n=4); adverse event (AE) unrelated to treatment (n=1); or other reason (n=1). Three participants have died (disease progression [n=2], unrelated infection [n=1]). At least one AE of any grade was seen in 35 (49%) participants, with 4 (6%) experiencing unrelated serious AEs. Eight (11%) patients had AEs of special interest (defined as grade 2 or higher ALT/AST elevations). Ten (14%) patients had AEs that led to dose interruption and one (1%) patient had dose reduction. Additional treatment duration and various subgroup analyses will be presented.

Rates of Early Recovery Following Thumb Carpometacarpal Arthroplasty: Comparing Ligament Reconstruction and Tendon Interposition, Abductor Pollicis Longus Suspensionplasty, and Suture Button Suspensionplasty

Abstract Background Several techniques have been previously described for the treatment of thumb carpometacarpal (CMC) arthritis, including trapeziectomy with ligament reconstruction and tendon interposition (LRTI), abductor pollicis longus suspensionplasty (APLS), or suture button suspensionplasty (SBS). It remains unclear whether a specific method produces faster recovery and more rapid return to function. The purpose of this study was to evaluate early clinical outcomes in patients undergoing thumb CMC arthroplasty stratified by method of treatment. Methods This study was conducted using a registry of patients undergoing thumb CMC arthroplasty using LRTI, APLS, or SBS. Patients were grouped by technique for comparison. Patient-reported outcomes were measured using Patient-Reported Outcome Measurement Information System (PROMIS) Upper Extremity, Pain Interference, and Pain Intensity scores and compared across cohorts using analysis of variance. Regression analysis was used to determine factors associated with early clinical outcomes. Results Note that 150 out of 201 patients met inclusion criteria for this study. Univariate regression demonstrated no difference between technique and achievement of minimal clinically important difference (MCID) by 1 year or ∆PROMIS scores at 1 and 3 months postoperatively. Stepwise multivariate regression analysis also found that technique did not contribute significantly to postoperative outcomes. Increased baseline PROMIS Upper Extremity scores were associated with lower odds of achieving MCID (odds ratio 0.80, p < 0.001). Baseline PROMIS scores were also associated with ∆PROMIS scores at 1 and 3 months postoperatively. Conclusion Patients undergoing thumb CMC arthroplasty via LRTI, APLS, or SBS can expect to experience similar improvements from baseline in the early postoperative period regardless of technique choice.

First experiences with automated annular suturing device in totally endoscopic aortic and mitral valve replacement.

To overcome some of the challenges of endoscopic minimally invasive valve surgery, an automated annular suturing device has been used in aortic and mitral valve replacement surgeries. The current study investigates early clinical outcomes of patients who received aortic or mitral valve replacement with the help of the RAM® device as first experiences in minimally invasive valve surgery. Between September 2020 and June 2023, 66 consecutive patients (mean age 61.8 ± 11 years) underwent endoscopic minimally invasive aortic or mitral valve replacement through right anterior mini-thoracotomy at 2 cardiac surgery referral centres in Germany. The RAM® device was used in all Patients. 3.5 and 5.0 sizes were used in 16.7% and 83.3% of patients, respectively. Aortic, mitral and double valve surgery was performed in 81.8%, 15.2% and 1.5% of patients, respectively. Clinical data were prospectively entered into our institutional database. Cardiopulmonary bypass time and cross-clamping time were 97.9 ± 20.9 and 66 ± 15.7 min, respectively. Intensive care unit and hospital stays were 1 [1-2] and 9 [7-13] days, respectively. No paravalvular leak and no other intraoperative complications occurred. 30-day and in-hospital mortality were zero. Conversion to sternotomy occurred in 1 (1.5%) patient due to bleeding. The usage of the RAM® device is a safe, feasible and effective approach to the endoscopic implantation of aortic or mitral valves and yield excellent early outcomes. Larger size studies are needed to evaluate the efficacy and safety of RAM® device.

The Use of Plant-Based Polysaccharide (PSP) Agents May Improve Early Outcomes Following Total Knee Arthroplasty-A Proof-of-Concept Study.

