Carilion Clinic Research Articles

Critical Challenges in Pluvicto Therapy: Incontinent and Anticoagulated Patients.

As molecular therapy continues to grow, unanticipated challenges may arise, requiring the institution's therapeutic team to reevaluate its therapeutic protocol to identify and address potential situations and challenges that may occur. This practical pointer will focus on the novel prostate cancer therapy Pluvicto (177Lu-vipivotide tetraxetan) and 2 unique situations and challenges of treating patients at the Theranostic Center at Carilion Clinic, an outpatient facility dedicated to targeted molecular therapy.

‘Ghost Networks’ Put Patients at Risk of Becoming More Ill

‘Ghost Networks’ Put Patients at Risk of Becoming More Ill

Endovascular Reconstruction of a Vertebral Artery After Traumatic Arteriovenous Fistula Using Flow Diversion: 2-Dimensional Operative Video.

*Department of Neurology, Virginia Tech Carilion Clinic School of Medicine, Roanoke, Virginia, USA; ‡Section of Neurosurgery, Carilion Clinic, Roanoke, Virginia, USA; §Neurointerventional Surgery, Department of Radiology, Carilion Clinic, Roanoke, Virginia, USA; ‖Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA Correspondence: Stephen Capone, MD, Department of Neurology, Virginia Tech Carilion School of Medicine, 3 Riverside Circle, Roanoke, VA24016, USA. Email: [email protected]

917. Infectious Diseases Consult Improves Management of Candidemia

Abstract Background Infectious Diseases consultations (IDC) have been associated with improved outcomes in multiple disease states with high morbidity/mortality like invasive candidiasis. This study evaluated management of candidemia at Carilion Clinic in patient with and without IDC. Methods A retrospective, observational cohort study was performed among hospitalized patients with candidemia who either received or did not receive an IDC between January 2014 and August 2020. Patients included had Candida species from at least one blood culture. Exclusions were death or transfer to a palliative care plan within 48 hours of culture, cultures from an outside facility, and patients that were pregnant or incarcerated. The primary outcome was a composite of all-cause mortality and recurrent candidemia within 90 days. Secondary outcomes included compliance with candidemia management bundle items such as echocardiography, ophthalmologic evaluation, receipt of susceptible antifungal, source control and repeated blood cultures. Results A total of 194 patients were included in the study. The population was 50.3% male sex and mean ± standard deviation age was 57.8 ± 17.2 years. In the study timeframe, 131 patients received an IDC while 62 did not receive an IDC. ICU level of care, vasopressor requirement and Candida Score ≥ 3 were all similar between the two groups. Candida albicans was the most common species in IDC and non-IDC groups (48.1% vs. 41.1%). Empiric therapy was more commonly an echinocandin in 138/194 (71.1%) and definitive therapy was fluconazole in 117/194 (60.3%). An improved primary composite outcome was observed in the IDC group (34.9% vs. 21.4%, p = 0.043). Patients receiving IDC had a higher rate of repeated cultures (100% vs. 92%) and ophthalmologic examination (54.2% vs. 20.6%). More patients in the IDC group were found to have infective endocarditis (10.7% vs. 1.6%, p = 0.04) as they were more likely to have echocardiographic imaging (86.2% vs. 57.1%, p< 0.0001). The median time to susceptible antifungal was 43 (27-61) hours without ICD and 35 (27-52) hours compared in those with IDC. Conclusion A more comprehensive workup by IDC was associated with more identification of endocarditis and less recurrence of candidemia within 90 days. Disclosures Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Lauren McDaniel, PharmD, BCIDP, Merck: Grant/Research Support.

