Faculty Bibliography

Traditionally, acetabular global overcoverage had been treated by open surgical dislocation of the hip and was a relative contraindication for hip arthroscopy. With advancing arthroscopic techniques, hip arthroscopy can successfully treat acetabular global overcoverage with less morbidity for the patient than an open hip procedure. Successful arthroscopic treatment of this condition is not for the beginner hip arthroscopist. Pitfalls of an arthroscopic technique include difficult entry into the joint and labral insufficiency with the inability to perform a repair and these difficulties should be understood ahead of the procedure. However, with careful, thoughtful technique, arthroscopic treatment of acetabular global overcoverage has successful outcomes and now should be considered the preferred option instead of open surgical dislocation of the hip.

Intestinal transplantation (ITx) is the definitive treatment for intestinal failure but has the highest rejection rate among solid organ transplants, requiring high doses of immunosuppressive medication, which is associated with high rates of infection, graft-versus-host disease, and malignancy. Transplant tolerance would overcome the need for long-term immunosuppression (ISP). Using nonmyeloablative conditioning, our laboratory has developed a novel swine model of hematopoietic stem cell transplantation (HSCT) that produces durable mixed chimerism (MC) and immune tolerance without toxicity. We investigated whether durable MC would promote tolerance of subsequently transplanted donor-matched intestinal allografts without ISP. Using miniature swine with a defined major histocompatibility complex (MHC), we performed HSCT across an MHC-class-I haplotype mismatch. Immunosuppressive therapy was stopped by day 45. MC was evaluated using flow cytometry, and mixed lymphocyte reaction assays were used to evaluate cellular responses. Subsequently, orthotopic ITx was performed without ISP using a donor that was MHC-matched to the HSCT donor. The recipients were observed for 4 weeks and euthanized for tissue collection and mechanistic assays. After HSCT, the recipients developed durable multilineage MC and apparent deletional tolerance. After ITx, recipients showed no clinical or histologic signs of rejection, and chimerism was unchanged. These results demonstrate the potential value of generating durable MC to achieve transplant tolerance.

Liver transplantation (LT) is the primary treatment for selected patients with hepatocellular carcinoma (HCC). However, HCC-related mortality post-LT remains a significant concern, with up to 10% of cases reported in international series. Identifying risk factors for adverse clinical outcomes is essential. We hypothesized that post-LT HCC-related mortality rates are higher in patients with a high (≥ 42) Comprehensive Complication Index (CCI) calculated at discharge. This study aims to compare post-LT HCC-related mortality rates between two groups of patients with high versus low CCI following LT for HCC. This study included data from seven collaborative European centers. A cohort of 1121 HCC patients transplanted between 2005 and 2019, surviving more than six months post-LT, was analyzed retrospectively. Patients were divided into two groups based on the CCI at discharge: Low-CCI Group (n = 942, 84.0%) and High-CCI Group (n = 179, 16.0%). An inverse probability of treatment weighting (IPTW) approach was applied for analysis. In the post-IPTW cohort, four multivariable logistic regression models with mixed effects identified independent risk factors for HCC-related death, overall death, recurrence, and early recurrence. A CCI score of ≥ 42 emerged as an independent risk factor across all models. Specifically, CCI ≥ 42 was associated with increased odds of HCC-related death (OR = 3.35; P < 0.0001), overall death (OR = 2.63; P < 0.0001), overall recurrence (OR = 2.09; P = 0.001), and early recurrence (OR = 1.88; P = 0.02). A CCI score at discharge should be considered a critical factor for recurrence and HCC-related mortality risk. Incorporating CCI into standard post-LT predictive models may enhance prognostic accuracy for adverse HCC outcomes.

Toddler visual attention development correlates with subsequent language, cognitive, and social developmental outcomes. This study investigates the association of maternal trauma on toddler looking behaviors in 39 mother-child dyads from the Western Cape Province, South Africa. At 15 months postpartum, maternal trauma was assessed using the Life Events Checklist and toddler multisensory attention skills were measured using the Multisensory Attention Assessment Protocol (MAAP) during eye-tracking. We used two-way mixed ANOVA to analyze the association of maternal trauma and MAAP condition with attention maintenance, intersensory matching, and attention shifting. This study provides support for the MAAP's reliability with a sample of 15-month-old toddlers from a low-income setting. We observed a significant interaction between MAAP condition and maternal trauma group on attention maintenance, but pairwise comparisons did not meet the threshold for statistical significance. In a stratified analysis, toddlers of mothers in the low trauma exposure group demonstrated significant differences in attention maintenance, intersensory matching, and attention shifting by condition. Unexpectedly, toddlers of mothers in the high trauma exposure group did not exhibit significant differences in these attentional skills, potentially indicating attentional adaptations. Further research is needed to explore the relationship between the intergenerational transmission of trauma on infant and toddler multisensory attention skills in low-income settings.

