Cleveland Clinic Research Articles

Comparison of outcomes and required tools between transvenous extraction of pacemaker and implantable cardioverter defibrillator leads: Insight from single high-volume center experience.

Reports of comparison with procedural outcomes for implantable cardioverter defibrillator (ICD) and pacemaker (PM) transvenous lead extraction (TLE) are old and limited. We sought to compare the safety, efficacy, and procedural properties of ICD and PM TLE and assess the impact of lead age. The study cohort included all consecutive patients with ICD and PM TLE in the Cleveland Clinic Prospective TLE Registry between 2013 and 2022. Extraction success, complications, and failure employed the definitions described in the HRS 2017 TLE guidelines. A total of 885 ICD leads, a median implant duration of 8 (5-11) years in 810 patients, and 1352 PM leads of 7 (3-13) years in 807 patients were included. Procedural success rates in ICD patients were superior to those of PM in >20 years leads but similar in ≤20 years leads. In the PM group, the complete success rate of TLE decreased significantly according to the increase of lead age, but not in the ICD group. ICD TLE required more extraction tools compared with PM TLE but cases with older leads required non-laser sheath extraction tools in both groups. The most common injury site in major complication cases differed between ICD and PM TLE, although major complication rates showed no difference in both groups (2.7% vs. 1.6%, p = .12). The procedural success rate by TLE is greater for ICD patients than PM patients with leads >20 years old but requires more extraction tools. Common vascular complication sites and the impact of lead age on procedural outcomes and required tools differed between ICD and PM TLE.

Outcomes of posterior sheath supplementation with Vicryl mesh in TAR-a single-center study.

In the Transversus Abdominis Release (TAR) procedure, ideally, the posterior sheath is completely reapproximated to establish an interface isolating the polypropylene mesh from visceral contents. When primary closure of the posterior sheath is unachievable, Vicryl mesh is commonly used to supplement the posterior sheath closure and an uncoated polypropylene mesh is placed superficial to the Vicryl mesh. The long-term implications of utilizing Vicryl mesh as an antiadhesive barrier are poorly understood. In this study, we aimed to assess our outcomes when utilizing Vicryl mesh to supplement the posterior sheath defects when placed underneath polypropylene mesh in patients undergoing posterior component separation. Adult patients who underwent VHR with concurrent TAR procedure with a permanent synthetic mesh and posterior sheath supplementation with Vicryl mesh in the Cleveland Clinic Center for Abdominal Core Health between January 2014 and December 2022 were queried retrospectively from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term mesh-related complications, and pragmatic hernia recurrence. 53 patients who underwent TAR procedure with posterior sheath supplementation using Vicryl mesh and had a minimum 12-month follow-up were identified. Of the53 patients, 94.3% presented with recurrent hernias, 73.6% had a midline hernia, 7.5% had a flank hernia, and 18.9% had concurrent parastomal hernia. The mean hernia width was 24.9 cm (± 8.8 cm). No Vicryl mesh-related operative complications were identified in our study, with no instances of mesh erosion, fistulas, or interventions for small bowel obstruction. Skin necrosis requiring reoperations was observed in three patients (5.7%), leading to permanent mesh excision in two cases (3.8%) without intraabdominal visceral involvement. Throughout the 12-month follow-up, 23 incidences (43.4%) of surgical site occurrences (SSOs) and surgical site occurrences requiring procedural intervention (SSOPI) were documented. Our findings suggest that posterior sheath supplementation with Vicryl mesh is a feasible approach to achieve posterior sheath closure in challenging abdominal wall reconstruction cases. Given the absence of notable mesh-related complications and a similar hernia recurrence rate to cases without posterior sheath supplementation, Vicryl mesh can be used to safely achieve posterior sheath closure in complex reconstructions with insufficient native tissue.

Abstract PO3-11-03: A Randomized Controlled Trial to Assess the Benefit of Art & Music Therapy on Quality of Life in Patient with Breast Cancer

