Faculty Bibliography

BACKGROUND/UNASSIGNED:Glenoid component positioning is an important and challenging aspect of total shoulder arthroplasty. The use of freehand technique with standard instrumentation or preoperative planning based on 2-dimensional computed tomography (CT) scans provides an opportunity for improvement in terms of component accuracy, precision, and deformity correction. These techniques have produced varying outcomes. METHODS/UNASSIGNED:Preoperative planning software (PPS), patient specific instrumentation (PSI), and intraoperative navigation (NAV) have been developed to improve the accuracy of implant placement and deformity correction with the ultimate goals of improved patient outcomes and implant longevity. Literature search was conducted on published and available studies comparing the accuracy of glenoid component placement and improvements in surgical and patient outcomes amongst the aforementioned techniques. RESULTS/UNASSIGNED:PPS, PSI, and NAV have demonstrated improved accuracy over freehand techniques with standard instrumentation. However, data demonstrating the clinical benefit and cost effectiveness of these new technologies are lacking. DISCUSSION/UNASSIGNED:In this paper, we reviewed the evidence available to answer the question of whether or not advanced shoulder arthroplasty technologies have been beneficial and reviewed future technologies in development such as virtual/mixed-reality and robotic assisted shoulder surgery. LEVEL OF EVIDENCE/UNASSIGNED:4.

OBJECTIVE:To evaluate whether functional, clinical, and self-reported tests reflect lumbar spinal stenosis patients' decisions to undergo or defer surgery. METHODS:Among 108 participants, 77 chose surgery (SG), and 31 opted to wait and see (WaSG) whether they got better spontaneously. Both groups were assessed at baseline (t0) and 3 months (t1), with additional self-reported measures at 6 (t2) and 12 months (t3). Key outcomes included corridor walk distance, chair sit-to-stand repetitions, grip strength, and various pain and disability indices. RESULTS:At baseline, SG reported higher leg pain (NPRS-leg: Δ = 1.66, P = 0.002) and poorer functional outcomes across multiple tests. By t1, both groups improved in disability, but SG showed greater reductions in the Oswestry Disability Index (Δ = 7.85, P = 0.001) and sustained improvements in leg pain at subsequent assessments. WaSG consistently engaged in more walking (mean Δ = 123.5 minutes, P < 0.001). Regression analyses indicated that surgery status, flexibility, and strength significantly predicted improvements in disability (adjusted R² = 0.296). Logistic regression identified predictors for surgery choice, including biological sex, leg pain intensity, walking performance, and weekly walking hours. CONCLUSION/CONCLUSIONS:Functional status, self-reported disability, and fear-avoidance beliefs in lumbar spinal stenosis patients reflect their subjective decision regarding surgery and highlight the importance of baseline leg pain, calf strength, walking-related parameters, and physical function in recovery. STUDY DESIGN/METHODS:Observational prospective cohort.

Coronary artery anomalies encompass a spectrum of congenital abnormalities affecting the origin, course, or termination of the major epicardial coronary arteries. Despite their rarity, coronary artery anomalies represent a significant burden on cardiovascular health due to their potential to disrupt myocardial blood flow and precipitate adverse cardiac events. While historically diagnosed postmortem, the widespread availability of imaging modalities has led to an increased recognition of coronary artery anomalies, particularly in adults. This review synthesizes current knowledge on the classification, mechanisms, and clinical implications of coronary anomalies, focusing on prevalent variants with significant clinical impact. We discuss strategies for medical and surgical management, as well as contemporary screening recommendations, acknowledging the evolving understanding of these anomalies. Given the breadth of possible variants and the limited data on some presentations, this review provides a framework to aid clinicians in the recognition and management of coronary anomalies, with a particular emphasis on their stratification by anatomical location. By consolidating existing knowledge and highlighting areas of uncertainty, this review aims to enhance clinical decision-making and improve outcomes for individuals with coronary anomalies.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Vestibular schwannomas demonstrate different responses after stereotactic radiosurgery (SRS), commonly including a transient loss of internal enhancement on postcontrast T1-weighted MRI thought to be due to an early reduction in tumor vascularity. We used dynamic contrast-enhanced based golden-angle radial sparse parallel (GRASP) MRI to characterize the vascular permeability changes underlying this phenomenon, with correlations to long-term tumor regression. METHODS:Consecutive patients with vestibular schwannoma who underwent SRS between 2017 and 2019, had a transient loss of enhancement after SRS, and had long-term longitudinal GRASP studies (6, 18, and 30 months) were included in this retrospective cohort analysis (n = 19). Using GRAVIS ( https://gravis-imaging.org/gravis/ ), an analysis pipeline for GRASP studies, we extracted the key parameters normalized to the venous sinus from a region of interest within the tumor. RESULTS:The peak, area under the curve (AUC), and wash-in phase slope were significantly reduced at 6, 18, and 30 months after SRS (corrected P < .05), even while the internal enhancement returned in the tumors. Larger pre-SRS tumors were more likely to have a greater reduction in peak ( P = .013) and AUC ( P = .029) at 6 months. In a subset of patients (N = 13) with long-term follow-up, the median percentage reduction in tumor volume was 58% at a median of 62 months. These patients showed a strong correlation between peak, AUC, and wash-in phase slope changes at 6 months and tumor volume at the last follow-up. CONCLUSION/CONCLUSIONS:After SRS and loss of internal contrast uptake within vestibular schwannomas, a slow vascular permeability dynamic persisted, suggesting the presence of postradiation processes such as fibrosis. We show for the first time, using GRASP, a quantitative assessment of the vascular radiobiological effect.

