Intermediate-term outcomes after robotic ureteral reconstruction for long-segment (≥4 centimeters) strictures in the proximal ureter: A multi-institutional experience.

PURPOSE: To report our intermediate-term, multi-institutional experience after robotic ureteral reconstruction for the management of long-segment proximal ureteral strictures. MATERIALS AND METHODS: We retrospectively reviewed our Collaborative of Reconstructive Robotic Ureteral Surgery (CORRUS) database to identify all patients who underwent robotic ureteral reconstruction for long-segment (≥4 centimeters) proximal ureteral strictures between August 2012 and June 2019. The primary surgeon determined the specific technique to reconstruct the ureter at time of surgery based on the patient's clinical history and intraoperative findings. Our primary outcome was surgical success, which we defined as the absence of ureteral obstruction on radiographic imaging and absence of obstructive flank pain. RESULTS: Of 20 total patients, 4 (20.0%) underwent robotic ureteroureterostomy (RUU) with downward nephropexy (DN), 2 (10.0%) underwent robotic ureterocalycostomy (RUC) with DN, and 14 (70.0%) underwent robotic ureteroplasty with buccal mucosa graft (RU-BMG). Median stricture length was 4 centimeters (interquartile range [IQR], 4-4; maximum, 5), 6 centimeters (IQR, 5-7; maximum, 8), and 5 centimeters (IQR, 4-5; maximum, 8) for patients undergoing RUU with DN, RUC with DN, and RU-BMG, respectively. At a median follow-up of 24 (IQR, 14-51) months, 17/20 (85.0%) cases were surgically successful. Two of four patients (50.0%) who underwent RUU with DN developed stricture recurrences within 3 months. CONCLUSIONS: Long-segment proximal ureteral strictures may be safely and effectively managed with RUC with DN and RU-BMG. Although RUU with DN can be utilized, this technique may be associated with a higher failure rate.

AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.

More than half of spinal cord injury (SCI) cases occur in the cervical region, leading to respiratory dysfunction due to damaged neural circuitry that controls critically important muscles such as the diaphragm. The C3-C5 spinal cord is the location of phrenic motor neurons (PhMNs) that are responsible for diaphragm activation; PhMNs receive bulbospinal excitatory drive predominately from supraspinal neurons of the rostral ventral respiratory group (rVRG). Cervical SCI results in rVRG axon damage, PhMN denervation, and consequent partial-to-complete paralysis of hemidiaphragm. In a rat model of C2 hemisection SCI, we expressed the axon guidance molecule, brain-derived neurotrophic factor (BDNF), selectively at the location of PhMNs (ipsilateral to lesion) to promote directed growth of rVRG axons toward PhMN targets by performing intraspinal injections of adeno-associated virus serotype 2 (AAV2)-BDNF vector. AAV2-BDNF promoted significant functional diaphragm recovery, as assessed by in vivo electromyography. Within the PhMN pool ipsilateral to injury, AAV2-BDNF robustly increased sprouting of both spared contralateral-originating rVRG axons and serotonergic fibers. Furthermore, AAV2-BDNF significantly increased numbers of putative monosynaptic connections between PhMNs and these sprouting rVRG and serotonergic axons. These findings show that targeting circuit plasticity mechanisms involving the enhancement of synaptic inputs from spared axon populations is a powerful strategy for restoring respiratory function post-SCI.-Charsar, B. A., Brinton, M. A., Locke, K., Chen, A. Y., Ghosh, B., Urban, M. W., Komaravolu, S., Krishnamurthy, K., Smit, R., Pasinelli, P., Wright, M. C., Smith, G. M., Lepore, A. C. AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.

Long-Distance Axon Regeneration Promotes Recovery of Diaphragmatic Respiratory Function after Spinal Cord Injury.

Compromise in inspiratory breathing following cervical spinal cord injury (SCI) is caused by damage to descending bulbospinal axons originating in the rostral ventral respiratory group (rVRG) and consequent denervation and silencing of phrenic motor neurons (PhMNs) that directly control diaphragm activation. In a rat model of high-cervical hemisection SCI, we performed systemic administration of an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential. PTEN antagonist peptide (PAP4) robustly restored diaphragm function, as determined with electromyography (EMG) recordings in living SCI animals. PAP4 promoted substantial, long-distance regeneration of injured rVRG axons through the lesion and back toward PhMNs located throughout the C3-C5 spinal cord. These regrowing rVRG axons also formed putative excitatory synaptic connections with PhMNs, demonstrating reconnection of rVRG-PhMN-diaphragm circuitry. Lastly, re-lesion through the hemisection site completely ablated functional recovery induced by PAP4. Collectively, our findings demonstrate that axon regeneration in response to systemic PAP4 administration promoted recovery of diaphragmatic respiratory function after cervical SCI.