Abstract Introduction: Quality of life (QoL) in oncology captures the well-being of a patient and is considered a significant outcome criterion. Breast cancer (BC) is the most diagnosed cancer in women, however, standardizing integrative therapies to alleviate the burden of cancer and improve QoL is still an unmet need. Art and music therapy might mitigate psychological and emotional distress. We sought to evaluate their efficacy compared to control among patients with BC during or after active therapy. Methods: Seventy-six treated patients with Stages I-III BC were randomly assigned to art, music therapy, or routine oncology care standard of care arm (SOC) for 3 months and received two sessions per month by a licensed therapist (including in-person/virtual and group sessions). The primary outcome was an improvement in QoL measured by the Functional Assessment of Cancer Therapy–Breast (FACT-B) questionnaire and secondary outcomes included: cognitive function measured by Functional Assessment of Cancer Therapy–Cognition (FACT-Cog), response to a 4-component Cleveland Clinic Visual Analog Scale (CCVAS), indicators of anxiety and depression assessed by the Generalized Anxiety Disorder-7 item (GAD-7) and Patient Health Questionnaire-9 item (PHQ-9). All questionnaires were assessed at baseline, 30, 90, and 180 days. Statistical considerations included stratified randomization, and a mean difference in 15 points between either of the interventions. SOC arm was considered relevant at the 3-month mark. Mean improvement within groups was performed using paired t-tests whereas independent t-tests were used to evaluate mean improvement between interventions (1 or 2 vs. SOC arm). All analyses were performed using SPSS version 26 (IBM, Armonk, NY). Results: Forty-five participants completed the study to date and were included in the interim analysis. Median age was 58 (57-59), white race (51.1%), patients on active treatment (45%), art therapy group (n=16), music therapy (n=15) and standard of care (n=14). Significant improvement was noted in the art therapy arm at 3 months in FACT-B physical well-being (p=0.04), functional well-being (p=0.008) domains as well as GAD-7 (p=0.003), PHQ-9 (p=0.04) and FACT-Cog section “impact on quality of life” (p=0.03). At 6 months, the art therapy arm demonstrated lower scores in the CCVAS questionnaire total score, emotional distress (p=0.01) and anxiety (p=0.004) scales. Music therapy participants reported a significant improvement only in GAD-7 index(p=0.04) at 3 and 6 months compared to SOC. No significant difference was found between art and music therapy arms. Conclusion: Art therapy patients exhibited significant improvement in overall QoL (including anxiety, depression, improvement in cognitive function) and 4-scale CCVAS (emotional distress, anxiety, depression, and pain). Music therapy improved anxiety scores (GAD-7). Art and music therapy should be considered in the care of patients to manage cancer associated distress and improve their quality of life. Table 1. Comparison of test changes from 3 months to baseline within groups Table 2. Comparison of test changes from 6 months to baseline within groups Citation Format: Maria Herran, Mohamed Mohanna, Saad Sabbagh, Barbara Dominguez, Kaylee Sarna, Rachel Upton-Rice, Angie Burdine, Zeina Nahleh. A Randomized Controlled Trial to Assess the Benefit of Art & Music Therapy on Quality of Life in Patient with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-03.

Abstract PO2-16-11: Real-World Data of Neuroendocrine Neoplasms of Breast

Abstract Background: Primary neuroendocrine neoplasms (NEN) of breast are rare and heterogeneous. WHO has classified NENs of non-endocrine organs into three distinct categories in 2022, however real-world data on outcomes of patients with NENs of non-endocrine organs under this new classification system are still sparse. Real world experience regarding demography, clinical presentation, treatment response, and prognosis can help identify potential areas of improvement in the management of breast NEN. Methods: Here, we present our findings from patients with NEN of breast in the Cleveland Clinic Foundation between 2000 and 2023. Pathology reports were reviewed to confirm NEN of breast origin. Neuroendocrine differentiation was determined by tumor histology and immunohistochemistry (IHC). For metastatic tumors at presentation, primary organ was determined by IHC and clinical presentation. Overall survival (OS) was from date of diagnosis of NEN. Recurrence is redemonstration of tumor following curative intent therapy, and progression is increase in tumor burden. T-test and log-rank test were used in statistical analyses. Results: Total of 97 patients were identified. Of these, 79 presented with localized disease, 18 were metastatic at presentation. 88 (91%) were invasive ductal carcinoma (IDC), and 64 (81%) were local disease at presentation and rest were metastatic. Gender spread was 92:5 (F:M). Patients with ER + disease was 84/96, PR + disease was 71, and 4/93 patients had overexpression of HER2. Median age was 70 at diagnosis. 11 patients underwent neoadjuvant chemotherapy, 15 patients underwent adjuvant chemotherapy (AC), and 58/84 patients underwent hormonal adjuvant therapy. For localized disease, median recurrence free survival (RFS) was 165 months (144-NA), and recurrence rate was 8/79 (10%). Recurrence rate for local IDC was 10% (6/64). Patients with metastatic disease at presentation had a median progression free survival (PFS) of 30 months, and progression rate was 7/18 (39%). For patients with metastatic disease, median lines of palliative therapy used was 2, with median duration of first line treatment being 3.5 months, and 10 months for second line. Most common surgical procedure was mastectomy, with 37% of patients undergoing management. Median duration from diagnostic biopsy to definitive surgery was 1 month. Median follow up was 28 months. Most common hormonal adjuvant option was anastrozole (58%), most common AC regimen was docetaxel and cyclophosphamide (39%), and most common first line palliative agent was letrozole (42%). Patients who underwent AC did not reach median OS, and patients who did not receive AC had a median OS of 148 months (p=0.8). Patients with grade 3 tumors had a median OS of 58.6 months, and grade 1 and 2 had a median OS of 148.1 months (p=0.5). Discussion: Current treatment strategies for NEN of breast mirror those of non-NEN of breast with similar histology and stage based on extrapolation of data. Recurrence rate was similar between IDC and SPC. In our cohort, survival was not significantly dependent on grade and use of AC. This might be due to the number of patients included in our study, as there was a non-significant trend towards lower OS in patients with high-grade neoplasms, and further limitations from retrospective design of study. Further research towards benefit of AC in NEN of breast and prognostic value of grading is necessary to explore management options in comparison to non-NEN of the breast. Citation Format: Serhan Unlu, Olisaemeka Ogbue, Gloria Lewis, Abdo Haddad, Hamed Daw, Baidehi Maiti. Real-World Data of Neuroendocrine Neoplasms of Breast [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-11.

