Publications by Year: 2025

Purpose: To compare the long-term outcomes of scleral-sutured intraocular lens (IOL) fixation using expanded polytetrafluoroethylene vs polypropylene sutures, with a focus on suture-related complications. Methods: A retrospective comparative review was conducted of 102 patients who underwent scleral-sutured IOL fixation between 2015 and 2019. Forty-eight eyes of 48 patients received 4-point fixation with expanded polytetrafluoroethylene sutures, and 55 eyes of 54 patients received 2-point fixation with polypropylene sutures. Postoperative complications, visual outcomes, and risk factors for suture-related complications were analyzed over a minimum follow-up of 5 years. Results: No instances of suture breakage were observed in either group over an average follow-up of 6.7 years. Suture exposure rates were 10.4% (5/48) for expanded polytetrafluoroethylene and 18.2% (10/55) for polypropylene (P = .27). The mean time to suture exposure was 2.7 ± 3.3 years in the expanded polytetrafluoroethylene group and 2.9 ± 2.5 years in the polypropylene group (P = .88). Mean logMAR visual acuity at final follow-up was 1.0 ± 1.2 in the expanded polytetrafluoroethylene group and 1.5 ± 1.2 in the polypropylene group (P = .06). The only significant risk factor for suture exposure was concurrent corneal transplantation or glaucoma surgery (odds ratio [OR], 9.3; P = .003). Surgical correction was required in all cases of exposure with expanded polytetrafluoroethylene sutures and in 2 cases with polypropylene sutures. One case of suture-associated infectious scleritis with endophthalmitis occurred in the expanded polytetrafluoroethylene group, and 1 case of endophthalmitis related to an explanted corneal graft occurred in the polypropylene group. Conclusions: Both expanded polytetrafluoroethylene and polypropylene sutures demonstrated durable outcomes with similar complication rates. Suture breakage was not observed in either group, and there were no differences in suture exposure rates between the 2 groups. Risk factors for suture exposure included the performance of a concurrent procedure.

INTRODUCTION: Alzheimer's disease (AD) is the most prevalent form of dementia and a major public health challenge. In the absence of a cure, accurate and innovative early diagnostic methods are essential for proactive life and healthcare planning. Speech metrics have shown promising potential for identifying individuals with mild cognitive impairment (MCI) and AD, prompting investigation into whether speech motor features can detect elevated risk even prior to cognitive decline. This preliminary study examined whether speech kinematic features measured during a color-word interference task could distinguish cognitively normal APOE-ε4 carriers (ε4+) from non-carriers (ε4-).

METHODS: Sixteen cognitively normal older adults (n = 9 ε4+, n = 7 ε4-) completed a sentence-based color-word interference task while three-dimensional electromagnetic articulography recorded lower-lip movements. Lip movement duration (s), average speed (mm/s), and range of movement (mm³) were extracted for three sentence segments: pre-interference, during-interference, and post-interference. Difference measures (ΔDuring-Pre, ΔDuring-Post) were computed to quantify task-related modulation. Descriptive statistics and independent t-tests were used to examine group-level trends. For classification, a support vector machine (SVM) with a degree-2 polynomial kernel and leave-one-out cross-validation evaluated all feature combinations derived from the 15 kinematic measures.

RESULTS: Although no group differences reached statistical significance after accounting for multiple testing, several features showed moderate effect sizes. The optimal SVM model achieved 87.5% cross-validated accuracy (precision 88.9%, sensitivity 88.9%, specificity 85.7%) using three features: (1) lip movement duration during the pre-interference segment, (2) average lip speed during interference, and (3) the change in lip movement range from pre- to during-interference segments (ΔDuring-Pre).

DISCUSSION: These findings suggest that lip kinematic responses to mild cognitive-motor interference may capture subtle neuromotor differences associated with APOE-ε4 status in cognitively intact older adults. The identified features point to potential alterations in anticipatory motor planning, interference susceptibility, and articulatory adaptability in ε4+ individuals. However, the small sample size, risk of overfitting, and sex imbalance limit interpretability. Thus, these results should be viewed as hypothesis-generating. Larger, sex-balanced, and longitudinal studies are needed to validate these candidate markers and clarify their role in multimodal early AD risk stratification.

INTRODUCTION: Accurate segmentation of brain regions in magnetic resonance imaging (MRI) is essential for diagnosing and managing neurological diseases. FreeSurfer is a widely used tool for brain MRI segmentation, but its limitations in speed and usability pose challenges in clinical practice. Neurophet AQUA, an advanced automated segmentation tool, aims to overcome these challenges by offering rapid and reliable segmentation. This study evaluates two segmentation pipelines: (1) a T1-based brain region segmentation pipeline, comparing the performance and reliability of Neurophet AQUA and FreeSurfer v7.3.2 using the standard recon-all pipeline in segmenting gray matter, white matter, and subcortical structures; and (2) a T2-FLAIR-based white matter lesion segmentation pipeline of Neurophet AQUA, assessing the detection of white matter hyperintensities (WMH).