Our study sought to investigate the effects of a topical plant-based polysaccharide (PSP) as an adjunctive hemostat to minimize blood loss and improve early clinical outcomes in patients undergoing primary TKA. In this multi-center and randomized proof-of-concept study, 61 patients undergoing TKA were randomly assigned to one of two groups: A) intraoperative utilization of PSP (n=31) or B) no intervention (n=30). The primary outcomes were blood loss and change in hemoglobin, measured preoperatively and 24 hours postoperatively. Other endpoints included postoperative complications, Knee Society Score (KSS), knee range of motion (ROM), and thigh circumference. There was no difference in postoperative change of hemoglobin or calculated blood loss between the PSP and control groups. The PSP group achieved elevated flexion at two weeks (100.1° vs. 86.6°, p<0.05) and better change in KSS from preop to 90 days (29.5 vs. 22.4, p<0.05) than the controls. Some early postoperative outcomes were improved, which suggests a potential benefit of using PSP in primary TKA. However, the clinical significance of these differences warrants further investigation in a larger randomized trial.

Early Clinical Outcomes in Patients of Carcinoma Cervix Treated With Volumetric Modulated Arc Therapy.

Objective Carcinoma cervix is one of the major cancers affecting Indian women. Concurrent chemo-radiotherapy is the standard of care in the treatment of carcinoma cervix. We aimed to study the outcomes and toxicity profile of volumetric modulated arc therapy (VMAT), an advanced modality of radiation delivery when used to treat patients with carcinoma cervix. Materials and methods Patients of carcinoma cervix belonging to FIGO (The International Federation of Gynecology and Obstetrics) stages IB2- IVA were recruited into the study. The patients were treated with VMAT to an EBRT (External Beam Radiation Therapy) dose of 50.4Gy in 28 fractions, which was followed by a brachytherapy schedule of 8Gy for each fraction to point A for three fractions. Toxicities were monitored weekly during the course of treatment and thereafter at every follow-up visit. A response assessment CECT (Contrast Enhanced Computed Tomography) scan was done three months after treatment and the response was recorded using RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Results Sixty-four patients were available for analysis and most of the patients belonged to stage IIB (50.3%) followed by stage IIIB (28.5%). The complete response rate was 90.6% at three months and at a median follow-up of 12 months, the overall survival was 100% and disease-free survival was 89.1%. An analysis of clinically significant toxicities (grade 2 or worse) showed that diarrhea was the most common (20.3%) followed by proctitis (14%) and anemia (9.3%). Conclusion The results of the study established that volumetric modulated arc therapy is an acceptable modality of treatment of carcinoma cervix with an attractive toxicity profile. However, longer follow-ups will provide valuable information regarding the long-term disease control and late toxicities of the treatment.

Early Clinical Outcomes of Patients With Stress-Induced Cardiomyopathy Receiving Acute Mechanical Support in the US

BackgroundThe role of acute mechanical circulatory support (aMCS) in patients with stress-induced cardiomyopathy (SIC) complicated by cardiogenic shock (CS) is not well studied. Here, we describe the incidence and outcomes of aMCS use in SIC-CS using a large national database. MethodsUsing the Nationwide Readmissions Database from January 2016 to November 2019, we identified patients hospitalized with SIC who received isolated intra-aortic balloon pump (IABP), microaxial flow pump (Impella, Abiomed), or extracorporeal membrane oxygenation (ECMO) during the index hospitalization. ResultsA total of 902 among 94,709 hospitalizations for SIC (1.0%) required aMCS during the index hospitalization: 611 had IABP (67.7%), 189 had Impella (21.0%) and 102 had ECMO (11.3%). Patients with ECMO or Impella had higher in-hospital mortality rates than those with IABP (37.3% vs 29.1% vs 18.5%, respectively). There was an increased adjusted risk of in-hospital death with Impella (adjusted odds ratio [aOR], 1.98; 95% CI, 1.12-3.49) and ECMO (aOR, 4.15; 95% CI, 1.85-9.32) vs IABP. Impella was associated with an increased adjusted risk of 30-day readmission compared to IABP (aOR, 2.53; 95% CI, 1.16-5.51). Patients with ECMO or Impella had a higher incidence of renal replacement therapy and vascular/bleeding complications compared to those who received IABP. ConclusionsIn this nationwide analysis using an administrative database, patients who received ECMO and Impella showed higher rates of in-hospital mortality, renal replacement therapy, and vascular/bleeding complications compared to those who received IABP. Patients with more comorbidities may receive more aggressive hemodynamic support which may account for observed mortality differences. Future prospective studies with objective and universal characterization of baseline clinical and hemodynamic characteristics of patients with CS secondary to SIC are needed.