Predictive Capability of Metabolic Panels for Postoperative Atrial Fibrillation in Cardiac Surgery Patients

IntroductionPostoperative atrial fibrillation (POAF) occurs in up to 65% of cardiac surgery patients and is associated with an increased risk for stroke and mortality. Electrolyte disturbances in sodium (Na+), potassium (K+), total calcium (Ca2+), chloride (Cl−), and magnesium (Mg2+) are predisposing factors for POAF, but these imbalances are yet to be used to predict POAF. The purpose of this study is to determine whether the development of POAF can be predicted by blood plasma ionic composition. MethodsMetabolic panels of patients with no prior history of atrial fibrillation who did (n = 763) and did not develop POAF (n = 2144) after cardiac surgery were obtained from the Carilion Clinic electronic medical record system. We initially evaluated serum Na+, K+, Ca2+, Cl−, and Mg2+ in the two groups using descriptive statistics via scatter and spaghetti plots and then with predictive modeling via logistic regression and random forest models. ResultsNeither scatter nor spaghetti plots of electrolyte data revealed a significant difference between those who did and did not develop POAF. Two logistic regression models and two random forest models with POAF status as the outcome were generated using the first observation for each electrolyte and the coefficient of the linear regression, which was obtained from a linear fit of the scatter plot. The random forest model using the first observation had a sensitivity of only 12.2%, but all four models had specificities more than 97%. ConclusionsNeither of the two logistic regression nor two random forest models were able to effectively predict the development of POAF from plasma ionic concentrations, but the random forest models effectively classified patients who would not develop POAF.

The Association between Weather and Emergency Department Visitation for Diabetes in Roanoke, Virginia.

Diabetes mellitus imposes a significant and increasing health burden on the US population. Our objective is to determine if weather is related to daily variations in emergency department (ED) visits for diabetes mellitus in Roanoke, Virginia. A time series of daily ED visits for diabetes mellitus at the Carilion Clinic in southwestern Virginia is associated with daily minimum temperature from 2010-2017. Associations between ED visits (through a 14-day lag period) and temperature are examined using generalized additive models and distributed lag nonlinear models. Heat and cold waves are identified at low and high thresholds, and ED visitation during these events is compared to prior control periods using a time-stratified case crossover approach. ED visits for diabetes exhibit a U-shaped relationship with temperature, with a higher relative risk (RR) during cold events (RR = 1.05) vs. warm events (RR = 1.02). When minimum temperatures are below freezing, ED visitation peaks starting 2days afterward, with RRs approaching 1.04. The RR on warm days (minimum temperature > 10°C) approaches 1.02 but peaks on the day of or the day following the elevated temperatures. Cold waves increase the odds of ED visits by up to 11% (p = 0.01), whereas heat waves exhibit no significant effect (p = 0.07). The increasing health burden linked to diabetes requires new research on environmental factors that might exacerbate related illness. When examined in the context of climate change impacts on local weather variations, these kinds of linkages between environment and disease can aid in facility staffing and public health messaging during extreme weather events.

<i>Ehrlichia chaffeensis</i><i>-</i>associated Hemophagocytic Lymphohistiocytosis: A Case Series and Literature Review

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon condition characterized by abnormal, excessive immune activation resulting in severe cytopenias from an uncontrolled inflammatory response. It can be primary/ familial or secondary/sporadic. Infections, particularly viral infections are a common cause of secondary HLH. HLH due to Human monocytic ehrlichiosis (HME) is very rare, hence we are reporting our cases. Objective: To review cases of Ehrlichia-associated HLH at our institution and perform a literature review regarding this entity. Methods: We reviewed cases of Ehrlichia-associated HLH for the previous two years at our institution (Carilion Clinic). We then performed a review of the published literature on it, using Pubmed. Results: Over the past two years, five cases of Ehrlichia-associated HLH were diagnosed at our hospital. The average age of the patients was 67 years with predominantly males. All the patients were pancytopenic, and a majority had abnormal liver function tests. Diagnosis of ehrlichiosis was made by serum polymerase chain reaction (PCR) assay on blood. Patients had further testing done because of lack of clinical improvement. All patients had significantly elevated ferritin levels. Bone marrow biopsy samples of all patients showed findings of hemophagocytosis. All, but one, patients were treated with doxycycline and a combination of etoposide and dexamethasone. Three patients recovered while two died. On review of medical literature, we found a total of only 36 cases of Ehrlichia-associated HLH, including our five cases. There were 19 adults and 17 children. Both population groups showed varying degrees of pancytopenia. Splenomegaly was relatively uncommon, seen in less than one-third of the patients. Ferritin and triglyceride levels were routinely elevated. Bone marrow biopsy showing hemophagocytosis was the confirmatory test in all patients. A significant number of patients, both adults and children, required a combination of doxycycline and chemotherapy (etoposide and dexamethasone) to achieve clinical cure. Children had a better prognosis than adults, with one child and four adults succumbing to their illness. Conclusions: Ehrlichia-associated HLH is a rare but emerging disease entity. In endemic areas, a high degree of suspicion is required to diagnose ehrlichiosis and HLH resulting from it. Early diagnosis and prompt initiation of treatment for HLH is key to a favorable outcome.