METHODS: Four main datasets were used. For the T1-based segmentation pipeline, the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset was used to compare the segmentation results of Neurophet AQUA and FreeSurfer, with quality assessed by expert evaluation. The MarkVCID dataset was used to evaluate the scan-rescan repeatability and inter-scanner reproducibility of Neurophet AQUA. For the T2-FLAIR-based pipeline, WMH segmentation performance was assessed using 2D and 3D FLAIR sequences from the ADNI dataset by comparing the segmentations to ground truth (GT) labels and calculating Dice similarity coefficients (DSC).

RESULTS: Segmentation quality and reliability showed that Neurophet AQUA and FreeSurfer achieved comparable performance in most regions, with no significant differences. However, Neurophet AQUA had significantly faster processing time. In intracranial volume (ICV) measurements, Neurophet AQUA showed better repeatability than FreeSurfer in both rescans (ICC: 0.999 vs. 0.991) and inter-scanner settings (ICC: 0.983 vs. 0.866). AQUA also demonstrated consistent WMH segmentation across 2D and 3D FLAIR images.

CONCLUSION: Neurophet AQUA demonstrated high segmentation accuracy and excellent repeatability in rescanned measurements, as well as exploratory evidence of inter-scanner reproducibility on T1-weighted MRI, showing comparable performance to established tools such as FreeSurfer. It also showed consistent WMH segmentation across FLAIR types. Neurophet AQUA is highly suitable for clinical applications that require accurate analysis, high repeatability and reproducibility, and rapid brain MRI processing, making it particularly well-suited for multicenter research studies.

Physical activity is important in the development of mental and physical well-being during childhood. We aimed to investigate physical activity levels among early pubertal youth presenting for gender-affirming care. Among 93 participants 8-14 years of age, who had physical activity level measured using the Physical Activity Questionnaire for Children (PAQ-C), participants designated male at birth had lower levels of physical activity than participants designated female at birth both before starting gonadotropin-releasing hormone analog treatment and during gender-affirming medical treatment (baseline PAQ-C scores 2.24±0.73 vs. 2.67±0.73, p=0.006).

Polygenic risk scores (PRSs) have generated considerable interest as a means of personalizing prostate cancer (PC) screening by stratifying individuals according to their genetic risk. The single-arm BARCODE1 study recently showed that PRS-based screening detected more PCs than prostate-specific antigen (PSA) testing or magnetic resonance imaging (MRI). The absence of a comparator arm limits the interpretability of this finding. We compared outcomes from BARCODE1 with those from two contemporaneous, large-scale screening trials-Göteborg-2 and ProScreen-that used MRI with or without a PC blood marker to risk-stratify men for biopsy. When standardized to 10 000 men tested, BARCODE1 biopsied more men (704 vs 386 and 338), diagnosed more low-grade PCs (126 vs 103 and 41), and detected fewer high-grade PCs (155 vs 178 and 165) versus Göteborg-2 and ProScreen. Combining PRS with PSA or MRI in BARCODE1 reduced the detection of high-grade PCs by 50-75% in comparison to Göteborg-2 and ProScreen. These findings reflect the limited risk discrimination of PRSs and their inability, unlike MRI and blood-based markers, to preferentially detect aggressive disease. PRS-based PC screening underperforms relative to current best practice and, on the basis of BARCODE1 data, should not be adopted in clinical practice.

BACKGROUND: Regenerative medicine is an evolving medical subspecialty dedicated to enhancing the body's natural healing mechanisms to repair or replace damaged tissues. By using autologous or allogeneic biologics, it offers the potential to restore function where conventional therapies have shown limited success. While this field holds great promise and continues to generate enthusiasm among both patients and clinicians, it remains in early stages of clinical validation. Therefore, it must be approached with careful optimism and responsible application, ensuring that its presentation, promotion, and use in clinical settings are grounded in evidence and ethical standards.

OBJECTIVE: To provide updated, evidence-based recommendations for the role of regenerative therapies in managing moderate to severe chronic low back pain.

METHODS: A multidisciplinary panel of experts, convened by the American Society of Interventional Pain Physicians (ASIPP), systematically reviewed the current evidence and incorporated patient perspectives to develop practical, evidence-informed recommendations. The process included defining key clinical questions, reviewing the literature, formulating evidence-based statements, and reaching consensus through structured discussions and formal voting.

