ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Clinical Implementation of Novel Spinal Cord Perfusion Pressure Protocol in Acute Traumatic Spinal Cord Injury at U.S. Level I Trauma Center: TRACK-SCI Study.

OBJECTIVE: We sought to report the safety of implementation of a novel standard of care protocol using spinal cord perfusion pressure (SCPP) maintenance for managing traumatic spinal cord injury (SCI) in lieu of mean arterial pressure goals at a U.S. Level I trauma center. METHODS: Starting in December 2017, blunt SCI patients presenting <24 hours after injury with admission American Spinal Injury Association Impairment Scale (AIS) A-C (or AIS D at neurosurgeon discretion) received lumbar subarachnoid drain (LSAD) placement for SCPP monitoring in the intensive care unit and were included in the TRACK-SCI (Transforming Research and Clinical Knowledge in Spinal Cord Injury) data registry. This SCPP protocol comprises standard care at our institution. SCPPs were monitored for 5 days (goal ≥65 mm Hg) achieved through intravenous fluids and vasopressor support. AISs were assessed at admission and day 7. RESULTS: Fifteen patients enrolled to date were aged 60.5 ± 17 years. Injury levels were 93.3% (cervical) and 6.7% (thoracic). Admission AIS was 20.0%/20.0%/26.7%/33.3% for A/B/C/D. All patients maintained mean SCPP ≥65 mm Hg during monitoring. Fourteen of 15 cases required surgical decompression and stabilization with time to surgery 8.8 ± 7.1 hours (71.4% <12 hours). At day 7, 33.3% overall and 50% of initial AIS A-C had an improved AIS. Length of stay was 14.7 ± 8.3 days. None had LSAD-related complications. There were 7 respiratory complications. One patient expired after transfer to comfort care. CONCLUSIONS: In our initial experience of 15 patients with acute SCI, standardized SCPP goal-directed care based on LSAD monitoring for 5 days was feasible. There were no SCPP-related complications. This is the first report of SCPP implementation as clinical standard of care in acute SCI.

Abdominal radical trachelectomy for treatment of deep infiltrating endometriosis of the cervix.

Surgical management of deep infiltrating endometriosis can be very challenging even for experienced gynecologists. Radical procedures like bowel resection and nephrectomy have been reported for treatment of the disease. Our aim is to report abdominal radical trachelectomy for treatment of deep infiltrating endometriosis of the cervix causing obstructive uropathy and diminished kidney function. We present a 38-year-old woman who was treated in our department for cervical endometriosis involving the vagina and left parametrium. Abdominal radical trachelectomy, insertion of a pig-tail catheter in the left ureter and end-to-end anastomosis of the uterus with the vagina was performed to remove the endometriotic lesion. Cooperation between gynecologists, urologists and nephrologists enabled fertility preservation as well as improvement of renal function. Deep infiltrating endometriosis is a complex disease that requires a multidisciplinary approach. Abdominal radical trachelectomy for cervical lesions seems feasible in this setting and helps preserve fertility.

Management of ureteric injuries during gynecological operations: 10 years experience.

OBJECTIVE(S): To present our 10 years experience in the management of ureteric injuries occurring during gynecological surgery. STUDY DESIGN: Seventy-six patients had a variety of injuries. In 29 cases, the ureteric damage was diagnosed intraoperatively. Management of early-diagnosed injuries included suturing, ligature removal, end-to-end anastomosis, and reimplantation of the ureter. In 47 cases, the injury was diagnosed postoperatively. Ureteric catheterization was attempted in all cases presenting with obstruction. Catheterization failures were managed with ureterolysis, and reimplantation. Small ureteric fistula were managed with catheterization, and large communications with reimplantation. Two cases with urinomas were treated with surgical evacuation and anastomoses. RESULTS: Management of early-diagnosed injuries was relatively easy in most cases. Postoperatively-diagnosed injuries were more difficult to treat. Catheterization failed in 28/44 (65.9%) ureters and surgical re-exploration was necessary. Long-term morbidity was minimal and no relapses occurred. CONCLUSION(S): Early recognition of a ureteric injury is the key to a complications-free repair. Unrecognized injuries cause prolonged morbidity, and their management can be difficult. Treatment of these injuries by experienced teams may minimize long-term consequences.