Comprehensive multidisciplinary phenotyping of patients with hypospadias. A pilot study.

INTRODUCTION: Hypospadias is an abnormal formation of the urethra, ventral skin, and corporal bodies. Location of the urethral meatus has historically been the phenotypic landmark that defines hypospadias. Nonetheless, classifications following location of the urethral meatus fail to consistently predict outcomes and have no correlation with the genotype. Description of the urethral plate is very subjective and difficult to reproduce. We hypothesize that the use of digital pixel cluster analysis and correlation to histological analysis can provide a novel method to describe the phenotype of patients with hypospadias. METHODS: A standardized hypospadias phenotyping protocol was developed. 1. Digital images of the anomaly, 2. Anthropometric assessment of penile dimensions (penile length, urethral plate length and width, glans width, ventral curvature), 3. Classification using the GMS score, 4. Tissue sampling (foreskin, glans, urethral plate, periurethral ventral skin) and H&E analysis by a blinded pathologist. A k-means colorimetric pixel cluster analysis was performed following the same anatomical landmark distribution as the histology samples. Analysis was performed using MATLAB v R2021b 9.11.0.1769968. RESULTS: A total of 24 patients prospectively enrolled with a standard protocol. Mean age at surgery was 16.25 months Urethral meatus was distal shaft in 7 patients, 8 coronal, 4 glanular, 3 midshaft, 2 penoscrotal. Average GMS score was 7.14 (±1.58). Average glans size was 15.71 mm (±2.33) and urethral plate width 5.57 mm (±2.06). Eleven patients underwent Thiersch-Duplay repair, 7 TIP, 5 MAGPI, and 1 a first stage preputial flap. Mean follow-up was 14.25 months ( ± 3.7 months). Two (8.3%) postoperative complications (1 urethrocutaneous fistula and 1 ventral skin wound dehiscence) were reported in the study period. Eleven (52.3%) patients with histological analysis had an abnormal pathology report. Of those, 6 (54%) had reported abnormal lymphocyte infiltration interpreted as chronic inflammation at the urethral plate. The second most common finding was hyperkeratosis visualized in the urethral plate in 4 (36.3%) and one with reported fibrosis in the urethral plate. K-means pixel analysis demonstrated a k1 mean of 64.2 for reported urethral plate inflammation vs 53.1 for non-reported urethral plate inflammation (p = 0.002) CONCLUSIONS: Current phenotyping of hypospadias using only anthropometric variables can be expanded including histological and pixel analysis correlation. Pixel clustering has a potential for a priori prediction of urethral plate quality beyond the current subjective assessment. A larger cohort will allow identification of possible predictive associations that might impact intraoperative decision-making and surgical outcomes.

Evaluation of Cardiovascular Autonomic Function during Inpatient Rehabilitation following Traumatic Spinal Cord Injury.

Assessment of the degree of impaired autonomic nervous system (ANS) function is not part of routine clinical practice during inpatient rehabilitation following traumatic spinal cord injury (SCI). The goal of this investigation was to determine the utility of the International Standards for Neurologic Classification of SCI (ISNCSCI) and the recently revised International Standards to document remaining Autonomic Function after SCI (ISAFSCI) in documenting cardiovascular ANS impairment during inpatient rehabilitation following traumatic SCI. Beat-to-beat recording of supine heart rate (HR) and blood pressure (BP) were collected at the bedside for estimation of total cardiovascular ISAFSCI score, cardio-vagal modulation (i.e., high frequency HR variability [HFHRV]) and sympathetic vasomotor regulation (i.e., Mayer wave component of systolic BP [SBPmayer]). A total of 41 participants completed baseline testing, which was conducted 11 ± 5 days from the admission ISNCSCI examination. There were no differences in supine HR or BP based on the ISNCSCI or ISAFSCI assessments. The HFHRV was generally lower with more distal lesions (r2 = 0.15; p = 0.01), and SBPmayer was significantly lower in those with American Spinal Injury Association Impairment Scale (AIS) A compared with AIS B, C, D (Cohen's d = -1.4; p < 0.001). There were no significant differences in HFHRV or SBPmayer in patients with or without ISAFSCI evidence of cardiovascular ANS impairment. These preliminary data suggest that neither the ISNCSCI nor the ISAFSCI are sensitive to changes in ANS cardiovascular function following traumatic SCI. Bedside assessment of HR and BP variabilities may provide insight, but are not readily available in the clinical setting. Further research is required to evaluate methods that accurately assess the degree of ANS impairment following traumatic SCI.

Orthostatic systemic and cerebral hemodynamics in newly injured patients with spinal cord injury.

BACKGROUND: Low blood pressure (BP) may lead to reduced cerebral blood flow velocity (CBFv) during an orthostatic challenge in newly injured patients with traumatic spinal cord injury (SCI), which, may relate to the neurological level of injury (NLI) as documented on the International Standards for the Neurologic Classification of SCI (ISNCSCI), or to evidence of cardiovascular autonomic impairment as determined by the International Standards to document remaining Autonomic Function after SCI (ISAFSCI). OBJECTIVE: To examine the influence of patient demographics, ISNCSCI and ISAFSCI scores on hemodynamic responses to a bedside sit-up test in newly injured patients with SCI. DESIGN: Cross-sectional, prospective analysis. METHODS: A modified sit-up test was conducted at the bedside with the hips at an angle between 45° and 90° and the legs horizontal, level with the hips. Heart rate, BP, and CBFv were recorded for 10 min in the supine and seated positions. RESULTS: Fifty-three newly injured patients (median 39.5 days post-injury) with traumatic SCI were enrolled. Overall, 28 (53%) patients met ISAFSCI criteria, and the number of criteria met (total score) was significantly related to orthostatic changes in CBFv. Change in SBP and change in CBFv were not significantly related, but NLI and total sensory score from the ISNCSCI were significant predictors of the change in CBFv. CONCLUSIONS: Total ISAFSCI score, NLI and sensory scores were positively associated with orthostatic changes in CBFv. Long term follow-up should be considered to determine the consequences of diminished CBFv on cognitive function and quality of life following SCI.