Blunt Cerebrovascular Injury Complications in Aging Adults: A National Trauma Database Study.

INTRODUCTION: Blunt cerebrovascular injury (BCVI) is defined as a nonpenetrating injury to the carotid or vertebral arteries which can be highly morbid. Because BCVI is rare, most studies have been devoted to triaging trauma patients for BCVI identification, with little data available regarding the complications these patients experience after initial evaluation. Here, we analyze the association of complications during admission for BCVI patients. METHODS: The National Trauma Databank was queried from 2007 to 2014 for adults ≥65 y old. Demographics, incidence of BCVI, and injury data were evaluated using univariate analysis. Rates of inpatient complications due to acutely acquired infections and strokes were evaluated using univariate and multivariable analysis. RESULTS: We identified 666,815 non-BCVI and 552 BCVI patients. Patients with a BCVI were typically male, White, younger (65-75-y-old), had three or more comorbidities, and had Medicare insurance. BCVI patients had a mild head injury upon arrival at the emergency department and experienced a motor vehicle accident/fall. The median length of stay in the intensive care unit, days spent on a ventilator, and presence of polytrauma were higher among BCVI patients. BCVI patients had increased odds of experiencing a stroke and pneumonia as complications while admitted compared to their non-BCVI counterparts. CONCLUSIONS: Postinjury, patients who suffered a BCVI had higher odds of stroke and pneumonia than patients who did not experience a BCVI. Additional studies are needed to determine the modifiable risk factors associated with BCVIs among aging adults.

Adjusting the Split: Examining Complications After Emergency Exploratory Laparotomy in Older Adults.

INTRODUCTION: Older adults experience higher rates of complications after an emergency exploratory laparotomy (EEL). To better understand the shift to an aging population in the United States, identifying how age may influence these complications in older patients is important. The current standard age category for older adult patients is ≥65. We analyzed postlaparotomy complications using a lower age split. METHODS: A retrospective analysis was done on patients who required an EEL from October 2015 to December 2019 at an academic medical center. Patient demographics and hospital course variables were collected. Differences in complications in patients aged ≥/<55 y and ≥/<65 y were measured using univariate and multivariable analyses. RESULTS: A total of 481 patients were reviewed. Both patient groups of ≥55 and ≥65 were typically male, White, had 3+ comorbidities, Medicare insurance, were retired, and presented in extremis to the emergency department. Patients aged ≥55 y had significant rates of pulmonary complications and inpatient mortality (odds ratio 2.2, 2.7, respectively). Patients aged ≥65 y had significant rates of genitourinary and cardiac complications (odds ratio 2.3, 1.8, respectively). CONCLUSIONS: Patients aged ≥55 y undergoing EEL had higher odds of experiencing pulmonary complications and death during their index hospitalizations, which was not present with the standard ≥/<65-y-old patient analysis. Those aged ≥65 y experienced index genitourinary and cardiac complications. The ≥/<55 age split has a unique set of complications that should be considered. Given the increased odds of inpatient mortality and types of complications in patients aged ≥55 y, the current age split for older adults should be reconsidered.

Noise-induced hearing loss in the contralateral ear during otologic and neurotologic surgeries.

OBJECTIVE: Noise-induced hearing loss in the non-surgical ear during otologic/neurotologic surgery has not been well studied. The purpose of this study was to evaluate changes in hearing that may occur in the contralateral (i.e., non-surgical) ear after various otologic/neurotologic surgeries due to noise generated by drills. We hypothesized that otologic/neurotologic surgeries, longer in duration, would suggest longer drilling times and result in decreased hearing in the contralateral ear as evidenced by a change post-operative pure tone air conduction thresholds when compared to pre-operative thresholds. METHODS: A retrospective chart review at a tertiary referral center. Adult patients (18-75 years old) who underwent otologic/neurotologic surgeries from May 1, 2016 through May 1, 2021 were considered for inclusion. Surgeries included vestibular schwannoma resection (translabyrinthine, middle cranial fossa, or retrosigmoid approaches), endolymphatic sac/shunt and labyrinthectomy for Meniere's disease, and tympanomastoid surgery for middle ear pathology (e.g., cholesteatoma). Patient characteristics obtained through record review included age, sex, surgical procedure, pre-operative and post-operative audiometric thresholds and word recognition scores (WRS) for the contralateral ear, and duration of surgery. RESULTS: No significant differences were observed for change in audiometric thresholds in the contralateral ear for any surgery when considering individual frequencies. Additionally, no significant change in WRS was observed for any surgical approach. CONCLUSIONS: The risk of hearing loss in the non-surgical ear during various otologic/neurotologic surgeries appears to be minimal when measured via routine clinical tests.

