Clinical Outcomes In Patients Research Articles

DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design.

Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Association of Age- and Body Mass Index-Stratified High On-Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients.

Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on-treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m2 or >22.6 kg/m2). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P=0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P=0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P=0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140-1.688]; P=0.001). No differences were shown in major bleeding. HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Angiographic Characteristics and Clinical Outcomes in Patients With Chronic Kidney Disease Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention: Insights From the cVAD PROTECT III Study.

Prior studies have found that patients with chronic kidney disease (CKD) have worse outcomes following percutaneous coronary intervention (PCI). There are no data about patients with advanced CKD undergoing Impella-supported high-risk PCI. We, therefore, aimed to evaluate angiographic characteristics and clinical outcomes in patients with CKD who received Impella-supported high-risk PCI as part of the catheter-based ventricular assist device PROTECT III study (A Prospective, Multi-Center, Randomized Controlled Trial of the IMPELLA RECOVER LP 2.5 System Versus Intra Aortic Balloon Pump [IABP] in Patients Undergoing Non Emergent High Risk PCI). Patients enrolled in the PROTECT III study were analyzed according to their baseline estimated glomerular filtration rate (eGFR). The primary outcome was 90-day major adverse cardiovascular and cerebrovascular events (the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization). Of 1237 enrolled patients, 1052 patients with complete eGFR baseline assessment were evaluated: 586 with eGFR ≥60 mL/min per 1.73 m2, 190 with eGFR ≥45 to <60, 105 with eGFR ≥30 to <45, and 171 with eGFR <30 or on dialysis. Patients with lower eGFR (all groups with eGFR <60) were more frequently females and had a higher prevalence of hypertension, diabetes, anemia, and peripheral artery disease. The baseline Synergy Between PCI With Taxus and Cardiac Surgery score was similar between groups (28.2±12.6 for all groups). Patients with lower eGFR were more likely to have severe coronary calcifications and higher usage of atherectomy. There were no differences in individual PCI-related coronary complications between groups, but the rates of overall PCI complications were less frequent among patients with lower eGFR. Major adverse cardiovascular and cerebrovascular events at 90 days and 1-year mortality were significantly higher among patients with eGFR <30 mL/min per 1.73 m2 or on dialysis. Patients with advanced CKD undergoing Impella-assisted high-risk PCI tend to have higher baseline comorbidities, severe coronary calcification, and higher atherectomy usage, yet CKD was not associated with a higher rate of immediate PCI-related complications. However, 90-day major adverse cardiovascular and cerebrovascular events and 1-year mortality were significantly higher among patients with eGFR<30 mL/min per 1.73 m2 or on dialysis. Future studies of strategies to improve intermediate and long-term outcomes of these high-risk patients are warranted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136392.

Treatment Patterns and Clinical Outcomes of Patients with Moderate to Severe Acute Graft-Versus-Host Disease: A Multicenter Chart Review Study

Treatment Patterns and Clinical Outcomes of Patients with Moderate to Severe Acute Graft-Versus-Host Disease: A Multicenter Chart Review Study

A high-fat diet promotes cancer progression by inducing gut microbiota–mediated leucine production and PMN-MDSC differentiation

A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.

Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China.

Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with COVID-19-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Among the infected group, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR]=8.197, 95% confidence interval [95% CI]=5.685-11.820, compared to no lesions), hypertension (adjusted OR=1.582, 95% CI=1.068-2.343), traditional systemic (adjusted OR=1.887, 95% CI=1.263-2.818), and nonsystemic treatment (adjusted OR=1.602, 95% CI=1.117-2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR=0.931, 95% CI=0.680-1.274, compared to no treatment), according to multivariable logistic regression analysis. A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension. ClinicalTrials.gov (No. NCT05961605).

Real-World Clinical Burden of Newly Diagnosed Heart failure in Thai Patients.

There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients. A retrospective review of all eligible adult patients' medical records from 2018 and 2019 was conducted at five hospitals.The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code "I50." Descriptive statistics was used to investigate patients' hospital burden and clinical outcome data. There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30days, 60days, 180days, and 1year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT). The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand.

