AptBCis1, An Aptamer-Cisplatin Conjugate, Is Effective in Lung Cancer Leptomeningeal Carcinomatosis.

Treatment of lung cancer leptomeningeal carcinomatosis (LM) remains challenging partly due to the biological nature of the blood-brain barrier (BBB). Cisplatin has limited effects on LM, and it is notorious for neurotoxicity. Aptamers are small oligonucleotides considered as antibody surrogates. Here we report a DNA therapeutics, AptBCis1. AptBCis1 is a cisplatin-conjugated, BBB-penetrating, and cancer-targeting DNA aptamer. Its backbone, AptB1, was identified via in vivo SELEX using lung cancer LM orthotopic mouse models. The AptB1 binds to EAAT2, Nucleolin, and YB-1 proteins. Treatment with AptBCis1 1 mg/kg (equivalent to cisplatin 0.35 mg/kg) showed superior tumor suppressive effects compared to cisplatin 2 mg/kg in mice with lung cancer LM diseases. The cerebrospinal fluid platinum concentration in the AptBCis1 group was 10% of that in the cisplatin group. The data suggested the translational potential of AptBCis1 in lung cancer with LM and in cancers in which platinum-based chemotherapy remains as the standard of care.

Systems profiling reveals recurrently dysregulated cytokine signaling responses in ER+ breast cancer patients' blood.

Cytokines operate in concert to maintain immune homeostasis and coordinate immune responses. In cases of ER+ breast cancer, peripheral immune cells exhibit altered responses to several cytokines, and these alterations are correlated strongly with patient outcomes. To develop a systems-level understanding of this dysregulation, we measured a panel of cytokine responses and receptor abundances in the peripheral blood of healthy controls and ER+ breast cancer patients across immune cell types. Using tensor factorization to model this multidimensional data, we found that breast cancer patients exhibited widespread alterations in response, including drastically reduced response to IL-10 and heightened basal levels of pSmad2/3 and pSTAT4. ER+ patients also featured upregulation of PD-L1, IL6Rα, and IL2Rα, among other receptors. Despite this, alterations in response to cytokines were not explained by changes in receptor abundances. Thus, tensor factorization helped to reveal a coordinated reprogramming of the immune system that was consistent across our cohort.

Design of a Compact Multicyclic High-Performance Atmospheric Water Harvester for Arid Environments.

Water scarcity remains a grand challenge across the globe. Sorption-based atmospheric water harvesting (SAWH) is an emerging and promising solution for water scarcity, especially in arid and noncoastal regions. Traditional approaches to AWH such as fog harvesting and dewing are often not applicable in an arid environment (<30% relative humidity (RH)), whereas SAWH has demonstrated great potential to provide fresh water under a wide range of climate conditions. Despite advances in materials development, most demonstrated SAWH devices still lack sufficient water production. In this work, we focus on the adsorption bed design to achieve high water production, multicyclic operation, and a compact form factor (high material loading per heat source contact area). The modeling efforts and experimental validation illustrate an optimized design space with a fin-array adsorption bed enabled by high-density waste heat, which promises 5.826 Lwater kgsorbent -1 day-1 at 30% RH within a compact 1 L adsorbent bed and commercial adsorbent materials.

Optimizing accrual to a large-scale, clinically integrated randomized trial in anesthesiology: A 2-year analysis of recruitment.

BACKGROUND: Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time. METHODS: This is an interim analysis of recruitment to a cluster-randomized trial investigating three nerve block approaches for mastectomy with immediate implant-based reconstruction: paravertebral block (arm 1), paravertebral plus interpectoral plane blocks (arm 2), and serratus anterior plane plus interpectoral plane blocks (arm 3). We monitored accrual and consent rates, clinician compliance with the randomized treatment, and availability of outcome data. Assessment after the initial year of implementation showed a slight imbalance in study arms suggesting areas for improvement in trial compliance. Specific improvement interventions included increasing the frequency of communication with the consenting staff and providing direct feedback to clinician investigators about their individual recruitment patterns. We assessed overall accrual rates and tested for differences in accrual, consent, and compliance rates pre- and post-improvement interventions. RESULTS: Overall recruitment was extremely high, accruing close to 90% of the eligible population. In the pre-intervention period, there was evidence of bias in the proportion of patients being accrued and receiving the monthly block, with higher rates in arm 3 (90%) compared to arms 1 (81%) and 2 (79%, p = 0.021). In contrast, in the post-intervention period, there was no statistically significant difference between groups (p = 0.8). Eligible for randomization rate increased from 89% in the pre-intervention period to 95% in the post-intervention period (difference 5.7%; 95% confidence interval = 2.2%-9.4%, p = 0.002). Consent rate increased from 95% to 98% (difference of 3.7%; 95% confidence interval = 1.1%-6.3%; p = 0.004). Compliance with the randomized nerve block approach was maintained at close to 100% and availability of primary outcome data was 100%. CONCLUSION: The clinically integrated randomized trial design enables rapid trial accrual with a high participant compliance rate in a high-volume anesthesiology practice. Continuous monitoring of accrual, consent, and compliance rates is necessary to maintain and improve trial conduct and reduce potential biases. This trial methodology serves as a template for the implementation of other large, low-cost randomized trials in anesthesiology.

