Guide Patient Selection Research Articles

Abstract IA01: Moving forward translation of targeted therapy with external beam radiation

Radiotherapy is an anatomically highly targeted treatment modality capable of eradicating cancer cells, including cancer stem cells (CSC). This precision makes radiotherapy an ideal partner for synergistic treatment with targeted drugs, combining local effects on the tumor with systemic molecular interventions. To evaluate the efficacy of such combined treatments on inactivation of CSC in translational research, it is essential to select the appropriate clinical endpoints for preclinical experiments, most importantly inactivation of CSC in vitro or local tumor control in vivo. This ensures that preclinical findings are better translatable to the clinical setting, bridging the gap between experimental models and patient outcomes. A critical factor in this translational pipeline is the use of appropriate in vitro and animal or explant models that as accurate as possible mimic the clinical tumor microenvironment and response dynamics. To account for inter-tumor heterogeneity, it is necessary to apply a panel of models that are well characterized on a molecular biological level. With the right preclinical systems in place, combination strategies can be refined to optimize timing, dosing and sequencing of therapies to maximize tumor control while minimizing damage to normal tissues. Biomarker-driven approaches and molecular pathway analysis are increasingly guiding patient selection and therapeutic personalization, thereby improving the likelihood of clinical success. Examples include biomarker-based studies such as the DELPHI trial for dose de-escalation in post-op HPV-positive head and neck cancer (HNSCC) and the INDIRA Miso study on escalation of PET hypoxic HNSCC. Promising examples of novel combinations with radiotherapy include not only small molecule or Immunotherapeutics, but also the use of radiotherapy integration with novel theranostic radiopharmaceuticals, genomic and radiomic data for adaptive treatment planning. By aligning preclinical and clinical strategies, these efforts are advancing the integration of targeted therapies with radiotherapy and improve loco-regional control, overall survival and quality of life for patients. Citation Format: Michael Baumann. Moving forward translation of targeted therapy with external beam radiation. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA01

The Prognostic Value of CRP/Alb Ratio in Predicting Overall Survival for Hepatocellular Carcinoma Treated with Transcatheter Intra-Arterial Therapy Combined with Molecular-Targeted Agents and PD-1/PD-L1 Inhibitors.

This study aimed to evaluate the prognostic value of C-reactive protein to albumin (CRP/Alb) ratio in hepatocellular carcinoma (HCC) treated with transcatheter intra-arterial therapy combined with molecular targeted agents (MTAs) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. Medical records of 271 consecutive patients with HCC receiving this combination therapy in China between 2019 and 2023 were retrospectively analyzed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses. The discriminatory capability of inflammation-based prognostic scores-including the CRP/Alb ratio, C-reactive protein and alpha-fetoprotein in immunotherapy (CRAFITY) score, modified Glasgow prognostic score (mGPS), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)-was assessed using the area under the curve (AUC). A total of 133 patients met the inclusion criteria. The optimal cutoff value for the binary classification of CRP/Alb ratio in predicting OS, as determined using X-tile software, was 0.02. Multivariate analysis identified the CRP/Alb ratio (hazard ratio [HR] = 2.61, p < 0.001), tumor size (HR = 2.45, p = 0.018), and extrahepatic metastases (HR = 1.93, p = 0.015) as independent predictors of OS. For PFS, significant factors included Eastern Cooperative Oncology Group Performance Status (HR = 1.55, p = 0.033) and macrovascular invasion (HR = 1.48, p = 0.046). Patients with higher CRP/Alb ratios were more likely to experience fever and fatigue. The CRP/Alb ratio demonstrated significantly higher AUCs than PLR and SII at 24 months (all p < 0.05) and showed comparable AUCs to CRAFITY score and mGPS at 12, 24, and 36 months. The CRP/Alb ratio is a valuable prognostic marker for predicting OS and treatment-related adverse events in HCC patients receiving transcatheter intra-arterial therapy combined with MTAs and PD-1/PD-L1 inhibitors. This ratio can be used as a simple and reliable biomarker for assessing prognosis and guiding patient selection in clinical practice.