Outcomes of Young Patients With Alcoholic Cirrhosis After First Hospitalization for Cirrhosis: A Carilion Clinic Experience.

Background Alcoholic cirrhosis though uncommon in young patients is being reported more frequently and related mortality is also increasing. Study aim To evaluate risk factors associated with mortality among young patients (<40 years) with alcoholic cirrhosis and older patients (> 40 years old) after their first hospitalization in a tertiary referral academic center. MethodsCarilion clinic’s electronic medical record (EPIC) was queried to identify all alcoholic patients hospitalized for the first time with either a new diagnosis of alcoholic cirrhosis or a prior diagnosis of this from 2008 to 2016 with follow-up through June 2018. Information on demographics, comorbidities, lab values, procedures, and mortality was extracted. The cumulative risks of long-term mortality after the first hospitalization were estimated using Kaplan-Meier curves and compared between the two groups; those < 40 years of age and those > 40 years of age. Demographic data, lab values, and comorbidities associated with cirrhosis were assessed using multivariable Cox proportional hazard analysis to determine risk factors associated with long-term mortality. ResultsWe identified 65 young patients out of a total of 325 patients admitted for the first time for alcoholic cirrhosis (mean age: 34.6 ± 4.7 yrs, 72.3% males, 74.4% current alcohol users, 52.3% current smokers, 12.6% current illicit drugs users). The one, three, and five-year cumulative mortality after the first hospitalization was 21.1 %, 31.1%, and 49.7% respectively. The median survival for young patients was longer as compared to the older patients (p<0.001); likely related to high early mortality in older patients who had many other comorbidities. On multivariate Cox proportional hazard analysis, increased age [hazard ratio (HR) 1.03; 95% confidence interval (CI), 1.01-1.05], neutrophils-to-lymphocytes ratio (NLR) at first hospital discharge (HR 1.02; 95% CI, 1.01-1.04), the presence of encephalopathy (HR, 1.93; 95% CI, 1.06-3.55), and initial MELD (model for end-stage liver disease) score (HR, 1.13; 95% CI, 1.08-1.19) were associated with increased risk of mortality. Though the majority of patients endorsed current alcohol and tobacco use before the admission, it was not significantly associated with mortality. Conclusions Five-year cumulative mortality for patients < 40 years of age with alcoholic cirrhosis after their first hospitalization is 49.7%. Old age, most recent NLR, hepatic encephalopathy, and MELD score on admission were associated with increased late mortality.

Gender-Specific Risk Factors Contributing to Mortality in Patients Hospitalized With Alcoholic Cirrhosis.

