Clinical Physiology Associates

BackgroundIt is uncertain whether the combination of immunotherapy and radiotherapy can provide survival benefits for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).MethodsWe retrospectively analyzed the impact of radiotherapy on the efficacy of immunotherapy and prognostic analysis in 113 patients with R/M HNSCC in our institution from 2018 to 2022. The Kaplan–Meier method was utilized for survival analysis, and Cox regression analysis was conducted to identify prognostic factors.ResultsThe median follow-up time was 14.0 months. During immunotherapy, 37 patients received radiotherapy, targeting primary tumors, lymph nodes, metastasis in liver, lung, bone, and other sites. We found that the group receiving immunotherapy combined with radiotherapy had higher objective response rate (67.6% vs 39.5%, p = 0.009) and disease control rate (94.6% vs 61.8%, p = 0.001) than those without radiotherapy. The median progression-free survival (20.0 months vs 4.0 months, p = 0.00098) and overall survival (not reached vs 26.0 months, p = 0.006) were improved in patients receiving radiotherapy compared to those not.ConclusionsThe combination of immunotherapy and radiotherapy demonstrates improved clinical outcomes in R/M HNSCC.

Abstract Background: Image based body composition is the gold standard for assessing skeletal muscle area and quality in cancer patients. In patients with pancreatic ductal adenocarcinoma (PDAC), the decrease in muscle area and quality can be particularly profound. Yet image-based muscle assessment in these patients may be impeded by the presence of edema at follow up caused by disease burden and/or treatment. Edema in superficial muscle can affect the Hounsfield units of surrounding tissue leading to overestimation of muscle area. Despite this, to our knowledge no studies have examined alternative methods of assessing muscle loss in PDAC patients in the context of edema. To address this gap, we examined the prevalence of edema in PDAC patients, its impact on change in total skeletal muscle area (SMA) between diagnosis and six month follow up, and the use of psoas muscle area (pSMA), which is less impacted by edema, as an alternative method of assessing muscle loss. Methods: The study population included sixty-nine PDAC patients from the multi-center Florida Pancreas Collaborative study with serial computed tomography (CT) scans obtained at diagnosis and six month follow up. Using the CT scans, we assessed edema by identifying opacification in the subcutaneous fat defining those with opacification as edematous. We examined the prevalence of edema at six-month follow up in the overall PDAC population and tested for differences by race and sex using Fisher’s Exact test. SMA and pSMA were quantified as surface area (cm2) at L3 with sliceOmatic software. SMA and pSMA percent change and mean change between diagnosis and follow up were calculated in the overall population and by edema status at follow up. Spearman correlation was used to test the interrelationship of SMA and pSMA according to edema status. Results: Prevalence of edema at follow up was 53.6% and did not significantly differ by race (p>0.76) or sex (p>0.05). In the overall population, SMA increased by 0.472% between diagnosis and follow up. When stratified by edema status, SMA increased in patients with edema (+3.06%) whereas SMA in patients without edema decreased (-2.52%). Conversely, pSMA decreased by 6.32% and this was consistent across edema status (-5.69% for present and -7.05% for absent). Finally, we observed that SMA and pSMA at follow up are strongly correlated in both the presence (r=0.72) and absence of edema (r=0.77). Conclusions: In this study, we observed that edema is prevalent in most PDAC patients at follow up contributing to an overestimation of SMA. This overestimation may introduce bias into understanding the impact of PDAC on muscle wasting, an important factor in cancer cachexia. Encouragingly, findings suggest pSMA may be a suitable proxy for total SMA and limit the impact of edema on SMA estimates. These findings have important implications for enhancing our understanding of muscle changes over the PDAC cancer care continuum and should be considered in future studies. Citation Format: Evan W. Davis, Margaret A. Park, Toni L. Basinski, J. Pablo Arnoletti, Francisca Beato, Mark Bloomston, Tiffany L. Carson, Tiago Biachi de Castria, Dung-Tsa Chen, Elena M. Cortizas, Sylvia L. Crowder, Maria Genilo-Delgado, Wade G. Douglas, Kevin L. Huguet, Kun Jiang, Pamela J. Hodul, Aleksandra Karolak, Dae Won Kim, John Koomen, Anjana A. Menon, Kenneth Meredith, Qianxing Mo, Shaffer R. Mok, Lina Moreno-Urazan, Sabeen Ahmed, Nathan Parker, Jose M. Pimiento, Ghulam Rasool, Lauren M. Sparks, Paul Stewart, Alexandra F. Tassielli, Jamie K. Teer, Dan Viet Tran, Jose G. Trevino, Vic Velanovich, Xuefeng Wang, Christopher J. Whelan, Sarah M. Judge, Andrew R. Judge, Jason B. Fleming, Daniel Jeong, Jennifer B. Permuth, on behalf of the Florida Pancreas Collaborative. Say it ain’t psoas: addressing edema in pancreatic cancer body composition analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4904.