Outcomes after arthroscopically assisted lower trapezius transfer with Achilles tendon allograft

Lower trapezius tendon transfer is 1 option to improve pain and function with massive irreparable rotator cuff tears. Magnetic resonance imaging (MRI) evaluation of tendon healing with the procedure has not yet been reported. The purpose of this study was to evaluate early tendon transfer healing using postoperative MRI scans and to assess early clinical outcomes in patients after arthroscopically assisted lower trapezius tendon transfer (AALTT) for massive irreparable rotator cuff tears. This was a single institution retrospective review of consecutive patients with massive irreparable rotator cuff tears who underwent AALTT with a single surgeon from January 2017 to July 2020 with a minimum 6-month follow-up. Patient information including age, sex, follow-up, prior surgical history, and type of work (sedentary or labor-intensive) was recorded. Preoperative and postoperative range of motion, external rotation strength, presence of a lag sign, and pain visual analog scale data were extracted from medical records. Patient-reported outcomes were extracted from patient charts. Six-month postoperative MRIs were reviewed for tendon transfer healing at both the greater tuberosity and the trapezius-allograft interface. A total of 19 patients met inclusion criteria with average age 56.7 (range, 29-72years). Of these patients, 17 (89.5%) were male. The average follow-up was 14.6 (range, 6-45) months. Fifteen (78.9%) patients had unsuccessful previous rotator cuff repair. Six-month MRI demonstrated complete healing of the transferred tendon in 17 of 19 patients (89.5%). There were significant improvements in postoperative pain visual analog scale (5.9±2 vs. 1.8±2), ASES score (44.6±18 vs. 71.2±24), and Patient Reported Outcomes Measurement Information System Physical (46.3±6 vs. 51.3±11) and in external rotation motion (10.5±17° vs. 40.5±13°) and strength (2.8/5±1 vs. 4.7/5±0.5) at final follow-up. All patients with a preoperative external rotation lag sign had reversal of their lag sign at final follow-up (15/15). Of 17 work-eligible patients, 13 (76.4%) were able to return to work. In this series, AALTT showed a high rate of healing of the transferred tendon on MRI by 6months postoperatively. The current findings of a high rate of early tendon transfer healing are consistent with the good early and mid-term outcomes that have been observed in AALTT and provide support for surgeon and patient expectations, postoperative rehabilitation, and return to work following AALTT for massive posterior superior rotator cuff tears.

Adductor Canal Blocks Are Not Associated With Improved Early Postoperative Outcomes in Patients Undergoing Total Knee Arthroplasty

Background: As length of stay after total knee arthroplasty (TKA) continues to shorten, interventions that may reduce early postoperative pain and complications must be studied. Peripheral nerve block is being explored as a potential means of improving pain management. The purpose of this study was to evaluate the impact of adductor canal block (ACB) on postoperative outcomes for patients undergoing TKA. Methods: We conducted a retrospective review of 565 patients who received unilateral TKA under spinal anesthesia with a periarticular anesthetic injection. Patients were divided by ACB status. Univariate comparisons and multivariate regression were used to compare outcomes for patients receiving ACBs vs those who did not. Results: Of the 565 patients, 167 received an ACB, and 398 did not. Patients who received an ACB were less likely to require nausea medication during the immediate postoperative period. Length of stay, narcotic consumption, rate of discharge to home, postanesthesia care unit recovery time, urinary retention, ability to complete physical therapy, and 30-day readmission rate did not differ significantly between groups. After risk adjustment, the only significant finding was decreased likelihood of nausea in patients receiving an ACB. Conclusion: ACBs appear to have little to no significant impact on early clinical outcomes in patients having TKA under spinal anesthesia with a periarticular anesthetic injection. Further study of larger patient cohorts is required to validate these findings.

Particle Therapy in Adult Patients with Pelvic Ewing Sarcoma-Tumor and Treatment Characteristics and Early Clinical Outcomes.