BACKGROUND:The anti-inflammatory and antimicrobial benefits of prebiotics may present an affordable and cost-effective strategy for not only the prevention but also treatment of malnutrition. Therefore, the present trial has been designed with the aim to evaluate the role of prebiotics on the gut microbiome of severe acute malnourished (SAM) children. METHODS:The study is designed as a prospective, double-blinded, triple-armed, multi-centered randomized controlled trial, with 6-59 months old uncomplicated SAM children recruited to the experimental group receiving ready-to-use therapeutic food (RUTF) plus prebiotics and the active comparator group receiving RUTF plus starch for 2 months duration (8 weeks). Healthy children with matching age and gender will be recruited to placebo comparator group and will receive starch as a placebo during the study period. A total of 58 participants will be recruited to each arm with 1:1:1 allocation ratio following a pre-defined inclusion and exclusion criteria. The results of the gut microbiome diversity will serve as the primary outcome, while weight-for-height/length z-score, mid-upper-arm circumference, neurodevelopment assessment, and body mass accumulation will serve as the secondary outcome. Data collection and evaluations will be conducted at baseline and at the end of the trial (week 8), while the safety monitoring will be conducted at every second week. For analysis, the principles of intention-to-treat will be followed. CONCLUSIONS:Conclusively, the results of the present trial would provide useful insights and high-quality data for the treatment and management of SAM children by evaluating the effect of RUTF plus prebiotic on the gut microbiome diversity of children, leading to medical evidence for designing the large-scale studies. TRIAL REGISTRATION/BACKGROUND:The present trial is registered at ClinicalTrials.gov with identifier No: NCT06155474 and registration date 4 December 2023.

BACKGROUND/UNASSIGNED:Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of probiotics to a specialized formula has also been proposed as a potential approach to possibly increase the benefit. We systematically reviewed specialized formulas for infants with CMA to inform the updated World Allergy Organization (WAO) DRACMA guidelines. OBJECTIVE/UNASSIGNED:To systematically review and synthesize the available evidence about the use of specialized formulas for the management of individuals with CMA. METHODS/UNASSIGNED:We searched from inception PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations, for randomized and non-randomized trials of any language investigating specialized formulas with or without probiotics. We included all studies irrespective of the language of the original publication. The last search was conducted in January 2024. We synthesized the identified evidence quantitatively or narratively as appropriate and summarized it in the evidence profiles. We conducted this review following the PRISMA, Cochrane methods, and the GRADE approach. RESULTS/UNASSIGNED:GG) showed no significant effect, as supported by low to very low CoE. CONCLUSIONS/UNASSIGNED:Currently available studies comparing eHF-CM, AAF, HRF, and SF provide very low certainty evidence about their effects in infants with IgE-mediated and non-IgE-mediated CMA. Our review revealed several limitations in the current body of evidence, primarily arising from concerns related to the quality of studies, the limited size of the participant populations and most importantly the lack of diversity and standardization in the compared interventions. It is therefore imperative for future studies to be methodologically rigorous and investigate a broader spectrum of available interventions. We encourage clinicians and researchers to review current World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines for suggestions on how to use milk replacement formulas in clinical practice and what additional research would be the most beneficial.

