Favorable Clinical Outcomes In Patients Research Articles

Long-term clinical outcomes of image-guided percutaneous coronary intervention in acute myocardial infarction from the Korea Acute Myocardial Infarction Registry.

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59-0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI.

Relationship between thrombus composition and prognosis in patients with acute ischemic stroke undergoing mechanical thrombectomy

BackgroundMechanical thrombectomy has emerged as the primary endovascular treatment for acute ischemic stroke. Numerous studies have investigated the relationship between thrombus composition and factors such as pharmacological thrombolysis, stroke etiology, mechanical thrombectomy, and radiological imaging. However, limited research has explored the association between thrombus composition and clinical outcomes. MethodsThis retrospective analysis examined the histopathological examination of thrombi retrieved from 50 patients with acute ischemic stroke between May 2020 and May 2023. The composition of the retrieved thrombi was assessed using HE staining to quantify the proportions of red blood cells, white blood cells, platelets, and fibrin. Based on the predominant composition of the thrombus, the patients were divided into two groups: erythrocyte-rich and fibrin-rich. Demographics, clinical characteristics, and clinical outcomes assessed by the National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) scores were collected retrospectively. ResultOf the 50 patients, 23 were classified in the erythrocyte-rich group, and 27 were classified in the fibrin-rich group. There were no significant differences between the two groups in terms of age, sex, stroke subtype, history of hypertension and diabetes, thrombus location, NIHSS scores, mRS scores on admission, the time interval from symptom onset to hospitalization and reperfusion, or the rate of successful reperfusion. However, erythrocyte-rich thrombi were associated with a shorter time interval from puncture to reperfusion. No significant differences were found in the red blood cell fraction and fibrin/platelet fraction between large artery atherosclerosis and cardioembolism. At the 90-day follow-up, patients with erythrocyte-rich thrombi exhibited lower NIHSS scores and more favorable functional outcomes (mRS scores of 0–2) compared to those with fibrin-rich thrombi. ConclusionErythrocyte-rich thrombi were linked to shorter time intervals from puncture to reperfusion and favorable clinical outcomes in patients with acute ischemic stroke. The composition of the thrombus may influence the thrombectomy strategy for endovascular therapy.

Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all (100%; 95% confidence interval [CI] 94-100.0%, p<0.001) patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 (98.3%; 95% CI [91.1-100%]) patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1-99.0%). Within 90 days, freedom from mortality was 95% (95% CI 86.1-99.0%]), without any cardiovascular deaths. Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favorable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

Determinants of serious in-hospital complications in patients with Killip class 1/2 ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

Killip classification has been used to stratify the risk of patients with acute myocardial infarction (AMI). There were many reports that Killip class 3 or 4 is closely associated with poor clinical outcomes. In other words, Killip class 1 or 2 is associated with favorable clinical outcomes in patients with AMI, especially when patients received primary percutaneous coronary intervention (PCI). However, some patients with Killip class 1/2 suffer from serious in-hospital complications. This study aimed to identify factors associated with serious in-hospital complications of ST-segment elevation myocardial infarction (STEMI) in patients with Killip class 1/2. The primary endpoint was serious in-hospital complications defined as the composite of in-hospital death and mechanical complications. We included 809 patients with STEMI, and divided them into the non-complication group (n = 791) and the complication group (n = 18). In-hospital death was observed in 14 patients (1.7%), and mechanical complications were observed in 4 patients (0.5%). Final TIMI flow ≤ 2 was more frequently observed in the complication group (33.3%) than in the non-complication group (5.4%) (p < 0.001). Multivariate logistic regression analysis revealed that serious in-hospital complication was associated with final TIMI flow grade ≤ 2 (Odds ratio 6.040, 95% confidence interval 2.042-17.870, p = 0.001). In conclusion, serious in-hospital complication of STEMI was associated with insufficient final TIMI flow grade in patients with Killip class 1/2. If final TIMI flow grade is suboptimal after primary PCI, we may recognize the potential risk of serious complications even when patients presented as Killip class 1/2.

Five-year clinical outcomes of scanning carbon-ion radiotherapy for prostate cancer.