Abstract Background Up to 40% of patients with acute severe ulcerative colitis (ASUC) do not respond to infliximab (IFX)(1). Insufficient drug exposure with low IFX serum concentrations is associated with non-response (1, 2). We investigated whether personalised TDM-driven induction dosing of IFX was superior to standard dosing. Methods In this prospective open-label, multi-centre randomised controlled trial (Netherlands, Norway and Ireland), hospitalised adult IFX-naïve and steroid-refractory ASUC patients were randomised 1:1 to standard (SD) or personalised dosing of IFX (PD). After an initial 5 mg/kg IFX infusion, SD consisted of 5 mg/kg IFX at week 2 and 6. In the PD group, additional 5 mg/kg IFX infusions were administered guided by a Bayesian pharmacokinetic algorithm (iDose) aiming at IFX serum concentrations >28 ug/mL from day 0-28 and >15 ug/mL from day 29-42 (measured with Quantum Blue IFX rapid test). After day 42, all patients received 5 mg/kg IFX maintenance every 8 weeks until day 182, with escalation at physician’s discretion. The primary composite endpoint was clinical and endoscopic response at day 42 (Lichtiger score <10 and ≥3 points decrease from baseline and UCEIS ≥2 points decrease with double central endoscopy read and adjudication). Key secondary endpoints included day 42 clinical response, day 42 endoscopic response, day 182 clinical remission (Lichtiger score ≤3), day 182 endoscopic remission (UCEIS ≤1 on all components), and safety (SAEs). Endoscopies were performed at baseline, day 42 and 182. Results 48 patients were included and received study treatment (23 PD/25 SD), 31 of whom completed treatment through week 26 (19 PD/12 SD). Median cumulative IFX dose until day 42 was 18.41 mg/kg [14.77, 20.27] for PD vs 13.79 mg/kg [10.38, 14.82] for SD (Table 1). The primary composite endpoint of clinical and endoscopic response at day 42 was not met (13/23 (56.5%) in PD vs 11/25 (44.0%) in SD; p=0.564) (Figure 1). PD showed a higher day 42 clinical response vs SD (21/23 (91.3%) vs 16/25 (64.0%); p=0.039), Day 42 endoscopic response was observed in 13/23 (56.5%) in PD and 11/25 (44.0%) in SD (p=0.564). Numerically more patients on PD had day 182 clinical remission (14/23 (60.9%) vs 9/25 (36.0%); p=0.148) and endoscopic remission (15/23 (65.2%) vs 9/25 (36.0%); p=0.082) compared to SD. SAEs occurred in 3/23 (13.0%) of patients on PD vs 5/25 (20.0%) of patients on SD (p=0.703) and included infection (2/23 (8.7%) vs 1/25 (4.0%)), thromboembolic event (0 vs 1/25 (4.0%)), colectomy (1/23 (4.4%) vs 2/25 (8.0%)), and death (0 vs 1/25 (4.0%)). Following an interim analysis, the trial was discontinued based on futility. Conclusion Personalised dosing of infliximab was not superior to standard dosing in acute severe ulcerative colitis.

