Recent publications
831
Background: Systemic treatment of metastatic appendiceal adenocarcinoma (AA) has been challenging due to a lack of well-established AA chemotherapy regimens and historical reliance on colorectal cancer (CRC) protocols. In the United States, but less commonly in Europe, bevacizumab is frequently incorporated in treatment of AA given its approved use for CRC. However, previously there have been no studies evaluating if there is a survival benefit attributable to bevacizumab in patients with AA. Methods: The Palantir Foundry system was used to extract data from the MD Anderson Cancer Center (MDA) electronic medical record for patients with biopsy-proven AA who received chemotherapy at MDA from 2015 to 2024. Only patients with complete staging and histopathology data were included in the analysis. Results: We identified 203 patients with AA who received chemotherapy at MDA and had complete tumor data. Of these, 43% (n=87) received bevacizumab at some point in their treatment. Patients who received bevacizumab were demographically similar to patients who received non-bevacizumab chemotherapy in terms of age at diagnosis, race, and sex; mucinous histology was more frequent in the bevacizumab cohort (52%, n=45 vs. 39%, n=45 in non-bevacizumab cohort). The 87 patients who received bevacizumab were treated with 1-6 lines of therapy per patient (mean = 1.57). The most frequently used bevacizumab-containing regimens were FOLFOX + bevacizumab (34%, n=46), FOLRIRI + bevacizumab (29%, n=40), 5-FU + bevacizumab (15%, n=21), and atezolizumab + bevacizumab (11%, n=15), with less common irinotecan + bevacizumab, TAS-102 + bevacizumab, and FOLFOXIRI + bevacizumab. Three regimens containing bevacizumab were discontinued due to complications: one instance of hand-foot syndrome attributed to xeloda, one instance of cardiomyopathy attributed to immunotherapy, and one bowel perforation with abdominal wall abscess attributed to bevacizumab. To determine if bevacizumab was associated with overall survival (OS) benefit we performed Kaplan-Meier analysis, with OS calculated from start of first line chemotherapy to death, in patients with metastatic AA who received either 5-FU doublet therapy alone or 5-FU doublet therapy with bevacizumab. Patients who received bevacizumab trended toward better OS (median 52 vs 25 months for doublet therapy alone, HR: 0.53, p= 0.059). The effect of bevacizumab was particularly notable in patients with signet ring cell histology; where bevacizumab use was associated with significantly longer OS (median OS 50 vs 14 months for doublet therapy alone, HR: 0.24, p= 0.034). Conclusions: Bevacizumab is frequently added to cytotoxic chemotherapy in the treatment of AA. These retrospective data suggest an OS benefit to adding bevacizumab to doublet chemotherapy, particularly in the case of signet ring cell histology.
816
Background: More than 44,000 patients are seen at MD Anderson Cancer Center annually. However, using the diverse, mostly unstructured, data from these patient encounters has been challenging and required manual chart reviews. In 2018, MD Anderson and Palantir Technologies (Denver, CO) began developing a unified, cloud-based, graphical user interface clinical informatics platform to extract, structure, and integrate data from the different data sources that comprise the electronic health record (EHR). Here, we describe our experience using this novel platform to apply a real-world evidence (RWE) approach to study patients with gastrointestinal (GI) malignancies. Methods: Institutional Review Board approval for retrospective chart review of patients with GI malignancies was previously obtained. The Foundry platform was used to incorporate more than 150 datasets, including structured data elements like lab values, unstructured data as the full text of clinical notes, and natural language processing (NLP) derived datasets. The datasets include unique patient identifiers to allow the merging of demographic, clinical, molecular, and outcomes information. The platform allows processing of the note text through NLP to extract non-discrete data elements into a discrete form. In addition, it continuously updates new data on daily bases, allowing the inclusion of new patients' information in an automated fashion. Results: From 2,013,048 patients with date of diagnosis ranging from 1944 to 2024, we have created datasets for colorectal adenocarcinoma (CRC, >50,000 patients, >8,000 with molecular data), pancreatic adenocarcinoma (PDAC, >13,000 patients), and appendiceal adenocarcinoma (AA, >3,000 patients). More than 50 variables have been integrated, including demographic information, stage, grade, overall survival, and molecular information. Focused manual validation of the automated extraction across the cohorts consistently demonstrated an accuracy of over 94%. Work is underway to extract additional features including DFS and PFS, sites of metastasis, and to build out additional cohorts for biliary tract, upper GI, and neuroendocrine tumors. Initial discovery efforts have already led to multiple publications including discovery of molecular causes of racial and ethnic disparities in CRC, survival impact of KRAS and co-mutations in PDAC, and prognostic utility of serum tumor markers in AA. Conclusions: Utilizing an automated, highly dynamic platform allowed integration of comprehensive datasets for multiparameter oncology data in patients with GI malignancies. This resulted in dramatic acceleration of cohort identification, outcomes analysis, and enabled utilizing a data-driven approach to guide decision making in an effort to enhance and optimize outcomes.