A functional mechanism for a non-coding variant near AGTR2 associated with risk for preterm birth.

BACKGROUND: Preterm birth (PTB), defined as delivery before 37 gestational weeks, imposes significant public health burdens. A recent maternal genome-wide association study of spontaneous PTB identified a noncoding locus near the angiotensin II receptor type 2 (AGTR2) gene. Genotype-Tissue Expression data revealed that alleles associated with decreased AGTR2 expression in the uterus were linked to an increased risk of PTB and shortened gestational duration. We hypothesized that a causative variant in this locus modifies AGTR2 expression by altering transcription factor (TF) binding. METHODS: To investigate this hypothesis, we performed bioinformatics analyses and functional characterizations at the implicated locus. Potential causal single nucleotide polymorphisms (SNPs) were prioritized, and allele-dependent binding of TFs was predicted. Reporter assays were employed to assess the enhancer activity of the top PTB-associated non-coding variant, rs7889204, and its impact on TF binding. RESULTS: Our analyses revealed that rs7889204, a top PTB-associated non-coding genetic variant is one of the strongest eQTLs for the AGTR2 gene in uterine tissue samples. We observed differential binding of CEBPB (CCAAT enhancer binding protein beta) and HOXA10 (homeobox A10) to the alleles of rs7889204. Reporter assays demonstrated decreased enhancer activity for the rs7889204 risk "C" allele. CONCLUSION: Collectively, these results demonstrate that decreased AGTR2 expression caused by reduced transcription factor binding increases the risk for PTB and suggest that enhancing AGTR2 activity may be a preventative measure in reducing PTB risk.

Giant Omphaloceles-Morbidity, Mortality, and Financial Impact of Early Versus Delayed Repair.

INTRODUCTION: We compared strategy outcomes and financial impact over the first two years of life (F2YOL) for patients with giant omphaloceles undergoing early repair (ER) (primary or staged) versus delayed repair (DR). METHODS: A retrospective review of giant omphaloceles (fascial defect > 5 cm/> 50% liver herniation) at a tertiary children's hospital between 1/1/2010 and 12/31/2019 was performed. Survival, length of stay, age at repair, ventilation days (VD), time to full enteral feeds, readmissions during the F2YOL, incidence of major associated anomalies, and total hospitalization charges during the F2YOL were compared. A subanalysis removing potential confounders and only including patients who underwent fascial closure within the F2YOL was also conducted. RESULTS: Thirty four giant omphaloceles (23DR and 11ER) were identified. The median age (days) at repair was 289 [148, 399] DR versus 10 [5, 21] ER, P < 0.001. Total cohort two-year survival was significantly higher in the DR group (95.7% versus 63.6%, P = 0.03). Including patients with a tracheostomy there was no significant difference in VD during the index hospitalization. Excluding tracheostomy patients, the DR group had significantly fewer VD during the index hospitalization, 15 [0, 15] versus 18 [10, 54], P = 0.02 and over the F2YOL 6.5 [ 0, 21] versus 18 [14, 43], P = 0.03. There were no significant differences in the incidence/type of major associated anomalies, time to full enteral feeds, index length of stay, total hospital days, total admissions, or associated hospital charges. On subanalysis, there was no significant difference in VD or survival at any time. CONCLUSIONS: Delayed and early repair strategies for giant omphaloceles have equivalent outcomes in the index hospitalization and over the course of the first two years of life. These findings are useful for family counseling and expectation setting.

