Citations

Mayo Clinic

Clear

231 citation(s) found for "Burton, D".

A Screening Tool to Predict Post-intensive Care Syndrome (PICS) in the Critically Ill
Philbrick, Kemuel L. , Clark, Mike , Harris, Burton H., Cornelius, P., Sonsalla, K., Karnatovskaia, Lioudmila V. , Valle, Kathryn T. del , Harris, B.

American Journal of Respiratory and Critical Care Medicine | May 11, 2025 | Volume: 211 | Issue: Supplement_1 | Pages: A1170-A1170

10.1164/ajrccm.2025.211.abstracts.a1170 Get It

Abstract RATIONALE: Many ICU patients experience physical, psychological, and cognitive impairments following resolution of critical illness, collectively referred to as post-intensive care syndrome (PICS). PICS has become widely recognized within the critical care field, but how to screen for PICS does not currently have consensus. Development of a validated, concise PICS screening tool would allow for rapid identification of this vulnerable and understudied population. Therefore, this study's goal was to develop and evaluate a screening tool to identify patients at risk for PICS. METHODS: We performed a prospective cohort study in a quaternary academic hospital. We included adults ≥ 18 years old with ≥48 hours spent in an ICU. Exclusion criteria were admission for suicide attempt, severe cognitive impairment/dementia, life expectancy <3 months, and non-English speaking. We assessed mental, cognitive, and physical function following ICU discharge and at 3 months using Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised, Montreal Cognitive Assessment-blind, and Barthel Index. Our team, including critical care physicians, psychiatrists, psychologists, physical and occupational therapists, and nurses, developed a brief 15-item PICS screening tool (5 questions/domain). This tool was administered after patients were discharged from ICU stay to general care to assess its effectiveness in predicting impairments in all 3 domains at discharge and again at three months after hospital discharge, in comparison to previously mentioned validated questionnaires. Youden index statistical methods were used to determine potential “cutoff” values (scores) for the tool to maximize sensitivity and specificity. RESULTS: A total of 194 patients from 6 ICUs were recruited and completed the initial questionnaire, and 109 (56%) patients completed 3-month follow-up. Median age was 65 years (IQR 57-72) and 49% (95/194) were female. Screening tool is depicted in Figure 1. Overall, the screening tool weakly-to-moderately correlated with continuous outcomes of the validated measures upon ICU discharge and 3-month follow-up. When evaluating sensitivity and specificity for individual domains, the tool had an area under the receiver operating curve of >0.7 for the following domains: cognitive, anxiety, and physical impairments, indicating moderate-to-good sensitivity and specificity. CONCLUSIONS: This PICS screening tool was correlated with validated measures of PICS upon ICU discharge and at 3-month follow-up for all three domains. The tool's strength lies in its concise nature, making it easier for those caring for this patient population to screen for long-term effects of an ICU stay. Our proposed next step is validation of the PICS screening tool in an external cohort.
Perioperative Health Care Disparities in the United States: A Systematic Review
Bradley, A. Steven, Bonner, Timethia , Youssef, Mohanad R. , Milam, Adam J. , Milam, Adam J , Burton, Brittany N. , Warner, David O. , Faloye, Abimbola O. , Toledo, Paloma

