Heterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling.

Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis. Genes in metabolic pathways were significantly downregulated in the AVF, whereas significant sex differences were not detected. Since gene expression patterns among the AVF group were heterogenous, the AVF group was divided into a 'normal' AVF (nAVF) group and an 'outliers' (OUT) group. The gene expression patterns of the nAVF and OUT groups were consistent with previously published data showing venous adaptive remodeling, whereas enrichment analyses showed significant upregulation of metabolism, inflammation and coagulation in the OUT group compared to the nAVF group, suggesting the heterogeneity during venous remodeling reflects early gene expression changes that may correlate with AVF maturation or failure. Early detection of these processes may be a translational strategy to predict fistula failure and reduce patient morbidity.

Common Data Elements and Databases Essential for the Study of Musculoskeletal Injuries in Military Personnel.

INTRODUCTION: Injuries are the leading cause of medical encounters with over 2 million medical encounters for musculoskeletal (MSK) conditions and over 700,000 acute injuries per year. Musculoskeletal injuries (MSKIs) are by far the leading health and readiness problem of the U.S. Military. The Proceedings of the International Collaborative Effort on Injury Statistics published a list of 12 data elements deemed necessary for injury prevention in the civilian population; however, there are no standardized list of common data elements (CDEs) across the DoD specifically designed to study MSKIs in the Military Health System (MHS). This study aims to address this gap in knowledge by defining CDEs across the DoD for MSKIs, establishing a CDE dictionary, and compiling other necessary information to quantify MSKI disease burden in the MHS. MATERIALS AND METHODS: Between November 2022 and March 2023, we conducted an environmental scan of current MSKI data metrics across the DoD. We used snowball sampling with active engagement of groups housing datasets that contained MSKI data elements to determine CDEs as well as information on readiness databases across the DoD containing up-to-date personnel information on disease, hospitalizations, limited duty days (LDDs), and deployability status for all military personnel, as well as MSKI-specific measures from the MHS Dashboard which tracks key performance measures. RESULTS: We identified 8 unique databases: 5 containing demographic and diagnostic information (Defense Medical Surveillance System, Medical Assessment and Readiness Systems, Military Health System Data Repository, Person-Data Environment, and Soldier Performance, Health, and Readiness Database); and 3 containing LDD information (Aeromedical Services Information Management System, eProfile, and Limited Duty Sailor Marines Readiness Tracker). Nine CDEs were identified: DoD number, sex, race, ethnicity, branch of service, rank, diagnosis, Common Procedural Terminology coding, and cause codes, as they may be captured in any database that is a derivative of the Military Health System Data Repository. Medical Assessment and Readiness Systems contained most variables of interest, excluding injury/place of region and time in service. The Limited Duty Sailor Marines Readiness Tracker contains a variable corresponding to "days on limited duty." The Aeromedical Services Information Management System uses the "release date" and "profile date" to calculate LDDs. The eProfile system determines LDDs by the difference between the "expiration date" and "approved date." In addition, we identified 2 measures on the MHS Dashboard. One measures the percentage of service members (SMs) who are on limited duty for longer than 90 days because of an MSKI and the other tracks the percentage of SMs that are not medically ready for deployment because of a deployment-limiting medical condition. CONCLUSIONS: This article identifies core data elements needed to understand and prevent MSKIs and where these data elements can be found. These elements should inform researchers and result in evidence-informed policy decisions supporting SM health to optimize military force readiness.

The Degree of Preoperative Hypoalbuminemia Is Associated with Risk of Postoperative Complications in Metabolic and Bariatric Surgery Patients.

BACKGROUND: The incidence and impact of hypoalbuminemia in bariatric surgery patients is poorly characterized. We describe its distribution in laparoscopic sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) patients undergoing primary or revision surgeries and assess its impact on postoperative complications. METHODS: The Metabolic and Bariatric Surgery Quality Improvement Program Database (2015 to 2021) was analyzed. Hypoalbuminemia was defined as Severe (< 3 g/dL), Moderate (3 ≤ 3.5 g/dL), Mild (3.5 ≤ 4 g/dL), or Normal (≥ 4 g/dL). Multivariable logistic regression was performed to calculate odds ratios of postoperative complications compared to those with Normal albumin after controlling for procedure, age, gender, race, body mass index, functional status, American Society of Anesthesia class, and operative length. RESULTS: A total of 817,310 patients undergoing Primary surgery and 69,938 patients undergoing Revision/Conversion ("Revision") surgery were analyzed. The prevalence of hypoalbuminemia was as follows (Primary, Revision): Severe, 0.3%, 0.6%; Moderate, 5.2%, 6.5%; Mild, 28.3%, 31.4%; Normal, 66.2%, 61.4%. Primary and Revision patients with hypoalbuminemia had a significantly higher prevalence (p < 0.01) of several co-morbidities, including hypertension and insulin-dependent diabetes. Any degree of hypoalbuminemia increased the odds ratio of several complications in Primary and Revision patients, including readmission, intervention, and reoperation. In Primary patients, all levels of hypoalbuminemia also increased the odds ratio of unplanned intubation, intensive care unit admission, and venous thromboembolism requiring therapy. CONCLUSION: Over 30% of patients present with hypoalbuminemia. Even mild hypoalbuminemia was associated with an increased rate of several complications including readmission, intervention, and reoperation. Ensuring nutritional optimization, especially prior to revision surgery, may improve outcomes in this challenging population.