RESULTS: A total of 35 authors contributed to the development of these guidelines, with 33 experts participating in the formal consensus process. Altogether, 19 recommendations were generated, with all of them achieving 100% agreement. These recommendations were informed by a comprehensive review of systematic reviews, randomized controlled trials (RCTs), and observational studies encompassing a broad range of regenerative therapies.Evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to determine certainty levels. Both qualitative and quantitative analyses were applied to synthesize the best available data, resulting in evidence-based recommendations summarized below.Intradiscal Injections (PRP): Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: ModerateIntradiscal Injections (BMAC): Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: ModerateEpidural Injections (PRP): Evidence Level: III, Fair; Consensus-Based Clinical Recommendation: ModerateFacet Joint Injections (PRP and MSCs): Evidence Level: IV, Limited; Consensus-Based Clinical Recommendation: Moderate Sacroiliac Joint Injections (PRP): Evidence Level: IV, Limited; Consensus-Based Clinical Recommendation:  Low Functional Spine Unit Injections Evidence Level: Very Low; Consensus-Based Clinical Recommendation:Low.

LIMITATIONS: The primary limitation of these guidelines is the scarcity of high-quality studies, with much of the available evidence derived from small or heterogeneous trials.

PRECAUTIONS: Regenerative therapies should be considered only after a thorough diagnostic evaluation confirming clinical necessity. Treatment decisions must account for the patient's medical condition, preferences, and expectations. Patients should be fully informed about the nature, potential benefits, risks, and costs of regenerative treatments, most of which are not covered by commercial insurance.These therapies may be used alone or in conjunction with other evidence-based modalities, such as structured exercise, physical therapy, behavioral therapy, or conventional medical management. Clinicians must follow all applicable U.S. Food and Drug Administration (FDA) regulations and adhere to safety and ethical standards outlined in these guidelines.

CONCLUSION: Based on current evidence, lumbar intradiscal injections of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are supported by Level III evidence. Lumbar epidural PRP injections are also supported by Level III evidence, while PRP injections for lumbar facet joints and sacroiliac joints are supported by Level IV evidence. Given the emerging status of biologic therapies and the limited quality of existing studies, the panel provides moderate, consensus-based recommendations for the use of all biologics in the lumbar spine.

BACKGROUND: Velopharyngeal insufficiency (VPI) is common in patients with repaired cleft palate. Speech surgery, which encompasses operative procedures to improve velopharyngeal function and speech resonance, is associated with postoperative obstructive sleep apnea (OSA). However, the relative risk of OSA between different speech surgery procedures remains unclear.

PURPOSE: The purpose of this study was to compare the relative risk of OSA following pharyngeal flap versus nonpharyngeal flap procedures, which included dynamic sphincter pharyngoplasty (DSP), Furlow palatoplasty, and buccal myomucosal flaps (BMMF).

DATA SOURCES: An electronic literature search was conducted utilizing PubMed, Cochrane, Embase, and Web of Science databases.

STUDY SELECTION: Eligible studies included patients with a history of repaired cleft palate and VPI requiring speech surgery, published between 1994 and 2024. Studies specifically included comparison data between pharyngeal flap and nonpharyngeal flap techniques. Exclusion criteria were case reports, abstracts, and reviews.

DATA EXTRACTION AND SYNTHESIS: Data were extracted per the the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Demographics, speech procedure data, OSA frequency, and follow-up data were recorded. The primary comparison was procedure type including pharyngeal flap versus non-pharyngeal flap procedures. Meta-analysis was performed using a random-effects model, with P values <.05 considered statistically significant.

MAIN OUTCOMES AND MEASURE: The primary outcome was relative risk of postoperative OSA between procedure types.

RESULTS: Four studies met inclusion criteria, which included 751 subjects. Pharyngeal flap use was associated with a significantly greater risk of postoperative OSA compared to nonpharyngeal flap procedures (pooled risk ratio = 2.45, 95% CI: 1.20 to 5.01, P = .01). Subgroup analysis demonstrated that palatal lengthening procedures had a significantly lower risk of OSA than pharyngeal flap (risk ratio = 0.39, P = .002); however, there was no difference in postoperative OSA between DSP and pharyngeal flap (P = .68) CONCLUSIONS AND RELEVANCE: Palatal lengthening procedures had a lower risk of postoperative OSA than pharyngeal flap. There was no difference in postoperative OSA between pharyngeal flap and DSP. As such, for patients with preoperative OSA or patients at high risk for developing OSA, it may be prudent to use palatal lengthening procedures as a first-line option for correction of VPI.

