Machine intelligence identifies soluble TNFa as a therapeutic target for spinal cord injury.

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis (TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNFα receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 h after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNFα signaling as a therapeutic target.

Convolutional Neural Network-Based Automated Segmentation of the Spinal Cord and Contusion Injury: Deep Learning Biomarker Correlates of Motor Impairment in Acute Spinal Cord Injury.

BACKGROUND AND PURPOSE: Our aim was to use 2D convolutional neural networks for automatic segmentation of the spinal cord and traumatic contusion injury from axial T2-weighted MR imaging in a cohort of patients with acute spinal cord injury. MATERIALS AND METHODS: Forty-seven patients who underwent 3T MR imaging within 24 hours of spinal cord injury were included. We developed an image-analysis pipeline integrating 2D convolutional neural networks for whole spinal cord and intramedullary spinal cord lesion segmentation. Linear mixed modeling was used to compare test segmentation results between our spinal cord injury convolutional neural network (Brain and Spinal Cord Injury Center segmentation) and current state-of-the-art methods. Volumes of segmented lesions were then used in a linear regression analysis to determine associations with motor scores. RESULTS: Compared with manual labeling, the average test set Dice coefficient for the Brain and Spinal Cord Injury Center segmentation model was 0.93 for spinal cord segmentation versus 0.80 for PropSeg and 0.90 for DeepSeg (both components of the Spinal Cord Toolbox). Linear mixed modeling showed a significant difference between Brain and Spinal Cord Injury Center segmentation compared with PropSeg (P < .001) and DeepSeg (P < .05). Brain and Spinal Cord Injury Center segmentation showed significantly better adaptability to damaged areas compared with PropSeg (P < .001) and DeepSeg (P < .02). The contusion injury volumes based on automated segmentation were significantly associated with motor scores at admission (P = .002) and discharge (P = .009). CONCLUSIONS: Brain and Spinal Cord Injury Center segmentation of the spinal cord compares favorably with available segmentation tools in a population with acute spinal cord injury. Volumes of injury derived from automated lesion segmentation with Brain and Spinal Cord Injury Center segmentation correlate with measures of motor impairment in the acute phase. Targeted convolutional neural network training in acute spinal cord injury enhances algorithm performance for this patient population and provides clinically relevant metrics of cord injury.

Intramural leiomyoma of the bladder.

Mesodermal tumors of the urinary bladder are rare and the majority of them are malignant. We report a case of an intramural leiomyoma of the bladder presenting with symptoms of a mild lower urinary tract infection. The patient was managed with partial cystectomy and the outcome was excellent.

Reconstruction of urethrovaginal fistula and vaginal atresia in an adolescent girl after an abdominoperineal-vaginal pull-through procedure.

OBJECTIVE: To report a rare case of urethrovaginal communication and vaginal atresia. DESIGN: To reconstruct the communication and the vaginal route. SETTING: Division of Pediatric and Adolescent Gynecology and Corrective Gynecological Surgery, University of Athens, and "Alexandra" Hospital. PATIENT(S): A 16-year-old girl with cyclic hematuria, periodic pelvic pain, and primary amenorrhea. INTERVENTION(S): Diagnostic studies, followed by an abdominoperineal-vaginal pull-through procedure. MAIN OUTCOME MEASURE(S): Reconstruction of the urethrovaginal fistula and vaginal route. RESULT(S): Normal menstruation through the vaginal route. CONCLUSION(S): A careful examination of every infant's external genitalia should be performed immediately after delivery. A urethrovaginal fistula should be corrected in time to facilitate menstrual flow and improve future reproductive potential.

Retroperitoneal endometriosis causing cyclical ureteral obstruction.

We report a case of retroperitoneal endometriosis involving the periureteral tissues of the left ureter. The patient suffered from cyclical symptoms of left ureteral obstruction during menstruation. Endometriosis of the ureter is not common and in this case the preoperative diagnosis presented difficulties due to the absence of any pathological findings during the clinicolaboratory evaluation of the patient before or after menstruation. The patient was managed with surgical resection of the affected ureteral segment and subsequent end-to-end anastomosis of the left ureter. A brief review of the subject is also presented.