Emergent Applications of Machine Learning for Diagnosing and Managing Appendicitis: A State-of-the-Art Review.

Background: Appendicitis is an inflammatory condition that requires timely and effective intervention. Despite being one of the most common surgically treated diseases, the condition is difficult to diagnose because of atypical presentations. Ultrasound and computed tomography (CT) imaging improve the sensitivity and specificity of diagnoses, yet these tools bear the drawbacks of high operator dependency and radiation exposure, respectively. However, new artificial intelligence tools (such as machine learning) may be able to address these shortcomings. Methods: We conducted a state-of-the-art review to delineate the various use cases of emerging machine learning algorithms for diagnosing and managing appendicitis in recent literature. The query ("Appendectomy" OR "Appendicitis") AND ("Machine Learning" OR "Artificial Intelligence") was searched across three databases for publications ranging from 2012 to 2022. Upon filtering for duplicates and based on our predefined inclusion criteria, 39 relevant studies were identified. Results: The algorithms used in these studies performed with an average accuracy of 86% (18/39), a sensitivity of 81% (16/39), a specificity of 75% (16/39), and area under the receiver operating characteristic curves (AUROCs) of 0.82 (15/39) where reported. Based on accuracy alone, the optimal model was logistic regression in 18% of studies, an artificial neural network in 15%, a random forest in 13%, and a support vector machine in 10%. Conclusions: The identified studies suggest that machine learning may provide a novel solution for diagnosing appendicitis and preparing for patient-specific post-operative complications. However, further studies are warranted to assess the feasibility and advisability of implementing machine learning-based tools in clinical practice.

Hospital Admissions for Abusive Head Trauma Before and During the COVID-19 Pandemic.

Importance: Several studies have demonstrated a decrease in the occurrence of child abuse in the US since the start of the COVID-19 pandemic. This finding has generated concern for missed cases due to the initial lockdowns and lack of childcare resources. Determining the association of the pandemic on hospitalizations for severe forms of abuse is essential to focus preventive efforts. Objective: To examine trends in abusive head trauma (AHT) before and during the COVID-19 pandemic. Design, Setting, and Participants: Retrospective, multicenter, repeated cross-sectional study, conducted January 1, 2016, through April 30, 2022, with data from tertiary care children's hospitals and contributors to the Pediatric Health Information System. Data were obtained for 2380 hospitalizations of children younger than 5 years with International Classification of Diseases, Tenth Revision, Clinical Modification codes for both abuse and head trauma. Main Outcomes and Measures: Monthly hospitalizations were analyzed using interrupted time-series analysis. Hospitalization severity (eg, intensive care unit stay) and clinical characteristics (subdural hemorrhages and retinal hemorrhages) were compared before and after the start of the pandemic. Results: We identified 2380 hospitalizations due to AHT (median age, 140 [IQR, 75.0-325.5] days) from 45 hospitals. The mean (SD) monthly incidence of AHT was 34.3 (5.8) before the COVID-19 pandemic compared with 25.6 (4.2) during COVID-19 (a 25.4% decrease). When the pre-COVID-19 and during COVID-19 periods were compared, there were no significant differences in severity or clinical characteristics. On interrupted time-series analysis, there was a significant decrease in the number of monthly hospitalizations (-8.1; 95% CI, -12.41 to -3.72; P < .001) in the first month of the pandemic. In the subgroup of children younger than 1 year, there was a significant decrease in monthly hospitalizations at the onset of the pandemic (-8.2; 95% CI, -12.02 to -4.43; P < .001) followed by a significant temporal increase across the COVID-19 period (P = .01). Conclusions and Relevance: The findings of this cross-sectional study suggest there was a significant decrease in monthly hospitalizations for AHT following the start of the pandemic in March 2020. Although there was no corresponding increase in hospitalization severity, the decrease during the pandemic may have been transient, as monthly hospitalizations for children younger than 1 year increased significantly over time during COVID-19, after the initial decrease.