Carbon-ion radiotherapy (CIRT) has been associated with favorable clinical outcomes in patients with prostate cancer. At our facility, all patients are treated using scanning CIRT (sCIRT). We retrospectively analyzed five-year clinical outcomes of prostate cancer treated with sCIRT to investigate treatment efficacy and toxicity. In this study, we included 253 consecutive prostate cancer patients treated with sCIRT at the Kanagawa Cancer Center from December 2015 to December 2017. The total dose of sCIRT was set at 51.6 Gy (relative biological effect) in 12 fractions over three weeks. We employed the Phoenix definition for biochemical relapse. The overall survival (OS), biochemical relapse-free (bRF) rate, and cumulative incidence of late toxicity were estimated using the Kaplan-Meier method. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. The median age of the patients was 70 years (range: 47-86 years). The median follow-up duration was 61.1 months (range: 4.1-80.3 months). Eight (3.2%), 88 (34.8%), and 157 (62.1%) patients were in the low-risk, intermediate-risk, and high-risk groups, respectively, according to the D'Amico classification system. The five-year OS and bRF were 97.5% and 93.3%, respectively. The five-year bRF rates for the low-risk, intermediate-risk, and high-risk groups were 87.5%, 93.7%, and 93.4%, respectively (p = 0.7215). The five-year cumulative incidence of Grade 2 or more late genitourinary and gastrointestinal toxicity was 7.4% and 1.2%, respectively. The results of this study show that sCIRT has a favorable therapeutic effect and low toxicity in the treatment of prostate cancer.

PR Interval as a Novel Therapeutic Target of Ivabradine Therapy-Prognostic Impact of Ivabradine-Induced PR Prolongation in Heart Failure Patients.

Ivabradine reduces heart rate by inhibiting the "funny current" expressed on the sinoatrial node and improves mortality and morbidity in patients with systolic heart failure and sinus tachycardia. The funny current is known to be expressed also on the atrioventricular node according to experimental studies. However, the impact of ivabradine on PR interval remained unknown. Patients with a left ventricular ejection fraction of less than 50% who received 1 month of ivabradine were screened. Electrocardiographic and echocardiographic data, particularly concerning heart rate, the PR interval, and trans-mitral flow pattern, were collected at baseline and 1-month follow-up. The primary endpoint was defined as the composite of cardiovascular death and hospital readmission for worsening heart failure following ivabradine administration. In the cohort of 29 enrolled patients (median age: 66 years, 62% male), the median baseline heart rate was 86 beats per minute and the median PR interval was 168 milliseconds. Following ivabradine administration, a significant decrease of 20 beats per minute in the heart rate and a significant increase of 24 milliseconds in the PR interval were observed. The truncated interval of the A-wave, detected in the trans-mitral flow, consistently demonstrated a negative correlation with the PR interval both before and after the administration of ivabradine. During a median of 1.8 years of follow-up, six patients reached the primary endpoint. A combination of heart rate reduction and PR prolongation following ivabradine administration, both of which were independent factors associated with the primary endpoint (p < 0.05 for both), was associated with greater freedom from the primary endpoint compared with either/neither of them (p = 0.002). Ivabradine seems to prolong PR interval, which is a novel surrogate marker of favorable clinical outcomes in patients with systolic heart failure. This effect may be associated with the dynamics of the trans-mitral flow pattern, in conjunction with heart rate and the PR interval. Clinical implications of PR interval-guided ivabradine therapy remains the future concern.

Clinical outcomes of intensive care unit patients infected with multidrug-resistant gram-negative bacteria treated with ceftazidime/avibactam and ceftolozane/tazobactam.