Imaging is a critical component in the diagnosis of congenital and developmental anomalies of the kidney and urinary tract. Many abnormalities, including obstructive uropathy, are now routinely detected antenatally. In postnatal imaging, there continue to be advances aimed at improving diagnostic accuracy while decreasing ionizing radiation exposure in children. In this chapter, we will review the imaging of developmental anomalies of the kidney and urinary tract with a brief overview of pathophysiology, epidemiology, and clinical manifestations of each disorder.
The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield’s motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the ‘plis de passage’ of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network.
Here, using microdissections of sixteen human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter, in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space to seed fMRI connectivity across 9,000 resting-state fMRI scans, which demonstrated the connectivity of these sites with the somato-cognitive action network. Intraoperative recordings during direct electrical central sulcus stimulation further identified inter-effector regions corresponding to plis de passage locations.
This work provides a critical step towards improved understanding of the somato-cognitive action network in both structural and functional terms. Further, our work has the potential to guide the development of refined motor cortex stimulation techniques for treating brain disorders, and operative resective techniques for complex surgery of the motor cortex.
Diabetes and chronic kidney disease (CKD) are highly prevalent among those of advanced age, and Diabetes is the leading cause of end-stage kidney disease (ESKD) in those over 60. While diagnosis of CKD in those of advance age is made by the same criteria (estimated glomerular filtration rate, eGFR) and albuminuria (urine Albumin to Creatinine Ratio, UACR), the effects of normal aging upon eGFR make diagnosis difficult especially in the absence of severe albuminuria. It is imperative that advanced age individuals with diabetes and CKD are treated in a multidisciplinary fashion recognizing the multiple comorbidities, and higher sensitivity to medication side effects. Translating recent advances in therapeutics from the general population to the advance age patients is challenging. We propose a guideline-based framework for the management of diabetes in CKD and discuss the pharmacological management with inhibitors of the renin-angiotensin system, sodium-glucose co-transporter two inhibitors (SGLT2i), non-steroidal mineralocorticoids and glucagon-like peptide 1 receptor agonists (GLP1-RA). We review the evidence that the benefits from these newer therapies apply equally to those with advanced age or younger and can be deployed in a multidisciplinary management program for diabetes.
Hospital performance is increasingly measured by length of stay, which accounts for 90% of inter-patient cost variations. We examined the impact of frailty on all-cause mortality in neurosurgical patients with length of stay > 30 days and analyzed the discrimination and independent association of the risk analysis index, 5-factor modified frailty index, and advanced patient age for predicting all-cause mortality. The older patients who underwent neurosurgical procedures between 2012 and 2020 in the American College of Surgeons National Surgical Quality Improvement Program, with length of stay > 30 days were included in this retrospective observational study. Receiver operating characteristic curves were employed to compare the discrimination and multivariable analyses for associations of the risk analysis index, 5-factor modified frailty index advanced patient age and all-cause mortality. Secondary analyses were performed for spine and cranial procedures. Overall, 3474 patients were included, patients had a median age of 60 years (IQR: 49–70), were male (58.6%), white (47.9%), and underwent spine (46.4%) and cranial (51.9%) procedures. Major complications (33.9%), and median length of stay 38 days (IQR: 33–48) were observed. Risk analysis index demonstrated superior discrimination (C-statistic 0.72, 95% confidence interval 0.69–0.74) than 5-factor modified frailty index (C-statistic 0.57, 95% confidence interval 0.54–0.60) and advanced patient age (C-statistic 0.59, 95% confidence interval 0.55–0.62). Risk analysis index also demonstrated a dose-dependent relationship and larger effects in multivariable analysis ( P < 0.001). Similar trends were observed for spine and cranial procedures in both Receiver operating characteristic and multivariable analysis. Taken together, frailty increased all-cause mortality dose-dependently, and risk analysis index exhibited a higher discrimination threshold and larger effect estimates than the 5-factor modified frailty index and advanced patient age. This study reflects the importance of preoperative assessment of frailty in the management of older neurosurgical patients and supports the use of risk analysis index in preoperative assessment to improve clinical outcomes of older patients. By identifying and assessing frailty, healthcare professionals can better personalize treatment plans for older patients to address age-related changes and challenges.
Purpose:
Appendiceal adenocarcinoma (AA) is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of AA relative to common tumors.