Association of Postoperative Delirium and Parkinson Disease After Common United States Surgical Procedures.

INTRODUCTION: To determine the association of Parkinson disease (PD) and postoperative delirium following common surgical procedures. METHODS: We performed a retrospective database analysis of the National Inpatient Sample. We used a matched sample of patients with and without PD who underwent any of ten common surgical procedures in the US, 2005-2014. Primary outcome measure was postoperative delirium for patients with and without PD. Secondary measures included disposition, length of stay, and hospital costs. RESULTS: There were 3,235,866 patients receiving any of the ten most common operative procedures, 2005-2014. There were 35,743 patients with and without PD matched based on age, sex, elective admission status, Charlson Comorbidity index, and presence of dementia. Median age was 77 y (interquartile range 72-82), median Charlson Comorbidity index was 1 (standard deviation 0-2), 46.6% were female, and 46.8% were admitted electively. The three most common operative procedures were hip arthroplasty (28.5%), knee arthroplasty (16.1%), and percutaneous coronary angioplasty (14.9%). Postoperative delirium was present in 1519 patients with PD compared to 828 matched patients without PD (4.2% versus 2.3%; P < 0.001). The adjusted odds ratio of postoperative delirium for PD compared to the matched cohort without PD was 1.88 (95% confidence interval 1.73-2.05). Those undergoing spinal fusion (adjusted odds ratio 2.99, 95% confidence interval 2.06-4.38) had the greatest odds of delirium. For patients with PD, adjusted length of stay, adjusted hospital costs, and adjusted odds of postacute care facility discharge were greater compared to the matched cohort without PD. CONCLUSIONS: Patients with PD are more likely to develop postoperative delirium and have a more complicated postoperative course with longer length of stay and greater hospitalization costs.

Common comorbid and secondary conditions leading to hospitalization in multiple sclerosis patients in the United States.

OBJECTIVE: To identify the burden of hospitalization and common primary admitting diagnoses among MS patients in the United States (US). BACKGROUND: The burden of hospitalizations and conditions leading to hospitalizations in MS patients in the US has not been well described. DESIGN/METHODS: Using the Nationwide Inpatient Sample for 2001-2010, all patients with principal or secondary diagnosis of MS were identified, and the principal admitting diagnoses were compared with that of non-MS patients. Trends in hospitalizations were studied in specific age groups (1-9 yrs, 10-19 yrs, 20-29 yrs, 30-39 yrs, 40-49 yrs, 50-59 yrs, 60-69 yrs,70-79 yrs, 80-84 yrs and ≥85 yrs), and population level rates were obtained and compared with non-MS patients to obtain rate ratios (RR) and odds ratios (OR). RESULTS: A total of 1,240,410 MS patients were identified representing 4 out of every 1000 US hospital admissions, with an estimated female/male ratio of 2.72/1. The median age for MS hospitalizations was 53 years (Interquartile range=18). The majority of all MS hospitalizations occurred in the 30-69-year age bracket (82.17 %). The average length of in-patient hospital stays for MS patients compared to the non-MS population was 5.8 vs. 4.5 days (p < 0.001), and more MS patients had Medicare insurance (50.36 % vs. 42.24 %, p < 0.001). Overall, conditions such as urinary tract infections (UTI) - (RR11.43, p < 0.001), septicemia (RR8.53, p < 0.001), pneumonia (RR2.84, p < 0.001), chronic skin ulcers (RR20.64, p < 0.001), and lower limb and femoral neck fractures (RR2.86, p < 0.001) were present with increased frequency among MS patients. Patterns of comorbidity varied markedly by age group. The estimated average annual in-hospital charges adjusted to 2010 dollars for all MS inpatient hospitalizations was 3 billion U.S. dollars. CONCLUSIONS: Patients with MS are admitted into hospital at a younger age, are hospitalized longer and consume more Medicare resources than the similar patients without MS in the general population. Infections account for a large proportion of MS-associated hospitalizations, from young adulthood onward. These findings are particularly significant in light of the increasing availability of disease modifying therapies with more potent immunosuppressive properties, as well as the accumulating data that systemic infection can drive MS relapses.

Diverticulitis in Older Adults: Is Cognitive Impairment Associated With Outcomes?