Colonoscopy utilization in rural areas by general surgeons: An analysis of the National Ambulatory Medical Care Survey.

BACKGROUND: One in three adults above 50 years old have not been screened for colorectal cancer as of 2013.1 Rural areas have even lower screening and have more general surgeons compared to gastroenterologists,2 offering surgeons as a reservoir for necessary services. METHODS: Public data from the 2006-2015 CDC National Ambulatory Medical Care Survey was analyzed using SAS. Number of colonoscopies performed by rural general surgeons, family medicine practitioners, and other specialties were compared to their urban counterparts. RESULTS: 21.91% of rural colonoscopies were performed by general surgeons, whereas 32.87% were performed by family medicine practitioners and 45.22% by other specialties including gastroenterologists. Rural general surgeons performed a greater percentage of annual rural colonoscopies than urban general surgeons (p < 0.05). CONCLUSION: General surgeons are fulfilling the need for colonoscopy in rural areas. Improvements to current colonoscopy training guidelines are imperative, especially for physicians who practice in rural areas.

Astrocyte progenitor transplantation promotes regeneration of bulbospinal respiratory axons, recovery of diaphragm function, and a reduced macrophage response following cervical spinal cord injury.

Stem/progenitor cell transplantation delivery of astrocytes is a potentially powerful strategy for spinal cord injury (SCI). Axon extension into SCI lesions that occur spontaneously or in response to experimental manipulations is often observed along endogenous astrocyte "bridges," suggesting that augmenting this response via astrocyte lineage transplantation can enhance axon regrowth. Given the importance of respiratory dysfunction post-SCI, we transplanted glial-restricted precursors (GRPs)-a class of lineage-restricted astrocyte progenitors-into the C2 hemisection model and evaluated effects on diaphragm function and the growth response of descending rostral ventral respiratory group (rVRG) axons that innervate phrenic motor neurons (PhMNs). GRPs survived long term and efficiently differentiated into astrocytes in injured spinal cord. GRPs promoted significant recovery of diaphragm electromyography amplitudes and stimulated robust regeneration of injured rVRG axons. Although rVRG fibers extended across the lesion, no regrowing axons re-entered caudal spinal cord to reinnervate PhMNs, suggesting that this regeneration response-although impressive-was not responsible for recovery. Within ipsilateral C3-5 ventral horn (PhMN location), GRPs induced substantial sprouting of spared fibers originating in contralateral rVRG and 5-HT axons that are important for regulating PhMN excitability; this sprouting was likely involved in functional effects of GRPs. Finally, GRPs reduced the macrophage response (which plays a key role in inducing axon retraction and limiting regrowth) both within the hemisection and at intact caudal spinal cord surrounding PhMNs. These findings demonstrate that astrocyte progenitor transplantation promotes significant plasticity of rVRG-PhMN circuitry and restoration of diaphragm function and suggest that these effects may be in part through immunomodulation.

Startle suppression after mild traumatic brain injury is associated with an increase in pro-inflammatory cytokines, reactive gliosis and neuronal loss in the caudal pontine reticular nucleus.

Mild traumatic brain injury (mTBI) can produce somatic symptoms such as headache, dizziness, fatigue, sleep disturbances and sensorimotor dysfunction. Sensorimotor function can be measured by tests such as the acoustic startle reflex (ASR), an evolutionarily conserved defensive response to a brief yet sharp acoustic stimulus. mTBI produces a long-lasting suppression of ASR in rodents and humans; however, the mechanism of this suppression is unknown. The present study examined whether inflammatory processes in the brainstem (particularly the caudal pontine reticular nucleus, PnC) could account for the suppression of ASR after mTBI, because the PnC is an essential nucleus of the ASR circuit. Furthermore, while inflammation after mTBI is commonly observed in brain regions proximal to the site of impact (cortex and hippocampus), the effects of mTBI in brainstem structures remains largely understudied. The present study demonstrated a suppression of ASR one day after injury and lasting at least three weeks after an mTBI, replicating previous findings. Within the PnC, transient elevations of IL-1ß and TNF-α mRNA were observed at one day after injury, while IL-1α mRNA exhibited a delayed increase at three weeks after injury. Reactive gliosis (via IBA-1-ir for microglia and GFAP-ir for astrocytes) were also observed in the PnC, at one day and seven days after injury, respectively. Finally, the number of giant neurons (the major functional cell population in the PnC) was decreased three weeks after injury. The results indicate that glial activation precedes neuronal loss in the PnC, and correlates with the behavioral suppression of the ASR. The results also raise implications for brainstem involvement in the development of post-traumatic symptoms.