A Review of Covered Abdominal Wall Defects: Cord Hernias Are Associated With Major Anomalies.

INTRODUCTION: Covered abdominal wall defects (CAWD) can be categorized into giant omphaloceles (GOs), nongiant omphaloceles (NGOs), and umbilical cord hernias (UCHs). We sought to evaluate differences in management and outcomes of the different CAWD, treated at a large tertiary children's hospital, with regards to survival and association with other major congenital anomalies. METHODS: A retrospective review of CAWD patients between January 2010 and January 2021 was conducted. GO was defined as a fascial defect >5 cm or >50% liver herniation. UCH were defined as fascial defects ≤ 2 cm. All others were classified as NGO. Type of repair, time to fascial closure, index hospitalization length of stay (LOS), and survival rates were compared. Four major anomaly categories were identified: cardiac, midline, Beckwith-Weidemann Syndrome, and other genetic anomalies. RESULTS: We identified 105 CAWD patients (UCH n = 40; GO n = 34; and NGO n = 31). Ninety percent of UCH underwent primary repair, 10% were never repaired. NGOs were repaired by primary or staged methods in 92.9% of cases and 7.1% by delayed repair. Primary or staged repair occurred in 32.4% of GOs and delayed repair occurred in 67.6%. The median days to repair was 181 [24,427] GO, 1 [1,3] NGO, and 1 [0,1] UCHs (P < 0.01). Index hospitalization median LOS (days) was 90 [55,157] GO, 23 [10,48] NGO, 9 [5,22] UCH, (P < 0.01). There were no statistical differences in survival rates, number of patients with major anomalies (GO 35.4%, NGO 51.5%, UCH 50%), or types of anomalies. CONCLUSIONS: UCHs and omphaloceles have similar incidences of major associated anomalies. Thus, all patients with a covered abdominal wall defect should undergo workup for associated anomalies.

Inhaled Nitric Oxide and Higher Necrotizing Enterocolitis Rates in Congenital Heart Disease Patients.

INTRODUCTION: Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. METHODS: We utilized International Classification of Diseases (ICD) codes to identify high risk congenital cardiac disease patients ≤6 mo of age, cared for at a tertiary children's hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared to controls in a multivariate analysis. RESULTS: Of the 352 patients, who met inclusion criteria, 77.6% had ductal dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 37.5% received other vasodilatory drugs. The overall NEC rate was 15.1%. On univariate analysis, DD-S, iNO use, and systemic vasodilators was associated with a significantly higher risk of NEC, while DD-P was associated with lower NEC risk. On multivariate analysis, only iNO (odds ratio 2.725, confidence interval [1.36-5.44]) and DD-S (odds ratio 2.279, confidence interval [1.02-5.11]) were independent risk factors for NEC. CONCLUSIONS: In patients with at-risk congenital cardiac disease lesions, a ductus dependent systemic circulation or iNO treatment is associated with an increased risk of developing NEC. The presence of iNO or DD-S should be utilized as markers of increased risk both in the prevention and workup of suspected NEC.

Utilization of Palliative and Hospice Care Among Pancreatic Cancer Patients at an Academic Center.

INTRODUCTION: Pancreatic ductal adenocarcinoma has the lowest 5-y relative survival of all solid tumor malignancies. Palliative care can improve the quality of life of both patients and their caregivers. However, the utilization patterns of palliative care in patients with pancreatic cancer are unclear. METHODS: Pancreatic cancer patients who were diagnosed between October 2014 and December 2020 at the Ohio State University were identified. Palliative care and hospice utilization and referral patterns were assessed. RESULTS: Of the 1458 pancreatic cancer patients, 55% (n = 799) were male, median age at diagnosis was 65 y (interquartile range [IQR]: 58, 73), and most were Caucasian (n = 1302, 89%). Palliative care was utilized by 29% (n = 424) of the cohort, with the initial consultation obtained after an average of 6 ± 9 mo from diagnosis. Patients who received palliative care were younger (62 y, IQR: 55, 70 versus 67 y, IQR: 59, 73; P < 0.001) and more frequently members of racial and ethnic minorities (15% versus 9%; P < 0.001) versus those who did not receive palliative care. Among the 344 (24%) patients who received hospice care, 153 (44%) had no prior palliative care consultation. Patients referred to hospice care survived a median of 14 d (95% CI, 12-16) after hospice referral. CONCLUSIONS: Only 3 out of 10 patients with pancreatic cancer received palliative care at an average of 6 mo from initial diagnosis. More than two out of every five patients referred to hospice had no previous palliative care consultation. Efforts to understand the impact of improved integration of palliative care into pancreatic cancer programs are needed.