In intensive care units (ICUs), infection rates range from 18 to 54%, which is five to ten times higher than those observed in other hospital units, with a mortality rate of 9% to 60%. In recent decades, the susceptibility pattern has changed and Gram-Negative Bacteria (GNB) have become a threat due to their high frequency of multidrug resistance associated with a scarcity of therapeutic options. However, the drugs Ceftolozane/Tazobactam (C/T) and Ceftazidime/Avibactam (C/A) are demonstrating good clinical and microbiological response in the treatment of severe nosocomial infections. Therefore, this study aims to evaluate the clinical outcome of patients with severe infections caused by Multidrug-Resistant (MDR) GNB treated with C/T and C/A. Our study evaluates a total of 131 patients who received treatment with C/T and C/A due to infections caused by MDR GNB within the period from 2018 to 2021. The main infections were urinary tract (46,6%) and respiratory (26,7%) infections. Pseudomonas aeruginosa was the prevailing agent in the sample evaluation (34.3%), followed by Klebsiella pneumoniae (30,1%). About 54,9% of patients showed a favorable response, with culture negativation in 66,4% of the samples, with no discrepancy in negativations when comparing ages: 67,7% in young and 66% in elderly patients. Among the patients, 62,6% received monotherapy with C/T and C/A with a better response observed with monotherapy compared to combination therapy (58,6% vs 41,4%). The overall mortality rate was 45%, with MDR GNB infections responsible for 33,9% of these deaths, and the others (66,1%) due to factors such as oncological, hematological, and degenerative neurological diseases. In regards to hematological aspect, 35,1% of patients showed changes, with 28,2% of them presenting anemia, 4,5% thrombocytopenia, and 2,5% thrombocytosis. Concerning the use of invasive devices, higher mortality was observed in patients on mechanical ventilation (52%). In this manner, it was possible to observe that therapy with C/T and C/A yielded a favorable clinical outcome in patients with severe infections caused by MDR GNB in the study. These drugs also demonstrated good tolerability regardless of age or the presence of preexisting comorbidities and were deemed safe when assessing adverse effects. Our data also demonstrate the importance of determining the mechanism of resistance to carbapenems so that these drugs can be used more effectively and rationally.

Improvement in Serum Creatinine Was Associated with Favorable Clinical Outcomes in Patients with Hepatorenal Syndrome: A Post Hoc Analysis of the CONFIRM Study

Improvement in Serum Creatinine Was Associated with Favorable Clinical Outcomes in Patients with Hepatorenal Syndrome: A Post Hoc Analysis of the CONFIRM Study

Systemic Inflammation Response Index Predicts Clinical Outcomes in Patients With Acute Ischemic Stroke (AIS) After the Treatment of Intravenous Thrombolysis.

Intravenous thrombolysis (IVT) is one of the most important means of therapy for patients with acute ischemic stroke (AIS). After cerebral infarction, the inflammatory response fulfills an essential role in the pathobiology of stroke, affecting the process of recanalization. Hence, we evaluated the usefulness of the systemic inflammatory response index (SIRI) for the prognosis of patients with AIS. A total of 161 patients suffering from AIS were retrospectively analyzed. SIRI was introduced and calculated using the absolute neutrophil, monocyte, and lymphocyte numbers from the admission blood work. The study outcomes were determined using a modified Rankin Scale (mRS) at the 3-month timepoint, and a favorable clinical outcome was calculated in the mRS score range of 0 to 2. The analysis of receiver operating characteristic (ROC) curves was performed to determine the values of the optimal cutoff of SIRI for the prediction of clinical outcomes. In addition, multivariate analyses were performed to investigate the association between clinical outcomes and SIRI. The ROC curve analysis revealed that the ideal SIRI cutoff was at 2.54 [area under the curve, 78.85%; 95% CI, 71.70% to 86.00%; sensitivity, 70.89%; and specificity, 84.14%]. Multivariate analysis indicated that SIRI ≤2.54 (odds ratio, 1.557, 95% CI, 1.269 to 1.840; P=0.021) was an independent predictor of favorable clinical outcomes in patients suffering from AIS after treatment with IVT. We preliminary speculate that SIRI may serve as an independent predictor of clinical outcomes with AIS following IVT.

Video-assisted thoracoscopic surgery for Andersson lesion in ankylosing spondylitis: A case report and literature review.