18F]Fluorthanatrace PET in Ovarian Cancer: Comparison with [18F]FDG PET, Lesion Location, Tumor Grade, and Breast Cancer Gene Mutation Status.

Poly(adenosine diphosphate-ribose) polymerase-1 (PARP1) inhibitors have improved ovarian cancer treatment outcomes. However, clinical response remains heterogeneous. Existing biomarkers, mainly breast cancer susceptibility genes 1 and 2 (BRCA1/2), are suboptimal. New tools are needed to guide patient selection. In this study, [18F]fluorthanatrace ([18F]FTT), a PET radiotracer for imaging PARP1, was compared with [18F]FDG and tumor features commonly assessed in ovarian cancer. Methods: Subjects with epithelial ovarian cancer underwent both [18F]FTT and [18F]FDG PET before new oncologic treatment. The SUVmax of [18F]FTT and [18F]FDG was compared between lesions. [18F]FTT SUVmax was compared with tumor location, tumor grade, and germline or somatic BRCA1/2 status. Linear mixed models were fitted to identify subject-level differences. Results: Fifty-five lesions were identified in 14 subjects. No correlation was found between [18F]FTT SUVmax and [18F]FDG SUVmax per lesion, supporting distinct molecular targets. [18F]FTT uptake varied widely across lesions, with no significant differences between mean SUVmax and tumor location, grade, or BRCA1/2 status. Conclusion: Our findings suggest that [18F]FTT PET may provide unique information on ovarian cancer distinct from [18F]FDG PET and commonly assessed tumor features. Our results imply a wide range of PARP1 expression in the studied ovarian tumors not explained by [18F]FDG PET, location, grade, or mutational status.

Role of Local Therapy for Metastatic Gastrointestinal Malignancies

AbstractOligometastatic disease is an increasingly recognized intermediate tumor state between locally confined and widely metastatic cancer. Oligometastatic gastrointestinal (GI) malignancies represent a heterogeneous spectrum of disease, and treatment strategies are tailored to each patient and are impacted by multiple factors. Recent advances in systemic therapies, imaging techniques, and local treatment modalities have revolutionized cancer treatment and present new opportunities to improve outcomes in patients with a limited burden of metastatic disease. However, there is currently a lack of consensus and robust literature to guide patient selection and treatment strategies, including the optimal role and timing of local therapies as adjuncts to standard-of-care systemic therapy. The intent of this review is to comprehensively discuss the role of local therapies in the modern management of oligometastatic GI malignancies.

Synthetic lethal strategies for the development of cancer therapeutics.

Synthetic lethality is a genetic phenomenon whereby the simultaneous presence of two different genetic alterations impairs cellular viability. Importantly, targeting synthetic lethal interactions offers potential therapeutic strategies for cancers with alterations in pathways that might otherwise be considered undruggable. High-throughput screening methods based on modern CRISPR-Cas9 technologies have emerged and become crucial for identifying novel synthetic lethal interactions with the potential for translation into biologically rational cancer therapeutic strategies as well as associated predictive biomarkers of response capable of guiding patient selection. Spurred by the clinical success of PARP inhibitors in patients with BRCA-mutant cancers, novel agents targeting multiple synthetic lethal interactions within DNA damage response pathways are in clinical development, and rational strategies targeting synthetic lethal interactions spanning alterations in epigenetic, metabolic and proliferative pathways have also emerged and are in late preclinical and/or early clinical testing. In this Review, we provide a comprehensive overview of established and emerging technologies for synthetic lethal drug discovery and development and discuss promising therapeutic strategies targeting such interactions.

Primary Embolization of Cerebral Arteriovenous Malformations With Intention to Cure: A Systematic Review of Literature and Meta-Analysis.

The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear. We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis. We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I 2 = 72%-94%). Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.

High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC

IntroductionDespite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable....