Associations between in-hospital daily protein intake and adverse clinical outcomes in older patients with heart failure.

The adverse effects of low daily protein intake (DPI) on clinical outcomes in patients with heart failure (HF) are known; however, an optimal DPI to predict event adverse outcomes remains undetermined. Moreover, whether protein restriction therapy for chronic kidney disease is applicable in patients with HF and renal dysfunction remains unclear. In this single-centre, ambispective cohort study, we included 405 patients with HF aged ≥65years (mean age, 78.6±7.5years; 50% women). DPI was estimated from consumption over three consecutive days before discharge and normalized relative to the ideal body weight [IBW, 22kg/m2×height (m)2]. The primary outcome was a composite of all-cause mortality and HF-related readmission within the 2year post-discharge period. During an average follow-up period of 1.49±0.74years, 100 patients experienced composite events. Kaplan-Meier survival curves revealed a significantly lower composite event-free rate in patients within the lowest quartile of DPI than in the upper quartiles (log-rank test, P=0.02). A multivariate Cox proportional hazards analysis after adjusting for established prognostic markers and non-proteogenic energy intake revealed that patients in the lowest DPI quartile faced a two-fold higher risk of composite events than those in the highest quartile [hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.08-3.82; P=0.03]. The composite event risk linearly increased as DPI decreased (P for nonlinearity=0.90), with each standard deviation (0.26g/kg IBW/day) decrease in DPI associated with a 32% increase in composite event risk (HR, 1.32; 95% CI, 1.10-1.71; P=0.04). There was significant heterogeneity in the effect of DPI, with the possible disadvantage of lower DPI in patients with HF with cystatin C-based estimated glomerular filtration rate <30mL/min/1.73m2. The cutoff value of DPI for predicting the occurrence of composite events calculated from the Youden index was 1.12g/kg IBW/day. Incorporating a DPI<1.12g/kg IBW/day into the baseline model significantly improved the prediction of post-discharge composite events (continuous net reclassification improvement, 0.294; 95% CI, 0.072-0.516; P=0.01). Lower DPI during hospitalization is associated with an increased risk of mortality and HF readmission independent of non-proteogenic energy intake, and the possible optimal DPI for predicting adverse clinical outcomes is >1.12g/kg IBW/day in older patients with HF. Caution is warranted when protein restriction therapy is administered to older patients with HF and renal dysfunction.

Treatment patterns and clinical outcomes in patients with metastatic triple-negative breast cancer: a large-scale data analysis using the Japanese claims database.

This study evaluated treatment patterns and clinical outcomes among patients with metastatic triple-negative breast cancer (mTNBC) in real-world clinical settings in Japan. The treatment patterns, time to next treatment or death (TTNTD), time to treatment discontinuation, adverse events of interest, and medical costs of treating patients with mTNBC in first-, second-, and third-line settings were investigated using data of patients meeting the inclusion criteria between January 2017 and March 2022 in a Japanese medical claims database. The treatment regimens for mTNBC were defined according to the Japanese Breast Cancer Society Clinical Practice Guidelines. In this study, 2236 patients with mTNBC (median age 66.0years; 99.8% female) were included in the first-line cohort. Of these, 46.6% and 20.8% were included in the second- and third-line cohorts, respectively. The two most frequently used treatments were capecitabine (19.1%) and S-1 (tegafur-gimeracil-oteracil) (14.5%) in the first-line cohort, eribulin (18.3%) and bevacizumab/paclitaxel (14.4%) in the second-line cohort, and eribulin (19.4%) and bevacizumab/paclitaxel (17.5%) in the third-line cohort. The TTNTD shortened as the line of therapy progressed (median 8.0, 6.5, and 5.2months for the first-, second-, and third-line treatments, respectively). Nausea/vomiting and neutropenia/leukopenia occurred in 62.8% and 18.3% of all patients, respectively. The medical total costs per day were 6.7, 10.2, and 12.9 thousand yen during the first-/second-/third-line treatments, respectively. This study provides insight into current treatment patterns for mTNBC in Japan. The cost-benefit balance worsens with later-line treatment and a high unmet need for mTNBC drug treatment remains.