Andersson lesion (AL), a phenomenon initially described by Andersson nearly 80 years ago, has been the subject of extensive research and various treatment modalities. The ongoing debate surrounding the need for anterior surgery in AL cases has spurred numerous proposed approaches. Despite the demonstrated efficacy of anterior surgery in achieving fusion and stabilization, its implementation is associated with prolonged operation time and heightened intraoperative bleeding. A 32-year-old male patient presented at our hospital in February 2019 with a 2-month history of bilateral lower extremity weakness and sensory disturbances. These symptoms were exacerbated by a recent fall. AL conbined with ankylosing spondylitis. A 1-stage posterior fixation and decompression procedure was performed to ensure spinal stability, minimize deformities, and reduce surgical trauma. To achieve these goals, a 2-stage approach was employed, which included video-assisted thoracoscope-guided vertebrectomy, spinal canal decompression, and bone graft fusion. No recurrences of significant pain, limb numbness, or other symptoms were reported, ultimately leading to an improved quality of life for the patient. We utilized video-assisted thoracoscopic surgery technology for anterior bone graft fusion in a patient with AL to minimize the trauma of secondary surgery. However, the 3-year follow-up showed insufficient bony fusion at the fracture site. Nevertheless, the patient maintained spinal stability with posterior internal fixation and no significant kyphosis or symptoms. Thus, standalone posterior fixation may suffice for favorable clinical outcomes in patients with AL.

Regulation of the stem‑like properties of estrogen receptor‑positive breast cancer cells through NR2E3/NR2C2 signaling.

Cancer stem cells (CSCs) are major drivers of metastasis, drug resistance and recurrence in numerous cancers. However, critical factors that can modulate CSC stemness have not been clearly identified. Nuclear receptor subfamily 2 group E member 3 (nr2e3) expression has been previously reported to be positively associated with drug sensitivity and favorable clinical outcomes in patients with estrogen receptor (ER)+ breast cancer. This suggests that nr2e3 expression may be inversely associated with CSC stemness in this type of tumor cells. The present study aimed to investigate the regulatory roles of NR2E3 in the stem-like properties of ER+ breast cancer cells and to identify the underlying mechanisms. Bioinformatics analysis was performed using the data derived from the Cancer Genome Atlas database. Nr2e3-specific shRNA and nuclear receptor subfamily 2 group C member 2 (nr2c2) overexpressed plasmids were constructed to silence and enhance the expression of nr2e3 and nr2c2, respectively. Transwell and wound healing experiments were conducted to evaluate the migration and invasion ability of MCF7 cells, while colony formation tests were used to evaluate the clonality. Flow cytometry was used to detect the percentage of CD44+CD24-/low cells. Reverse transcription-quantitative PCR and western blotting were performed to detect expression at the mRNA and protein levels. The results showed that compared with normal breast tissues and MCF10A cells, the expression of nr2e3 was increased in ER+ breast tumor tissues and cell lines. Nr2e3 silencing promoted the migration, invasion and colony-forming ability of the ER+ MCF7 cells. It also increased the expression of epithelial-mesenchymal transition markers and stem cell-related transcription factors, in addition to the percentage of CD44+CD24-/low cells. The expression of nr2e3 and nr2c2 was found to be positively correlated. Nr2e3 knockdown decreased the mRNA and protein expression levels of nr2c2, whereas nr2c2 overexpression reversed the elevated CD44+CD24-/low cell ratio and the increased migratory activity caused by nr2e3 silencing. The results of the present study suggest that NR2E3 may serve an important role in modulating the stem-like properties of ER+ breast cancer cells, where NR2E3/NR2C2 signaling may be a therapeutic target in ER+ breast cancer.

First-pass effect in posterior acute ischemic stroke undergoing endovascular thrombectomy: A systematic review and meta-analysis