Parenchymal obliteration by renal masses: Functional and oncologic implications

ObjectivesMost renal tumors merely displace nephrons while others can obliterate parenchyma in an invasive manner. Substantial parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) may have oncologic implications; however, studies regarding PVR remain limited. Our objective was to evaluate the oncologic implications associated with PVR using improved methodology including more accurate and objective tools. Patients/MethodsA total of 1,222 patients with non-metastatic renal tumors managed with partial nephrectomy (PN) or radical nephrectomy (RN) at Cleveland Clinic (2011-2014) with necessary studies were retrospectively evaluated. Parenchymal volume analysis via semiautomated software was used to estimate split renal function and preoperative parenchymal volumes. Using the contralateral kidney as a control, %PVR was defined: (parenchymal volumecontralateral–parenchymal volumeipsilateral) normalized by parenchymal volumecontralateral x100%. PVR was determined preoperatively and not altered by management. Patients were grouped by degree of PVR: minimal (<5%, N = 566), modest (5%-25%, N = 414), and prominent (≥25%, N = 142). Kaplan-Meier was used to evaluate survival outcomes relative to degree of PVR. Multivariable Cox-regression models evaluated predictors of recurrence-free survival (RFS). ResultsOf 1,122 patients, 801 (71%) were selected for PN and 321 (29%) for RN. Overall, median tumor size was 3.1 cm and 6.8 cm for PN and RN, respectively, and median follow-up was 8.6 years. Median %PVR was 15% (IQR = 6%-29%) for patients selected for RN and negligible for those selected for PN. %PVR correlated inversely with preoperative ipsilateral GFR (r = -0.49, P < 0.01) and directly with advanced pathologic stage, high tumor grade, clear cell histology, and sarcomatoid features (all P < 0.01). PVR≥25% associated with shortened recurrence-free, cancer-specific, and overall survival (all P < 0.01). Male sex, ≥pT3a, tumor grade 4, positive surgical margins, and PVR≥25% independently associated with reduced RFS (all P < 0.02). ConclusionsObliteration of normal parenchyma by RCC substantially impacts preoperative renal function and patient selection. Our data suggests that increased PVR is primarily driven by aggressive tumor characteristics and independently associates with reduced RFS, although further studies will be needed to substantiate our findings.

Reduced time spent with patients and decreased satisfaction in work during COVID-19 pandemic