Beyond the cuff: a consideration of factors that affect sexual function after benign hysterectomy.

PURPOSE OF REVIEW: Hysterectomy is the most common gynecologic surgical procedure performed on women in the United States. While there are data supporting that hysterectomy for benign indication often does not reduce sexual function and may in fact improve sexual function as fibroids and endometriosis are resected, it remains unclear if there are factors within the perioperative period that affect sexual function in the years following surgery. To date, there is no consensus on what factors can optimize patients' sexual function after hysterectomy. RECENT FINDINGS: We present the current literature that assesses factors which may contribute to sexual function after hysterectomy. Preoperative demographic factors, including increasing age, pelvic pain, and preoperative sexual dysfunction, play a large role in postoperative sexual function. Perioperatively, there is a growing amount of data suggesting that premenopausal salpingo-oophorectomy at the time of hysterectomy may increase the risk of sexual dysfunction after hysterectomy, and no conclusive evidence that subtotal hysterectomy improves sexual function. The route of hysterectomy and technique of cuff closure can impact sexual function after hysterectomy due to the risk of shortening the vaginal length. SUMMARY: There is a lack of high-quality evidence that can provide a consensus on factors to optimize sexual function after hysterectomy. A growing area of research in the excision of endometriosis procedures is the consideration of nerve-sparing surgery. Considering the many variables that exist when counseling a patient on benign hysterectomy and its effects on sexual function, it is critical to understand the current research that exists with regards to these factors.

Preventing Readmissions of Hepatic Encephalopathy: Strategies in the Acute Inpatient, Immediate Postdischarge, and Longitudinal Outpatient Setting.

Hepatic encephalopathy (HE) is a strong predictor of early hospital readmission in patients with cirrhosis. Early hospital readmission increases health care costs and is associated with worse survival. Herein we provide an overview of strategies to prevent hospital readmissions in patients with HE, divided into 3 contexts: (a) acute inpatient, (b) immediate postdischarge, and (c) longitudinal outpatient setting.

Semi-supervised Learning for Generalizable Intracranial Hemorrhage Detection and Segmentation.

Purpose To develop and evaluate a semi-supervised learning model for intracranial hemorrhage detection and segmentation on an out-of-distribution head CT evaluation set. Materials and Methods This retrospective study used semi-supervised learning to bootstrap performance. An initial "teacher" deep learning model was trained on 457 pixel-labeled head CT scans collected from one U.S. institution from 2010 to 2017 and used to generate pseudo labels on a separate unlabeled corpus of 25 000 examinations from the Radiological Society of North America and American Society of Neuroradiology. A second "student" model was trained on this combined pixel- and pseudo-labeled dataset. Hyperparameter tuning was performed on a validation set of 93 scans. Testing for both classification (n = 481 examinations) and segmentation (n = 23 examinations, or 529 images) was performed on CQ500, a dataset of 481 scans performed in India, to evaluate out-of-distribution generalizability. The semi-supervised model was compared with a baseline model trained on only labeled data using area under the receiver operating characteristic curve, Dice similarity coefficient, and average precision metrics. Results The semi-supervised model achieved a statistically significant higher examination area under the receiver operating characteristic curve on CQ500 compared with the baseline (0.939 [95% CI: 0.938, 0.940] vs 0.907 [95% CI: 0.906, 0.908]; P = .009). It also achieved a higher Dice similarity coefficient (0.829 [95% CI: 0.825, 0.833] vs 0.809 [95% CI: 0.803, 0.812]; P = .012) and pixel average precision (0.848 [95% CI: 0.843, 0.853]) vs 0.828 [95% CI: 0.817, 0.828]) compared with the baseline. Conclusion The addition of unlabeled data in a semi-supervised learning framework demonstrates stronger generalizability potential for intracranial hemorrhage detection and segmentation compared with a supervised baseline. Keywords: Semi-supervised Learning, Traumatic Brain Injury, CT, Machine Learning Supplemental material is available for this article. Published under a CC BY 4.0 license. See also the commentary by Swimburne in this issue.