IntroductionIdentification of gender-specific prognostic factors in patients with alcoholic liver cirrhosis (ALC) is integral to understanding disease severity and mortality rates. We gathered data on various widely-used laboratory values and comorbid conditions among male and female patients with ALC after initial hospitalization. These individual risk factors were assessed for their relationship with mortality based on gender.MethodsWe performed a retrospective observational study of hospitalized patients with either a new or prior diagnosis of ALC from 2008 to 2016 with follow-up through June 2018. The electronic medical record (EMR) was queried for demographics, comorbidities, lab values, and mortality. The cumulative risks of mortality after the first hospitalization were estimated using Kaplan-Meier curves and compared among both genders. Demographic data, lab values, and comorbidities associated with cirrhosis were assessed using multivariate Cox proportional hazard analysis to determine risk factors associated with mortality.ResultsWe identified 247 male patients (mean age 54.19 ± 13.14 years) and 78 female patients (mean age 51.10 ± 11.60 years) hospitalized at Carilion Clinic with a diagnosis of ALC. About 70% (male) and 46% (female) endorsed alcohol use at the time of admission, 10% (male) and 13% (female) endorsed illicit drug use, and 56% (male and female) endorsed tobacco use. The one-, three- and five-year cumulative mortality after the first hospitalization was 43.4%, 53.2%, and 61.6%, respectively for males and 24.1%, 59.0%, and 67.2%, respectively for females. Median survival for younger male patients with ALC (age < 40 years old) after the first hospitalization was significantly different compared to the older male patients (age > 40 years) (p=0.0009), but age was not a significant factor for survival of female patients.Multivariate analysis further shows that illicit drug use, creatinine level at the time of admission, and age > 40 years had the highest hazard ratios for risk of mortality in male patients.For female patients, history of hepatic encephalopathy (HE) and blood urea nitrogen (BUN) level at the time of discharge were both associated with increased risk of mortality, with a history of HE being associated with a higher hazard ratio for risk of mortality.ConclusionAge, illicit drug use, and creatinine level were risk factors associated with mortality for male patients with ALC but not female patients. Hepatic encephalopathy and BUN were risk factors associated with mortality for female patients. The mortality for male patients was about twice the mortality of female patients at one year, but three-year and five-year mortality was higher in female patients.

BMP4 to increase connexin43 expression and interaction with β-catenin in glioblastoma stem cells.

e14045 Background: Glioblastoma multiforme (GBM) is the most commonly occurring and most lethal primary central nervous system tumor. Treatment for GBM involves an aggressive combination of surgical resection, radiotherapy, and temozolomide chemotherapy. While intensive therapy has shown marginal improvement in prognosis, the median survival for GBM patients remains between twelve to fourteen months. The aggressiveness of GBM is attributed to the cellular heterogeneity and the invasive nature of the tumor, as well as the presence of glioblastoma cancer stem cells (GSCs). GSCs are a subpopulation of slowly dividing cells within GBM tumors that can survive chemotherapy and irradiation treatments targeting proliferating cells. The remaining quiescent GSCs can then enter an active state of self-renewal and differentiation through asymmetric division that contributes to tumor recurrence by recapitulating the heterogeneous tumor in relatively short order. Previously, we have identified a non-junctional, tumorigenic function for the gap junction protein connexin43 (Cx43) through its interaction with microtubules in GSCs. However, when GSCs are differentiated, this interaction decreases while Cx43 expression increases, suggesting an alternate function for Cx43. Bone Morphogenic Proteins (BMPs) have been implicated in GSC differentiation and their role in human tumorigenesis has remained largely unknown in GSCs. In this study, we aim to determine the effect of BMP on Cx43 expression and localization in GSCs. Methods: In this study, we used GBM patient-derived GSCs isolated from two GBM tumors following resection at Carilion Clinic, and maintained in stem cell medium. The effect of BMP4 signaling on Cx43 expression and localization in GSCs was determined using RT-qPCR, immunofluorescence, western blot, and co-immunoprecipitation. Results: Preliminary data show that BMP4 treatment increases Cx43 expression at the protein and mRNA levels through nuclear translocation and transcriptional activity of β-catenin. In addition, BMP4 treatment increases the interaction between Cx43 and β-catenin at the plasma membrane. Further studies are underway to determine the implications of disrupting Cx43/β-catenin interaction in GSC differentiation. Conclusions: While additional experiments are needed, our findings may be adapted as a prognostic indicator to determine patients’ susceptibility to traditional GBM therapies, and aid in novel therapeutic development to eradicate GSCs in GBM and prevent tumor recurrence following treatment.

Does completing advanced endoscopy fellowship improve outcomes after endoscopic mucosal resection?