Clinical features, management, and outcomes of patients with sterile endophthalmitis associated with intravitreal bevacizumab injection: retrospective case series.

To evaluate clinical features, treatment protocol, outcomes, and complications that developed in this case series of 24 patients who had consecutive sterile endophthalmitis after intravitreal bevacizumab (IVB) injection. In this retrospective case series, IVB was repackaged in individual aliquots from the three batches that were used on the same day. IVB was injected into 26 eyes of 26 patients due to diabetic macular edema, age-related macular degeneration, and branch retinal vein occlusion. All patients had intraocular inflammation. Patients were divided into two groups severe and moderate inflammation according to the intraocular inflammation. The medical records of all patients were reviewed. At each follow-up visit, the complete ophthalmologic examination was performed, including best corrected visual acuity (BCVA), intraocular pressure, biomicroscopy, and posterior fundus examination. Twenty-four of 26 patients were included in the study. Two patients were excluded from this study since they didn't come to follow-up visits. The mean BCVA was 1.00 ± 0.52 Log MAR units before IVB. At the final visit, the BCVA was 1.04 ± 0.47 Log MAR units. These differences were not significant (p = 0.58). Of the 24 eyes, 16 eyes had severe, and 8 eyes had moderate intraocular inflammation. Eleven eyes in the severe inflammation group underwent pars plana vitrectomy due to intense vitreous opacity. Smear, culture results, and polymerase chain reaction results were negative. Sterile endophthalmitis may occur after IVB injection. Differential diagnosis of sterile endophthalmitis from infective endophthalmitis is crucial to adjust the appropriate treatment and prevent long-term complications due to unnecessary treatment.

Predictors of Disease Progression and Adverse Clinical Outcomes in Patients with Moderate Aortic Stenosis Using an Artificial Intelligence-Based Software Platform.

Moderate Aortic Stenosis (AS) patients have a higher risk of adverse clinical outcomes than the general population. How this risk compares to those with severe AS, along with factors associated with outcomes and disease progression, is less clear. We analyzed serial echoes (from 2017-2019) from a single healthcare system using Tempus Next (Chicago, IL) software. AS severity was defined according to American Heart Association/American College of Cardiology (AHA/ACC) guidelines. Outcomes of interest included death or heart failure (HF) hospitalization. We used Cox proportional hazards models and logistic regression to identify predictors of clinical outcome and disease progression, respectively. From 82,805 echoes for 61,546 patients, 1,770; 914; 565; and 1,463 patients had no, mild, moderate, or severe AS, respectively. Both moderate and severe AS patients experienced a similar prevalence of adverse clinical outcomes (p=0.45) that was significantly higher than patients without AS (p<0.01). Among moderate AS patients, atrial fibrillation (AF) (HR=3.29, 95% CI=1.79-6.02, p<0.001) and ESRD (HR=3.34, 95% CI=1.87-5.95, p<0.001) were associated with adverse clinical outcomes. One-third of moderate AS patients with a subsequent echo (139/434) progressed to severe AS within one year. In conclusion, moderate AS patients can progress rapidly to severe AS and experience a similar risk of adverse clinical outcomes; predictors include AF and low LVEF. Machine learning algorithms may help identify these patients. Whether these patients may warrant earlier intervention merits further study.

The relationship between baseline nutritional status with subsequent parenteral nutrition and clinical outcomes in cancer patients undergoing cytoreductive surgery: a retrospective study

IntroductionHyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cytoreductive Surgery (CRS) is the preferred treatment for peritoneal malignancies. This highly complex operation is associated with a high incidence of complications, particularly due to malnutrition. This study aimed to investigate the potential association between preoperative nutritional status and postoperative clinical outcomes in adult cancer patients who underwent CRS/HIPEC for peritoneal malignancy.MethodsA retrospective study with 140 adult cancer patients, on parenteral nutrition (PN) (n = 40) and not on PN (n = 100) who underwent CRS with or without HIPEC, was conducted.ResultsPatients who received PN had significantly longer post-operative, hospital, and ICU LOS than those who did not (p = 0.001). ICU admission was significantly higher in the non-PN receiving group compared to the PN receiving group. When compared to the PN group, the majority of patients not receiving PN were at low risk of malnutrition (91% vs. 75%, p = 0.020), whereas 17.5% of PN patients were at risk of malnutrition during hospitalization. Multiple regression analyses revealed a strong positive relationship between patients with increased risk of malnutrition and ICU LOS (p = 0.047).DiscussionRoutine preoperative nutrition assessment is essential to identify patients who are at higher nutritional risk, and nutrition support should be provided preoperatively.