Paravertebral and erector spinae plane blocks decrease length of stay compared with local infiltration analgesia in autologous breast reconstruction.

BACKGROUND: Autologous breast reconstruction is associated with significant pain impeding early recovery. Our objective was to evaluate the impact of replacing surgeon-administered local infiltration with preoperative paravertebral (PVB) and erector spinae plane (ESP) blocks for latissimus dorsi myocutaneous flap reconstruction. METHODS: Patients who underwent mastectomy with latissimus flap reconstruction from 2018 to 2022 were included in three groups: local infiltration, PVB, and ESP blocks. Block effect on postoperative length of stay (LOS) and the association between block status and pain, opioid consumption, time to first analgesic, and postoperative antiemetic administration were assessed. RESULTS: 122 patients met the inclusion criteria for this retrospective cohort study: no block (n=72), PVB (n=26), and ESP (n=24). On adjusted analysis, those who received a PVB block had a 20-hour shorter postoperative stay (95% CI 11 to 30; p<0.001); those who received ESP had a 24-hour (95% CI 15 to 34; p<0.001) shorter postoperative stay compared with the no block group, respectively. Using either block was associated with a reduction in intraoperative opioids (23 morphine milligram equivalents (MME)), 95% CI 14 to 31, p<0.001; ESP versus no block: 23 MME, 95% CI 14 to 32, p<0.001). CONCLUSIONS: Replacing surgical infiltration with PVB and ESP blocks for autologous breast reconstruction reduces LOS. The comparable reduction in LOS suggests that ESP may be a viable alternative to PVB in patients undergoing latissimus flap breast reconstruction following mastectomy. Further research should investigate whether ESP or PVB have better patient outcomes in complex breast reconstruction.

Regional Blocks Benefit Patients Undergoing Bilateral Mastectomy with Immediate Implant-Based Reconstruction, Even After Discharge.

BACKGROUND: There is limited evidence that regional anesthesia reduces pain in patients undergoing mastectomy with immediate implant-based reconstruction. We sought to determine whether regional blocks reduce opioid consumption and improve post-discharge patient-reported pain in this population. METHODS: We retrospectively reviewed patients who underwent bilateral mastectomy with immediate implant-based reconstruction with and without a regional block. We tested for differences in opioid consumption by block receipt using multivariable ordinal regression, and also assessed routinely collected patient-reported outcomes (PROs) for 10 days postoperatively and tested the association between block receipt and moderate or greater pain. RESULTS: Of 754 patients, 89% received a block. Non-block patients had an increase in the odds of requiring a higher quartile of postoperative opioids. Among block patients, the estimated probability of being in the lowest quartile of opioids required was 25%, compared with 15% for non-block patients. Odds of patient-reported moderate or greater pain after discharge was 0.54 times lower in block patients than non-block patients (p = 0.025). Block patients had a 49% risk of moderate or greater pain compared with 64% in non-block patients on postoperative day 5. There was no indication of any reason for these differences other than a causal effect of the block. CONCLUSION: Receipt of a regional block resulted in reduced opioid use and lower risk of self-reported moderate and higher pain after discharge in bilateral mastectomy with immediate implant-based reconstruction patients. Our use of PROs suggests that the analgesic effects of blocks persist after discharge, beyond the expected duration of a 'single shot' block.

Change in Systemic Arterial Pulsatility Index (SAPi) during Heart Failure Hospitalization is Associated with Improved Outcomes.