Anesthesia & Analgesia | May 5, 2025 | Volume: 141 | Issue: 6 | Pages: 1297-1322

10.1213/ane.0000000000007510 | PMID 40323058 Get It

Perioperative health inequities remain a critical issue, contributing to unequal patient outcomes and financial costs despite increasing awareness and efforts to address these disparities. This systematic review evaluated anesthesiology literature from 2010 to 2023 on perioperative health care disparities related to race, ethnicity, gender, and socioeconomic status. The review aimed to identify gaps and propose research and opportunities for intervention. A comprehensive literature search was conducted using PubMed, Embase, Scopus, and Web of Science, with studies included if they focused on perioperative disparities in the United States, were published in anesthesiology journals, and met criteria for methodological rigor. The review was registered with International Prospective Register of Systematic Reviews (PROSPERO); data extraction followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and study quality was assessed with the Newcastle-Ottawa scale. Out of 1050 abstracts screened, 116 articles were reviewed for full text, with 59 studies meeting inclusion criteria. Included studies comprised retrospective cohort studies, cross-sectional analyses, a case-control study, and a randomized controlled trial, covering various surgical procedures and sample sizes from 100 to over 21 million patients. Disparities were noted in peripartum management (n = 14), mortality (n = 12), complications (n = 8), regional anesthesia use (n = 6), and pain management (n = 3), with evidence of poorer outcomes in Black and Hispanic women, older adolescents, and patients who were uninsured or on Medicaid. This review highlights the persistence of significant perioperative disparities and identifies gaps, such as limited exploration of the causes of these disparities, limited examination of disparities during the preoperative and intraoperative period, and few interventions to address these identified disparities. Reducing these disparities requires stakeholder engagement, multifaceted approaches, culturally agile training for health care teams, enhanced decision support tools, and a more diverse health care workforce. Continued research and targeted interventions at individual, community, and societal levels are essential for improving perioperative outcomes.
Factors Associated With Stroke Recurrence After Initial Diagnosis of Cervical Artery Dissection
Mandel, Daniel , Shu, Liqi , Chang, Christopher , JACK, N , Henninger, Nils , Muppa, Jayachandra , Affan, Muhammad , Lodhi, Omair ul haq , Heldner, Mirjam R. , Omran, Setareh Salehi , Crandall, Ross , Lester, Evan, Araúz, Antonio , Boulanger, Marion , Sousa, João André , Barata, Vasco , Castro‐Chaves, Paulo , Brito, Maria Teresa , Khan, Muhib , Mallick, Dania, Rothstein, Aaron , Khazaal, Ossama , Traenka, Christopher , Sousa, Diana Aguiar de , Soares, Mafalda , Rosa, Sara , Zhou, Lily , Gandhi, Preet , Field, Thalia S. , Mancini, Steven, Pan, Kelly , Dantu, Vishnu , Baumgartner, Karl , Nolte, Christian H. , Choi, Richard , Macdonald, J , Ghannam, Malik , Almajali, Mohammad , Sanchez, Sebastian , Zine-Eddine, Fayçal, Poppe, Alexandre Y. , Fonseca, Ana Catarina , Baptista, Maria Fortuna , Cruz, Diana , Marco, Giovanna De , Griffin, Kim J. , Kuohn, Lindsey , Frontera, Jennifer , Amar, Jordan , Grisendi, Ilaria , Nzwalo, Hipólito , Liebeskind, David S. , Molaie, Amir , Cavalier, Annie, Kam, Wayneho , Grory, Brian Mac , Kasab, Sami Al , Eltatawy, Ali , Chervak, Lina , Rivas, Roberto Chulluncuy, Bakradze, Ekaterina , Tran, Thanh Lam , Ortiz-Garcia, Jorge , Muddasani, Varsha , Vishnu, Venugopalan Y. , Yaddanapudi, Sridhara , Adams, L, Browngoehl, Abigail, Dunston, Randy, Lynch, Zachary, Penckofer, Mary , Mayer, Silvia, Zubair, Adeel , Cheng, Yee Kuang, Ferreira, Vítor Mendes , Asad, Syed Daniyal , Sarwat, Zoha, Balabhadra, Anvesh , Patel, Shivam , Secchi, Thaís , Mantovani, Gabriel Paulo , Krishnaiah, Balaji , Lingam, Sivani, Khasiyev, Farid , Linares, Guillermo , Mannino, Marina , Terruso, Valeria, Vassilopoulou, Sofia , Tentolouris-Piperas, Vasileios , Wall, Victor Carrasco , Indraswari, Fransisca , Jamal, Sleiman El , Liu, Shilin, Alvi, Muhammad , Sarvath, Mohammed, Kass‐Hout, Tareq , Shi, Feina , Zhang, Jinhua , Said, Jamil , Mongare, Newnex, Sen, Shayak, Ghani, Mohammad R , Elnazeir, Marwa , Xiao, Han , Khan, Farhan , Mohammadzadeh, Nahid , Furie, Karen L. , Mandel, Daniel M , Jack, Naomi , Leon Guerrero, Christopher R , Henninger, Nils , Muppa, Jayachandra , Heldner, Mirjam R , Antonenko, Kateryna , Seiffge, David , Arnold, Marcel , Salehi Omran, Setareh , Crandall, Ross , Lopez Mena, Diego , Arauz, Antonio , Boulanger, Marion , Touzé, Emmanuel , Sousa, Joao Andre , Sargento-Freitas, Joao , Barata, Vasco , Castro-Chaves, Paulo , Brito, Maria Teresa , Khan, Muhib , Rothstein, Aaron , Khazaal, Ossama , Kaufman, Josefin E , Engelter, Stefan T , Traenka, Christopher , Aguiar de Sousa, Diana , Soares, Mafalda , Rosa, Sara , Zhou, Lily W , Gandhi, Preet , Field, Thalia S , Metanis, Issa , Leker, Ronen R , Dantu, Vishnu , Baumgartner, Karl , Burton, Tina , von Rennenberg, Regina , Nolte, Christian H , Choi, Richard , MacDonald, Jason , Bavarsad Shahripour, Reza , Guo, Xiaofan , Ghannam, Malik , Almajali, Mohammad , Samaniego, Edgar A , Sanchez, Sebastian , Rioux, Bastien , Poppe, Alexandre , Fonseca, Ana Catarina , Fortuna Baptista, Maria , Cruz, Diana , Romoli, Michele , Longoni, Marco , Keser, Zafer , Kuohn, Lindsey , Frontera, Jennifer , Giles, James , Zedde, Marialuisa , Pascarella, Rosario , Grisendi, Ilaria , Nzwalo, Hipolito , Liebeskind, David S. , Molaie, Amir , Kam, Wayneho , Mac Grory, Brian , Al Kasab, Sami , Anadani, Mohammad , Kicielinski, Kimberly , Eltatawy, Ali , Chervak, Lina , Aziz, Yasmin , Bakradze, Ekaterina , Rodrigo Gisbert, Marc , Requena, Manuel , Saleh Velez, Faddi , Garcia, Jorge Ortiz , Muddasani, Varsha , de Havenon, Adam H , Vishnu, Venugopalan Y , Adams, Latasha , Ranasinghe, Tamra , Penckofer, Mary , Siegler, James E , Mayer, Silvia , Willey, Joshua , Zubair, Adeel , Cheng, Yee Kuang , Sharma, Richa , Marto, João Pedro , Mendes Ferreira, Vítor , Klein, Piers , Nguyen, Thanh N , Asad, Syed Daniyal , Balabhadra, Anvesh , Martins, Sheila , Mantovani, Gabriel , Kim, Young Dae , Krishnaiah, Balaji , Elangovan, Cheran , Qureshi, Abid Y , Fridman, Sebastian , Alvarado-Bolanos, Alonso , Khasiyev, Farid , Linares, Guillermo , Mannino, Marina , Terruso, Valeria , Vassilopoulou, Sofia , Tentolouris-Piperas, Vasileios , Martinez Marino, Manuel , Carrasco Wall, Victor , Indraswari, Fransisca , El Jamal, Sleiman , Liu, Shilin , Sarvath, Mohammed , Morsi, Rami Z , Kass-Hout, Tareq , Shi, Feina , Zhang, Jinhua , Sokhi, Dilraj , Simpkins, Alexis N , Ghani, Mohammad , Elnazeir, Marwa , Xiao, Han , Khan, Farhan , Stretz, Christoph , Goldstein, Eric D , Furie, Karen L , Yaghi, Shadi , Seiffge, David , Nehme, Ahmad , Sargento‐Freitas, João , Kaufmann, Josefin E. , Engelter, Stefan T. , Metanis, Issa , Shahripour, Reza Bavarsad , Guo, Xiaofan , Keser, Zafer , Giles, James , Zedde, Marialuisa , Pascarella, Rosario , Aziz, Yasmin , Rodrigo‐Gisbert, Marc , Requena, Manuel , Velez, Faddi G. Saleh , Havenon, Adam de , Ranasinghe, Tamra , Siegler, James E. , Sharma, Richa , Marto, João Pedro , Klein, Piers , Nguyen, Thanh N. , Kim, Young Dae , Elangovan, Cheran , Alvarado‐Bolaños, Alonso , Martínez-Marino, Manuel , Ali, Farman, Morsi, Rami Z. , Simpkins, Alexis N. , Gomez, Roberto, Sen, Shayak, Kala, Narendra , Stretz, Christoph , Goldstein, Eric , Yaghi, Shadi