Association between the geriatric nutritional risk index and clinical outcomes among peritoneal dialysis patients: A meta-analysis.

To identify the relationship between the geriatric nutritional risk index (GNRI) and clinical outcomes in patients receiving peritoneal dialysis (PD). The PubMed, EBASE, Web of Science and CNKI databases were searched for available studies up to December 25, 2023. The primary outcome was all-cause mortality, and the secondary outcomes included the incidence of PD dropout, major adverse cardiac and cerebrovascular events (MACCEs), technique failure and peritonitis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the predictive value of the GNRI for the occurrence of the above endpoints. Ten cohort studies with 3897 patients were included. The pooled results demonstrated that a lower GNRI was significantly associated with a greater incidence of all-cause mortality (HR = 0.71, 95% CI: 0.55-0.91; P = .007). In addition, a decreased GNRI predicted the occurrence of dropout from PD (HR = 0.971, 95% CI: 0.945-0.998, P = .034) and MACCE (HR = 0.95, 95% CI: 0.92-0.98, P = .001). However, no significant associations of the GNRI with technique failure (P = .167) or peritonitis (P = .96) were observed. A low GNRI is significantly associated with poor clinical outcomes and might serve as a novel and valuable prognostic indicator among PD patients.

FT4-to-FT3 ratio is a novel prognostic marker in subacute combined spinal cord degeneration patients.

The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD. This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC). About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, P < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; P < 0.001). We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.

Impact of Ethno-racial Factors on Clinical Outcomes and Health Care Utilization in Chronic Pancreatitis.

Healthcare disparities adversely affect clinical outcomes in racial and ethnic minorities. Chronic pancreatitis (CP) is a complex disorder, and pressures for time and cost-containment may amplify the disparity for minorities in this condition. This study aimed to assess ethno-racial differences in the clinical outcomes of CP patients cared for at our institution. This is a study of CP patients with available ethno-racial information followed at our pancreas center. We reviewed their demographics, comorbidities, clinical outcomes, and resource utilization: pain, frequent flares (≥ 2/year), local complications, psychosocial variables, exocrine, and endocrine insufficiency, imaging, endoscopic procedures, and surgeries. The outcomes underwent logistic regression to ascertain association(s) with covariates and were expressed as odds ratio (95% confidence intervals). Of the 445 CP patients, there were 23 Hispanics, 330 Non-Hispanic Whites, 47 Non-Hispanic Blacks, 16 Asian Americans, and 29 patients from Other/mixed races. Over a median follow-up of 7years, no significant differences in the pain profile (p = 0.36), neuromodulator use (p = 0.94), and opioid use for intermittent (p = 0.34) and daily pain (p = 0.80) were observed. Frequent flares were associated with Hispanic ethnicity [2.98(1.20-7.36); p = 0.02], despite adjustment for smoking [2.21(1.11-4.41); p = 0.02)] and alcohol [1.88(1.06-3.35); p = 0.03]. Local complications (pseudocysts, mesenteric thrombosis, and biliary obstruction), exocrine and endocrine dysfunction, and healthcare resource utilization (cross-sectional imaging, endoscopic procedures, celiac blocks, or surgeries) were comparable across all ethno-racial groups. Although no significant differences in clinical outcomes, and health resource utilization were noted across ethno-racial groups, Hispanic ethnicity had significant association with CP flares. This study calls for further investigation of an understudied minority population with CP.

Clinical Significance of Residual Ischemia in Acute Myocardial Infarction Complicated by Cardiogenic Shock Undergoing VA-ECMO.