Study Objective: To identify Change in Systemic Arterial Pulsatitlity index (ΔSAPi) as a novel hemodynamic marker associated with outcomes in heart failure (HF). Design: The ESCAPE trial was a randomized controlled trial. Setting: The ESCAPE trial was conducted at 26 sites. Participants: 134 patients were analyzed (mean age 56.8 ± 13.4 years, 29% female). Interventions: We evaluated the change in SAPi, ([systemic pulse pressure/pulmonary artery wedge pressure) obtained at baseline and at the final hemodynamic measurement in the ESCAPE trial. Main Outcome Measures: Change in SAPi, (ΔSAPi), was analyzed for the primary outcomes of death, heart transplant, left ventricular assist device (DTxLVAD) or hospitalization, (DTxLVADHF) and secondary outcome of DTxLVAD using Cox proportional hazards regression. Results: Median change in SAPi was 0.81 (IQR 0.20-1.68). ΔSAPi in uppermost quartile was associated with reductions in DTxLVADHF (HR 0.55 [95% CI 0.32, 0.93]). ΔSAPi in the uppermost and lowermost quartiles combined was similarly associated with significant reductions in DTxLVADHF (HR 0.62 [95% CI 0.41, 0.94]). ΔSAPi higher than 1.17 was associated with improved DTxLVADHF. ΔSAPi was also associated with troponin levels at discharge (regression coefficient p = 0.001) and trended with 6-minute walk at discharge (Spearman correlation r = 0.179, p = 0.058). Conclusion: ΔSAPi was strongly associated with improved HF clinical profile and adverse outcomes. These findings support further exploration of Δ SAPi in the risk stratification of HF.

Outcomes and Resource Utilization in Liver Transplant Recipients Who Underwent Expedited Transplant Evaluation.

BACKGROUND: Expedited liver transplant evaluations of critically ill patients can be challenging due to limited time for data gathering and psychosocial evaluation. AIMS: To compare clinical outcomes between expedited and traditional transplant evaluation patients and assess for differences in outpatient resource utilization and staff burden between groups. DESIGN: Adult liver transplant recipients who underwent transplant from 2015 to 2019 were included. Expedited evaluation was defined as time from initiating transplant evaluation to transplant listing <2 weeks. Primary outcomes included rates of graft rejection, graft failure, and death within 1-year posttransplant. Secondary outcomes included number of acute care visits, office visits, and medical record documentation made by transplant staff within 1-year posttransplant. Outcomes were compared using Cox regression models. RESULTS: Of the 335 patients included, 92 (27.5%) were expedited and 243 (72.5%) were traditional. Expedited patients were significantly younger, had greater MELD scores, and required more inpatient care and life support at time of transplant. There was no significant difference in risk of graft rejection (HR 1.3, P = .4), graft failure (HR 1.3, P = .6), or mortality (HR 1.0, P = .9) between groups. Expedited transplant was not associated with increased healthcare or staff utilization: acute care visits (rate ratio 0.9, P = .7), office visits (ß = -1.05, P = .2), and medical record documentation (ß = 3.4, P = 0.4). CONCLUSIONS: Despite being more critically ill, patients requiring expedited transplant evaluation have favorable outcomes after transplant and do not require more intensive staff time and resources compared to traditional candidates.

Growing pains: strategies for improving ergonomics in minimally invasive gynecologic surgery.

PURPOSE OF REVIEW: To evaluate factors contributing to the development of work-related musculoskeletal disorders (WMSDs) and review strategies for mitigating ergonomic strain in minimally invasive gynecologic surgery. RECENT FINDINGS: Factors associated with increased ergonomic strain and the development of WMSDs include increasing patient body mass index (BMI), smaller surgeon hand size, noninclusive design of instruments and energy devices and improper positioning of surgical equipment. Each type of minimally invasive surgery (laparoscopic, robotic, vaginal) confers its own ergonomic risk to the surgeon. Recommendations have been published regarding optimal ergonomic surgeon and equipment positioning. Intraoperative breaks and stretching are effective in reducing surgeon discomfort. Formal training in ergonomics has not yet been widely implemented, but educational interventions have been effective in reducing surgeon discomfort and can improve surgeon recognition of suboptimal ergonomics. SUMMARY: Considering the serious downstream effects of WMSDs on surgeons, it is imperative to implement strategies for WMSD prevention. Optimal positioning of the surgeons and operative equipment should be routine. Intraoperative breaks and stretching should be incorporated during procedures and between every case. Formal education in ergonomics should be provided to surgeons and trainees. Additionally, more inclusive instrument design by industry partners should be prioritized.

Plasmonic Response of Complex Nanoparticle Assemblies.