Background: The benefits of mechanical thrombectomy in low NIHSS score (<6) is unclear and undergoing investigation. Current acute stroke guidelines do not address the utilization of computed tomography angiography (CTA) in low NIHSS largely due to a paucity of data leading to great variation in clinical practice. Understanding the predictive value of NIHSS subitems for LVO may help guide imaging selection. Methods: Acute stroke consultations seen in the emergency department in 227 facilities (27 states) from July 1, 2021 to December 31, 2021 were extracted from the TeleCare by TeleSpecialists TM database. The encounters with CTA performed were reviewed for LVO detected, and NIHSS score with individual subitems. Logistic regression analysis was performed on the NIHSS subitems in total and at NIHSS cutoff points of ≤6, ≤4, and ≤2. Results: A total of 12,668 patients had complete NIHSS subitems available with 1,459 (11.5%) having an LVO and 11,209 without an LVO were extracted. There is a significant difference in the ORs for each subitem. The ORs for patients with NIHSS ≤6 subitems: Level of Consciousness 1.11 (p=0.626), Consciousness Questions 1.36 (p<0.001), Consciousness Commands 1.94 (p<0.001), Best Gaze 1.61 (p=0.061), Visual Field 1.65 (p<0.001), Facial palsy 1.71 (p <0.001), Motor Arm-left 1.43 (p <0.001), Motor arm-right 1.03 (p=0.840), Motor leg-left 0.97 (p=0.758), Motor leg-right 0.83 (p=0.103), Limb ataxia 1.09 (p=0.545), Sensory 0.67 (p=0.001), Language 1.92 (p<0.001), Dysarthria 1.81 (p<0.001), and Neglect 5.78 (p<0.001). Trends in subitems with each lower cutoff were increased odds of LVO with Consciousness Commands, Visual Fields, Language, and Neglect, and lower odds of LVO with Sensation. Conclusions: This analysis shows the limitations of the NIHSS subitems to predict LVO. Despite the trend of lower odds of LVO for Sensation, even with the NIHSS cutoff of ≤2 there would have been 7 LVOs missed. There are 6 subitems showing statistical significance at an NIHSS cutoff of ≤2 which suggests that an NIHSS cutoff, even with these identified subpoints, is not a good CTA candidate selection tool for the detection of all LVOs.

Research-based articles published in medical journals are key to communicating the results of clinical trials, systematic reviews, and meta-analyses. But there are challenges inherent in the communication process. While clinicians rely on the information they read in medical journals to help guide clinical decision-making, most are overwhelmed by the amount of information being published and many receive only limited training on how to critically assess what they read. This can result in suboptimal clinical decision-making, leading to inefficient use of health care resources, avoidance of interventions that may be indicated and useful, or use of interventions that do more harm than good. A literature search of PubMed® was conducted to answer the question, what are the challenges affecting the interpretation of clinical trial results reported in the medical literature that may adversely affect clinical decision making and patient outcomes and how can those challenges be overcome? Results of this review indicate it remains challenging for readers to fully appreciate the nuances that affect the accuracy, utility, and applicability of reported data, and opportunities exist for future continuing professional development interventions to address this challenge by giving health care professionals the knowledge and skills to critically evaluate and interpret literature-based information. The objective of this article is to assist new and aspiring clinicians as well as experienced practitioners in critically assessing the medical literature so they can be informed about the latest medical advances in their areas of specialty and interest and confidently and appropriately integrate this knowledge into clinical practice. This article aspires to be a tool for residency and fellowship program directors, clerkship faculty, mentors, and other HCPs engaged in clinical education.