Although culprit-only revascularization during the index procedure has been recommended in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), the reduction of residual ischemia is also emphasized to improve clinical outcomes. However, few data are available about the significance of residual ischemia in patients undergoing mechanical circulatory supports. This study aimed to evaluate the effects of residual ischemia on clinical outcomes in AMI patients undergoing venoarterial-extracorporeal membrane oxygenation (VA-ECMO). AMI patients with multivessel disease who underwent VA-ECMO due to refractory CS were pooled from the RESCUE and SMC-ECMO registries. The included patients were classified into three groups according to residual ischemia evaluated using the residual SYNTAX score (rSS): rSS = 0, 0 < rSS ≤ 8, and rSS > 8. The primary outcome was 1-year all-cause death. A total of 408 patients were classified into the rSS = 0 (N = 100, 24.5%), 0 < rSS ≤ 8 (N = 136, 33.3%), and rSS > 8 (N = 172, 42.2%) groups. The cumulative incidence of the primary outcome differed significantly according to rSS (33.9% vs. 55.4% vs. 66.1% for rSS = 0, 0 < rSS ≤ 8, and rSS > 8, respectively, overall P < 0.001). In a multivariable model, rSS was independently associated with the risk of 1-year all-cause death (HRadj 1.03, 95% CI 1.01-1.05, P = 0.003). Conversely, the baseline SYNTAX score was not associated with the risk of the primary outcome. Furthermore, when patients were stratified by rSS, the primary outcome did not differ significantly between the high and low delta SYNTAX score groups. In AMI patients with refractory CS who underwent VA-ECMO, residual ischemia was associated with an increased risk of 1-year mortality. Future studies are needed to evaluate the efficacy and safety of revascularization strategies to minimize residual ischemia in patients with CS supported with VA ECMO. REtrospective and Prospective Observational Study to Investigate Clinical oUtcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock (RESCUE), NCT02985008.

Outcomes of ticagrelor versus high dose clopidogrel in CYP2C19 intermediate metabolizer undergoing percutaneous coronary intervention for acute coronary syndromes

Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) has not come to an agreement. The current study was to evaluate the clinical benefit of ticagrelor when compared with high dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected via electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction (MI), stroke, stent thrombosis within 12 month. The secondary outcome was Bleeding Academic Research Consortium (BARC) scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs 9.52 per 100 patient-years; IPTW-adjusted hazard ratio (HR) 0.71; 95% confidence interval (CI): 0.32-1.58; adjusted log-rank P=0.396), but the incidence rate of BARC type 2, 3 or 5 bleeding events was statistically higher in LOF-ticagrelor group than LOF-clopidogrel group (13.53 vs 6.16 per 100 patient-years; IPTW-adjusted HR: 2.29; 95% CI: 1.10-4.78; adjusted log-rank P=0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.

Long-term outcome of percutaneous vertebroplasty versus conservative treatment for osteoporotic vertebral compression fractures: a retrospective cohort study with three-year follow-up

BackgroundOsteoporotic vertebral compression fractures (OVCF) appear to be more common as the population ages. Previous studies have found that percutaneous vertebroplasty (PVP) can achieve better short-term clinical outcomes than conservative treatment (CT) for OVCF. However, the long-term outcomes of PVP compared with CT for OVCF has been rare explored. This study was designed to explore the clinical outcomes of PVP or CT within 3 years after OVCF.MethodsThis study reviewed the clinical outcomes of patients who underwent PVP or CT for OVCF in a single center from January 2015 to December 2019. The back pain visual analogue scale (VAS), Oswestry disability index (ODI) and satisfaction rate were compared between the two groups at baseline, 1 week, 1 month, 3 months, 6 months, 12 months, 24 months and 36 months after treatment.OutcomesThe baseline data including gender, age, bone mineral density, body mass index, back pain VAS, and ODI were not significantly different between the two groups. The back pain VAS and ODI of CT patients were significantly higher than those of PVP group at 1 week, 1 month, 3 months, 6 months and 12 months after treatment. The satisfaction rate in the PVP group were significantly higher than those in the CT group at 1 week, 1 month, 3 months and 6 months after treatment. Subsequently, the back pain VAS and ODI showed no significant difference between the two groups at 24 and 36 months. In addition, there was no significant difference in treatment satisfaction between the two groups at 36 months. There was no significant difference in the rate of new vertebral compression fractures between the two groups within 36 months after treatment.ConclusionThe clinical outcomes within 12 months after PVP and patient satisfaction rate within 6 months after PVP were significantly higher than CT. However, during 12 months to 36 months, this advantage generated by PVP was gradually diluted over time. Compared with CT, the long-term effect of PVP on OVCF should not be overestimated.