Stroke | March 27, 2025 | Volume: 56 | Issue: 6 | Pages: 1413-1421

10.1161/strokeaha.124.048215 | PMID 40143807 Get It

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.
Innovative telehospitalist model optimizes medical triage in collaboration with community emergency departments: A cross-sectional study
Koch, Adam T. , Keuseman, Rachel , Parikh, Riddhi S. , Legler, Sean R. , Boyapati, Renu Bhargavi, Lawson, Donna K. , Burton, M. Caroline , Keuseman, Rachel L, Parikh, Riddhi, Ayanian, Shant , Pagali, Sandeep , Boyapati, Renu Bhargavi, Fischer, Karen M. , Dugani, Sagar B. , Pagali, Sandeep R.

Journal of Telemedicine and Telecare | January 23, 2025 | Volume: 32 | Issue: 1 | Pages: 32-39

10.1177/1357633x241311957 | PMID 39846202 Get It

Introduction Optimal hospital bed utilization requires innovative patient care models. We studied a novel hospitalist model utilizing telemedicine to facilitate collaboration with affiliated emergency departments (EDs) and support medical triage and care of ED patients with high likelihood of hospital admission. Methods Telehospitalists based at a tertiary care facility collaborated with four community EDs in the same healthcare network between January 1, 2022, and April 30, 2023. Telehospitalists supported ED clinicians in medical care decisions and facilitated patient disposition. Emergency department length of stay (LOS) and disposition were evaluated, as were hospital LOS, 30-day readmission, and in-hospital mortality. For patients discharged from the ED, 7-day ED readmission and subsequent hospitalization were evaluated. Results Telehospitalists discussed 550 “admit-likely” patients with ED clinicians: 105 patients (19.1%) discharged from the ED and avoided admission; 322 patients (58.5%) were admitted to local or nearby community hospitals; 123 patients (22.4%) transferred to the tertiary care facility. Emergency department LOS differed significantly among disposition groups, including patients discharged home (10.2 h), admitted to local hospitals (12.6 h), and transferred to tertiary care hospitalist services (14.9 h; p < 0.001). Hospital LOS and in-hospital mortality were not significantly different among disposition groups. Patients admitted locally had lower 30-day readmission compared to those transferred to tertiary care facility (odds ratio = 0.59 [0.36, 0.99], p = 0.048). Discussion Telehospitalists as triage clinicians is an innovative approach to support local ED clinicians and patients. Telehospitalists optimized hospital bed utilization and healthcare system resources by facilitating safe discharges to home and expediting tertiary care transfers when necessary.
Does Management of Postoperative Nausea and Vomiting Differ by Patient Demographics? An Evaluation of Perioperative Anesthetic Management—An Observational Study
Goldson, Kareem V., Burton, Brittany N. , Warner, David O., Youssef, Mohanad R. , Milam, Adam J. , Hanson, Kristine T. , Milam, Adam J , Brennan, Emily , Faloye, Abimbola O. , Habermann, Elizabeth B.