Harvi Cardiovascular Modeling Accurately Predicts Hemodynamic Improvements Produced by a New Direct Cardiac Compression Device.

Despite advancements in mechanical circulatory support (MCS) technology, persistent critical complications related to blood contact remain unresolved. To provide a safer alternative therapy, CorInnova is developing a non-blood contacting direct cardiac compression (DCC) device for MCS. To support product development toward clinical trials, a simulation platform has been developed to predict clinical outcomes under patient-specific conditions, guiding patient selection for clinical trials. The Harvi simulation was validated using preclinical in vivo data from experimental studies with the CorInnova device, with n = 28 hemodynamic samples simulated from animal data (n = 4 ovine). After confirming validation, further simulation was performed to predict additional hemodynamic outcomes not captured in animal studies. The simulated effects of CorInnova device therapy were not significantly different from animal data for cardiac output, systemic arterial blood pressure, mean pulmonary artery pressure, central venous pressure, or left ventricular pressure (p > 0.050). Harvi accurately predicts the effects of the CorInnova device in heart failure conditions and can be used in preparation for future clinical trials.

Five Criteria Predict Induction and Ablation of Supraventricular Tachycardia.

Current guidelines recommend electrophysiological study (EPS) and ablation for primary treatment of supraventricular tachycardia (SVT), but there is little information to guide patient selection for the procedure. The purpose of this study was to identify preoperative features that would predict whether patients with signs or symptoms of tachycardia were likely to have SVT induced and ablated at EPS. We performed a retrospective chart review of 1089 patients referred for EPS and ablation of SVT at 2 high volume centers. The population consisted of a derivation cohort of 810 patients and a validation cohort of 279 patients. We evaluated various clinical, EKG, and monitor features to determine which ones correlated with SVT induction or ablation. Five preoperative findings predicted a high probability that SVT would be induced and ablated at EPS: 1. A characteristic EKG recording of SVT. 2. Termination of SVT with adenosine. 3. Termination of SVT or symptoms with vagal maneuvers. 4. An episode of SVT lasting ≥ 30 s on a monitor recording. 5. Pre-excitation on the baseline EKG. Patients exhibiting at least one of these features had a high probability of SVT induction and ablation, while those exhibiting none had a low probability (Induction, 76% vs. 19%, RR = 3.96 (2.76-5.69), p < .001; Ablation, 88% versus 26%, RR = 3.32 (2.48-4.46), p < .001). A point-based score was derived and validated that can be used to estimate the probability of induction and ablation for individual patients. Simple criteria classify patients as having a high or low probability of SVT induction and ablation at EPS. They can be used as a guide for clinical decision making when considering invasive testing for patients with symptoms of tachycardia.

Immunotherapy in Oral Cancer

Abstract Squamous cell carcinoma of the head-and-neck (HNSCC) ranks sixth in global cancer incidence and poses significant challenges in terms of morbidity and mortality. The tumor microenvironment in HNSCC is a complex milieu involving immune cells, stromal elements, and cytokines, among other factors. Immunotherapy has emerged as a potent therapeutic avenue, particularly through immune checkpoint inhibitors (ICIs), for modulating this intricate environment. ICIs have garnered approval for first-line use in recurrent and metastatic HNSCC. However, recent clinical observations underscore the variability in treatment response to immunotherapy. This necessitates a thorough exploration of diverse ICI agents and combination strategies to optimize therapeutic outcomes. A comprehensive assessment and focused investigation of the immune contexture in HNSCC patients undergoing ICI therapy are pivotal for advancing treatment efficacy. Numerous innovative immunotherapeutic modalities, including chimeric antigen receptor-T-cell therapy, oncolytic virus therapy, and vaccination strategies, are actively under development. Furthermore, identifying robust biomarkers to guide patient selection for immunotherapy is of paramount importance. The quest for optimal combination regimens incorporating novel immunotherapies represents a recent paradigm shift in the management of HNSCC. This review is a concise summary of the clinical progress and ongoing trials in immunotherapy for HNSCC, highlighting the dynamic landscape of treatment approaches in this challenging disease context.