INTRODUCTION: Older age is associated with increased prevalence of both diverticulitis and cognitive impairment. The association between cognitive impairment and outcomes among older adults presenting to the emergency department (ED) for diverticulitis is unknown. METHODS: Adults aged ≥65 y presenting to an ED with a primary diagnosis of colonic diverticulitis were identified using the Nationwide Emergency Department Sample (2016-2019) and stratified by cognitive impairment status in this retrospective cohort study. Multivariable Poisson regression models adjusted for patient age, sex, Elixhauser Comorbidity Index, primary payer status, and presence of complicated diverticulitis quantified relative risk of a) inpatient admission, b) operative intervention, and c) in-hospital mortality comparing patients with or without a diagnosis code suggestive of cognitive impairment. RESULTS: Among 683,444 older adults with an ED encounter for diverticulitis from 2016 to 2019, there were 468,226 patients with isolated colonic diverticulitis and 26,388 (5.6%) with comorbid cognitive impairment. After adjustment, the risk of inpatient admission for those with cognitive impairment was 18% higher than for those without cognitive impairment (adjusted relative risks [aRR]: 1.18, 95% confidence interval [CI]: 1.17-1.20). Those with cognitive impairment were 34% more likely to undergo colectomy than those without cognitive impairment (aRR: 1.34, 95% CI: 1.24-1.44). Older adults with cognitive impairment had a 32% greater mortality than those without cognitive impairment (aRR: 1.32, 95% CI: 1.05-1.67). CONCLUSIONS: Among older adults presenting for ED care with a primary diagnosis of colonic diverticulitis, individuals with cognitive impairment had higher rates of hospitalization, operative intervention, and in-hospital mortality than those without cognitive impairment.

An Evaluation of Sex-Based Differences in Surrogate Consent for Older Adults Undergoing Surgical Intervention.

INTRODUCTION: Differences between female and male patients have been identified in many facets of medicine. We sought to understand whether differences in frequency of surrogate consent for operation exist between older female and male patients. MATERIALS AND METHODS: A descriptive study was designed using data from the hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program. Patients age 65 y and older who underwent operation between 2014 and 2018 were included. RESULTS: Of 51,618 patients identified, 3405 (6.6%) had surrogate consent for surgery. Overall, 7.7% of females had surrogate consent compared to 5.3% of males (P < 0.001). Stratified analysis based on age categories showed no difference in surrogate consent between female and male patients aged 65-74 yy (2.3% versus 2.6%, P = 0.16), but higher rates of surrogate consent in females than males among patients aged 75-84 y old (7.3% versus 5.6%, P < 0.001) and age ≥85 y (29.7% versus 20.8%, P < 0.001). A similar relationship was seen between sex and preoperative cognitive status. There was no difference in preoperative cognitive impairment in female and male patients age 65-74 y (4.4% versus 4.6%, P = 0.58), but higher rates of preoperative cognitive impairment were seen in females than males for those age 75-84 (9.5% versus 7.4%, P < 0.001) and aged ≥85 y (29.4% versus 21.3%, P < 0.001). Matching for age and cognitive impairment, there was no significant difference between rate of surrogate consent in males and females. CONCLUSIONS: Female patients are more likely than males to undergo surgery with surrogate consent. This difference is not based on patient sex alone - females undergoing operation are older than their male counterparts and more likely to be cognitively impaired.

Palliative Care in a Pandemic: A Multicenter Cohort of Critically Ill Patients with Coronavirus Disease 2019.

Background: Trends in mortality, palliative care, and end-of-life care among critically ill patients with coronavirus disease 2019 (COVID-19) remain underreported. We hypothesized that use of palliative care and end-of-life care would increase over time, because improved understanding of the disease course and prognosis would potentially lead to more frequent use of these services. Patients and Methods: Adult patients with severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) during pandemic wave one (W1: March 2020 to September 2020) or wave two (W2: October 2020 to June 2021) admitted to an intensive care unit (ICU) in one of six northeastern U.S. hospitals were identified and clinical characteristics obtained. Vaccination data were unavailable. Outcomes of interest included mortality, palliative care consultation, and any end-of-life care (including hospice and comfort care). Results: There were 1,904 critically ill patients with COVID-19: 817 (42.9%) in W1 and 1,087 (57.1%) in W2. Patients received mechanical ventilation more often during W1 than W2 (52.9% vs. 46.3%; p = 0.004), with no difference in ICU or hospital length of stay between waves. Mortality between W1 and W2 was similar (31.2% vs. 30.9%; p = 0.888). There was no difference in use of palliative care or any end-of-life care between waves. Patients who died during W2 versus W1 were more likely to have received both mechanical ventilation (77.1% vs. 67.1%; p = 0.007) and palliative care services (52.1% vs. 41.2%; p = 0.009). However, logistic regression adjusted for demographics, baseline comorbid disease, and clinical characteristics showed no difference in mortality (odds ratio [OR], 1.15; 95% confidence interval [CI], 0.89-1.48), palliative care (OR, 1.08; 95% CI, 0.84-1.40), or any end-of-life care (OR, 1.05; 95% CI, 0.82-1.34) in W2 versus W1. Conclusions: Mortality among critically ill patients with COVID-19 has remained constant across two pandemic waves with no change in use of palliative or end-of-life care.