Anesthesiology | January 9, 2025 | Volume: 142 | Issue: 4 | Pages: 704-715

10.1097/aln.0000000000005367 | PMID 39786950 Get It

Background: Disparities in postoperative nausea and vomiting and its prophylaxis may exist based on race, ethnicity, and socioeconomic status. The objective was to evaluate whether patients from racial and ethnic minority groups and patients from lower socioeconomic status backgrounds received less appropriate postoperative nausea and vomiting prophylaxis and experienced higher rates of postoperative and postdischarge nausea and vomiting. Methods: This retrospective cohort study included 23,333 adults who underwent major surgeries (total knee arthroplasty, cholecystectomy, hysterectomy, and prostatectomy) from 2017 to 2022 in a single, multistate hospital system. Outcomes included prophylactic antiemetic administration according to consensus guidelines, as well as the occurrence of postoperative and postdischarge nausea and vomiting, with predictors being patient race and ethnicity, payor type, and community-level socioeconomic status. Results: About 45% (n = 10,407) of patients received guideline-recommended postoperative nausea and vomiting prophylaxis. Regression models showed statistically significant differences in appropriate postoperative nausea and vomiting prophylaxis by race and ethnicity, as well as community-level socioeconomic status, with Black (odds ratio, 0.76; 95% CI, 0.63 to 0.92) and Hispanic (odds ratio, 0.82; 95% CI, 0.70 to 0.96) patients having lower odds of receiving appropriate antiemetic prophylaxis compared to non-Hispanic White patients. Approximately 11% of patients (n = 2,522) experienced postoperative nausea and vomiting in the postanesthesia care unit, and about 19.5% of patients (n = 4,540) experienced postdischarge nausea and vomiting. No significant differences in postoperative nausea and vomiting were observed in the postanesthesia care unit among different groups; however, Black, Hispanic, other races and ethnicities, and patients with Medicaid had higher odds of postdischarge nausea and vomiting. Conclusions: The study identified differences in appropriate postoperative nausea and vomiting prophylaxis by race and ethnicity, as well as community-level socioeconomic status. There were no differences in postoperative nausea and vomiting by the predictors, but there were higher odds of postdischarge nausea and vomiting by race and ethnicity and payor. This study underscores the importance of data stratification in quality measures to identify disparities in perioperative care; it can lead to changes in perioperative anesthetic management. Further research should explore these associations in a broader cohort and address potential confounding sources.
The Association of Food Security With Hypertensive Disorders of Pregnancy: A National Health Interview Survey Analysis
Burton, Brittany N. , Sykes, Alexis, Canales, Cecilia , Ibarra, Andrea J. , Chang, En, Dahan, Jonathan, Milam, Adam J. , Yu, Tina , Cha, Catherine, Milam, Adam J , Chang, En

The Journal of Clinical Hypertension | December 17, 2024 | Volume: 27 | Issue: 1 | Pages: No page available