Predictors of Outcomes After Gastric Peroral Endoscopic Myotomy for Refractory Gastroparesis: A Systematic Review.

Gastroparesis is a debilitating gastroduodenal disorder for which gastric peroral endoscopic myotomy (GPOEM) has emerged as an efficacious treatment option. However, response to GPOEM varies between 50% and 80%, such that preoperative predictors of treatment success are needed to guide patient selection. We performed a systematic review to identify predictors of clinical and functional response to GPOEM among adult patients with gastroparesis (PROSPERO: CRD42023457359). MEDLINE, Embase, and CENTRAL databases were searched systematically for studies reporting outcomes after GPOEM in September 2023. A narrative synthesis of predictive factors on univariable and multivariable analysis was performed with consideration of response rates through meta-analysis and evaluation of discrimination if prognostic models were developed. Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) was used for risk of bias assessment. Of 1899 articles reviewed, 30 were included. The GPOEM response rate was 63.1% (95% confidence interval 56.3%-69.5%) with most studies defining clinical success on the basis of improvement in gastroparesis cardinal symptom index (87%, 26/30). Older age, shorter duration of gastroparesis, nondiabetic etiology, lower body mass index, and response to intrapyloric botulinum toxin were associated with positive response to GPOEM on multivariable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation. Currently, there are limited reproducible predictors of response to GPOEM among patients with refractory gastroparesis. Robust prospective studies investigating scalable, reproducible, and actionable biomarkers of treatment response are required.

Human GM-CSF/IL-3 enhance tumor immune infiltration in humanized HCC patient-derived xenografts

Background & AimsResponses to immunotherapies in hepatocellular carcinoma (HCC) are suboptimal with no biomarkers to guide patient selection. “Humanized” mice represent promising models to address this deficiency but are limited by variable chimerism and underdeveloped myeloid compartments. We hypothesized that expression of human GM-CSF and IL-3 increases tumor immune cell infiltration, especially myeloid-derived cells, in humanized HCC patient-derived xenografts (PDXs). Material and MethodsNOG (NOD/Shi-scid/IL-2Rγnull) and NOG-EXL (huGM-CSF/huIL-3 NOG) mice conditioned with Busulfan underwent i.v. injection of human CD34+ cells. HCC PDX tumors were then implanted subcutaneously (SQ) or orthotopically (OT). Following serial blood sampling, mice were euthanized at defined tumor sizes. Tumor, blood, liver, and spleen were analyzed by flow cytometry and immunohistochemistry. ResultsHumanized NOG-EXL mice demonstrated earlier and increased human chimerism compared to humanized NOG mice (82.1% vs 43.8%, p<0.0001) with increased proportion of human monocytes (3.2% vs 1.1%, p=0.001) and neutrophils (0.8% vs 0.3%, p=0.02) in circulation. HCC tumors in humanized NOG-EXL mice had increased human immune cell infiltration (57.6% vs 30.2%, p=0.04), noting increased regulatory T cells (14.6% vs 6.8%, p=0.04), CD4+ PD-1 expression (84.7% vs 32.0%, p<0.01), macrophages (1.2% vs 0.6%, p=0.02), and neutrophils (0.5% vs 0.1%, p<0.0001). No differences were observed in tumor engraftment or growth latency in SQ tumors, but OT tumors required implantation at two rather than four weeks post-humanization for successful engraftment. Finally, utilizing adult bone marrow instead of fetal livers enabled partial HLA-matching to HCC tumors but required more CD34+ cells. ConclusionsHuman GM-CSF and IL-3 expression in humanized mice resulted in features more closely approximating the immune microenvironment of human disease, providing a promising model for investigating critical questions in immunotherapy for HCC. Impact and ImplicationsThis study introduces a unique mouse model at a critical point in the evolution of treatment paradigms for patients with hepatocellular carcinoma (HCC). Immunotherapies have become first line treatment for advanced HCC; however, response rates remain low with no clear predictors of response to guide patient selection. In this context, animal models that recapitulate human disease are greatly needed. Leveraging xenograft tumors derived from patients with advanced HCCs and a commercially available immunodeficient mouse strain that expresses human GM-CSF and IL-3, we demonstrate a novel but accessible approach for modeling the HCC tumor microenvironment.

Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension.

The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved. We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular-pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660-0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656-0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference -0.072, 95% CI -0.123 to -0.020, p = 0.006, and -0.043, 95% CI -0.067 to -0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all). Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.

Impact of psychosocial factors on the success of neuromodulation treatment for patients with persistent pain

IntroductionSignificant interindividual variability in spinal cord stimulation (SCS) outcomes exists. Due to its high cost and risks of complications, criteria to guide patient selection for SCS trials and their outcomes...

A Proposed Patient Selection Algorithm for Total Joint Arthroplasty Same-Day Discharge From an Ambulatory Surgery Center

BackgroundIdentifying appropriate patients for same-day discharge (SDD) total joint arthroplasty (TJA) is critical for maintaining optimal patient safety and outcomes. This study investigated patient outcomes after SDD TJA at a single ambulatory surgery center (ASC) and proposes a TJA patient-selection algorithm based on findings and existing literature. MethodsA retrospective chart review of 660 patients was performed between July 2019 and October 2021 for all patients who underwent primary TJA in a single ASC. Successful SDD, length of surgery, estimated blood loss (EBL), complications, and readmission events were recorded for each patient. There were 20 total complications in 331 primary total knee arthroplasties (TKAs) (6.0%) and 15 total complications in 329 primary total hip arthroplasties (THAs) (4.6%). ResultsThere was one direct admission to the hospital in TKA patients and four direct admissions in THA patients, making the successful SDD rate 99.7% in TKAs, 98.8% in THAs, and 99.2% overall. In the TKA cohort, body mass index was associated with total complications (r = −0.15, P = 0.006); comorbidities with wound complications (P = 0.006); and EBL was with readmissions (r = 0.30, P < 0.001), revision surgery (r = 0.12, P = 0.04), and total complications (r = 0.16, P = 0.03). In the THA cohort, body mass index was weakly associated with wound complications (r = −0.12, P = 0.02), EBL was with emergency department visits (r = 0.18, P = 0.002) and total complications (r = 0.14, P = 0.01). However, there was no direct association between any of the analyzed characteristics and direct admission. ConclusionsIn our ASC cohort, patients had low rates of perioperative complications and hospital admissions, supporting the safety of SDD TJA using our proposed evidence-based algorithm to guide patient selection for SDD.

Predictors of long-term success after high-density mapping-guided substrate ablation procedures for ventricular tachycardia in patients with ischemic cardiomyopathy.

High-density (HD) substrate mapping may increase success of catheter ablation targeting ventricular tachycardia (VT). However, despite its use, recurrent VT is not uncommon. We aim to investigate factors that are associated with outcomes after HD mapping-guided substrate ablation procedures for VT in patients with ischemic cardiomyopathy. Observational cohort study includes patients with ischemic heart disease who underwent HD mapping-guided substrate ablation of VT. Baseline and procedural characteristics were associated with outcomes after VT ablation. VT ablation employing HD mapping was performed in 80 patients. Median follow-up was 2.3 years. VT-free survival at one, two, and five years were 65%, 49%, and 40%. One-, two-, and five-year implantable cardioverter defibrillator (ICD) shock-free survival rates were 90%, 81%, and 70%. Complications occurred in 3 patients (3.8%, 1 vascular, 2 tamponades). Left ventricular ejection fraction (LVEF) and 45 W (vs. 35 W) ablation power were associated with VT-free survival. High ablation power was also associated with shock-free survival. All-cause mortality during follow-up was associated with higher age, the presence of chronic obstructive pulmonary disease (COPD), LVEF, and urgent ablation. In patients with ischemic cardiomyopathy that had HD substrate mapping-guided VT ablation, ablation power was associated with both VT-free and shock-free survival, underlining the importance of effective target elimination. All-cause mortality during follow-up was associated with several factors (age, COPD, LVEF, and urgent vs. elective ablation), which could be used to guide patient selection for VT ablation.