Non-Operative Shoulder Dysfunction in the United States Military.

INTRODUCTION: Recent epidemiological evidence shows that shoulder and upper-arm complaints impose a substantial burden on the armed forces of the United States and create significant challenges for all components of the physical fitness domain of total force fitness. Clinicians, epidemiologists, and health-services researchers interested in shoulder and upper-arm injuries and their functional limitations rarely have objective, validated criteria for rigorously evaluating diagnostic practices, prescribed treatments, or the outcomes of alternative approaches. We sought to establish and quantify patient volume, types of care, and costs within the Military Health System (MHS) in assessing and managing active duty members with nonoperative shoulder and upper-arm dysfunction. MATERIALS AND METHODS: We performed a retrospective cohort study using data from the MHS Data Repository and MHS MART (M2) from fiscal year 2014 to identify active duty individuals with a diagnosis of shoulder and upper-arm injury or impairment defined by one of the International Classification of Disease Ninth Edition diagnosis codes that were selected to reflect nonoperative conditions such as fractures or infections. Statistical analyses include descriptive statistics on patient demographics and clinical visits, such as the range and frequency of diagnoses, number and types of appointments, and clinical procedure information following the diagnosis. We also examined treatment costs related to shoulder dysfunction and calculated the total cost to include medications, radiological, procedural, and laboratory test costs for all shoulder dysfunction visits in 2014 and the average cost for each visit. We further examined the category of each medication prescribed. RESULTS: A total of 55,643 individuals met study criteria and accrued 193,455 shoulder-dysfunction-related clinical visits in fiscal year 2014. This cohort represents approximately 4.8% of the 1,155,183 active duty service members assigned to the United States and its territories during FY 2014. Most patients were male (85.32%), younger (85.25% were under 40 years old), and Caucasian/White (71.12%). The most common diagnosis code was 719.41 (pain in joint, shoulder region; 42.48%). The majority of the patients 42,750 (76.8%) had four or fewer medical visits during the study period and 12,893 (23.2%) had more than four visits. A total of 4,733 patients (8.5%) underwent arthrocentesis aspiration or injection. The total cost for all visits was $65,066,767.89. The average and median cost for each visit were $336.34 (standard deviation was $1,493.87) and $163.11 (range was from 0 to $84,183.88), respectively. Three out of four patients (75.3%) underwent radiological examinations, and 74.2% of these individuals had more than one radiological examination. Medications were prescribed to 50,610 (91.0%) patients with the three most common being IBUPROFEN (12.21%), NAPROXEN (8.51%), and OXYCODONE-ACETAMINOPHEN (5.04%), respectively. CONCLUSIONS: Nearly 1 in 20 active duty military service members presented for nonoperative care of shoulder and/or upper-arm dysfunction during FY2014. Further examinations of the etiology and potential impact of shoulder/upper-arm dysfunction on force readiness are clearly warranted, as are additional studies directed at identifying best practices for preventing injury-related dysfunction and determining best practices for the treatment of shoulder dysfunction to optimize service member fitness and force readiness.

Indoor Versus Outdoor: Does Occupational Sunlight Exposure Increase Melanoma Risk? A Systematic Review.

INTRODUCTION: Melanoma is the fifth most common cancer diagnosed in the United States, representing 5.6% of all new cancer cases. There are conflicting reports correlating a relationship between primarily outdoor occupations, associated with increased exposure to direct sunlight, and the incidence of cutaneous melanoma. Our objective was to outline and critically evaluate the relevant literature related to chronic occupational exposure to sunlight and risk of developing cutaneous melanoma. METHODS: The study protocol for this systematic review was submitted to the International Prospective Register of Systematic Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. For each relevant study included, the following information was extracted: author names, publication year, study name, study design, age, exposure assessment, outcome, comparison, number of cases, case ascertainment, and descriptive and adjusted statistics. Study quality and evidence certainty was assessed using the Grading of Recommendations, Assessment, Development and Evaluations model. RESULTS: The initial database search yielded 1629 articles for review and following full-text screening, a total of 14 articles were included for final analysis. Of the studies included, seven articles were retrospective case control and seven were cohort studies. The studies did not report any differences in the likelihood of cutaneous melanoma development based upon membership in the outdoor versus indoor occupation groups included in each study. CONCLUSIONS: Overall, the articles included in this systematic review did not report an increased risk of developing cutaneous melanoma among individuals with outdoor occupations. Further investigation is required to determine if other occupational or life-style-related risk factors exist, to help support the development of individualized skin screening recommendations and improve the early detection of melanoma in all populations.