Introduction: Multiple clinical trials support an extended treatment window for thrombectomy for large vessel occlusions (LVO) and the treatment of distal occlusions, leading to increased numbers of patients requiring advanced imaging during acute stroke evaluation. Across hospital systems, there is great variation in advanced imaging protocols for acute stroke patients. The goal of this study is to provide a descriptive analysis of the real-world practices in facilities across the United States. Methods: Acute stroke consultations seen by TeleSpecialists, LLC physicians in the emergency department in 227 facilities (27 states) from July 1, 2021 to December 31, 2021 were extracted from the TeleCare TM database. The encounters were reviewed for age, ethnicity, stroke risk factors, last known normal (LKN), arrival time, thrombolytics candidate, door to needle (DTN) time, advanced imaging, LVO, if Neurointerventionalist (NIR) accepted case, premorbid modified Rankin Score (p-mRS), and NIHSS score. Comparison of baseline characteristics and time benchmarks between advanced imaging group (computed tomography angiography (CTA) with optional CT perfusion (CTP)) vs no advanced imaging group (CT only) was performed. Analysis of the location of the occlusion and of the specific vessels being accepted for intervention was performed. Results: There were 29,187 acute stroke consultations seen with 12,641 (43.3%) receiving advanced imaging. The median DTN time for advanced imaging group was 44 minutes (33, 59) vs 41 minutes (30.5, 54) with no advanced imaging group, p = 0.158. There was a higher NIHSS score and lower p-mRS in the advanced imaging group. Analysis of patients with LVO showed lower DTN times, higher NIHSS scores, lower p-mRS, and shorter LKN to arrival times in the patients accepted for thrombectomy. Majority of cases accepted for thrombectomy were left M1 (31.4%) or right M1 (26.6%) occlusions. A significantly lower percentage of patients accepted for intervention had left M2 (10%) and right M2 (6%) occlusions. Conclusion: Advanced imaging in a large real-world data set of acute stroke patients did not significantly delay DTN times. The ability to maintain DTN times is likely related to thrombolytics being prioritized and a parallel process.

Introduction: Analyses from early- and late-window thrombectomy trials for acute large vessel occlusion (LVO) stroke have consistently demonstrated a strong time-dependent treatment effect for best outcomes. The utilization of an artificial intelligence (AI)-based care coordination platform to support LVO diagnosis and treatment has the potential to assist in reducing door to puncture times and improve outcomes. Hypothesis: Utilization of an AI-based care platform in the management of LVO patients may significantly decrease door to Neurointerventionalist (NIR) notification time. Methods: Acute stroke consultations seen by TeleSpecialists, LLC physicians in the emergency department in 166 facilities (17 states) that utilized VIZ.AI software or did not have an AI software from December 1, 2021 through March 31, 2022 were extracted from the Telecare TM database. Facilities that neurology does not initiate contact with NIR were excluded. The encounters were analyzed by age, ethnicity, last known normal, arrival time, initial telemedicine stroke code activation time (TCA), candidacy for thrombolytics, door to needle time (DTN), advanced imaging, presence of LVO, time NIR accepted, premorbid modified Rankin Score, and NIHSS score. Patients were divided into two groups (utilization and non-utilization of the AI platform) and median door to NIR notification times were compared. There was a 4 minute shorter time to TCA at AI hospitals. Results: A total of 14,116 patients (8,557 AI and 5,559 non-AI) were included. The median door to NIR notification time for AI was 50 minutes (40, 82) and non-AI was 89.5 minutes (59.3, 122), p <0.001. There was a small but significantly shorter time (3 minutes) from door to TCA at AI hospitals. Median DTN times for thrombolytics was also lower with AI, 40 minutes (30, 52) vs 44 minutes (32, 57.5) for non-AI, p=0.018. The AI group had more advanced imaging performed, a higher percentage of LVOs identified, and a higher percentage accepted by NIR. Conclusion: Hospital utilization of an AI-based care coordination platform was associated with a significant decrease of 39.5 minutes in the time to NIR contact, increase in patients taken for intervention, and lower DTN times for thrombolytics.