Abstract PO3-05-04: Characteristics and clinical outcome of patients with HR positive HER2 low metastatic breast cancer treated with CDK 4/6 inhibitors

Abstract Introduction Breast cancer (BC) is a disease characterized by significant intra- and intertumoral heterogeneity. Hence, it is not surprising that new subtypes with distinct biological features are being discovered, even among previously well-defined BC groups. Recently, HER2-low BC emerged as a new entity with specific clinical behavior, response to treatment and prognosis. HER2-low is a subset of HER2-negative BC, with HER2 immunohistochemical (IHC) score of 1+ or 2+, without HER2 gene amplification measured by in situ hybridization (ISH). As new therapeutic options become available for HER2-low patients, the best treatment sequence is yet to be determined. Furthermore, it is important to distinguish whether there is a difference in the response to standard treatment lines, such as CDK 4/6 inhibitors in metastatic HR positive BC patients, depending on HER2-low status. Methods A retrospective study of 369 metastatic BC (mBC) cases who started CDK 4/6 inhibitor therapy from January 2018 through December 2022 at University Hospital Centre Zagreb was conducted, with prior Ethics Committee approval. All patients with HR positive HER2 negative mBC, determined by standard IHC and ISH, were included in the research. Patient demographics and clinical presentation, tumor characteristics and treatment information were collected. Progression-free survival (PFS) analysis was done with the final data cut-off date being June 1st, 2023. Type 1 right censoring was performed. The data was analyzed using the Kaplan-Meier method and Cox proportional-hazards regression for clinically relevant covariates (age, line of treatment, de novo metastatic disease, endocrine resistance, liver metastases, and detected PIK3CA mutation). Results Median follow-up was 23 months. Of the 283 patients included, 146 (51.59%) had HER2-low disease. A change in HER2 expression between primary tumor and metastasis was found in 16.96% (N=48) patients. Of them,10.25% (N=29) who were initially HER2-low, were found to be HER2-0 in metastatic disease. Meanwhile, 6.71% (N=19) of patients had a change in HER2 expression from 0 to low upon becoming metastatic. In the HER2-low group, 47.06% (N=45) patients had a PIK3CA mutation as opposed to 33.33% (N=30) in the HER2-0 group. Odds ratio for a PIK3CA mutation in HER2-low patients was 1.86 (95% confidence interval (CI): 1.01-3.43, p-value 0.046). Median PFS in the HER2-low group was 18 months (95% confidence interval (CI): 14-24) versus 23 (95% CI: 18-30) in the HER2-0 group. Using multivariable analysis an adjusted hazard ratio of 1.15 (95% CI:0.84-1.57; p-value  0.389) was calculated. Covariates associated with a statistically significant increased risk of disease progression were a higher line of therapy (HR 1.39, 95% CI 1.36-1.71, p-value 0.002) and the presence of liver metastases (HR 2.17, 95% CI 1.42-3.32, p-value 0.0004). A covariate associated with a statistically significant longer PFS was de novo metastatic disease (HR 0.63, 95% CI 0.41-0.97, p-value 0.034). Conclusion There was a trend toward worse PFS in HER2-low mBC that did not reach statistical significance. HER2-low patients were more likely to harbor PIK3CA mutations than HER2-0 patient group. Longer follow-up and a larger cohort are needed in order to make definitive conclusions. Citation Format: Katarina Čular, Kristina Kanceljak, Ana Magdalena Glas, Dora Gudelj, Marija Križić, Marina Popović, Natalija Dedić Plavetić, Maja Sirotković-Skerlev, Stjepko Pleština, Tajana Silovski. Characteristics and clinical outcome of patients with HR positive HER2 low metastatic breast cancer treated with CDK 4/6 inhibitors [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 PO3-05-04.