10.1111/jch.14952 | PMID 39686846 Get It

ABSTRACTFood security is one of the most researched social determinants of health (SDoH), however, there is a lack of literature on the impact of food security on cardiovascular disease in pregnancy. The primary objective was to examine the association between food security with hypertensive disorders of pregnancy. We performed a cross‐sectional analysis of 2019–2022 data from the National Health Interview Survey. The study population included women of childbearing age who were either pregnant or recently pregnant. Logistic regression models were developed to examine the association between food security and hypertensive disorders of pregnancy. Of the 1635 women included in the analysis, the rate of hypertensive disorders of pregnancy was 11.1% and the rate of low and very low food security was 5.3% and 4.0%, respectively. The prevalence was 5.8% for hyperlipemia, 0.3% for cardiovascular disease, and 10.5% for diabetes mellitus. The odds of hypertensive disorders of pregnancy were statistically significantly increased among women with low food security compared to women with high food security (odds ratio [OR] 2.40, 95% confidence interval [CI]: 1.19–4.81) after adjusting for age, race, ethnicity, insurance status, body mass index, hyperlipidemia, diabetes mellitus, and cardiovascular disease. Further studies are needed to elucidate the causes of hypertensive disorders of pregnancy and interventions to address including the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and food pantries, as it may be more feasible to address issues of food security among pregnant women.
An international Delphi consensus on patient preparation for metabolic and bariatric surgery
Clyde, Danielle , Adib, Reza, Baig, Sarfaraz Jalil , Bhasker, Aparna Govil , Catalain, Copaescu, Clare, Ken , Beaux, Andrew de, Drummond, Gillian, Fawal, Hayssam, Ghanem, Omar M. , Hopkins, George, Kothari, Shanu N. , Kow, Lilian , Faria, Sílvia Leite , Madhok, Brij, Mahon, David, Miller, Karl , Nimeri, Abdelrahman , O’Kane, Mary , Poggi, Luis , Saliminen, Paulina, Sarkar, Rupa , Shenfine, Jon, Sogg, Stephanie , Suter, Michel , Taha, Safwan , Tahrani, Abd A. , Voon, Kelvin , Welbourn, Richard , Lamb, Peter , Mahawar, Kamal , Yang, Wah , Salminen, Paulina , Kermansaravi, Mohammad , Zerrweck, Carlos , Yang, Wah , Byrne, James Patrick , Cameron, David, Fried, Martin , Graham, Yitka N. H. , Goel, Ramen , Husain, Farah Anwari , Joyce, Brian, Miras, Alexander Dimitri , Moussa, Osama , Neto, Manoel Galvão , Parmar, Chetan D. , Peterli, Ralph , Stenberg, Erik , Vilallonga, Ramón , Robertson, Andrew G.

Clinical Obesity | December 14, 2024 | Volume: 15 | Issue: 2 | Pages: No page available

10.1111/cob.12722 | PMID 39673462 Get It

SummaryGlobal obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m2), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources. Updated in 2022, ASMBS and IFSO guidelines aim to standardise MBS indications, reflecting current understanding and emphasising comprehensive preoperative assessments. Yet, clinical variability persists, necessitating consensus‐based recommendations. This modified Delphi study engaged 45 global experts to establish consensus on perioperative management in MBS. Experts selected from bariatric societies possessed expertise in MBS and participated in a two‐round Delphi protocol. Consensus was achieved on 90 of 169 statements (53.3%), encompassing multidisciplinary team composition, patient selection criteria, preoperative testing, and referral pathways. The agreement highlighted the critical role of comprehensive preoperative assessments and the integration of healthcare professionals in MBS. These findings offer essential insights to standardise perioperative practices and advocate for evidence‐based guidelines in MBS globally. The study underscores the need for unified protocols to optimise outcomes and guide future research in MBS.
Phase I study of a recombinant attenuated oncolytic virus, MEDI5395 (NDV–GM-CSF), administered systemically in combination with durvalumab in patients with advanced solid tumors
Davar, Diwakar , Carneiro, Benedito A. , Dy, Grace K. , Harrington, Kevin J. , Patel, Sandip Pravin , Samson, Adel , Agrawal, Sonia, Fan, Chunling , Gong, Maozhen , Burton, J.L., Tu, Eric , Durham, Nicholas M. , Laubscher, Kevin, Arnaldez, Fernanda I. , Zamarin, Dmitriy , Harrington, Kevin , Davar, Diwakar , Sheth, Siddharth H , Borad, Mitesh J. , Galanis, Evanthia , Agrawal, Sonia, Chen, Yuyan , Burton, Jenny

Journal for ImmunoTherapy of Cancer | November 17, 2024 | Volume: 12 | Issue: 11 | Pages: e009336