Blood-Based Biomarkers of Repetitive, Subconcussive Blast Overpressure Exposure in the Training Environment: A Pilot Study.

Because of their unknown long-term effects, repeated mild traumatic brain injuries (TBIs), including the low, subconcussive ones, represent a specific challenge to healthcare systems. It has been hypothesized that they can have a cumulative effect, and they may cause molecular changes that can lead to chronic degenerative processes. Military personnel are especially vulnerable to consequences of subconcussive TBIs because their training involves repeated exposures to mild explosive blasts. In this pilot study, we collected blood samples at baseline, 6 h, 24 h, 72 h, 2 weeks, and 3 months after heavy weapons training from students and instructors who were exposed to repeated subconcussive blasts. Samples were analyzed using the reverse and forward phase protein microarray platforms. We detected elevated serum levels of glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 (UCH-L1), nicotinic alpha 7 subunit (CHRNA7), occludin (OCLN), claudin-5 (CLDN5), matrix metalloprotease 9 (MMP9), and intereukin-6 (IL-6). Importantly, serum levels of most of the tested protein biomarkers were the highest at 3 months after exposures. We also detected elevated autoantibody titers of proteins related to vascular and neuroglia-specific proteins at 3 months after exposures as compared to baseline levels. These findings suggest that repeated exposures to subconcussive blasts can induce molecular changes indicating not only neuron and glia damage, but also vascular changes and inflammation that are detectable for at least 3 months after exposures whereas elevated titers of autoantibodies against vascular and neuroglia-specific proteins can indicate an autoimmune process.

Surrogate consent for surgery among older adult patients.

BACKGROUND: Surrogate consent for surgery is sought when a patient lacks capacity to consent for their own operation. The purpose of this study is to describe older adults who underwent surgical interventions with surrogate consent. METHODS: A descriptive analysis was performed using data from the American College of Surgeons National Surgical Quality Improvement Program Geriatric Surgery Pilot collected from 2014 to 2018. All patients included were ≥65 years old and underwent a surgical procedure. Demographic and preoperative health characteristics were evaluated to examine differences between those with and without surrogate consent. RESULTS: In total, 51,618 patients were included in this study, and 6.6% underwent an operation with surrogate consent. Surrogate consent was more common among older patients (median age 83 vs 73, P < .001), female patients (7.7% vs 5.3%, P < .001), patients undergoing emergency as opposed to elective procedures (21.9% vs 1.6%, P < .001), patients with cognitive impairment (50.5% vs 2.4%, P < .001), and patients who were dependent on others for activities of daily living (41.9% vs 4.1%, P < .001). Nearly half of patients with a diagnosis of cognitive impairment signed their own consent. CONCLUSION: Surrogate consent was more common among patients who were older, female, had a higher comorbidity burden, and had preoperative disability. Nearly half of patients with documented cognitive impairment signed their own consent. These results indicate that further research is needed to understand how surgeons determine which patients require surrogate consent.

Methylation-based Cell-free DNA Signature for Early Detection of Pancreatic Cancer.

OBJECTIVES: The potential of DNA methylation alterations in early pancreatic cancer (PC) detection among pancreatic tissue cell-free DNA seems promising. This study investigates the diagnostic capacity of the 4-gene methylation biomarker panel, which included ADAMTS1, BNC1, LRFN5, and PXDN genes, in a case-control study. METHODS: A genome-wide pharmacoepigenetic approach identified ADAMTS1, BNC1, LRFN5, and PXDN genes as putative targets. Tissue samples including stage I-IV PC (n = 44), pancreatic intraepithelial neoplasia (n = 15), intraductal papillary mucinous neoplasms (n = 24), and normal pancreas (n = 8), and cell-free DNA, which was acquired through methylation on beads technology from PC (n = 22) and control patients (n = 10), were included. The 2-∆ct was the outcome of interest and underwent receiver operating characteristic analysis to determine the diagnostic accuracy of the panel. RESULTS: Receiver operating characteristic analysis revealed an area under the curve of 0.93 among ADAMTS1, 0.76 among BNC1, 0.75 among PXDN, and 0.69 among LRFN5 gene. The combination gene methylation panel (ADAMTS1, BNC1, LRFN5, and PXDN) had an area under the curve of 0.94, with a sensitivity of 100% and specificity of 90%. CONCLUSIONS: This methylation-based biomarker panel had promising accuracy for PC detection and warranted further validation in prospective PC surveillance trials.