Abstract PO1-01-08: The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study

Abstract Background: Data suggest that concomitant intake of proton pump inhibitors (PPI) may create drug-drug interactions, potentially impacting efficacy of agents including palbociclib, which is widely used in the treatment of metastatic hormone-receptor-positive/HER2-negative (HR+/HER2-) breast cancer. In the open label, randomized, phase 3 PALLAS trial, the addition of palbociclib for two years to standard adjuvant endocrine therapy (ET) in patients with HR+/HER2- early breast cancer (EBC) did not improve invasive disease-free survival (IDFS) compared to adjuvant ET alone. We explored whether concomitant use of PPIs could have affected clinical outcomes in patients treated with palbociclib in PALLAS. Methods: This is an exploratory, unplanned analysis of the PALLAS trial (AFT-05/ABCSG-42/PrE0109/BIG-14-13, NCT02513394), which enrolled 5796 patients with stage II-III HR+/HER2- EBC. Patients were randomized to receive either 2 years of palbociclib (125 mg oral capsules once daily on days 1-21 of a 28-day cycle) with adjuvant ET or ET alone. Primary endpoint was IDFS in the intention-to-treat population. The present exploratory analysis included patients who received at least one dose of palbociclib. Definitions of IDFS, distant relapse-free survival (DRFS) and overall survival (OS) were according to the PALLAS protocol (STEEP criteria), using first day of palbociclib intake as start date. Only PPI concomitant intake during palbociclib treatment was considered. To determine the association of concomitant PPI use with IDFS, DRFS, and OS, uni- and multivariable Cox models with time-dependent PPI (the latter adjusted for age, prior chemotherapy, progesterone receptor, grade, tumor stage, nodal stage, body mass index (BMI)) were used. Also, the association between PPI use and neutropenia was investigated in patients initiating PPI prior to randomization vs never. Odds ratios (OR) unadjusted and adjusted for age and BMI estimated with logistic regression models are reported. Results: Of 2840 patients treated with palbociclib + ET, 533 (18.8%) had concomitant PPI and palbociclib intake. Median duration of PPI intake was 10.8 months (interquartile range 2.3-22.3). Most patients received omeprazole as PPI (n=265, 49.7%). PPI intake was significantly associated with older age, post-menopausal status, use of aromatase inhibitors as ET, higher BMI, and worse ECOG status (all p&amp;lt; 0.001). Concomitant PPI intake was not significantly associated with survival outcomes (Table 1). Unadjusted all grade neutropenia rates were slightly lower in patients who initiated PPI prior study start vs patients never initiating (79% vs 85%, unadjusted OR 0.66, 95%CI 0.50-0.88). After adjustment for BMI and age, the difference between the groups decreased (adjusted OR = 0.77, 95%CI 0.57-1.04). Similar effect sizes were found for grade 3/4 neutropenia rates (54% vs 64%, unadjusted OR 0.66, 95%CI 0.52-0.83, adjusted OR 0.81, 95%CI 0.64-1.03). Conclusions: Our exploratory analysis did not demonstrate a statistically significant relationship between concomitant use of PPIs and palbociclib and survival outcomes of patients in the PALLAS trial. Nonetheless, careful consideration of concomitant medications and of drug-drug interactions is important when studying novel agents in the adjuvant breast cancer setting. Support: AFT, Pfizer; https://acknowledgments.alliancefound.org Table 1. Association between PPI intake and survival outcomes. Citation Format: Elisa Agostinetto, Georg Pfeiler, Dominik Hlauschek, Erica Mayer, Matteo Lambertini, Evandro de Azambuja, Meritxell Bellet- Ezquerra, Jane Meisel, Gabor Rubovszky, Nicholas Zdenkowski, Yelena Novik, Manuel Ruíz - Borrego, Karen Gelmon, Eleftherios Mamounas, Hiroji Iwata, Dongrui Lu, Lidija Sölkner, Christian Fesl, Michael Gnant, Angela DeMichele. The impact of drug-drug interactions between palbociclib and proton pump inhibitors on clinical outcomes of patients with hormone receptor positive, HER2-negative, early breast cancer: an exploratory analysis of the PALLAS study [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 PO1-01-08.