ObjectivesFirst-pass effect (FPE) has been shown to be a predictor of favorable clinical outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Literature regarding FPE for posterior circulation AIS is sparse; we conducted a systematic review and meta-analysis to explore FPE in posterior circulation stroke undergoing EVT. Materials and MethodsWe conducted a systematic review of the English literature in PubMed, Embase, Scopus, and Web of Science. FPE was defined as thrombolysis in cerebral infarction (TICI) 2c-3 and modified FPE (mFPE) was defined as TICI 2b-3 in one pass. Definitions of non-FPE and non-mFPE varied among studies. The primary outcome of interest was modified Rankin Scale (mRS) 0-2. Secondary outcomes of interest were mRS 0-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity was assessed with Q statistic and I2 test. ResultsSeven studies with 417 patients in the mFPE group, 942 in the non-mFPE group, 545 in the FPE group, and 1023 in the non-FPE group were included. Overall, FPE was associated with greater rates of 90-day mRS 0-2 (OR= 2.78, 95% CI= 2.11-3.65; P-value< 0.001) and mRS 0-3 (OR= 2.67, 95% CI= 1.98-3.60; P-value< 0.001); however, there was significant heterogeneity among studies for both mRS 0-2 (I2= 69%; P-value< 0.001) and mRS 0-3 (I2= 69%; P-value< 0.001). FPE and non-FPE were associated with similar rates of sICH (OR= 0.65, 95% CI= 0.40-1.07; P-value= 0.09), and no heterogeneity was observed (I2= 0%; P-value= 0.95). FPE was associated with lower rates of mortality (OR= 0.44, 95% CI= 0.33-0.58; P-value< 0.001), although heterogeneity was observed (I2= 58%; P-value= 0.01). ConclusionsFPE is associated with favorable clinical outcomes in patients undergoing EVT for posterior circulation AIS. Future studies should work to further quantify the impact of FPE on outcomes in the posterior circulation.

In-vitro model to mimic T cell subset change in human PDAC organoid co-culture

PurposeImmunotherapies have largely failed as treatment options for pancreatic ductal adenocarcinoma (PDAC). In this field, clinical translational studies into personalized treatment are of fundamental importance. In our study, we model tumor-cell immune-cell interactions in a co-culture of primary human PDAC organoids and matched peripheral blood mononuclear cells (PBMCs).MethodsUsing flow cytometry, we evaluated changes in T cell subtypes upon co-culture of patient-derived PDAC organoids and matched PBMCs.ResultsAfter co-culturing PDAC organoids with PBMCs, we observed changes in CD4+, CD8+ and Treg cell populations. We observed favorable clinical outcome in patients whose PBMCs reacted to the co-culture with organoids.ConclusionThis experimental model allows to investigate interactions between patient derived PDAC organoids and their PBMCs. This co-culture system could serve as a preclinical platform to guide personalized therapeutic strategies in the future.

Resection of Cervical Dumbbell-Shaped Schwannoma Using Posterior Unilateral Approach: Impact on Postoperative Cervical Function and Clinical Outcomes.

A retrospective comparative study. This study aimed to evaluate the radiographical changes in cervical sagittal alignment (CSA) and clinical outcomes after tumor resection using a posterior unilateral approach without spinal fixation for patients with cervical dumbbell-shaped schwannoma (DS). Seventy-three patients with DS who were followed up for at least 2years were included. The Eden classification was used to designate the types of DS. The CSA and range of motion (ROM) were analyzed using radiographs. The clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) score and JOA cervical myelopathy questionnaire. The CSA in the neutral, flexion, and extension position and cervical ROM were not significantly reduced in the follow-up period. The JOA scores showed significant improvement after surgery. The postoperative radiographic parameters and clinical outcomes of Eden type II or III DS, which needed facetectomy for the resection, did not show any statistically significant difference compared with those of Eden type I tumor, which was resected without facetectomy. Fifty-two cases (71.2%) achieved gross total resection, whereas 21 cases (28.8%) remained in partial resection (PR). One case underwent reoperation due to the regrowth of the remnant tumor whose margin was at the entrance of the intervertebral foramen. Tumor resection using the posterior unilateral approach preserved CSA and resulted in favorable clinical outcomes in patients with DS. When the resection ends in PR, the proximal margin of the remnant tumor should be located distally away from the entrance of the foramen to prevent regrowth.

Intrinsic suppression of type I interferon production underlies the therapeutic efficacy of IL-15-producing natural killer cells in B-cell acute lymphoblastic leukemia

BackgroundType I interferons (IFN-Is), secreted by hematopoietic cells, drive immune surveillance of solid tumors. However, the mechanisms of suppression of IFN-I-driven immune responses in hematopoietic malignancies including B-cell acute lymphoblastic...