To report dosimetric characteristics and early clinical outcomes in patients with pelvic Ewing sarcoma undergoing particle therapy. Patients ≥ 18 years old with pelvic Ewing sarcoma treated in adjuvant or definitive settings were considered for this retrospective analysis. Proton therapy was carried out with 45-60 Gy (RBE) (1.5-2 Gy (RBE) per fraction) and carbon ion therapy for recurrent disease with 51 Gy (RBE) (3 Gy (RBE) per fraction). Local control (LC), disease control (DC) and overall survival (OS) were calculated using the Kaplan-Meier method. For our sample, 21 patients were available, 18 of whom were treated for primary, 3 for locally recurrent and 16 for inoperable disease. The median CTV and PTV were 1215 cm3 and 1630 cm3. Median Dmean values for the PTV, bladder and rectum and median V40 Gy for the bowel for patients undergoing proton therapy were 56 Gy (RBE), 0.6 Gy (RBE), 9 Gy (RBE) and 15 cm3, respectively. At the end of particle therapy, G 1-2 skin reactions (n = 16/21) and fatigue (n = 9/21) were the main reported symptoms. After a median follow-up of 21 months, the 2-year LC, DC and OS were 76%, 56% and 86%, respectively. Particle therapy in adult pelvic Ewing sarcoma is feasible and provides excellent dosimetric results. First clinical outcomes are promising; however, further long-term follow-up is needed.

Impact of Patency of the Carotid Terminus and Middle Cerebral Artery on Early Clinical Outcomes in Patients with Acute Internal Carotid Artery Occlusion and Mild Symptoms

Introduction: Both collateral flow via the internal carotid artery (ICA) terminus (ICT) and initial mild symptoms might be associated with favorable outcomes in patients with acute ICA occlusion (ICAO). This study aimed to address the association between early clinical outcomes and patency of the ICT and middle cerebral artery (MCA) in patients with acute ICAO with mild symptoms. Methods: Of 1,214 consecutive patients with acute ischemic stroke or transient ischemic attack due to large vessel occlusion, patients with ipsilateral ICAO and initial National Institutes of Health Stroke Scale (NIHSS) score ≤5 were retrospectively enrolled. We examined the associations between clinical factors including patency of the ICT and MCA and recurrence of stroke or early neurological deterioration (REND). Significant early neurological deterioration was defined as increment in NIHSS score ≥1 during hospital stay. Results: Thirteen of the 35 patients who were finally enrolled had REND (37%), and median modified Rankin scale (mRS) score at discharge was 1 (interquartile range, 0–4). Initial NIHSS score (4 vs. 1, p < 0.001) and rates of diabetes mellitus (61.5% vs. 13.6%, p = 0.007), intravenous thrombolysis (IVT) (30.9% vs. 0%, p = 0.014), and mechanical thrombectomy (MT) (23.1% vs. 0%, p = 0.044) were significantly higher in patients with REND rather than in those without. The rate of patent ICT and MCA was comparable between groups. Except for 1 patient who underwent MT promptly after IVT immediately after REND, 3 patients initially treated with IVT deteriorated after the procedure. One patient without patent ICT and MCA did not meet the indications for MT. In 2 other patients with patent ICT and MCA, MT was not initially performed, but was eventually performed because of REND due to thrombus migration, and both were discharged with an mRS score of 5. Conclusion: The overall clinical outcomes of patients with acute ICAO with mild symptoms were not depending on the patency of the ICT and MCA, but initial treatment with IVT alone might risk unfavorable outcomes due to thrombus migration in patients with patent ICT and MCA.

Early clinical outcomes following navigation-assisted baseplate fixation in reverse total shoulder arthroplasty: a matched cohort study

Accurate placement of the glenoid baseplate is an important technical goal of reverse total shoulder arthroplasty (RSA). The use of computer navigated instrumentation has been shown to improve the accuracy and precision of intraoperative execution of preoperative planning. The purpose of this study was to compare early clinical outcomes of patients undergoing navigated RSA vs. a non-navigated matched cohort. A retrospective review of a prospectively collected shoulder arthroplasty database was used to identify 113 patients from a single institution who underwent navigated primary RSA with a minimum 2-year follow-up. A matched cohort of 113 non-navigated RSAs was created based on sex, age, follow-up, and preoperative diagnosis. Preoperative and postoperative range of motion, functional outcome scores, and complications were reported. A total of 226 shoulders with a mean age of 71 years were evaluated after navigated (113) or non-navigated (113) RSAs. The mean follow-up was 32.8 months (range: 21-54 months). At the final postoperative follow-up, the navigated group had better active forward elevation (135° vs. 129°, P=.023), active external rotation (39° vs. 32°, P=.003), and Constant scores (71.1 vs. 65.5, P=.003). However, when comparing improvements from the preoperative state, there was no statistically significant difference in range of motion or functional outcome scores between the groups. Complications occurred in 1.8% (2) of patients undergoing navigated RSA compared with 5.3% (6) in the non-navigated group (P=.28). Scapular notching (3.1% vs. 8.0%, P=.21) and revision surgery (0.9% vs. 3.5%, P=.37) were more common in non-navigated shoulders. At early follow-up, navigated and non-navigated RSAs yielded similar rates of improvement in range of motion and functional outcome scores. Notching and reoperation was more common in non-navigated shoulders, but did not reach statistical significance. Longer follow-up and larger cohort size are needed to determine if intraoperative navigation lengthens the durability of RSA results and reduces the incidence of postoperative complications.