Background: The COVID-19 pandemic disrupted the healthcare system, affecting physician wellbeing. The consequences of reduced time spent with patients at bedside during the pandemic has not been investigated. The objectives of this study include assessing time spent with patients, physician wellbeing and patient satisfaction before and during the pandemic. Methods: A total of 182 internal medicine physicians used Hill-Rom tracking devices to measure time spent at bedside while on the teaching hospital medicine service between September 2019 and November 2020 at Cleveland Clinic in Cleveland, Ohio. Time spent before and after March 2020, the outbreak of the pandemic were compared. Physicians’ wellbeing was evaluated before and during the pandemic using the Accreditation Council for Graduate Medical Education survey. Patients’ satisfaction was assessed via the Hospital Consumer Assessment of Healthcare Providers and Systems questionnaire and correlated to bedside time. Results: From 88,661 time records collected during the 65-week study, 44,710 (50.43%) met the quality standards and were included in the analysis. The average time spent at bedside per patient before and during the pandemic was 12.12 and 7.85 minutes, respectively. Time decreased by 3.33 minutes for interns, 6.10 minutes for residents, and 2.70 minutes for staff. The pandemic correlated with physicians’ decreased vitality and meaning in work. Patients’ satisfaction did not correlate with bedside time. Conclusion: Internal medicine physicians spent less time with patients during the pandemic and had worsened vitality and satisfaction with work. Physicians’ time spent at bedside did not correlate with patients’ satisfaction.

Dystonia in the Middle East - The Cleveland Clinic Abu Dhabi Experience

Dystonia in the Middle East - The Cleveland Clinic Abu Dhabi Experience

B-2 | Outcomes of percutaneous pulmonary valve implantation: Cleveland Clinic Experience

B-2 | Outcomes of percutaneous pulmonary valve implantation: Cleveland Clinic Experience

29. Focused Subspecialty Training In Plastic Surgery Residency: An Objective Assessment Of The Cleveland Clinic Pilot Program

29. Focused Subspecialty Training In Plastic Surgery Residency: An Objective Assessment Of The Cleveland Clinic Pilot Program

Role of aortic valve replacement in moderate aortic stenosis: a 10-year outcomes study

ObjectivePatients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit...

Proportion and predictors of FVC decline in patients with interstitial lung disease

RationaleThe proportion of patients who develop progressive pulmonary fibrosis (PPF), along with risk factors for progression remain poorly understood. ObjectivesTo examine factors associated with an increased risk of developing PPF among patients at a referral center. MethodsWe identified patients with a diagnosis of interstitial lung disease (ILD) seen within the Cleveland Clinic Health System. Utilizing a retrospective observational approach we estimated the risk of developing progression by diagnosis group and identified key clinical predictors using the FVC component of both the original progressive fibrotic interstitial lung disease (PFILD) and the proposed PPF (ATS) criteria. ResultsWe identified 5934 patients with a diagnosis of ILD. The cumulative incidence of progression over the 24 months was similar when assessed with the PFILD and PPF criteria (33.1 % and 37.9 % respectively). Of those who met the ATS criteria, 9.5 % did not meet the PFILD criteria. Conversely, 4.3 % of patients who met PFILD thresholds did not achieve the 5 % absolute FVC decline criteria. Significant differences in the rate of progression were seen based on underlying diagnosis. Steroid therapy (HR 1.46, CI 1.31–1.62) was associated with an increased risk of progressive fibrosis by both PFILD and PPF criteria. ConclusionRegardless of the definition used, the cumulative incidence of progressive disease is high in patients with ILD in the 24 months following diagnosis. Some differences are seen in the risk of progression when assessed by PFILD and PPF criteria. Further work is needed to identify modifiable risk factors for the development of progressive fibrosis.

Novel Machine Learning Identifies 5 Asthma Phenotypes Using Cluster Analysis of Real-World Data

Asthma classification into different subphenotypes is important to guide personalized therapy and improve outcomes. To further explore asthma heterogeneity through determination of multiple patient groups by using novel machine learning (ML) approaches and large-scale real-world data. We used electronic health records of patients with asthma followed at the Cleveland Clinic between 2010 and 2021. We used k-prototype unsupervised ML to develop a clustering model where predictors were age, sex, race, body mass index, prebronchodilator and postbronchodilator spirometry measurements, and the usage of inhaled/systemic steroids. We applied elbow and silhouette plots to select the optimal number of clusters. These clusters were then evaluated through LightGBM's supervised ML approach on their cross-validated F1 score to support their distinctiveness. Data from 13,498 patients with asthma with available postbronchodilator spirometry measurements were extracted to identify 5 stable clusters. Cluster 1 included a young nonsevere asthma population with normal lung function and higher frequency of acute exacerbation (0.8 /patient-year). Cluster 2 had the highest body mass index (mean ± SD, 44.44 ± 7.83 kg/m2), and the highest proportion of females (77.5%) and Blacks (28.9%). Cluster 3 comprised patients with normal lung function. Cluster 4 included patients with lower percent of predicted FEV1 of 77.03 (12.79) and poor response to bronchodilators. Cluster 5 had the lowest percent of predicted FEV1 of 68.08 (15.02), the highest postbronchodilator reversibility, and the highest proportion of severe asthma (44.9%) and blood eosinophilia (>300 cells/μL) (34.8%). Using real-world data and unsupervised ML, we classified asthma into 5 clinically important subphenotypes where group-specific asthma treatment and management strategies can be designed and deployed.