Infant feeding and post-weaning health: Evidence from turn-of-the-century London.

Evidence on the post-weaning benefits of early-life breastfeeding is mixed, and highly context-dependent. Moreover, this evidence is drawn almost exclusively from modern settings, limiting our understanding of the relationship between breastfeeding and subsequent health in the past. We provide novel evidence on the nature and reach of these post-weaning benefits in a historical setting, drawing on a rich new longitudinal dataset covering nearly 1000 children from the Foundling Hospital, an orphanage in turn-of-the-century London. We find that even after the cessation of breastfeeding, ever-breastfed status reduced mortality risk and raised weight-for-age in infancy, that exclusive breastfeeding conferred additional benefits, and that breastfeeding duration had little impact. We also find a U-shaped pattern in weight-for-age by time since weaning, indicating a deterioration in health shortly after weaning, followed by a recovery. The early post-weaning advantages associated with breastfeeding, however, did not persist into mid-childhood. This indicates that any protective effects of earlier breastfeeding attenuated with age, and suggests a strong role for catch-up growth. This study contributes to the data and empirical settings available to explore the relationship between infant feeding and post-weaning health, and helps shed light on the contribution of changing breastfeeding norms to trends in health in twentieth-century Britain.

Can an Academic RVU Model Balance the Clinical and Research Challenges in Surgery?

OBJECTIVE: The purpose of this study is to identify perceptions of academic surgeons regarding academic productivity and assess its relationship to clinical productivity. We hypothesized that these perceptions would vary based on respondent characteristics including clinical activity and leadership roles. DESIGN: This retrospective, survey-based study was performed from August 26, 2019 to September 26, 2019. SETTING: The setting was academic surgical departments across the US. PARTICIPANTS: The survey instrument was administered to faculty members of the Association of Program Directors in Surgery. A total of 105 academic surgeons responded. RESULTS: Most respondents were Program Directors (59%) of general surgery programs. Of the participants, 30% identified as Professor, 36% as Associate Professor, and 15% as Assistant Professor. Respondents agreed that multiple academic pursuits or factors should count towards academic productivity including the following (in descending order): completing a first-authored manuscript (98.8%), completing a senior-authored manuscript (97.7%), chairing a national committee (94.1%), serving on a national committee (88.2%), completing a second-authored manuscript (88.0%), completing a first lecture (83.7%), completing a middle-authored manuscript (71.8%), completing a lecture (whether or not repeated) (70.9%), impact factor of journal (60.7%), and attendance at grand rounds (57.0%). Perspectives did not vary significantly based on surgeon demographics, clinical setting, or leadership role (p > 0.05). CONCLUSIONS: Perceptions regarding what constitutes academic productivity and merit a reduction in clinical expectation are remarkably similar across multiple surgeon characteristics including demographics, academic title, leadership role, and practice environment.

An Observational Study of the Pharmacokinetics of Surgeon-Performed Intercostal Nerve Blockade With Liposomal Bupivacaine for Posterior-Lateral Thoracotomy Analgesia.

BACKGROUND: Intercostal nerve blocks with liposomal bupivacaine are commonly used for thoracic surgery pain management. However, dose scheduling is difficult because the pharmacokinetics of a single-dose intercostal injection of liposomal bupivacaine has never been investigated. The primary aim of this study was to assess the median time to peak plasma concentration (Tmax) following a surgeon-administered, single-dose infiltration of 266 mg of liposomal bupivacaine as a posterior multilevel intercostal nerve block in patients undergoing posterolateral thoracotomy. METHODS: We chose a sample size of 15 adults for this prospective observational study. Intercostal injection of liposomal bupivacaine was considered time 0. Serum samples were taken at the following times: 5, 15, and 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours. The presence of sensory blockade, rescue pain medication, and pain level were recorded after the patient was able to answer questions. RESULTS: Forty patients were screened, and 15 patients were enrolled in the study. Median (interquartile range [IQR]) Tmax was 24 (12) hours (confidence interval [CI], 19.5-28.5 hours) with a range of 15 minutes to 48 hours. The median (IQR) peak plasma concentration (Cmax) was 0.6 (0.3) µg/mL (CI, 00.45-0.74 µg/mL) in a range of 0.3-1.2. The serum bupivacaine concentration was undetectable (<0.2 µg/mL) at 96 hours in all patients. There was significant variability in reported pain scores and rescue opioid medication across the 15 patients. More than 50% of patients had return of normal chest wall sensation at 48 hours. All patients had resolution of nerve blockade at 96 hours. No patients developed local anesthetic toxicity. CONCLUSIONS: This study of the pharmacokinetics of liposomal bupivacaine following multilevel intercostal nerve blockade demonstrates significant variability and delay in systemic absorption of the drug. Peak serum concentration occurred at 48 hours or sooner in all patients. The serum bupivacaine concentration always remained well below the described toxicity threshold (2 µg/mL) during the 96-hour study period.