Hypersensitive C-reactive protein-albumin ratio is associated with stroke-associated pneumonia and early clinical outcomes in patients with acute ischemic stroke.

ObjectivesWe aimed to explore the association between the baseline hypersensitive C‐reactive protein‐albumin ratio (CAR) and stroke‐associated pneumonia (SAP) during hospitalization and the short‐term prognosis in patients with acute ischemic stroke (AIS).MethodsWe enrolled 766 patients with AIS and collected their admission baseline characteristics, including their National Institutes of Health Stroke Scale score, CAR, age, atrial fibrillation, dysphagia, sex, stroke severity (A2DS2) score, and other information. The occurrence of SAP within 7 days after stroke, length of hospital stay, and physical condition at discharge were also recorded. The patients’ Modified Rankin Scale (mRS) scores and mortality 3 months after AIS were further evaluated at follow‐up. All patients were divided into four groups based on the quartiles of the admission CAR (Q1 <1.3, Q2 1.3–3.7, Q3 3.7–9.3, Q4 ≥9.3).ResultsDuring hospitalization, 92 (11.9%) patients were diagnosed with SAP. The patients with SAP had a higher CAR than the non‐SAP patients (p < .001). In the multivariate‐adjusted model, the patients in the Q3 and Q4 groups had a higher SAP risk (aOR was 5.21 and 17.72, p‐trend < .001) than those in the lowest quartile. The area under the curve for the CAR's ability to predict SAP was 0.810 in the receiver operating characteristic curve analysis and had a similar predictive efficacy as the A2DS2 score (p <.05). The length of stay in the SAP group was almost the same as that in the non‐SAP group, but the clinical outcomes were worse at discharge and at the 3‐month follow‐up in the SAP group. In addition, the patients in the higher CAR quartiles at admission were more likely to have poorer clinical outcomes.ConclusionsPatients with AIS with a high CAR at admission are more likely to develop SAP during hospitalization and have poor short‐term clinical outcomes. These findings might help to timely identify patients at high risk of SAP and provide a basis for further research on prophylactic antibiotic therapy.

Reduction in hospital length of stay and increased utilization of telemedicine during the "return-to-normal" period of the COVID-19 pandemic does not adversely influence early clinical outcomes in patients undergoing total hip replacement: a case-control study.

Background and purposeElective total hip replacement (THR) was halted in our institution during the COVID-19 surge in March 2020. Afterwards, elective THR volume increased with emphasis on fast-track protocols, early discharge, and post-discharge virtual care. We compare early outcomes during this “return-to-normal period” with those of a matched pre-pandemic cohort.Patients and methodsWe identified 757 patients undergoing THR from June to August 2020, who were matched 1:1 with a control cohort from June to August 2019. Length of stay (LOS) for the study cohort was lower than the control cohort (31 vs. 45 hours; p < 0.001). The time to first postoperative physical therapy (PT) was shorter in the study cohort (370 vs. 425 minutes; p < 0.001). More patients were discharged home in the study cohort (99% vs. 94%; p < 0.001). Study patients utilized telehealth office and rehabilitation services 14 times more frequently (39% vs. 2.8%; p < 0.001). Outcomes included post-discharge 90-day unscheduled office visits, emergency room (ER) visits, complications, readmissions, and PROMs (HOOS JR, and VR-12 mental/physical). Mann–Whitney U and chi-square tests were used for group comparisons.ResultsRates of 90-day unscheduled outpatient visits (5.0% vs. 7.3%), ER visits (5.0% vs. 4.8%), hospital readmissions (4.0% vs. 2.8%), complications (0.04% vs. 0.03%), and 3-month PROMs were similar between cohorts. There was no 90-day mortality.InterpretationA reduction in LOS and increased telehealth use for office and rehabilitation visits did not adversely influence 90-day clinical outcomes and PROMs. Our findings lend further support for the utilization of fasttrack arthroplasty with augmentation of postoperative care delivery using telemedicine.