It was reported that about 60% of the physicians in the USA believed that their Gastroenterology fellowship poorly prepared them for large polyp resection. The aim of this study was to compare endoscopic mucosal resection (EMR) efficacy and complication rates between skilled general gastroenterologists who perform high volume of EMR and advanced endoscopists. We identified 140 patients with documented large colonic polyps treated by 4 providers using EMR technique at Carilion Clinic, in Roanoke, Virginia, USA between 01/01/2014-12/31/2017, with follow-up through 10-2018. Information on demographics, clinical and pathological features of high-risk polyps (i.e., size, histology, site, and degree of dysplasia), timing of surveillance endoscopies, tools used during resection, and skills of performing endoscopist's were extracted. The cumulative risks of polyp recurrence after first resection using EMR technique were estimated using Kaplan-Meier curves. One hundred and forty patients were identified (mean age, 64.1±11.2 years; 47.1% males). Fifty-five polyps (39.3%) were removed by 2 skilled gastroenterologists and 85 (60.7%) were removed by advanced endoscopists. Most of the polyps resected were located in the right colon (63.6%) and roughly half of the polyps were removed in piecemeal fashion. At follow-up endoscopy, the advanced endoscopy group had lower polyp recurrence rates. The median recurrence after polypectomy was significantly different between the groups (0.88 and 1.03 years for skilled gastroenterologists who did not complete and completed EMR hands-on workshops; respectively vs. 3.99 years for the advanced endoscopist who did not complete EMR hands-on workshop, P=0.03). There is a need for additional EMR training since polyp recurrence was significantly different between the groups despite high rates of piecemeal resection in the advanced endoscopy groups.

START NOW: An Effective Mental Health Intervention

Dr. Robert Trestman, at the Carilion Clinic and Virginia Tech Carilion School of Medicine, has co-developed START NOW, a successful group psychotherapy intervention specifically targeting mental health issues in prisoners. It combines elements of cognitive behavioral therapy to form skills-based learning. Furthermore, START NOW is easily accessible, cost-effective, and designed for use in settings with limited resources. Due to its success within correctional institutions, START NOW is being adapted for use in fields such as adolescent conduct issues and opioid misuse.

Outcomes of Gastrointestinal Polyps Resected Using Underwater Endoscopic Mucosal Resection (UEMR) Compared to Conventional Endoscopic Mucosal Resection (CEMR).

ObjectiveUnderwater endoscopic mucosal resection (UEMR) is reported to be superior to conventional endoscopic mucosal resection (CMER) for the complete resection of large polyps and may offer increased procedural efficiency.AimsTo compare recurrence rates and adverse events between UEMR and CEMR and define risk factors related to recurrence. Also, to assess recurrence rates in piecemeal endoscopic mucosal resection (EMR) based on the number of pieces resected.MethodsWe identified all patients with large polyps treated using the UEMR technique at Carilion Clinic, Roanoke, VA, USA between January 1, 2014 and December 31, 2017 with follow-up through October of 2018. We matched the UEMR patients with patients treated using the CEMR technique (1:2 matching, respectively). The Kaplan-Meier curve was used to estimate the cumulative risks of polyp recurrence. The Cox proportional hazard analysis was used to assess risk factors for developing polyp recurrence.ResultsSixty-eight patients (mean age: 63.4 ± 12.5 years; 52.9% males) with polyps removed using the UEMR technique (Group 1) were matched with 122 patients (mean age: 64.4 ± 10.0 years; 51.6% males) who had polyps removed using CEMR (Group 2). Polyps resected in fewer pieces (≤ 3) had lower recurrence rates compared to the ones resected in >3 pieces. Right colon polyps removed using UEMR had a lower recurrence rate compared to right colon polyps resected using CEMR. Polyp size and a high degree of dysplasia were associated with a high risk of polyp recurrence after resection. Completing advanced endoscopy training was also associated with a lower risk of recurrence.ConclusionUEMR had a lower recurrence rate compared with CEMR for right colon polyps. Factors associated with recurrence included the degree of training, high-grade dysplasia, and polyp size.