BACKGROUND AND PURPOSE/OBJECTIVE:Perfusion and perfusion-related parameter maps obtained using dynamic susceptibility contrast (DSC) MRI and dynamic contrast enhanced (DCE) MRI are both useful for clinical diagnosis and research. However, using both DSC and DCE MRI in the same scan session requires two doses of gadolinium contrast agent. The objective was to develop deep-learning based methods to synthesize DSC-derived parameter maps from DCE MRI data. MATERIALS AND METHODS/METHODS:Independent analysis of data collected in previous studies was performed. The database contained sixty-four participants, including patients with and without brain tumors. The reference parameter maps were measured from DSC MRI performed following DCE MRI. A conditional generative adversarial network (cGAN) was designed and trained to generate synthetic DSC-derived maps from DCE MRI data. The median parameter values and distributions between synthetic and real maps were compared using linear regression and Bland-Altman plots. RESULTS:Using cGAN, realistic DSC parameter maps could be synthesized from DCE MRI data. For controls without brain tumors, the synthesized parameters had distributions similar to the ground truth values. For patients with brain tumors, the synthesized parameters in the tumor region correlated linearly with the ground truth values. In addition, areas not visible due to susceptibility artifacts in real DSC maps could be visualized using DCE-derived DSC maps. CONCLUSIONS:DSC-derived parameter maps could be synthesized using DCE MRI data, including susceptibility-artifact-prone regions. This shows the potential to obtain both DSC and DCE parameter maps from DCE MRI using a single dose of contrast agent. ABBREVIATIONS/BACKGROUND:=plasma volume.

Macrophages are essential immune cells that play crucial roles in inflammation and tissue homeostasis, and are important regulators of metabolic processes, such as the metabolism of glucose, lipids, and amino acids. The regulation of macrophage metabolism by circadian clock genes has been emphasized in many studies. Changes in metabolic profiles occurring after the perturbation of macrophage circadian cycles may underlie the etiology of several diseases. Specifically, chronic inflammatory disorders, such as atherosclerosis, diabetes, cardiovascular diseases, and liver dysfunction, are associated with poor macrophage metabolism. Developing treatment approaches that target metabolic and immunological ailments requires an understanding of the complex relationships among clock genes, disease etiology, and macrophage metabolism. This review explores the molecular mechanisms through which clock genes regulate lipid, amino acid, and glucose metabolism in macrophages, and discusses their potential roles in the development and progression of metabolic disorders. The findings underscore the importance of maintaining circadian homeostasis in macrophage function as a promising avenue for therapeutic intervention in diseases involving metabolic dysregulation, given its key roles in inflammation and tissue homeostasis. Moreover, reviewing the therapeutic implications of circadian rhythm in macrophages can help minimize the side effects of treatment. Novel strategies may be beneficial in treating immune-related diseases cause by shifted and blunted circadian rhythms via light exposure, jet lag, seasonal changes, and shift work or disruption to the internal clock (such as stress or disease).