Classification and treatment of vaginal strictures at the donor-recipient anastomosis after uterus transplant

To describe the incidence and management of vaginal stricture after uterus transplantation (UTx) in the US, to propose a grading system to classify stricture severity, and to identify risk factors for stricture formation. Prospective cohort study. University Hospital. Recipients undergoing UTx from 2016-2023 at Baylor University Medical Center in Dallas, Cleveland Clinic, the University of Pennsylvania, and the University of Alabama at Birmingham were monitored postoperatively with regular pelvic examinations. Stricture was defined as vaginal narrowing of <3 cm in patients with graft survival of at least 7 days. Demographic and surgery characteristics. Stricture development and severity (grade 1 for diameter 2-<3 cm, grade 2 for 1-<2 cm, or grade 3 for <1 cm). Of the 45 UTx from 2016-2023 (16 deceased donors and 29 living donors), 3 were excluded from the analysis because of graft loss within 7 days. Of the 42 remaining recipients, 39 (92.9%) had Mayer-Rokitansky-Küster-Hauser syndrome and 3 (7.1%) had a prior hysterectomy. Twenty-eight (66.7%) UTx recipients developed postoperative vaginal strictures with a median time to stricture of 33 days (interquartile range 19-53 days). Most strictures were of moderate severity, with 4 (14.3%) strictures categorized as grade 1, 19 (67.9%) as grade 2, and 5 (17.9%) as grade 3. History of Mayer-Rokitansky-Küster-Hauser syndrome and preoperative recipient vaginal length were significant risk factors for stricture, after adjustment for donor and recipient age and body mass index, anastomosis technique, total ischemia time, center, and year. Patients with longer preoperative vaginal length had a lower risk of stricture (hazard ratio 0.45, 0.29-0.70). The severity grading of the stricture was associated with the effectiveness of a nonoperative treatment approach (grade 1 vs. grade 3). No patients with grade 3 strictures improved with self-dilation alone; all required surgical repair and/or dilation under anesthesia. Conversely, for grade 1 or 2 strictures, self-dilation alone was successful in 47.8% (11/23), and no grade 1 strictures required surgical repair. Vaginal stricture is a common postoperative complication after UTx, affecting >65% of recipients. Short preoperative vaginal length and history of müllerian agenesis in the recipient are significant risk factors. Vaginal self-dilation was effective for some mild to moderate strictures, although dilation under anesthesia or surgical repair was required in most cases. Dallas UtErus Transplant Study (DUETS) at Baylor University Medical Center (NCT02656550), Uterine transplantation for the treatment of uterine factor infertility at the Cleveland Clinic (NCT02573415), The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial (UNTIL) (NCT03307356).

Surgical versus medical management of patients with primary hyperaldosteronism and indeterminate adrenal vein sampling: A 10-year experience of the Cleveland Clinic.

In patients with primary hyperaldosteronism (PA), adrenal vein sampling (AVS) can identify patients suitable for unilateral adrenalectomy. However, in AVS with an indeterminate aldosterone-to-cortisol lateralization (ACL) ratio of 3.0-4.0, clinical guidance is unclear. The authors screened all patients undergoing AVS at the Cleveland Clinic from October 2010 to January 2021 and identified 18 patients with indeterminate ACL results. Ten underwent adrenalectomy and eight continued medical management. The surgical group was younger (58.5 vs. 68 years, p=.17), and more likely to have a unilateral imaging adrenal abnormality (90% vs. 38%, p=.043) and a lower contralateral suppression index (0.63 vs. 1.1, p=.14). Post-treatment, the surgical group had a significant reduction in diastolic blood pressure (-5.5mmHg, p=.043) and aldosterone (4.40 vs. 35.80ng/mL, p=.035) and required fewer anti-hypertensive medications (2 vs. 3, p=.015). These findings may support the benefit of adrenalectomy in a select group of patients with indeterminate ACL.

Billing for Electronic Patient-Physician Communications: An Ethical Analysis.