S0191 Comparing Pathologic Features of Different Colonic Segments in Non-Hereditary Young Onset Colorectal Cancer

INTRODUCTION: Young patients with non-hereditary colorectal cancer (CRC) have unfavorable pathologic characteristics. The features and survival outcomes in different colonic segments are to be determined. METHODS: In this retrospective observational study we randomly selected patients (aged 18–50) with a histopathologic diagnosis of CRC at Carilion Clinic, Roanoke, from 2002 to 2017. Patients with inflammatory bowel disease and predisposing genetic syndromes were excluded. Demographics, polyp and tumor features, and mortality were obtained from the electronic medical record. Two pathologists reviewed histopathology to minimize diagnostic variability. The cumulative risk of mortality among patients with different pathologic features was estimated using Kaplan Meier curves. RESULTS: We identified 139 patients (Mean age, 41.6 ± 6.9 years; 53.2% males) with non-hereditary CRC. Thirty percent of tumors were located in the right colon (RC), 35.4% in the left colon (LC), and 34.5% in the rectum (Rec). In patients with resected tumors, a cancer-adjacent polyp was identified in 78.8% (RC), 73.7% (LC), and 47.4% (Rec). Lymphovascular invasion (LVI) was present in 59.0% compared to 38% (LC) and 25% (Rec). Perineural invasion (PNI) was present in 25.0% compared to 10.8% (LC) and 14.35% (Rec). RC tumor budding was (14%) compared to 13.1% (LC) and 2.9% (Rec), and tumor deposits in 30% compared 18.9% (LC) and 17.7% (Rec). Intratumoral lymphocytes were present in 32.1% (RC) compared to 15.8% (LC) and 3.03% (Rec). Intratumoral neutrophils were present in 3.6% in the RC compared to 10.5% (LC) and 3.03% (Rec). Thirty-two percent (RC) had Crohn’s like response compared to 26.3% (LC) and 3.0% (Rec). Microsatellite instability (MSI) accounted for 9.4% of (RC) tumors and 8.1% of (LC) tumors but was not present in rectal tumors. Among patients who had repeat colonoscopy for surveillance, about 90.0% of patients with RC cancer did not receive surveillance colonoscopy within 1 year of cancer diagnosis compared to 42% (LC) and 55.6% (Rec). Patients with Rec cancer had decreased survival compared to patients diagnosed with RC and LC cancers (P = 0.04) (Figure 1). CONCLUSION: Right colon tumors accounted for higher rates of unfavorable pathologic features compared to left colon and rectal tumors. Adherence to USMSTF surveillance recommendations is poor, especially in RC tumors. Patients with rectal cancer had the poorest survival outcomes compared to right and left colon tumors.Figure 1.: Interval time of diagnosis until last visit based on segment.

S0140 A Retrospective Analysis of Tumor Budding, Staging, Invasion, and Immune Response in Patients Diagnosed With Non-Hereditary Young Onset Colorectal Cancer