EPEN-22. Molecularly aggressive ependymomas treated with Image guided pencil beam proton therapy: consecutive patient Indian experience

AIM: To assess the toxicities and early clinical outcomes in patients of primary and recurrent ependymomas treated with image guided pencil beam scanning proton beam therapy (PBS-PBT). MATERIALS AND METHODS: Between January 2019- December 2021, we analyzed consecutive patients of ependymomas treated with image guided PBS-PBT. They were also analyzed molecularly, and all recurrent/re-irradiated patients were considered for craniospinal irradiation (CSI). Acute toxicities were assessed based on NCI CTC v5.0, local control and radiological response by 3-monthly MRI post therapy. RESULTS: Seventeen consecutive patients with ependymoma (13 Grade III and 4 Grade II) (median age-9 years) were analyzed. 9 patients were primary, 7 were treated at first recurrence and 1 at second recurrence. Majority had posterior fossa (PF) tumors (12) followed by supratentorial (ST) (3) and spine (2). Among PF ependymomas, 10 had global loss of H3K27me3, whereas amongst ST, 1 had YAP1 fusion, 1 had L1CAM positivity and other, negative L1CAM and p65/RELA on immunohistochemistry. Gross/near-total resection was achieved in 87% patients. Primary ependymomas were treated with focal radiotherapy; and among recurrent cases, 7 received CSI followed by primary site boost to a total median dose of 55CGE (50.2-55.8CGE). Grade 2 dermatitis, grade 2 and 3 hematological toxicities (CSI) were noted in 3,2 and 2 patients respectively. Grade 2 fatigue noted in 53% of all and 71% receiving CSI. With a median follow-up of 10 months (2-24 months), local control (LC) and disease-free survival (DFS) was 87.5% (primary-100%, recurrent-75%) and overall survival (OS) was 94% (primary-100%, recurrent-88%). CONCLUSION: Our experience of treating patients of ependymoma with complete resection followed by PBS-PBT including CSI is encouraging with low acute toxicities. Recurrent/molecularly aggressive cases may be considered for CSI. Keywords: PT, proton beam therapy, ependymomas, primary and recurrent

Prostate Cancer Treatment with Pencil Beam Proton Therapy Using Rectal Spacers sans Endorectal Balloons.

PurposeProton beam radiotherapy (PBT) has been used for the definitive treatment of localized prostate cancer with low rates of high-grade toxicity and excellent patient-reported quality-of-life metrics. Technological advances such as pencil beam scanning (PBS), Monte Carlo dose calculations, and polyethylene glycol gel rectal spacers have optimized prostate proton therapy. Here, we report the early clinical outcomes of patients treated for localized prostate cancer using modern PBS–PBT with hydrogel rectal spacing and fiducial tracking without the use of endorectal balloons.Materials and MethodsThis is a single institutional review of consecutive patients treated with histologically confirmed localized prostate cancer. Prior to treatment, all patients underwent placement of fiducials into the prostate and insertion of a hydrogel rectal spacer. Patients were typically given a prescription dose of 7920 cGy at 180 cGy per fraction using a Monte Carlo dose calculation algorithm. Acute and late toxicity were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 5. Biochemical failure was defined using the Phoenix definition.ResultsFrom July 2018 to April 2020, 33 patients were treated (median age, 75 years). No severe acute toxicities were observed. The most common acute toxicity was urinary frequency. With a median follow-up of 18 months, there were no high-grade genitourinary late toxicities; however, one grade 3 gastrointestinal toxicity was observed. Late erectile dysfunction was common. One treatment failure was observed at 21 months in a patient treated for high-risk prostate cancer.ConclusionEarly clinical outcomes of patients treated with PBS–PBT using Monte Carlo–based planning, fiducial placement, and rectal spacers sans endorectal balloons demonstrate minimal treatment-related toxicity with good oncologic outcomes. Rectal spacer stabilization without the use of endorectal balloons is feasible for the use of PBS–PBT.

Volume of contrast to creatinine clearance ratio predicts early mortality and AKI after TAVI.

