Faculty Bibliography

BACKGROUND:Because of advances in medical treatment of heart failure, patients are living longer than in previous eras and may approach the need for advanced therapies, including heart transplantation, at older ages. This study assesses practices surrounding heart transplant in older adults (> 70 years) and examines short- and medium-term outcomes. METHODS AND RESULTS/RESULTS:This study is a retrospective analysis using the United Network for Organ Sharing (UNOS) database from 2010 to 2021. The absolute number of older adults being transplanted is increasing. Older adults were more likely to have had a prior malignancy or ischemic cardiomyopathy and less likely to be on extra-corporeal membrane oxygenation or have a high UNOS status prior to transplant. Mortality at 1-year was higher for older adults (27.8% vs. 23.4%), but at 5 years there was no significant difference (22.3% vs. 19.4%.). Older adults were more likely to die of malignancy or infection. Adults under 70 were more likely to die of cardiovascular causes or graft failure. There was less rejection in older adults. Mortality has not changed for older adults transplanted before versus after the 2018 UNOS allocation change. CONCLUSIONS:Carefully selected older adults may be considered for heart transplantation, given similar intermediate-term mortality.

BACKGROUND: While prior studies have recommended immediate flap coverage within 72 hours of injury for soft tissue reconstruction for traumatic extremity injuries, recent evidence in the setting of advanced wound care techniques de-emphasizes the need for immediate coverage. Negative-pressure wound therapy (NPWT) has been an essential tool for extending the time to definitive soft tissue coverage. This study sought to elucidate the impact of preoperative NPWT use on the success of microsurgical reconstruction. METHODS: A literature search was conducted using the following databases from their inception up to February 2023: PubMed, OVID databases (Embase and Cochrane Library), Web of Science, and Scopus. Of 801 identified articles, 648 were assessed and 24 were included. Cases were divided based on whether NPWT was used preoperatively or not. Timing to definitive coverage, injury details, and basic demographics were recorded. Rates of flap failure, infection, bone nonunion, reoperation, and complications were compared between groups. RESULTS: A total of 1,027 patients and 1,047 flaps were included, of which 894 (85.39%) received preflap NPWT. The average time to definitive coverage for the NPWT and non-NPWT groups was 16 and 18 days, respectively. The NPWT group experienced lower postoperative complication rates than the non-NPWT group in all reported complications except for deep infections. Compared with the non-NPWT group, the NPWT group experienced lower rates of any flap failure (3.69 vs. 9.80%) and partial flap failure (2.24 vs. 6.54%). CONCLUSION/CONCLUSIONS: Preoperative NPWT was associated with reduced postoperative complications, most importantly flap failure rates. This merits further investigation into the decision-making process for traumatic extremity reconstruction. Future prospective studies adopting standardized protocols with longer follow-up are required to better understand the potentially beneficial role of preoperative NPWT use in soft tissue reconstruction.

INTRODUCTION/BACKGROUND:Accurate operative scheduling is essential for the appropriation of operating room (OR) resources. We sought to implement a machine learning (ML) model to predict primary total hip (THA) and total knee arthroplasty (TKA) case time. METHODS:A total of 10,590 THAs and 12,179 TKAs between July 2017 and December 2022 were retrospectively identified. Cases were chronologically divided into training, validation, and test sets. The test set cohort included 1,588 TKAs and 1,204 THAs. There were four machine learning algorithms developed: linear ridge regression (LR), random forest (RF), XGBoost (XGB), and explainable boosting machine (EBM). Each model's case time estimate was compared to the scheduled estimate measured in 15-minute "wait" time blocks ("underbooking") and "excess" time blocks ("overbooking"). Surgical case time was recorded, and SHAP (Shapley Additive exPlanations) values were assigned to patient characteristics, surgical information, and the patient's medical condition to understand feature importance. RESULTS:The most predictive model input was "median previous 30 procedure case times." The XGBoost model outperformed the other models in predicting both TKA and THA case times. The model reduced TKA 'excess time blocks' by 85 blocks (P < 0.001) and 'wait time blocks' by 96 blocks (P < 0.001). The model did not significantly reduce 'excess time blocks' in THA (P = 0.89) but did significantly reduce 'wait time blocks' by 134 blocks (P < 0.001). In total, the model improved TKA operative booking by 181 blocks (2,715 minutes) and THA operative booking by 138 blocks (2,070 minutes). CONCLUSIONS:Machine learning outperformed a traditional method of scheduling total joint arthroplasty (TJA) cases. The median time of the prior 30 surgical cases was the most influential on scheduling case time accuracy. As ML models improve, surgeons should consider machine learning utilization in case scheduling; however, prior 30 surgical cases may serve as an adequate alternative.

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study.