BACKGROUND AND OBJECTIVES/UNASSIGNED:variants. METHODS/UNASSIGNED:variants were included. We used standardized tools to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder, and adaptive behavioral skills of patients. RESULTS/UNASSIGNED:= 0.04). DISCUSSION/UNASSIGNED:variants.

PURPOSE/UNASSIGNED:The recent SENZA-PDN study showed that high-frequency (10kHz) spinal cord stimulation (SCS) provided significant, durable pain relief for individuals with painful diabetic neuropathy (PDN), along with secondary benefits, including improved sleep quality and HRQoL. Given that metabolic factors and chronic neuropathic pain are related, we evaluated potential secondary effects of 10kHz SCS on hemoglobin A1c (HbA1c) and weight in SENZA-PDN participants with type 2 diabetes (T2D). PATIENTS AND METHODS/UNASSIGNED:). RESULTS/UNASSIGNED:= 0.005), respectively. These reductions were accompanied by a mean pain reduction of 79.8% and a mean decrease in pain interference with sleep of 65.2% at 24 months across all cohorts. CONCLUSION/UNASSIGNED:This is the first study of SCS to demonstrate long-term, significant, and clinically meaningful reductions in HbA1c and weight in study participants with PDN and T2D, particularly among those with elevated preimplantation HbA1c and BMI. Although the mechanism for these improvements has yet to be established, the results suggest possible direct and indirect metabolic benefits with 10kHz SCS in addition to durable pain relief. TRIAL REGISTRATION/UNASSIGNED:ClincalTrials.gov Identifier, NCT03228420.

Patients who receive solid organ transplants often require lifelong immunosuppression, which increases their risk for hematologic disorders. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential curative treatment option for these patients. However, there is still a lack of understanding and guidance on graft-vs-host disease (GVHD) immunosuppression regimens, potential complications, and outcomes in patients with solid organ transplants who undergo HSCT. The rate of solid organ transplantation continues to increase annually, making this a common clinical scenario that hematologists encounter. In this case series, we present three patients who underwent liver, kidney and cardiac transplants and each developed hematological malignancies requiring allogeneic stem cell transplant. This is the first case report of two patients who received post-transplant cyclophosphamide with mycophenolate mofetil and tacrolimus GVHD prophylaxis. We also review recent advances in GVHD prophylaxis in allogeneic HSCT and solid organ transplantation including immune tolerance and immunosuppression-free protocols. Our case series support the use of post-transplant cyclophosphamide with mycophenolate mofetil and tacrolimus as post-transplant GVHD prophylaxis, which does not appear to compromise solid organ graft function. Our case series also provides evidence that allogeneic HSCT is a feasible and potentially life-saving treatment option in patients who develop hematologic malignancies after solid organ transplantation.

Due to the development of next-generation sequencing technology and an increased appreciation of their role in modulating host immunity and their potential as therapeutic agents, the human microbiome has emerged as a key area of interest in various biological investigations of human health and disease. However, microbiome data present a number of statistical challenges not addressed by existing methods, such as the varying sequencing depth, the compositionality, and zero inflation. Solutions like scaling and transformation methods help to mitigate heterogeneity and release constraints, but often introduce biases and yield inconsistent results on the same data. To address these issues, we conduct a systematic review of compositional data transformation, with a particular focus on the connection and distinction of existing techniques. Additionally, we create a new framework that enables the development of new transformations by combining proportion conversion with contrast transformations. This framework includes well-known methods such as Additive Log Ratio (ALR) and Centered Log Ratio (CLR) as special cases. Using this framework, we develop two novel transformations-Centered Arcsine Contrast (CAC) and Additive Arcsine Contrast (AAC)-which show enhanced performance in scenarios with high zero-inflation. Moreover, our findings suggest that ALR and CLR transformations are more effective when zero values are less prevalent. This comprehensive review and the innovative framework provide microbiome researchers with a significant direction to enhance data transformation procedures and improve analytical outcomes.