Functional neurologic disorder (FND) is an underrecognized but important cause of acute neurological presentations in the postpartum period, particularly among culturally diverse patient populations. We present the case of a female Nepali immigrant (G5P3023 [fifth pregnancy, three term births, zero preterm births, two pregnancies that ended before 20 weeks, three living children]) in her late 30s with no prior medical or psychiatric history. She developed sudden neurological deficits on postoperative Day 0 following an uncomplicated Cesarean delivery. Approximately 11 hours after delivery, the patient became dizzy, pale, and diaphoretic, then developed right-upper and bilateral-lower extremity paralysis with impaired eye and mouth opening. A code stroke was initiated. Extensive workup (including computed tomography head, computed tomography angiography head/neck, and magnetic resonance imaging brain) was unremarkable. Neurological deficits resolved within hours after ammonia inhalant stimulation. The patient was ultimately diagnosed with postpartum FND. This case highlights key diagnostic and management challenges in distinguishing FND from stroke, catatonia, and dissociative states in medically complex postpartum patients. It also underscores the importance of trauma-informed, culturally sensitive approaches to diagnosis and care. Our discussion explores the limited but evolving literature on postpartum FND-potentially inclusive of sensory-motor mismatch, loss of agency, hormonal shifts, and psychosocial stressors-while also exploring strategies for culturally grounded psychoeducation. Clinicians must vigilantly watch for functional presentations postpartum to avoid unnecessary interventions and promote holistic recovery. Cross-disciplinary collaboration among psychiatry, neurology, and obstetrics is essential for optimal care.

BACKGROUND: In recent years, rising costs associated with managing spinal pain and other musculoskeletal disorders have been well documented. Prior to the COVID-19 pandemic, the use of interventional techniques to manage spinal pain and other musculoskeletal disorders had steadily increased. However, the pandemic disrupted chronic pain management, including interventional procedures and opioid use, reflecting a broader reduction in healthcare services.

OBJECTIVES: To provide an updated assessment of interventional technique utilization for chronic pain management in the U.S. Medicare population from 2000 to 2024.

STUDY DESIGN: Retrospective cohort study examining trends and factors influencing interventional technique use for chronic pain management within the traditional fee-for-service (FFS) Medicare population in the United States between 2000 and 2024.

METHODS: Data were obtained from the Centers for Medicare & Medicaid Services (CMS) master database, specifically the physician/supplier procedure summary, covering the years 2000 through 2024.

RESULTS: Service rates for interventional pain management per 100,000 Medicare beneficiaries significantly declined by 16.8% cumulatively from 2019 to 2024, corresponding to an average annual decrease of 3.6%. This contrasts with the 2010-2019 period, during which a cumulative increase of 14.5% was observed, along with an average annual growth rate of 1.5%. The steepest decline occurred between 2019 and 2020, with a 15.4% reduction coinciding with the onset of the COVID-19 pandemic.

LIMITATIONS: The analysis is limited to traditional (FFS) Medicare beneficiaries, excluding Medicare Advantage Plans, which represented nearly 54% of Medicare enrollment in 2024. Additionally, as with all retrospective claims-based studies, inherent limitations of coding accuracy and incomplete clinical detail apply.

CONCLUSION: From 2019 to 2024, the use of interventional pain management techniques declined significantly. Contributing factors likely include the lingering effects of COVID-19, economic pressures, the Affordable Care Act, and evolving local coverage determination (LCD) policies.

PURPOSE: Immunoglobulin-M (IgM) is the first antibody class produced during an immune response, playing a crucial role in early defense mechanisms. Its large pentameric or hexameric structure, however, prevents it from crossing the placenta from mother to fetus during pregnancy. We sought to determine whether IgM is amenable to transamniotic fetal delivery utilizing a healthy rodent model.

METHODS: Fetuses (n = 42) from three time-dated pregnant dams received intra-amniotic injections on gestational day 17 (E17, term = E21-22) of either a solution of human IgM antibodies suspended in saline (n = 27) or just saline (n = 15), the latter to control for IgM interspecies homology. Samples from 9 fetal and annexial sites (umbilical cord, gestational membranes, placenta, and fetal spleen, thymus, intestine, liver, bone marrow, and serum) were procured at term for semi-quantitative fluorescence ELISA. Statistical comparisons were performed with and without nesting to account for individual mothers (p < 0.05).

RESULTS: Overall survival was 90.5 % (38/42) with no significant differences between the groups. In non-nested comparisons, significantly elevated relative fluorescence was detected in IgM exposed animals at all sites studied (p < 0.001 for spleen, thymus, umbilical cord, gestational membranes, placenta, thymus, liver, bone marrow, and serum and p = 0.001 for intestine). In nested comparisons, all sites also showed significantly elevated fluorescence in the IgM exposed group (p = 0.009 to <0.001) except for spleen (p = 0.064).

CONCLUSIONS: Fetal administration of immunoglobulin-M (IgM) is viable via the transamniotic route. Transamniotic fetal immunotherapy (TRAFIT) utilizing IgM may become a valuable minimally invasive option for prevention and/or treatment of select perinatal infections.

LEVEL OF EVIDENCE: N/A (animal and laboratory study).

TYPE OF STUDY: animal and laboratory study.