The epidemiology of concurrent infection in patients with pyogenic spine infection and its association with early mortality: A nationwide cohort study based on 10,695 patients

BackgroundGenerally, a sufficient duration of relevant antibiotics based on an appropriate culture combined with proper surgical treatment guarantees a favorable clinical outcome in patients with pyogenic spine infections. However, a patient’s condition often deteriorates as concurrent infections occur in other organs, leading to mortality. Therefore, this study aimed to investigate the epidemiology of concurrent infections in patients with a pyogenic spine infection and estimate the rates and risks of early mortality. MethodsPatients with a pyogenic spine infection were identified using a national claims database that includes the entire population. The epidemiology of the six types of concurrent infections was investigated, and the corresponding early mortality rates and risks were estimated. The results were validated internally by bootstrapping and externally by defining two additional cohorts for sensitivity analysis. ResultsAmong 10,695 patients with a pyogenic spine infection, the prevalence of the six types of concurrent infections was 11.3 % for urinary tract infections, 9.4 % for intra-abdominal infections, 8.5 % for pneumonia, 4.6 % for septic arthritis or osteomyelitis of the extremities, 0.7 % for central nervous system infections, and 0.5 % for cardiac infections. Patients with a concurrent infection had approximately 4-fold greater mortality than those without (3.3 % vs. 0.8 %). The early mortality rates were particularly higher in patients with multiple or specific types of concurrent infections, including central nervous system infections, cardiac infections, and pneumonia. In addition, the mortality trends differed significantly according to the number and type of concurrent infections. ConclusionsThese data on six types of concurrent infection among patients with pyogenic spinal infection can be used as a source of reference by clinicians.

Early Tumor Shrinkage as a Predictor of Favorable Treatment Outcomes in Patients With Extensive-Stage SCLC Who Received Programmed Cell Death-Ligand 1 Inhibitor Plus Platinum-Etoposide Chemotherapy: A Prospective Observational Study

IntroductionIn recent years, programmed cell death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy was found to have favorable clinical outcomes in patients with extensive-stage SCLC (ES-SCLC). The usefulness of early tumor shrinkage (ETS) has been reported in various types of cancers. Nevertheless, there have been few reports evaluating ETS in ES-SCLC. Therefore, this study aimed to evaluate the role of ETS in the clinical outcomes of patients with ES-SCLC receiving chemoimmunotherapy. MethodsWe prospectively identified 46 patients with ES-SCLC who received PD-L1 inhibitor plus platinum-etoposide chemotherapy at 10 institutions in Japan between September 2019 and October 2021. Of them, 35 patients were selected for analyses. ResultsThe responders (progression-free survival [PFS] ≥ 6.0 mo) had significantly greater tumor shrinkage at the first evaluation than the nonresponders (PFS < 6.0 mo) (65.0% versus 53.7%, p = 0.03). We defined the cutoff value for ETS as a 57% change from the baseline on the basis of the receiver operating characteristic results to determine the optimal tumor shrinkage rate at the first evaluation for identifying responders. The patients with ES-SCLC who achieved ETS had longer PFS and overall survival than those who did not achieve ETS (5.6 versus 4.0 mo, log-rank test p = 0.001 and 15.0 versus 8.3 mo, log-rank test p = 0.02). In the multivariate analyses, ETS was significantly associated with PFS and overall survival (hazard ratio = 0.27, 95% confidence interval: 0.12–0.63, p = 0.002 and hazard ratio = 0.34, 95% confidence interval: 0.13–0.85, p = 0.02). ConclusionsOur prospective observational study indicated that ETS was related to favorable clinical outcomes for patients with ES-SCLC receiving PD-L1 inhibitor plus platinum-etoposide chemotherapy.

BCL11B Mutations Are Associated with Higher CD8+ T-Cell Percentage and Favorable Clinical Outcomes in Patients with T-Cell Acute Lymphoblastic Leukemia.

BCL11B Mutations Are Associated with Higher CD8+ T-Cell Percentage and Favorable Clinical Outcomes in Patients with T-Cell Acute Lymphoblastic Leukemia.