This review paper analyzes the ethical implications of billing patients for electronic communication with physicians through electronic health records, a practice already adopted by medical institutions such as the Cleveland Clinic. The analysis assesses how billing aligns with pillars of medical ethics which include beneficence, respect for persons, and justice. Although billing may enhance communication, improve patient care, and alleviate physician burnout, concerns arise over potential consequences on patient autonomy, trust, and health care disparities. The review delves into the intricate balance of these ethical principles by first considering the potential benefits of incentivizing concise questions and improving physician workload management through billing. By reducing messages, this approach can potentially mitigate burnout and enhance care. It also acknowledges potential drawbacks such as deterring patients because of financial constraints and eroding trust in physicians and the medical team. It emphasizes the necessity of thoroughly examining all aspects of this intricate ethical dilemma to formulate a nuanced solution that protects patient well-being while respecting physicians. We propose a middle-ground approach involving nominal and transparent billing on the basis of the question's complexity, urgency, and level of expertise required in the response. Transparent billing policies, up-front communication of costs, and potential fee waivers on the basis of socioeconomic status can address equity concerns and maintain patient trust. Striking a balance between the potential benefits and drawbacks of billing for patient questions is crucial in maintaining ethical patient-physician interactions and equitable health care provision. The analysis underscores the importance of aligning online patient-physician communication with ethical principles within the evolving digital health care landscape.

Tissue Inhibitor Metalloproteinase-2·IGF-Binding Protein 7 for the Prediction of Acute Kidney Injury following Cardiac Surgery

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication associated with increased morbidity and mortality. Tissue inhibitor metalloproteinase-2·insulin-like growth factor-binding protein 7 (TIMP-2·IGFBP7) determines tubular stress markers, which may occur prior to tubular damage. Previous studies on the use of TIMP-2·IGFBP7 for the prediction of CSA-AKI showed divergent results. Therefore, this study aimed to explore the predictive value of TIMP-2·IGFBP7 measurements for the early detection of acute kidney injury (AKI) and short-term adverse outcomes after cardiac surgery. Methods: In the prospective cohort study, blood and urine samples were collected 6–12 h after cardiac surgery. Blood samples to monitor serum creatinine levels were additionally extracted from days 1 to 7. AKI was defined based on the KDIGO consensus guidelines. AKI within 7 days following surgery was the primary outcome. The initiation of renal replacement therapy, in intensive care unit mortality, and the combination of both were secondary outcomes. Results: A total of 557 patients were enrolled; 134 (24.06%) of them developed AKI and 33 (5.9%) had moderate or severe AKI. AKI developed more frequently in elderly patients with diabetes or with higher baseline serum creatinine levels. Patients with AKI had higher EuroSCORE II, Cleveland Clinic Score, and simplified renal index (SRI) than those without AKI. Urinary TIMP-2·IGFBP7 was significantly higher in patients with AKI. The area under the curve was 0.66 in predicting all AKI and 0.70 in predicting stages 2 and 3 AKI. The resulting sensitivity and specificity were 44.0% and 83.9%, respectively, for a calculated threshold TIMP-2·IGFBP7 value of 0.265 (ng/mL)2/1,000. The TIMP-2·IGFBP7 values, SRI score, and age were significantly associated with AKI within 7 days postoperatively. A total of 33 patients reached the composite endpoint; the percentage of patients who reached the composite endpoint in the TIMP-2·IGFBP7 of >0.265 (ng/ml)2/1,000 group was significantly higher than that of ≤0.265 (ng/mL)2/1,000 group. Conclusions: Postoperative implementation of TIMP-2·IGFBP7 improved the prediction of CSA-AKI and may aid in identifying patients at risk of short-term adverse outcomes. We identified an ideal calculated cutoff value of 0.265 (ng/mL)2/1,000 for the prediction of CSA-AKI among all AKI patients.

Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review.

Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency with monotherapy. The burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology. The aim of this study was to evaluate the effect of concurrent anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (onabot) treatment on median monthly migraine days (MMD) in patients with chronic migraine, through a retrospective study. The electronic medical records of Cleveland Clinic patients either concurrently (dual therapy) or consecutively (monotherapy) treated with anti-CGRP mAbs and onabot between June 2018 and November 2021 were extracted. Only adult patients (≥ 18years of age) were included in this study. MMDs for 194 concurrently treated (86.6% female and a median [interquartile range] age of 51 [41-61] years) and 229 consecutively treated (88.2% female and median age of 47 [IQR 39-57] years) patients were examined at baseline, after first therapy of either anti-CGRP mAb or onabot, and following dual therapy for 3 consecutive months. The reduction of MMDs for each treatment group were compared. The same approach was utilized to compare consecutive monotherapy at separate times (n = 229) and dual-therapy groups. The initial treatment of the dual-therapy group reduced the median (IQR) MMDs from 30 (30-30) to 15 (12-30) [p < 0.0001]. After initiation of dual therapy, the median MMDs was further decreased from 15 (12-30) to 8 (3-22) [p < 0.0001]. A majority [132/194 (68.0%)] of the dual-therapy patients reported a ≥ 50% reduction in MMD and 90/194 (46.4%) reported a ≥ 75% reduction. For the consecutive monotherapy group, median MMDs changed from a baseline of 30 (25-30) to 15 (8-25) from onabot monotherapy and decreased from 25 (15-30) to 12 (4-25) after anti-CGRP mAb monotherapy. Almost half (113/229 [49.3%] from onabot, and 104/229 [45.4%] from anti-CGRP mAb) of these patients achieved a ≥ 50% reduction in MMDs and a minority (38/229 [16.6%] from onabot, and 45/229 [19.7%] from anti-CGRP mAb) achieved a reduction of ≥ 75%. Additionally, dual therapy showed significant improvement in MMDs compared with monotherapy of either treatment (p < 0.0001). Dual therapy of anti-CGRP mAbs and onabot may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action.

Abstract CT261: Phase II trial of nivolumab in combination with talazoparib in patients with unresectable or metastatic melanoma and mutations in BRCA or BRCA-ness

Abstract Novel therapies are needed for anti-PD-1 refractory metastatic melanoma. Few therapies rationally target biologically selected subpopulations of melanoma. In the Cleveland Clinic Familial Melanoma Registry, a high rate of germline mutations in proteins that regulate DNA repair were seen. PARP inhibitors can lead to synthetic lethality and clinical benefit in patients with BRCA mutations or mutations associated with DNA damage repair (“BRCAness phenotype”). Additionally, preclinical models have shown that PARP inhibitors lead to STING activation, raising the hypothesis that combination therapy with anti-PD-1 could augment immune responses. We conducted a phase II trial evaluating the combination of the PARP inhibitor talazoparib with nivolumab in patients with metastatic melanoma harboring germline or somatic DNA repair mutations. We enrolled a cohort of patients with multiple melanoma subtypes including cutaneous melanoma (3), melanoma arising from a blue nevus (2) and uveal melanoma (2). Mutant DNA repair genes included BAP1 (4), BRCA2 (1), ATM (1), ATR (1) and ARID2 (1), 3 of which were germline. The patient population had highly refractory disease with 6 of 7 patients having progression after ipilimumab + nivolumab (5 of these were primary progression). The 7th patient had a recurrence after adjuvant nivolumab. Of the 7 patients enrolled, all progressed within 6 months (using RECIST and iRECIST criteria).The toxicity profile was consistent with known profile of PARP inhibitors (anemia). Although patient enrollment was limited, this study suggests that in heavily pretreated patients selected for DNA repair mutations the combination of PARP inhibitors and anti-PD-1 has no effect on RECIST-based tumor response. Additional studies are needed. Possible alternative selection strategies include evaluating for genomic evidence of homologous recombination repair deficiency (HRD) or targeting specific mutations (BRCA). TABLE 1: NAND Patient Characteristics and Treatment Outcome Age Subtype of Melanoma Gene Alteration Somatic or Germline TMB BRAF Status Prior Therapy Status of Prior IO response Clinical Trial Response 76 Cutaneous ATM Germline N/A WT Nivolumab Progression after Adjuvant Progression 32 Cutaneous ATR Somatic 4.2 V600E Ipilimumab + Nivolumab Primary Progression Progression 75 Uveal BRCA2 and BAP1 Germline 1.3 WT Ipilimumab + Nivolumab Primary Progression Progression 45 Cutaneous/Blue Nevus BAP1 Somatic 0.0 WT Ipilimumab + Nivolumab Primary Progression Progression 51 Cutaneous/Blue Nevus BAP1 Germline 1.6 WT Ipilimumab + Nivolumab Primary Progression Progression 69 Uveal BAP1 Somatic 1.6 WT Pembrolizumab Primary Progression Progression 61 Cutaneous ARID2 Somatic 17.9 WT Ipilimumab + Nivolumab Secondary Resistance Progression Citation Format: James Isaacs, Tamara A. Sussman, Lucy B. Kennedy, Joshua Arbesman, Brian Gastman, Millennia Zhou, Emily Zabor, Claudia Diaz-Montero, Jennifer Ko, Pauline Funchain. Phase II trial of nivolumab in combination with talazoparib in patients with unresectable or metastatic melanoma and mutations in BRCA or BRCA-ness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT261.