Interleukin-6, C-Reactive Protein, and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data.

Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials. Optimal timing of hsCRP/IL-6 measurement poststroke is unknown, as early blood levels may be confounded by the inflammatory response to brain infarction. Using individual-participant data from a systematic review, we performed a time-course analysis to investigate the association between hsCRP/IL-6 and recurrent events stratified by timing of sampling. The prespecified coprimary end points after sample measurement were: (1) recurrent major adverse cardiovascular events (first major coronary event, recurrent stroke, or vascular death) and (2) recurrent stroke (ischemic, hemorrhagic, or unspecified). The poststroke dynamics of IL-6/hsCRP were analyzed by plotting their median (interquartile interval) concentrations within each tenth of the sampling timeframe. Acute/postacute phases were defined for each biomarker according to the shape of this relationship. There were data for 9798 patients from 11 studies (19 891 person-years follow-up, 10 observational cohorts, and 1 randomized trial). Each marker was measured once. IL-6 was markedly elevated <24 hours poststroke compared with postacute levels (≥24 hours; 11.6 versus 3.02 pg/mL; P<0.001). HsCRP was elevated for 10 days. IL-6 was associated with recurrent major adverse cardiovascular events in the postacute phase (≥24 hours; risk ratio, 1.30 [CI, 1.19-1.41], per unit logeIL-6), but not in the acute phase (<24 hours; risk ratio, 1.10 [CI, 0.98-1.25]; Pinteraction=0.03). After adjustment for risk factors/medication, the association remained for postacute IL-6 when analyzed per logeunit (risk ratio, 1.16 [CI, 1.05-1.66]) and per quarter increase (risk ratio, 1.55 [CI, 1.19-2.02]; Q4 versus Q1), but not if measured acutely. Similar findings were observed for recurrent stroke. There was no evidence of time-dependent interaction with hsCRP. Timing of sample measurement after stroke modifies the association with recurrent major adverse cardiovascular events for IL-6 but not hsCRP. These data inform future randomized controlled trial designs incorporating biomarker-based selection of patients for anti-inflammatory therapies.

Non-invasive imaging to guide percutaneous coronary revascularization in chronic total occlusion: a systematic review and meta-analysis

Abstract Background and aims Whether recanalization of coronary chronic total occlusions (CTO) leads to improved patient outcomes is uncertain. We set out to investigate the use of noninvasive imaging modalities to guide patient selection for percutaneous recanalization of coronary chronic total occlusions (CTO-PCI) and its association with outcomes. Methods Systematic review and meta-analysis of studies involving patients undergoing CTO-PCI to detail use of preprocedural non-invasive imaging, change in clinical endpoints and the occurrence of clinical events in these patient cohorts. PubMed and Embase, the Cochrane Database of Systematic Reviews, the PROSPERO database and the Clinical Trials Registry were searched for relevant randomized and observational studies up to May 2023. This study is registered with PROSPERO. The study primary endpoint was a composite of all-cause death and nonfatal myocardial infarction (MI), with a secondary composite endpoint of cardiovascular death, nonfatal MI and target vessel revascularization (TVR). Additional endpoints were individual components of the composite endpoints along with changes in angina burden, LV ejection fraction, ischemic burden, and infarct extent after PCI. Results Of 1264 publications retrieved, 31 studies (26 observational and 5 randomized) were finally included for a total of 7260 patients. Guidance to CTO-PCI varied greatly among included studies, with only a minority implementing routine preprocedural inducible ischemia and myocardial viability assessment. At a median of 3.1 years (range 1-5 years), the primary endpoint occurred at a rate of 3.1 events per 100 patient-years (95%CI: 2.4-3.7). When non-invasive imaging was used to guide CTO-PCI, patients with myocardial ischemia and/or viability, a reduced risk for the primary endpoint was observed (OR 0.3 95%CI 0.2-0.5) compared to CTO-PCI without evidence of myocardial ischemia and/or viability. CTO-PCI was associated with improvements in SAQ summary score, LVEF, reduction of ischemic burden, improvement in myocardial perfusion (all P-values &amp;lt; 0.01), with no change in the burden of myocardial scarring. At meta-regression analysis, a greater improvement in LVEF was observed in studies enrolling patients with lower average baseline LVEF (≤ 45%) (R2 = 63%, p &amp;lt; 0.0001). Conclusions CTO-PCI led to a significant improvement in symptom status (reduction of chest pain) and LV ejection fraction. CTO-PCI guided by the presence of ischemia and/or viability was associated with improved patient outcomes compared with CTO-PCI in the absence of ischemia and/viability, or in patients where non-invasive imaging testing was not performed. Future randomized clinical trials testing whether ischemia and viability-guided CTO-PCI improves clinical outcomes are lacking and warranted.PRISMA Flow diagramGraphical abstract