OBJECTIVES/OBJECTIVE:Triglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL. We hypothesized that in the liver, in addition to promoting cytosolic LD formation, FITM2 would also transfer TG from its site of synthesis in the ER membrane to nascent VLDL particles within the ER lumen. METHODS:Experiments were conducted using a rat hepatic cell line (McArdle-RH7777, or McA cells), an established model of mammalian lipoprotein metabolism, and mice. FITM2 expression was reduced using siRNA in cells and by liver specific cre-recombinase mediated deletion of the Fitm2 gene in mice. Effects of FITM2 deficiency on VLDL assembly and secretion in vitro and in vivo were measured by multiple methods, including density gradient ultracentrifugation, chromatography, mass spectrometry, stimulated Raman scattering (SRS) microscopy, sub-cellular fractionation, immunoprecipitation, immunofluorescence, and electron microscopy. MAIN FINDINGS/RESULTS:1) FITM2-deficient hepatic cells in vitro and in vivo secrete TG-depleted VLDL particles, but the number of particles is unchanged compared to controls; 2) FITM2 deficiency in mice on a high fat diet (HFD) results in decreased plasma TG levels. The number of apoB100-containing lipoproteins remains similar, but shift from VLDL to low density lipoprotein (LDL) density; 3) Both in vitro and in vivo, when TG synthesis is stimulated and FITM2 is deficient, TG accumulates in the ER, and despite its availability this pool is unable to fully lipidate apoB100 particles; 4) FITM2 deficiency disrupts ER morphology and results in ER stress. PRINCIPAL CONCLUSIONS/CONCLUSIONS:The results suggest that FITM2 contributes to VLDL lipidation, especially when newly synthesized hepatic TG is in abundance. In addition to its fundamental importance in VLDL assembly, the results also suggest that under dysmetabolic conditions, FITM2 may be an important factor in the partitioning of TG between cytosolic LDs and VLDL particles.

OBJECTIVE:To test whether treatment of mild chronic hypertension (CHTN) in pregnancy is associated with lower rates of unplanned maternal healthcare utilization postpartum. METHODS:This was a secondary analysis of the CHTN and pregnancy (CHAP) study, a prospective, open-label, pragmatic, multicenter, randomized treatment trial of pregnant people with mild chronic hypertension. All patients with a postpartum follow-up assessment were included. The primary outcome was unplanned healthcare utilization, defined as unplanned postpartum clinic visits, Emergency Department or triage visits, or unplanned hospital admissions within six weeks postpartum. Differences in outcomes were compared between study groups (Active Group: blood pressure goal of<140/90 mm Hg, and Control Group: blood pressure goal of <160/105 mm Hg) and factors associated with outcomes were examined using logistic regression. RESULTS:A total of 2,293 patients were included with 1,157 (50.5%) in the active group and 1,136 (49.5%) in the control group. Rates of unplanned maternal postpartum health care utilization did not differ between treatment and control groups, (20.2% vs 23.3%, p=0.07, aOR 0.84, 95% CI 0.69-1.03. However, Emergency Department or triage/maternity evaluation unit visits were significantly lower in the Active group (10.2% vs 13.2%, p=0.03, aOR 0.76, 95% 0.58-0.99). Higher BMI at enrollment and cesarean delivery were associated with higher odds of unplanned postpartum healthcare utilization. CONCLUSION/CONCLUSIONS:While treatment of mild CHTN during pregnancy and postpartum was not significantly associated with overall unplanned healthcare resource utilization, it was associated with lower rates of postpartum Emergency Department and triage visits.

Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of Advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits reverse cholesterol transport by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HC) and 20 patients with T1DM, 10 to 19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of CML-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells' uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized LDL. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.

In critically ill patients, fluid resuscitation with balanced crystalloids close to plasma osmolarity have a lower risk of electrolyte imbalances and demonstrated better clinical outcomes compared to normal saline (NS). While lactated ringer's (LR) has shown benefit over NS, plasma-lyte (PL) with a higher osmolarity and different electrolyte formulation is hypothesized to be superior. We performed a retrospective observational cohort study over 37 months at a tertiary hospital. Inclusion criteria were hospitalization in the surgical intensive care unit (SICU), trauma indication, ≥18 years old, and received either PL or LR. All PL administrations and every fifth patient with LR as resuscitation were included in order to match the sample size in each group. Primary outcomes were SICU length of stay (LOS), hospital LOS, and mortality. Secondary outcomes were biomarker changes from baseline. There were 113 patients in both PL and LR groups. The PL arm had higher APACHE II scores (16 vs 13, P = .033) and were more likely ventilated (39.3% vs 20.4%, P = .002) compared to LR. Median hospital LOS (12.0 vs 8.0, P < .001) and SICU LOS (6.0 vs 3.0, P < .001) are significantly longer in PL group compared to the LR group. However, there was no difference in in-hospital mortality (5.3% vs 3.5% P = .519) and SICU mortality (9.7% vs 5.3%, P > .208) between PL and LR. Overall, PL use was associated with prolonged hospital and SICU LOS. PL use did not demonstrate mortality benefit. However, patients were more critically ill in PL group based on higher APACHE II scores and higher rates of mechanical ventilation, which could be contributing to these unfavorable outcomes.