10.1136/jitc-2024-009336 | PMID 39551600 Get It

Background MEDI5395 is a recombinant attenuated Newcastle disease virus engineered to express a human granulocyte-macrophage colony-stimulating factor transgene. Preclinically, MEDI5395 demonstrated broad oncolytic activity, augmented by concomitant programmed cell death-1/programmed cell death ligand-1 (PD-L1) axis blockade. Durvalumab is an anti-PD-L1 immune checkpoint inhibitor approved for the treatment of various solid tumors. We describe the results of the first-in-human study combining intravenous MEDI5395 with durvalumab in patients with advanced solid tumors. Methods This phase I, open-label, multicenter, dose-escalation, dose-expansion study recruited adult patients with advanced solid tumors, who had relapsed or were refractory or intolerant to ≥1 prior line of standard treatment. MEDI5395 was administered intravenously as six doses over 15–18 days. The dose-escalation phase assessed four-dose levels (108, 109, 1010, 1011 focus forming units (FFU)) of MEDI5395, with sequential or delayed durvalumab. Durvalumab 1500 mg was administered intravenously every 4 weeks up to 2 years. The dose-expansion phase was not initiated. The primary objectives were to evaluate safety and tolerability, dose-limiting toxicities (DLTs) and the dose and schedule of MEDI5395 plus durvalumab administration. Secondary objectives included the assessment of the efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MEDI5395. Results 39 patients were treated with MEDI5395; 36 patients also received durvalumab. All 39 patients experienced ≥1 treatment-emergent adverse event (TEAE), most commonly fatigue (61.5%), nausea (53.8%) and chills (51.3%). Grade 3–4 TEAEs occurred in 27 (69.2%) patients; these were deemed MEDI5395-related in 12 (30.8%) patients. Two patients experienced a DLT, and the maximum tolerated dose of MEDI5395 with sequential and delayed durvalumab at study termination was 1011 and 1010 FFU, respectively. Four patients (10.3%) achieved a partial response (PR). Patients with PR or stable disease tended to have higher baseline PD-L1 and CD8+ levels in their tumor tissue. A tendency to dose-dependent pharmacokinetics of the viral genome was observed in whole blood and a tendency to dose-dependent viral shedding was observed in saliva and urine. Neutralizing antibodies were observed in all patients but did not appear to impact efficacy negatively. Conclusion This study demonstrates the feasibility, safety and preliminary efficacy of MEDI5395 with durvalumab in patients with advanced solid tumors. Trial registration number NCT03889275
Additional criteria on scintigraphic testing for diagnosis of rapid colonic transit in patients with chronic diarrhea
Lupianez‐Merly, Camille , Dilmaghani, Saam , Jencks, Kara J. , Eckert, Deborah J., Ryks, Michael, Burton, Duane, Camilleri, Michael , Jencks, Kara , Eckert, Deborah

Neurogastroenterology & Motility | September 20, 2024 | Volume: 36 | Issue: 11 | Pages: No page available

10.1111/nmo.14917 | PMID 39300973 Get It

AbstractBackgroundColonic transit (CT) measured by validated scintigraphy using 111In‐labeled activated charcoal particles is summarized using geometric center (GC) of isotopic distribution in four colonic regions and stool at 24 and 48 h. Diagnosis of rapid CT is currently based on GC24 ≥4.4 in females and >4.7 in males, which lack sensitivity. Our aim was to evaluate, in patients with chronic diarrhea with normal CT by GC24 and GC48, the diagnostic utility of CT change (∆GC) relative to sex‐matched normal values.MethodsWe evaluated two adult patient cohorts: 701 clinical patients (1994–2023) with chronic diarrhea and 76 research participants with irritable bowel syndrome with diarrhea (N = 63) or bile acid diarrhea (BAD, N = 13). Results of ∆GC were compared to 220 healthy controls' 95th percentiles (%ile) (≥2.0 females and ≥2.2 males). In the research cohort, we also analyzed (Spearman correlation) colonic ∆GC with ascending colon emptying T1/2 (AC T1/2), average stool frequency and consistency based on a daily diary, total fecal bile acid (BA) concentration, and % primary BA in a single stool sample.Key ResultsAmong 701 clinical patients with normal GC24, 160 (22.3%) had rapid CT based on ∆GC 95th %ile in health. Among 76 research participants, an additional 20.6% IBS‐D and 23% BAD had rapid CT ∆GC. Younger age and absence of diabetes mellitus were predictive of rapid ∆GC. ∆GC significantly correlated with AC T1/2 and with fecal BA.Conclusions & Inferences∆GC identified an additional 21%–23% patients with rapid colonic transit among patients with diarrhea and normal GC24.
Necessity of posterior osteotomies for mild flexible cervical deformity correction
Eastlack, Robert K. , Lakomkin, Nikita , Tran, Stacie , Jelousi, Michael, Soroceanu, Alex, Passias, Peter, Protopsaltis, Themistocles S. , Klineberg, Eric O. , Hamilton, D. Kojo , Burton, Douglas C. , Shaffrey, Christopher I. , Mundis, Gregory M. , Smith, Justin S. , Bess, Shay R. , Lafage, Virginie , Kim, Han Jo , Ames, Christopher Pearson