The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. A large retrospective multicenter cohort of 1381 patients treated with TAVI was analyzed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and 1 year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl ≥ 2.2 was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.09–1.22, p < 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (odds ratio: 1.18, 95% CI: 1.08–1.28, p < 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01–3.60, p = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21–3.11, p = 0.006) but not CV/CrCl was associated with the risk of 1‐year mortality after TAVI. CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

374 Volume of contrast to creatinine clearance ratio predicts early mortality and AKI after TAVI

Abstract Aims The volume of contrast to creatinine clearance ratio (CV/CrCl) is a useful indicator of the risk of acute kidney injury (AKI) in patients undergoing percutaneous interventional procedures. Association between CV/CrCl and adverse outcome after transcatheter aortic valve implantation (TAVI) was suggested but it is not well established. Methods and results A large retrospective multicentre cohort of 1381 patients treated with TAVI was analysed to assess the association between CV/CrCl and the risk of AKI and mortality at 90 days and one year after TAVI. Patients receiving renal replacement therapy at the time of TAVI were excluded. CV/CrCl was associated with the risk of AKI and 90 days mortality after TAVI after adjustment for age, sex, diabetes, baseline left ventricular function, baseline chronic kidney disease (CKD), previous myocardial infarction and peripheral vascular disease (HR: 1.16, 95% CI: 1.09–1.22, P &amp;lt; 0.0001). Importantly, CV/CrCl was associated with the adverse outcome independently from the presence of baseline CKD (p for interaction = 0.22). CV/CrCl was independently associated with the individual components of the composite primary outcome including AKI (OR: 1.18, 95% CI: 1.08–1.28, P &amp;lt; 0.0001) and 90 days mortality (HR: 1.90, 95% CI: 1.01–3.60, P = 0.047) after TAVI. AKI (HR: 1.94, 95% CI: 1.21–3.11, P = 0.006) but not CV/CrCl was associated with the risk of 1-year mortality after TAVI. Conclusions CV/CrCl is associated with excess renal damage and early mortality after TAVI. Procedural strategies to minimize the CV/CrCl during TAVI may improve early clinical outcomes in patients undergoing TAVI.

Percutaneous Aspiration Thrombectomy for Arterial Thromboembolic Occlusion Following Percutaneous Transluminal Angioplasty: Technical Success Rates and Clinical Outcomes.

We aimed to analyze the technical success rate of manual percutaneous aspiration thrombectomy (PAT) in patients with peripheral arterial thromboembolism as a complication of infrainguinal percutaneous transluminal angioplasty (PTA) and we sought to evaluate the 30-day postintervention clinical outcome. We retrospectively identified 29patients (men/women, 18/11; mean age, 74 years) who underwent infrainguinal PAT to treat thromboembolic complications of infrainguinal PTA. Primary and secondary technical successes were defined as residual stenosis of < 50 % of the vessel diameter after PAT alone and PAT with additional PTA, respectively. Clinical outcome parameters (e. g., amputation, need for further intervention) were evaluated during the first 30 days after intervention. The primary and secondary technical success rates were 58.6 % (17/29) and 79.3 % (23/29), respectively. Clinical outcome data were available for 93.1 % (27/29) of patients. No further intervention was required within 30 days in 81.5 % (22/27) of patients. Four patients underwent minor amputations owing to preexisting ulcerations (Rutherford Category 5), and no patients underwent major amputations (Rutherford Category 6). Revascularization of the previously treated vessel segment with PTA was necessary on the first postintervention day in one patient. Manual PAT, with PTA if needed, has a good technical success rate and satisfactory early clinical outcome in patients with iatrogenic thromboembolic complications after infrainguinal PTA. · Manual PAT is a possible first-choice treatment of infrainguinal PTA-induced acute thromboembolism.. · Performing additional PTA increases the success rate of manual PAT.. · Unlike catheter-directed intraarterial lysis, manual PAT carries no risk of bleeding.. · Schicho A, Bäumler W, Verloh N et al. Percutaneous Aspiration Thrombectomy for Arterial Thromboembolic Occlusion Following Percutaneous Transluminal Angioplasty: Technical Success Rates and Clinical Outcomes. Fortschr Röntgenstr 2022; 194: 291 - 295.