PURPOSE/OBJECTIVE:The aim of this paper is to compare outcomes of patients who underwent combined gynecologic procedures with ventral hernia repair (VHR) with patients that underwent only VHR. METHODS:Patients who underwent VHR with a combined gynecological procedure from 2012 to 2023 were retrospectively identified in the Abdominal Core Health Quality Collaborative and categorized into two groups with surgical wound contamination in mind. Group one included patients with concomitant salpingo-oophorectomy (SO), bilateral tubal ligation (BTO), and/or ovarian cystectomy (OC) without hysterectomy. Group two consisted of patients who underwent hysterectomy with or without SO/BTO/OC/ER. C-Sections were excluded. Mesh location was 90% in the sublay space for both groups. Patients who underwent VHR without any concomitant procedure were the control group. Propensity score matching (PSM; ratio 3:1 for control vs. group one and 1:1 for control vs. group two) was performed based on relevant demographic and perioperative covariates (age, hernia width, operative approach, ASA class, BMI, mesh used, current smoker, wound status, year of operation, and recurrent). Postoperative outcomes at 30 days were compared between group one and control and between group two and control based on post-PSM cohorts. RESULTS:Out of 13,982 patients undergoing VHR, 279 (2%) also underwent a concurrent gynecological procedure. Following PSM, 88 patients in Group 1 were matched with 264 patients that underwent VHR alone. Similarly, 186 patients in Group 2 were compared with 186 patients in the control group. Operative time was significantly higher in both groups as compared to control (p < 0.001). A longer LOS and more EBL were observed group 2 but not group 1. No statistically significant differences were observed in either group regarding surgical site infection (SSI), surgical site occurrence (SSO), Surgical site occurrences requiring procedural interventions (SSOPI), recurrence of hernia, reoperations, or readmissions. CONCLUSION/CONCLUSIONS:This study compares the outcomes of patients that underwent VHR with simultaneous gynecological procedure to patients with VHR alone. Combining hernia repair and gynecologic surgery did not appear to have an adverse impact on clinical outcomes. Our study suggests that further collaboration between gynecology and general surgery can be considered for management of concurrent abdominopelvic pathologies.

PURPOSE/UNASSIGNED:Urine calcium excretion is greater after dinner and urine volumes are lower. The result is higher urine calcium concentrations, which may confer greater risk of stone formation, at night. We considered whether night-time administration - as compared with daytime administration - of thiazides would be more effective for stone prevention. MATERIALS AND METHODS/UNASSIGNED:We performed 12-hour urine collections in 7 patients taking 25 mg of chlorthalidone (CTD) and 10 patients taking 25 mg of hydrochlorothiazide (HCTZ). Participants completed urine collections at baseline, again after a week of morning medication administration, and again after a week of evening administration, all on repeated self-selected diets. RESULTS/UNASSIGNED:Chlorthalidone reduced urine calcium excretion for both 12-hour periods whether administered in the morning or in the evening: morning dosing lowered urine calcium from 130±70 mg/gram Cr at baseline, to 76±52 mg/gram Cr (P<0.02); evening dosing lowered it to 87±51 mg/gram Cr, which was not significant. On the other hand, HCTZ did not reduce urine calcium excretion regardless of the time of administration: mean 24-hour urine calcium excretion (UCa) was 124±38 mg/gram Cr at baseline and 106±40 mg/gram Cr when HCTZ was given in AM, and 117±54 mg/gram Cr when given in PM. CONCLUSION/UNASSIGNED:We conclude that the long-acting and more effective CTD is a preferable agent for stone prevention. Time of administration does not appear to be important, although morning administration may more effectively address higher post-dinner calcium excretion. The most commonly used thiazide (HCTZ) is shorter acting, frequently dosed once per day, but does not appear to reduce urine calcium excretion at this dose.

BACKGROUND/UNASSIGNED:Attention Deficit Hyperactivity Disorder (ADHD) among children younger than 6 years is quite impairing, nearly half these youth with ADHD experience school exclusion from mainstream preschool classes due to related emotional and behavioral outbursts. While a range of behavior rating scales and subjective measures are used to assess these youth, objective methods of assessment and prediction derived from technology have potential to improve therapeutic and academic interventions outcomes for these youths. We hypothesized that biometric sensors would provide objective, highly sensitive and specific information regarding the physiological status of children prior to an impulsive outburst and could be feasibly implemented using a wearable device in the special education classroom. METHODS/UNASSIGNED: = 5 youth from the first grade) of a specialized therapeutic day-school for youth with ADHD and other psychiatric and developmental disorders to examine feasibility of obtaining continuous physiological data associated with behavioral and emotional outbursts through smartwatch use. Children wore a sensor watch during their daily classroom activities for two weeks and trained observers collected data using behavioral logs. Using Ecological Momentary Assessment methodology, to examine correlations between objective sensor data and observer observation. Data collected from parents regarding prior night's sleep was also examined. RESULTS/UNASSIGNED:All participants completed the study. With a few tolerability or palatability issues. Associations were found between physiological and behavioral/questionnaire data. The methodology holds promise for reliably measuring behavioral and emotional outbursts in young children. CONCLUSIONS/UNASSIGNED:among severely dysregulated pre-school aged youth throughout a full school day. This study established the feasibility of utilizing sensor derived physiological data as an objective biomarker of ADHD within the special education therapeutic classroom. Further research with larger samples is required to build a more robust and personalized AI predictive model.