INTRODUCTION: Tumor budding is an adverse prognostic factor in colorectal cancer, has been studied extensively in patients with somatic, microsatellite stable variants, and is found in 20–40% of such cases. However, the presence and significance of this histopathologic phenomenon in young patients diagnosed with non-hereditary colon cancer is to be determined. In this study, our aim was to ascertain presence of tumor budding in young patients diagnosed with non-hereditary cancer and investigate correlations of this prognostic feature with other prognostic factors such as staging, invasion, and immune response trends. METHODS: In this retrospective observational study, we selected young patients (18–50 years old) with histopathologic diagnosis of non-hereditary colorectal adenocarcinoma at Carilion Clinic, Roanoke, from 2002 to 2017 and followed through 2011–2019. Patients with inflammatory bowel disease and those with predisposing genetic syndromes were excluded. Patient demographics, polyps’ features, cancer features, colonoscopy reports, and mortality were obtained from electronic medical record. Two pathologists reviewed pathology slides to minimize inter-pathologist variability in histologic diagnosis. The cumulative risk of mortality among patients with different pathologic features were estimated using Kaplan Meier curves. RESULTS: One hundred and thirty nine patients (mean age, 41.6 ± 6.9 years) with non-hereditary colorectal cancer were identified. One hundred and four of these cases displayed tumor budding on histology (74.8%). Tumor budding was significantly correlated with lymphovascular and perineural invasion (P < 0.01 for both). Tumor budding grade was also significantly correlated with high cancer stage (P < 0.01), with intratumoral lymphocyte and neutrophil presence (P < 0.01) and the presence of tumor deposits (P < 0.01). Lastly, the occurrence of a Crohn-like response, a histologic indicator for an immune reaction to the colon cancer, was noted to be significantly higher in neoplasms affected by higher grade tumor budding (P < 0.01). CONCLUSION: Tumor budding was found in the majority (74.8%) of young non-hereditary colorectal cancer patients, suggesting that this phenomenon is much more prevalent in this subpopulation than in the somatic, microsatellite stable colorectal cancer group. Tumor budding was also significantly correlated with low and high tumor stages as well as lymphovascular and perineural invasion in young patients with non-hereditary colon cancer.Table 1.: Table summarizing tumor budding correlations with staging, invasion, and immune response trends

Changes in Vascular Smooth Muscle and Collagen Content in Placental Vessels in Preeclampsia [04L

INTRODUCTION: Preeclampsia results in part from abnormal myometrial invasion by placental spiral arteries. It is unknown if and how fetal vessels remodel to compensate for these changes. We sought to characterize preeclampsia-associated vascular remodeling by comparing vessels within villi of placentas collected from preeclamptic and normotensive patients. METHODS: Carilion Clinic IRB approval was obtained prior to patient enrollment. Singleton pregnancies complicated by preeclampsia and normotensive controls were identified on Labor and Delivery. Placental biopsies were collected following delivery. Smooth muscle (alpha-SMA) and Type III collagen (COLIII) were identified by immunostaining of cryostat sections. Confocal microscopy was used to measure areas of alpha-SMA and COLIII positivity surrounding vessels. Ratios of alpha-SMA or COLIII positivity to vessel area were calculated. These ratios, which represent relative smooth muscle and collagen content, were compared between vessels from preeclamptic and normotensive placentas. RESULTS: Measurements from 342 vessels from 10 placentas (from five preeclamptic patients and five controls) were included in this analysis. Compared to vessels within placentas of normotensive patients, placental vessels of preeclamptic patients demonstrated a significantly reduced area of alpha-SMA positivity (2.48 vs 3.97; P=.008). A trend was seen towards decreased collagen surrounding vessels in preeclamptic placentas, though this was not statistically significant (4.33 vs 5.66; P=.054). CONCLUSION: Preeclampsia is associated with a decrease in vascular smooth muscle within placental villi and may be associated with decreased collagen content. This may represent a mechanism to increase transplacental flow of oxygen in the setting of impaired spiral artery remodeling, but further studies are needed to clarify this relationship.

Pericyte Coverage and Microvessel Caliber: Association with Smoking Status and Body‐Mass‐Index in Normal and Pre‐eclamptic Pregnancies

Pre‐eclampsia (PE) is a hypertensive disorder of pregnancy that is a major cause of maternal and fetal morbidity and mortality worldwide. Current evidence suggests that PE may result from shallow implantation of the developing fetus into the uterus, leading to abnormal formation of uteroplacental blood vessels. Pericytes play critical roles in neovessel formation and are thought to also have a role in blood flow regulation in microvascular networks. Little is known however about their function in the placenta and how this may be altered in disease. Here, we sought to determine whether differences exist in placental microvessel caliber or pericyte coverage between normal and PE pregnancies. We also examined whether modifiable risk factors might impact the observed phenotypes. Human placental tissue was obtained from normal and PE pregnancies (IRB protocol approved by Carilion Clinic). Tissue sections were antibody labeled, imaged by confocal microscopy, and assessed for vascular‐specific metrics. For comparative analysis, placental tissue from WT mice was sectioned, labeled, and imaged by confocal to optimize protocols and assess for pericyte localization. Measurements were collected using ImageJ/FIJI, and statistical analysis for human samples compared results from PE vs. normal controls. Researchers were blinded to disease state until after analysis was complete. Forty patients were enrolled in the study: 20 had normal pregnancies, and 20 had pregnancies complicated by PE. A significant difference (p &lt; 0.005) was found in gestational age at birth between groups. Pre‐eclampsia was associated with larger overall microvessel caliber, diminished capillary size for microvasculature associated with pericytes, and diminished pericyte number relative to controls. BMI and smoking status were both inversely correlated with pericyte number. The phenotypic changes observed in placental microvessels from PE pregnancies may be related to placental hypoxia and are associated with modifiable risk factors known to underlie other microvascular diseases.