Optical properties of nanoparticle assemblies reflect distinctive characteristics of their building blocks and spatial organization, giving rise to emergent phenomena. Integrated experimental and computational studies have established design principles connecting the structure to properties for assembled clusters and superlattices. However, conventional electromagnetic simulations are too computationally expensive to treat more complex assemblies. Here we establish a fast, materials agnostic method to simulate the optical response of large nanoparticle assemblies incorporating both structural and compositional complexity. This many-bodied, mutual polarization method resolves limitations of established approaches, achieving rapid, accurate convergence for configurations including thousands of nanoparticles, with some overlapping. We demonstrate these capabilities by reproducing experimental trends and uncovering far- and near-field mechanisms governing the optical response of plasmonic semiconductor nanocrystal assemblies including structurally complex gel networks and compositionally complex mixed binary superlattices. This broadly applicable framework will facilitate the design of complex, hierarchically structured, and dynamic assemblies for desired optical characteristics.

Practice Patterns and Outcomes of Patients With Retained Gastric Food Content Encountered During Endoscopy.

INTRODUCTION: Retained gastric food content encountered during upper endoscopy may reduce diagnostic accuracy and increase the risk of aspiration. The aim of this study was to evaluate endoscopists' practice patterns and clinical outcomes in patients with retained gastric food content encountered during endoscopy. METHODS: Consecutive patients with retained gastric food content during first-time endoscopy at Loma Linda University Health (January 2016-March 2021) were identified. Primary endpoints were a complete examination (deep duodenal intubation) and 30-day postprocedural respiratory adverse events. RESULTS: Of 17,868 patients undergoing endoscopy, 629 (3.5%) (mean age 55 ± 17 years) met inclusion criteria. Moderate sedation was performed in 506 (80.4%), anesthesiologist-assisted sedation in 16 (2.5%), and general anesthesia in 107 (17.0%) patients. 534 (84.9%) patients received a complete examination, and endoscopist-specific completion rates varied by quintile among 26 endoscopists (range 70.3%-98.0%, P < 0.0001). Large food gastric content decreased (adjusted odds ratio [aOR] 0.3, 95% confidence interval [CI] 0.2-0.4) while obtaining mucosal biopsies increased (aOR 2.5, 95% CI 1.4-4.7) the likelihood of complete examination after adjusting for endoscopist-specific completion rates. Subsequently, 58 (9.2%) patients required repeat endoscopy within 30 days. During follow-up, 41 (6.5%) patients developed respiratory adverse events including 21 (3.3%) requiring ventilatory support. Hospitalized patients (aOR 37.8, 95% CI 4.9-289.0) compared with outpatients and large compared with small gastric food content (aOR 2.1, 95% CI 1.1-4.2) increased the likelihood of respiratory adverse events. DISCUSSION: Although deep duodenal intubation was achieved in most patients receiving endoscopy, the rate of complete examination varied among individual endoscopists and the extent of food burden. Respiratory adverse events occurred almost exclusively in hospitalized patients and were associated with high morbidity including half developing respiratory failure.

Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors.

Background: Whether influenza vaccination (FV) is associated with the severity of immune-related adverse events (IRAEs) in patients with advanced thoracic cancer on immune checkpoint inhibitors (ICIs) is not fully understood. Methods: Patients enrolled in this retrospective cohort study were identified from the Vanderbilt BioVU database and their medical records were reviewed. Patients with advanced thoracic cancer who received FV within 3 months prior to or during their ICI treatment period were enrolled in the FV-positive cohort and those who did not were enrolled in the FV-negative cohort. The primary objective was to detect whether FV is associated with decreased IRAE severity. The secondary objectives were to evaluate whether FV is associated with a decreased risk for grade 3-5 IRAEs and better survival times. Multivariable ordinal logistic regression was used for the primary analysis. Results: A total of 142 and 105 patients were enrolled in the FV-positive and FV-negative cohorts, respectively. There was no statistically significant difference in patient demographics or cumulative incidences of IRAEs between the two cohorts. In the primary analysis, FV was inversely associated with the severity of IRAEs (OR 0.63; p=0.046). In the secondary analysis, FV was associated with a decreased risk for grade 3-5 IRAEs (OR 0.42; p=0.005). Multivariable Cox regression showed that FV was not associated with survival times. Conclusions: Our study showed that FV does not increase toxicity for patients with advanced thoracic cancer on ICIs and is associated with a decreased risk for grade 3-5 IRAEs. No statistically significant survival differences were found between patients with and without FV.

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit.