Journal of Neurosurgery: Spine | September 14, 2024 | Volume: 41 | Issue: 6 | Pages: 757-764

10.3171/2024.5.spine231223 | PMID 39270323 Get It

OBJECTIVE Correction of mild flexible cervical deformity (CD) via the posterior approach has been described with and without the use of posterior osteotomies (POs), despite a lack of clarity regarding their necessity or risks. The purpose of this study was to determine whether the use of POs when correcting mild flexible CD leads to improved clinical or radiographic outcomes, as well as defining the relative risks in utilizing them. METHODS A prospective multicenter registry of operative CD patients was analyzed. Inclusion criteria were cervical kyphosis > 10°, cervical scoliosis > 10°, cervical sagittal vertical axis (cSVA) > 4 cm, or chin-brow vertical angle > 25°. Mild deformity was defined by a cSVA of 3–5 cm and/or kyphosis < 15°. Flexibility was defined by a C2–7 angular change > 5° on preoperative flexion/extension radiographs. Patients who received a posterior column osteotomy (PCO) (Ames grades 1 and 2) were compared with patients who did not undergo a PCO (noPCO) as well as those who underwent a three-column osteotomy (3CO) (Ames grades 3–6). RESULTS Ninety-five patients (33 PCO, 49 noPCO, 13 3CO) met the inclusion criteria. Both the number of levels fused (9.2 vs 7.7, p = 0.001) and the estimated blood loss (EBL) (1027 vs 486 mL, p = 0.012) were higher in the PCO cohort. Patients in the noPCO group were more likely to have a cervical apex of kyphosis (71.1%, p = 0.046), while those undergoing 3COs were more likely to have a thoracic apex (58.3%, p = 0.005). Preoperative cSVA (PCO vs noPCO: 45.4 vs 37.9 cm, p = 0.084), T1 slope (32.5° vs 29.6°, p = 0.376), C2–7 lordosis (−8.9° vs −9.2°, p = 0.942), and modified Japanese Orthopaedic Association (mJOA) score (13.4 vs 13.5, p = 0.854) were similar; however, both Neck Disability Index (NDI) (55.6 vs 42, p = 0.002) and numeric rating scale (NRS) neck (7.2 vs 5.8, p = 0.028) scores were higher in the PCO group before surgery. When adjusting for the use of an anterior approach, there was no significant difference in 1-year postoperative cSVA (35.7 and 35.6 cm, respectively; p = 0.969), C2–7 lordosis (13.7° and 10.1°, respectively; p = 0.393), and patient-reported outcome measures (NRS, NDI, and mJOA) between the PCO and noPCO groups. Two-year radiographic outcomes were largely similar, except for C2 slope, which was higher in the PCO group (29.1° vs 18°, p = 0.026). The overall complication rates progressively increased with more complex osteotomy use (noPCO 68.8% vs PCO 71.9% vs 3CO 75%) but did not reach significance (p = 0.063). CONCLUSIONS The use of POs for mild flexible adult CD may not be necessary to achieve desirable radiographic correction. They are associated with greater EBL and fusion burden. Further studies are needed to fully delineate the risks of adverse events for various types of osteotomies.