Early Cardiac Rehab to Reduce Heart Failure Readmissions

Background The Centers for Medicare and Medicaid Services (CMS) initiated Cardiac Rehab (CR) coverage for heart failure (HF) patients in 2014. Coverage is limited to HF patients who meet specific criteria. Carilion Clinic, a not-for-profit, integrated healthcare organization composed of seven hospitals in Virginia, has attempted to bridge a gap in service for this patient population by providing an 8 session free CR program. This program, which was made available prior to 2014, is accessible to patients with a HF diagnosis. Objectives The aim of the 8-session free CR program for HF patients is to improve the health of this population and reduce readmissions. By providing monitored exercise sessions, education, and reinforcement of learned materials, patients are encouraged to become knowledgeable and responsible partners in their own healthcare. The 8-session program, which consists of rehab sessions twice weekly for one month, allows for early identification and intervention when problems present. Methods This IRB-approved study used a retrospective quasi-experimental comparison group design incorporating Epic Electronic Medical Record analysis for HF patients discharged between March 2013 and December 2017. Early CR attendance (within six weeks of discharge from the hospital) and readmission rates were evaluated in this study. HF patients who attended CR monitored, CR unmonitored, and the free 8 session program were included. A chi-square test was used to compare the readmission rates of patients who attended early CR and those who did not. The treatment group was identified as HF patients who had attended at least one CR visit within the first 6 weeks following discharge. The comparison group was identified as all HF patients who had not been admitted to the hospital during the previous one-year period, were discharged to home/self-care, and did not attend CR within six weeks of being discharged from the hospital. 30-day and 6-week readmission rates were compared between the treatment and comparison groups. Results Out of 8,613 HF patients, 205 (2.4%) attended at least one session of CR within six weeks post discharge. Readmission rates for comparison group versus treatment group were: 2.7% versus 1.0% for 30-day readmission for HF (p=0.13); 14% versus 5.9% for 30-day all-cause readmission (p Conclusions Statistically significant study results support early access to CR in reducing re-hospitalization rates. Study limitations include unbalanced sample sizes which increased variance and lowered statistical power, potential bias due to exclusion of mortality outcomes, and operationalization of CR as attendance to only one session. Current CMS criteria does not permit early access to CR and limits enrollment to a specific sub-group of this patient population. Future studies are needed with designs that further explore the impact of CR on HF readmissions. Based on the results of this study, CMS and health care systems may consider implementation of early unrestricted access to CR with the aim of improving the health of this patient population and reducing re-hospitalization rates.

The Impact of Heat Waves on Emergency Department Visits in Roanoke, Virginia

The Impact of Heat Waves on Emergency Department Visits in Roanoke, Virginia

A Model for Advancing Nurse Well-Being:: Future Directions for Nurse Leaders

Burnout results from experiencing persistent work-related stressors. We introduce and update a model of whole-person well-being to manage or mitigate the stressors that may otherwise generate burnout. The updated model incorporates Nursing Leadership Influence on Professional Burnout. The model was affirmed by original research at Carilion Clinic, Roanoke, Virginia, with 1296 nurses. Nurses exhibiting higher socio-relational well-being and lower depersonalization of patients experienced far lower emotional exhaustion—a core element of burnout and depression. Practical actions nurse leaders can take to promote greater well-being among nurses are reviewed.