Impact of early vs late palliative care referrals on healthcare utilization in patients with pancreatic cancer.

PURPOSE: The purpose of this study was to examine the impact of early versus late palliative care referral (PCR) following pancreatic cancer diagnosis. METHODS: Patients diagnosed with PDAC who received a PCR between 2014 and 2020 at a major academic institution were identified. PCR was classified as early (< 30 days) or late (≥ 30 days) based on time from definitive diagnosis. Data were obtained on number of emergency department (ED) visits, intensive care unit (ICU) admissions, and hospital admissions. RESULTS: Among 1458 patients with PDAC, 419 (28.7%) received PCR, among which 67.3% (n = 282) received a late PCR. Of those who received PCR, the majority were White (85%) and male (54.8%), with a median age of 62 years at time of diagnosis. Patients who received an early PCR more commonly presented with stage 4 disease at diagnosis (early: n = 91, 69% vs. late: n = 132, 47%), whereas patients who received a late PCR more commonly presented with stage 1, 2, or 3 disease (early: n = 40, 30.5% vs. late: n = 150, 53.2%) (p < 0.001). Patients who received early PCR had fewer median ED visits (1 vs. 2, p < 0.001) and hospital admissions (1 vs. 2, p < 0.001) compared with patients who received late PCR. However, after performing recurrent-event Cox-proportional hazards models, the timing of PCR did not impact hospital admission (HR 0.88, 95% CI 0.68, 1.14; p = 0.3). CONCLUSION: Timing of PCR for patients with PDAC was not associated with healthcare utilization. Further prospective trials are needed to study the patient-centered impact of early integration of palliative care services into multidisciplinary pancreatic cancer teams.

Genetic, Inflammatory, and Epithelial Cell Differentiation Factors Control Expression of Human Calpain-14.

Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease resulting in eosinophilic esophageal inflammation. We recently found that EoE susceptibility is associated with genetic variants in the promoter of CAPN14, a gene with reported esophagus-specific expression. CAPN14 is dynamically up-regulated as a function of EoE disease activity and after exposure of epithelial cells to interleukin-13 (IL-13). Herein, we aimed to explore molecular modulation of CAPN14 expression. We identified three putative binding sites for the IL-13-activated transcription factor STAT6 in the promoter and first intron of CAPN14 Luciferase reporter assays revealed that the two most distal STAT6 elements were required for the ∼10-fold increase in promoter activity subsequent to stimulation with IL-13 or IL-4, and also for the genotype-dependent reduction in IL-13-induced promoter activity. One of the STAT6 elements in the promoter was necessary for IL-13-mediated induction of CAPN14 promoter activity while the other STAT6 promoter element was necessary for full induction. Chromatin immunoprecipitation in IL-13 stimulated esophageal epithelial cells was used to further support STAT6 binding to the promoter of CAPN14 at these STAT6 binding sites. The highest CAPN14 and calpain-14 expression occurred with IL-13 or IL-4 stimulation of esophageal epithelial cells under culture conditions that allow the cells to differentiate into a stratified epithelium. This work corroborates a candidate molecular mechanism for EoE disease etiology in which the risk variant at 2p23 dampens CAPN14 expression in differentiated esophageal epithelial cells following IL-13/STAT6 induction of CAPN14 promoter activity.