An Updated Evaluation of the Management of Nerve Gaps: Autografts, Allografts, and Nerve Transfers.

Within the past decade, there have been multiple innovations in the field of nerve surgery. In this review, we highlight critical changes and innovations that have helped advance the field and present opportunities for further study. This includes the modification and clarification of the classification schema for nerve injuries which informs prognosis and treatment, and a refined understanding and application of electrodiagnostic studies to guide patient selection. We provide indications for operative intervention based on this nerve injury classification and propose strategies best contoured for varying injury presentations at differing time points. Lastly, we discuss new developments in surgical techniques and approaches based on these advancements.

Assessment of predictors of acute kidney injury and progression to chronic kidney disease following bariatric surgery

BackgroundDespite the overall safety of metabolic and bariatric surgery (MBS), the potential for postoperative complications such as acute kidney injury (AKI) remains a critical concern. Decade-old studies from our institution reported rates of AKI following MBS between 5.8% and 8.6%, with factors such as higher body mass index (BMI), diabetes, and hypertension identified as potential contributors. However, the incidence and factors associated with AKI following MBS have remained underexplored in contemporary literature. ObjectivesTo investigate the incidence and risk factors associated with postoperative AKI, as well as the potential for progression to CKD and renal failure. SettingQuaternary academic medical center with a high-volume MBS practice. MethodsA retrospective review of adult patients undergoing primary laparoscopic MBS between 2008 and 2022 to identify patients who developed AKI, defined as postoperative increase in serum creatinine (sCr) by .3 mg/dL within 72 hours. A multivariable logistic regression was constructed to identify potential AKI risk factors. ResultsAmong 1697 patients, the incidence of AKI was 3.0% (n = 51). The distribution of AKI was not significantly different between procedure types. There was no significant correlation between anesthesia medications given and the occurrence of AKI. Male gender was the most significant predictor of AKI (adjusted odds ratio [aOR] = 3.87, 95% confidence interval {CI} [2.14–6.99]), followed by hypertension (aOR = 2.12, 95% CI [1.03–4.83]) and longer surgical duration (aOR = 1.19, 95% CI [1.05–1.35]) per 30 minutes. Of those who developed AKI, 7 (13.7%) required dialysis acutely for management, while 3 patients (5.9%) progressed to chronic renal failure and required transplant. ConclusionsAKI is a rare but serious complication following MBS that occurs in approximately 3% of cases. AKI incidence is higher in male patients, those with hypertension, insulin-requiring diabetes, renal insufficiency, and longer procedure durations. Heightened awareness of the identified risk factors should help guide patient selection, and additional efforts should be directed towards refining postoperative follow-up.