INTRODUCTION: Survival benefit of immune checkpoint inhibitor (ICI) therapy in lung cancer is not fully understood. METHODS: PubMed-cataloged publications through February 14, 2022, were queried for randomized controlled trials of ICI in lung cancer, and identified publications were reviewed for inclusion. Reported Cox hazard ratios (HRs) for overall survival were transformed to Cox-TEL HR for ICI short-term survivors (ST-HR) and difference in proportions for patients with long-term survival (LT-DP). Meta-analyses were performed using a frequentist random-effect model. Outcomes of interest were pooled overall survival Cox HR, ST-HR, and LT-DP in NSCLC, stratified by programmed death-ligand 1 (PD-L1) level (primary outcome) and ICI treatment line (secondary). RESULTS: A total of nine publications representing eight clinical trials were selected for meta-analysis. Primary analysis yielded the following metrics for patients with PD-L1 expression less than 1%, more than or equal to 1%, and more than or equal to 50%, respectively: pooled Cox HR, 0.71 (95% confidence interval [CI]: 0.62-0.82), 0.74 (95% CI: 0.68-0.82), and 0.62 (95% CI: 0.54-0.70); pooled ST-HR, 0.91 (95% CI: 0.79-1.05), 0.88 (95% CI: 0.82-0.94), and 0.70 (95% CI: 0.60-0.83); and pooled LT-DP, 0.10 (95% CI: 0.00-0.20), 0.09 (95% CI: 0.06-0.12), and 0.11 (95% CI: 0.05-0.17). Results of secondary analysis revealed LT-DP of approximately 10% across treatment lines. CONCLUSIONS: This study reveals an approximately 10% long-term survival probability increment in ICI long-term survivors across PD-L1-positive subpopulations in both ICI treatment lines. Furthermore, ST-HR was consistently poorer than Cox HR. For patients with PD-L1 less than 1%, neither LT-DP nor ST-HR achieved statistical significance. The analysis provides greater insight into the treatment effect of ICI in published trials.

Analysis of Cancer Survival Associated With Immune Checkpoint Inhibitors After Statistical Adjustment: A Systematic Review and Meta-analyses.

Importance: Appropriate clinical decision-making relies on accurate data interpretation, which in turn relies on the use of suitable statistical models. Long tails and early crossover-2 features commonly observed in immune checkpoint inhibitor (ICI) survival curves-raise questions as to the suitability of Cox proportional hazards regression for ICI survival analysis. Cox proportional hazards-Taylor expansion adjustment for long-term survival data (Cox-TEL) adjustment may provide possible solutions in this setting. Objective: To estimate overall survival and progression-free survival benefits of ICI therapy vs chemotherapy using Cox-TEL adjustment. Data Sources: A PubMed search was performed for all cataloged publications through May 22, 2022. Study Selection: The search was restricted to randomized clinical trials with search terms for ICIs and lung cancer, melanoma, or urothelial carcinoma. The publications identified were further reviewed for inclusion. Data Extraction and Synthesis: Cox proportional hazards ratios (HRs) were transformed to Cox-TEL HRs for patients with short-term treatment response (ie, short-term survivor) (ST-HR) and difference in proportions for patients with long-term survival (LT-DP) by Cox-TEL. Meta-analyses were performed using a frequentist random-effects model. Main Outcomes and Measures: Outcomes of interest were pooled overall survival (primary outcome) and progression-free survival (secondary outcome) HRs, ST-HRs, and LT-DPs. Subgroup analyses stratified by cancer type also were performed. Results: A total of 1036 publications was identified. After 3 levels of review against inclusion criteria, 13 clinical trials (7 in non-small cell lung cancer, 3 in melanoma, and 3 in urothelial carcinoma) were selected for the meta-analysis. In the primary analysis, pooled findings were 0.75 (95% CI, 0.70-0.81) for HR, 0.86 (95% CI, 0.81-0.92) for ST-HR, and 0.08 (95% CI, 0.06-0.10) for LT-DP. In the secondary analysis, the pooled values for progression-free survival were 0.77 (95% CI, 0.64-0.91) for HR, 1.02 (95% CI, 0.84-1.24) for ST-HR, and 0.10 (95% CI, 0.06-0.14) for LT-DP. Conclusions and Relevance: This systematic review and meta-analysis of ICI clinical trial results noted consistently larger ST-HRs vs Cox HRs for ICI therapy, with an LT-DP of approximately 10%. These results suggest that Cox HRs may not provide a full picture of survival outcomes when the risk reduction from treatment is not constant, which may aid in the decision-making process of oncologists and patients.