Experimental design:
We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with AA at our institution (from 10/2004-9/2022) for whom circulating tumor DNA (ctDNA) mutation profiling (liquid biopsy) was performed (n=168) and extracted clinicopathologic and outcomes data. Of these 168 patients 57 also had tissue-based tumor mutational profiling allowing for evaluation of concordance between liquid and tissue assays.
Results:
The mutational landscape of ctDNA in AA is distinct from tissue-based sequencing, with TP53 being the most frequently mutated (46%). Relative to other tumors, AA appears less likely to shed ctDNA, with only 38% of metastatic AA patients having detectable ctDNA (OR 0.26, p < 0.0001 relative to CRC). When detectable the median VAF was significantly lower in AA (0.4% vs. 1.3% for CRC, p≤0.001). High grade, signet-ring or colonic-type histology, metastatic spread beyond the peritoneum, and TP53 mutation were associated with detectable ctDNA. With respect to clinical translation, patients with detectable ctDNA had worse overall survival (HR = 2.32, p = 0.048). In the Guardant Health cohort actionable mutations were found in 93 patients (13.0%).
Conclusions:
Although metastatic AA tumors are less likely to shed tumor DNA into the blood relative to CRC, ctDNA profiling in AA has clinical utility.
Background: TEE is increasingly recognized as a valuable imaging modality during cardiac arrest (CA) resuscitation, particularly for assessing the area of maximal compression (AMC) during CPR. Small single center studies have shown that compression of the left ventricular outflow tract or the aortic root (AMC-LVOT/Ao) is common during CPR, and that when CPR is performed with the AMC over the LV, this results in higher ETCO2, and ROSC. This study aimed to investigate the AMC and its relationship to ETCO2, and ROSC, hypothesizing that patients experiencing AMC-LVOT/Ao have lower ETCO2 and are less likely to achieve ROSC.
Methods: A prospective, multicenter cohort study of patients with out-of-hospital and in-hospital CA (OHCA/IHCA) in whom TEE was performed during CPR comparing AMC over the LV (AMC-LV) vs AMC-LVOT/Ao. The study was conducted through the Resuscitative TEE Collaborative Registry, an ongoing multicenter research network involving 37 hospitals (NCT04972526). Collected data included patient and procedure characteristics, hemodynamics, and outcomes according to Utstein-style guidelines. Primary outcome was ROSC, and the secondary outcome was ETCO2 at the time of AMC determination. We performed univariate analysis and multivariate regression evaluating variables known to impact resuscitation outcomes.
Results: 271 patients including 205 OHCA and 66 IHCA were included. Only 133 (49%) of the total cohort had AMC-LV, with AMC-LVOT/Ao in 47% of OHCA and 42.1% of IHCA. There was no significant difference in the location of the AMC when analyzed by demographic characteristics, height, weight, or comorbidities between patients who received manual vs mechanical CPR. In OHCA, there was no difference in ROSC between AMC-LV and AMC-LVOT/Ao, however the group of patients with AMC-LVOT/Ao had on average 10 units lower ETCO2 compared to AMC-LV (Beta -10; 95% CI -19 - 1.5; p = 0.023). In IHCA, after controlling for factors known to impact outcomes, patients with AMC-LVOT/Ao had significantly lower probability of ROSC (OR 0.25, 95% CI 0.06-0.88; p=0.038).
Conclusion: Obstruction of the LVOT/Ao during CPR is a common finding in CA patients evaluated with TEE. This multicenter study extends previous animal and smaller clinical studies suggesting the mechanistic association between the AMC during CPR, with ETCO2 and ROSC, and the potential of TEE-guided resuscitation to improve the effectiveness of CPR.
Outpatient parenteral antimicrobial therapy (OPAT) has become more common in infectious diseases practice settings. Similarly, OPAT-related publications have also increased. The objective of this article was to summarize clinically important OPAT-related publications from 2023. Eighty-one articles were found on initial search, with 52 meeting inclusion criteria. A survey containing the 19 articles that had at least one citation was sent to an email listserv of multidisciplinary clinicians with OPAT experience. This article summarizes the “top 10” 2023 OPAT articles from the survey results.
Hip disarticulation is a morbid procedure for those whose bony or soft tissues are unable to be salvaged. It involves extensive resection, and the patient featured in this report expressed mechanical pain from their sacroiliac joint (SIJ) as well as phantom limb pain (PLP). Spinal cord stimulation is known to assist with neuropathic pain syndromes, and SIJ fusion is effective in these cases of multifactorial pain. This report presents a successful off-label use of thoracic spinal cord stimulation in a complex pain condition consisting of coexisting PLP and mechanical SIJ pain in a hip disarticulation patient.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.
Information
Address
Albuquerque, United States
Website