Socioeconomically Distressed Communities Index independently predicts major adverse limb events after infrainguinal bypass in a national cohort.

BACKGROUND: Socioeconomic status is a major determinant of not only quality of life, but also mortality and health care-related outcomes. We hypothesized that patients coming from distressed communities would have worse short- and long-term limb related outcomes after infrainguinal bypass. METHODS: The infrainguinal bypass national Vascular Quality Initiative datasets for 2003 to 2018 were used. Clinical data were paired with the Distressed Communities Index (DCI) score before extraction. The DCI accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies at the zip code level, with a range of 0 (no distress) to 100 (severe distress). Severely distressed communities were defined as DCI greater than 75 for univariate analysis. Hierarchical multivariable modeling adjusted for baseline and operative risk factors, and clustering at the hospital level. RESULTS: The 9711 patients who underwent infrainguinal bypass from severely distressed communities (out of 40,109 total) were younger, more likely to smoke, disproportionately African American, with more comorbid disease (all P < .05). Patients from less distressed communities had lower rates of critical limb ischemia (56% DCI ≤ 75 vs 60% DCI > 75; P < .0001) and prior amputation (4.7 vs 6.3%; P < .0001). There was no difference in in-hospital mortality (1.3% vs 1.3%; P = .906) or major adverse cardiovascular events (4.1% vs 3.7%; P = .097). However, patients from distressed communities had higher rates of major adverse limb events (MALE; 11.7% vs 14.4%; P < .0001), and the components amputation, thrombectomy, and revision. After risk adjustment, DCI remained an independent predictor of in-hospital MALE (odds ratio, 1.05 per 25 DCI points; 95% confidence interval [CI], 1.02-1.08; P = .001) and long-term MALE (hazard ration [HR] 1.02; 95% CI, 1.00-1.04; P = .045). DCI is predictive of long-term graft occlusion (HR, 1.04; 95% CI, 1.00-1.07; P = .028) and amputation (HR, 1.09; 95% CI, 1.06-1.12; P < .0001). CONCLUSIONS: The DCI is an independent predictor of MALE after infrainguinal bypass. Patients from distressed communities are at an increased risk of long-term graft occlusion, which is disproportionately treated with amputation instead of surgical limb-saving alternatives. Socioeconomic factors impact vascular disease and surgical outcomes with disparities that warrant further investigation.

Effect of Travel Time for Thyroid Surgery on Treatment Cost and Morbidity.

Regionalizing surgical care to high-volume centers has improved outcomes for endocrine surgery. This shift is associated with increased travel time, costs, and morbidity within certain patient populations. We examined travel time-related differences in demographics, health-care utilization, thyroid-specific disease, and cost for patients undergoing thyroid surgery at a single high-volume center. Data were extracted from the 2005 to 2014 ACS-NSQIP and clinical data repository for patients undergoing thyroid surgery. Travel times between patients' home address and the hospital were calculated using Google Earth under assumptions of standard road conditions and speed restrictions. Travel time was divided into <2 hours versus ≥2 hours. Primary outcomes were hospital cost and 30-day morbidity. Factors associated with travel time and primary outcomes were analyzed using appropriate bivariate tests and multivariable regression modeling. A total of 1046 thyroid procedures were included, with median (IQR) travel time of 68.8 (40.1-107.2) minutes. Eight hundred forty-seven (80.9%) patients traveled <2 hours compared with 199 (19.1%) traveled ≥2 hours. Patients traveling ≥2 hours were more likely to have complex thyroid disease (37.7% vs 27.6%, P = 0.005), uninsured status (31.1% vs 11.8%, P < 0.001), lower preoperative morbidity risk (2.3% vs 2.7%, P = 0.02), and longer length of stay (1.21 vs 1.07 days, P = 0.04), but similar median operative times (163 vs 165 minutes, P = 0.89). Average cost was higher for patients traveling ≥2 hours ($7300 vs $6846 [2014 USD], P = 0.05). Despite observed patient differences, hospital costs and postoperative morbidity did not differ after adjustment. Existing management practices and the nature of the disease process may be protective against the potential negative effects of regionalization.