655. Combination Eravacycline Therapy for Carbapenem-Resistant Acinetobacter baumannii Pneumonia

Abstract Background Acinetobacter baumannii typically causes infections in debilitated, hospitalized patients and is difficult to treat due to multiple virulence factors and the presence of intrinsic and acquired antibiotic resistance mechanisms leading to frequent isolation of multi-drug resistant (MDR) phenotypes. Due to problematic pharmacokinetics and/or dose-limiting toxicities of salvage agents, combination therapy with aminoglycosides, ampicillin/sulbactam, polymyxins, minocycline, or tigecycline, is often used. Eravacycline has demonstrated greater in-vitro potency against A. baumannii compared to other tetracycline derivatives making it potentially the more appealing option. However, its utility is hindered by a lack of data supporting pharmacodynamic targets and adequate dosing strategies for CRAB. The goal of this case series was to describe our experience with the use of combination eravacycline therapy for the treatment of CRAB pneumonia. Methods This case series included all patients ≥ 18 years of age, diagnosed with SARS-CoV-2, ≥ 1 sputum culture positive for CRAB and a clinical diagnosis of new bacterial pneumonia, who received at least one dose of eravacycline between April 1st and October 1st, 2020. The primary outcome was clinical resolution of CRAB pneumonia. Secondary outcomes evaluated microbiological resolution, need for extended durations of therapy, and frequency of re-starting CRAB therapy within 48 hours of completion. Results In total, 25 patients were included in this case series. The median duration of combination therapy was 10 days. Most patients (96%) received eravacycline + ampicillin/sulbactam, with 7 of those patients also receiving inhaled colistin (Table 2). In total, 17 (68%) patients achieved clinical resolution of CRAB pneumonia. Post-treatment sputum cultures were collected in 18 patients, of which 13 (72%) achieved microbiological resolution. One patient received &amp;gt; 14 days of therapy and no patients re-initiated therapy within 48 hours of eravacycline completion. Table 1:Baseline CharacteristicsTable 2:Study Outcomes Conclusion In this small case series, eravacycline showed favorable clinical outcomes in patients with CRAB pneumonia. In light of limited treatment options, this agent can be considered for CRAB pneumonia salvage therapy. Disclosures All Authors: No reported disclosures.

Prognostic nutritional index of early post-pembrolizumab therapy predicts long-term survival in patients with advanced urothelial carcinoma.

Pembrolizumab has been widely used to treat advanced urothelial carcinoma that has progressed after first-line platinum-based chemotherapy. Because its clinical benefits are limited, biomarkers that can predict a good response to pembrolizumab are required. The prognostic nutritional index (PNI), calculated using the serum albumin level and peripheral lymphocyte count, has been evaluated as a predictive biomarker in cancer immunotherapy. The present study investigated the application of PNI as a predictive biomarker for pembrolizumab response in patients with advanced urothelial cancer. A retrospective study was conducted on 34 patients treated with pembrolizumab at Shiga University of Medical Science Hospital between January 2018 and July 2022. The posttreatment PNI (post-PNI) was calculated within 2 months of starting pembrolizumab. The present study investigated the association between post-PNI and objective response, overall survival (OS) and progression-free survival (PFS). The patient cohort was stratified into two categories, high and low post-PNI groups, with a cutoff value of post-PNI at 40. The higher post-PNI group demonstrated a better disease control rate than the lower post-PNI group (complete response + partial response + stable disease, 75 vs. 21%, P=0.004). Regarding median OS, the higher post-PNI group exhibited a significantly longer survival time than the lower post-PNI group (23.1 vs. 2.9 months, P<0.001). Similarly, the higher post-PNI group exhibited a significantly longer PFS than the lower post-PNI group (10.2 vs.1.9 months, P<0.001). Multivariate analysis showed that a higher post-PNI value was an independent predictor for OS (hazard ratio, 0.04; 95% confidence interval, 0.01-0.14; P<0.001) and PFS (hazard ratio, 0.12; 95% confidence interval, 0.04-0.35; P<0.001). The present study indicated that the post-PNI was a predictor of favorable clinical outcomes in patients treated with pembrolizumab for advanced urothelial carcinoma.