Dual antithrombotic therapy on early clinical outcomes in patients with atrial fibrillation after percutaneous coronary intervention: a nationwide study in the era of NOAC

Abstract Background/Introduction Recent evidence has confirmed low bleeding risk with double antithrombotic therapy, combining oral anticoagulant (OAC) and single platelet inhibitor, in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Among the Asian AF population, most of the patients received dual antiplatelet therapy (DAPT) without OACs, even after the introduction of non-vitamin K oral anticoagulants (NOACs). Purpose The current nationwide study assessed 3-month ischemic and bleeding risks of DAPT in comparison to triple antithrombotic therapy among the Korean AF population undergoing PCI. Methods We analyzed the claims records of 11,039 patients (mean age 70 years, 66.3% male, and mean CHA2DS2-VASc score 3.2) between 2013 to 2018. Patients were categorized into triple therapy group with vitamin K antagonists (VKAs-TT), or NOACs (NOACs-TT), and DAPT group according to the antithrombotic therapy after PCI. 3-month risks of ischemic stroke, non-fatal myocardial infarction, any in-hospital death, and major bleeding were compared between groups after baseline adjustment using inverse probability weighting. Results A total of 1,786, 1,997, and 7,256 patients were allocated to the VKAs-TT, NOACs-TT, and DAPT groups. The DAPT group had a higher prevalence of prior MI and coronary revascularization, but had lower thromboembolic and bleeding risks than the triple antithrombotic therapy groups (mean CHA2DS2-VASc score 3.8, 4.1, and 3.5; and mean HAS-BLED score 3.3, 3.4, and 3.1 for VKAs-TT, NOACs-TT, and DAPT groups, respectively). The NOACs-TT group was associated with a lower risk of ischemic stroke (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.20–0.70) and any in-hospital death (HR 0.70, 95% CI 0.49–0.98) compared with the VKAs-TT group. The DAPT group showed a lower risk of ischemic stroke (HR 0.41, 95% CI 0.27–0.63) and major bleeding (HR 0.55, 95% CI 0.37–0.84) than the VKAs-TT group, especially in patients without prior OAC treatment. The DAPT group showed a comparable ischemic risk against the NOACs-TT group, although the risk of major bleeding was lower in the DAPT group, especially among old age (HR 0.47, 95% CI 0.29–0.78) or OACs-naive patients (HR 0.50, 95% CI 0.29–0.86). Conclusion Among the Asian AF population, using short-term DAPT for 3-month after PCI was associated with a lower risk of bleeding without increasing ischemic risk compared to triple antithrombotic therapy with OAC. This may be a therapeutic option in very high bleeding risk patients who have had complex PCI necessitating focus on DAPT in the initial 3 month period. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was supported by grant no 3020200200 from the Seoul National University Hospital Research Fund, by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health &amp; Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202013B14), and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (grant 2020R1F1A106740). Figure 1Figure 2

Antitumor Activity of the Novel BTK Inhibitor TG-1701 Is Associated with Disruption of Ikaros Signaling in Patients with B-cell Non-Hodgkin Lymphoma.

Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non-Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance of phosphoproteomic profiling for the early identification of BTKi responders remains underexplored. A set of six clinical samples from an ongoing phase I trial dosing patients with chronic lymphocytic leukemia (CLL) with TG-1701, a novel irreversible and highly specific BTKi, were characterized by phosphoproteomic and RNA sequencing (RNA-seq) analysis. The activity of TG-1701 was evaluated in a panel of 11 B-NHL cell lines and mouse xenografts, including two NF-κB- and BTKC481S-driven BTKi-resistant models. Biomarker validation and signal transduction analysis were conducted through real-time PCR, Western blot analysis, immunostaining, and gene knockout (KO) experiments. A nonsupervised, phosphoproteomic-based clustering did match the early clinical outcomes of patients with CLL and separated a group of "early-responders" from a group of "late-responders." This clustering was based on a selected list of 96 phosphosites with Ikaros-pSer442/445 as a potential biomarker for TG-1701 efficacy. TG-1701 treatment was further shown to blunt Ikaros gene signature, including YES1 and MYC, in early-responder patients as well as in BTKi-sensitive B-NHL cell lines and xenografts. In contrast, Ikaros nuclear activity and signaling remained unaffected by the drug in vitro and in vivo in late-responder patients and in BTKC481S, BTKKO, and noncanonical NF-κB models. These data validate phosphoproteomic as a valuable tool for the early detection of response to BTK inhibition in the clinic, and for the determination of drug mechanism of action.