An Obesity-Centric Approach with and Without Anti-Obesity Medications Compared to the Usual-Care Approach to Management of Patients with Obesity and Type2 Diabetes in an Employer Setting: A Pragmatic Randomized Controlled Trial (EMPOWER-T2D).

This study aimed to compare weight loss and glycated hemoglobin (HbA1c)-reduction effects of two obesity-centric, weight-loss management approaches (with or without anti-obesity medication) versus usual glucose-centric care in patients with obesity and type2 diabetes. Single-center, randomized, open-label, 3-armed, parallel-group, pragmatic, noninferiority trial, July 2020 to August 2022. Adults enrolled in the Cleveland Clinic Employee Health Plan (body mass index [BMI] ≥ 30kg/m2, type2 diabetes diagnosis, HbA1c > 7.5%) were randomized to usual glucose-centric management ("Usual-Care" group) or one of two obesity-centric management strategies: participation in a weight management program plus anti-obesity medication ("WMP + AOM" group), or WMP participation without anti-obesity medication ("WMP-Only" group). Primary endpoints were changes in weight and HbA1c, baseline to month12. Due to enrollment and retention challenges, largely related to COVID-19, only 74/300 planned participants were randomized and the study was terminated early. Participants were predominantly female (59%), median (interquartile range [IQR]) age 53.5 (47, 60) years, 68% white, with baseline median (IQR) BMI and HbA1c of 37.4 (34.2, 42.7) kg/m2 and 8.8% (7.9%, 10.4%), respectively. At month12, mean (90% confidence interval [CI]) percentage weight change in the Usual-Care, WMP-Only, and WMP + AOM groups was - 4.5% (- 6.5%, - 2.5%), - 6.7% (- 8.7%, - 4.7%), and - 8.7% (- 10.7%, - 6.8%), respectively; mean (90%CI) HbA1c change was - 1.7% (- 2.1%, - 1.2%), - 2.2% (- 2.7%, - 1.8%), and - 2.2% (- 2.6%, - 1.7%), respectively. WMP + AOM was superior to Usual-Care for weight change (P = 0.02); both WMP + AOM and WMP-Only were noninferior (P ≤ 0.01) to Usual-Care for change in HbA1c. Including anti-obesity medication was associated with superior weight loss with noninferior HbA1c reductions, warranting further evaluation in larger study populations of obesity-focused approaches to type2 diabetes management. Graphical abstract available for this article. ClinicalTrials.gov NCT03799198.

Efficacy and safety of a transaortic approach to midventricular and apical septal myectomy

ObjectiveThe study objective was to evaluate the safety and efficacy of a transaortic approach to midventricular and apical septal myectomy in patients with hypertrophic cardiomyopathy with left ventricular outflow tract or midventricular obstruction. MethodsFrom January 2018 to August 2023, 940 patients underwent transaortic septal myectomy at the Cleveland Clinic, of whom 682 (73%) had midventricular or apical resection. Patients who underwent isolated basal myectomies were excluded. Templated operative reports designated septal regions resected as basal (opposition to mitral valve up to the leaflet tips), midventricular (leaflet tips to just beyond the papillary muscle heads), and apical (apical third of the ventricle). Myocardial resection specimen weights, intraventricular gradients, and clinical outcomes were assessed. ResultsOf the 682 patients, 582 (85%) had basal plus midventricular resection and 78 (11%) had basal, midventricular, and apical resection. Mean preoperative intraventricular gradient was 102 ± 41 mm Hg. Median resection weight was 10 g (15th, 85th percentiles: 7, 15), and mean postoperative intraventricular gradient was 16 ± 10 mm Hg, with 625 (96%) patients achieving gradients 36 mm Hg or less. There were no iatrogenic mitral or aortic valve injuries. Permanent pacemaker placement was required in 38 patients (5.6%), of whom 8 (1.2%) had normal preoperative conduction. Operative mortality occurred in 1 patient (0.1%) after an intraoperative ventricular septal defect. ConclusionsMost patients undergoing septal myectomy for relief of obstruction required resection beyond the basal septum. With specialized instrumentation, detailed imaging and knowledge of variable septal anatomy, resecting midventricular and apical septal muscle can be safely and effectively achieved through a transaortic approach.