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The regenerative potential of mammalian peripheral nervous system (PNS) neurons after injury is critically limited by their slow axonal regenerative rate1. Since a delayed target re-innervation leads to irreversible loss of function of target organs2, accelerated axonal regeneration is required to enhance functional outcomes following injury. Regenerative ability is influenced by both injury-dependent and injury-independent mechanisms3. Among the latter, environmental factors such as exercise and environmental enrichment have been shown to affect signalling pathways that promote axonal regeneration4. Several of these pathways, including modifications in gene transcription and protein synthesis, mitochondrial metabolism and release of neurotrophins, can be activated by intermittent fasting (IF)5,6. IF has in turn been shown to increase synaptic plasticity7,8 and neurogenesis9, partially sharing molecular mechanisms with axonal regeneration. However, whether IF influences the axonal regenerative ability remains to be investigated. Here we show that IF promotes axonal regeneration after sciatic nerve crush in the mouse via an unexpected mechanism that relies upon the gram + gut microbiome and an increase of the gut bacteria-derived metabolite indole-3-propionic acid (IPA) in the serum. IPA production by Clostridium sporogenes is required for efficient axonal regeneration, and delivery of IPA after sciatic injury significantly enhances axonal regeneration, accelerating recovery of sensory function. Mechanistically, RNA sequencing analysis from sciatic dorsal root ganglia suggested a role for neutrophil chemotaxis in the IPA-dependent regenerative phenotype that was confirmed by the inhibition of neutrophil chemotaxis. Our results demonstrate for the first time the ability of a microbiome derived metabolite, such as IPA, in facilitating regeneration and functional recovery of sensory axons via an immune-mediated mechanism. Since IPA is a naturally occurring metabolite with a very favourable toxicity profile, it represents a realistic translational possibility for human axonal injuries.

Context . Low birth weight (LBW) is associated with infant morbidity and mortality. This is the first study of LBW in Kansas using vital statistics to determine maternal and health care system factors associated with LBW. Outcomes . Low birth weight. Objective . Determine if prenatal care, maternal socio-demographic or medical factors, or insurance status were associated with LBW. Methods . Birth certificate data were merged with Medicaid eligibility data and subjected to logistic regression analysis. Results . Of the 37,081 single vaginal births, LBW rates were 5.5% overall, 10.8% for African Americans, and 5% for White Americans. Lacking private insurance was associated with 34% more LBW infants (AOR 1.34; 95% CI 1.13–1.58), increased comorbidity, and late or less prenatal care. Low birth weight was associated with maternal medical comorbidity and with previous adverse birth outcomes. Conclusions . Insurance status, prenatal care, and maternal health during pregnancy are associated with LBW. Private insurance was consistently associated with more prenatal care and better outcomes. This study has important implications regarding health care reform.

BACKGROUND: Motor vehicle collisions (MVCs) are the second leading cause of injury among octogenarians. Physicians and families lack outcomes-based data to assist in the decision-making process concerning injury treatment in this population. The purpose of this study was to evaluate 1-year postdischarge mortality in octogenarian MVC patients, cause of death, and patterns predictive of mortality. METHODS: A 10-year retrospective review was conducted of trauma patients 80 years and older who were involved in an MVC and were subsequently discharged alive. Data collected included demographics, injury severity and patterns, hospitalization details, and outcomes. State death database and hospital records were queried to determine cause of death for patients who died within 12 months of hospital discharge. Analyses were conducted to explore if a relationship existed between severity of injury and injury patterns to 12-month postdischarge mortality. RESULTS: Among the 199 patients included in this study, mean (SD) age and Injury Severity Score (ISS) was 84.2 (3.3) years and 9.3 (8.2), respectively. Twenty-two patients (11.1%) died within 12 months. Among these patients, cause of death was directly related to trauma in nine (40.9%), likely related to trauma in seven (31.8%), and unrelated to trauma in six (27.3%). More severely injured patients (ISS >15, p = 0.0041) and those admitted to the intensive care unit (ICU) (p = 0.0051) were more likely to die within 12 months of discharge. Results indicated a trend toward higher mortality in patients with pneumonia. Rib, hip, and pelvic fractures; spinal injuries; intubation upon hospital arrival; and need for mechanical ventilation were not associated with higher postdischarge mortality rates. CONCLUSION: The commonly held belief that the majority of octogenarians with MVC-related trauma die within 1 year of hospital discharge is refuted by this study. Only injury severity, ICU admission, and ICU duration were predictive of mortality within 12 months following discharge. LEVEL OF EVIDENCE: Prognostic study, level III. Language: en

“Water filled view of balloon dilation”—a new technique, to enhance the visualization of esophageal stricture dilation

Introduction/Aim: Management options for PCES following HN 2M & 3F) underwent endoscopic dilation of PCES following H&N cancer treatment. The following protocol to access PCES for endoscopic dilation was used in a stepwise approach (Step 1,2,3). Endoscopic dilation techniques: 1) Antegrade dilation-Conventional technique: In 3 patients, wire guided endoscopic dilation with Savary dilators was performed under conscious sedation. Dilation to 15 mm was achieved in 4 wks. 2) Antegrade dilation- Laryngeal Jack assisted technique: In a 57 yr. female, the stricture opening could not be identified at endoscopy. A novel approach, the Laryngeal Jack technique (elevation of the larynx from the posterior pharyngeal wall and maintaining the position with a Dedo laryngoscope suspended in a stabilizer) was used to identify the opening of the PCES under general anesthesia with the assisance of ENT team.Wire guided endoscopic dilation of the PCES was done to 12 mm. In 2 mo, the stricture was dilated to 16 mm. 3) Combined approach- Laryngeal Jack technique and Retrograde Esophageal Membranotomy: In a 41 yr. female with complete dysphagia (even to saliva), PCES opening could not be identified despite the Laryngeal Jack technique under general anesthesia. After the removal of PEG tube(24 Fr), a 6-mm endoscope(EG1840, Pentax)was passed into the stomach and up into the esophagus. A complete esophageal membranous obstruction was noted. After transillumination from above through the laryngoscope, the thinnest portion of the membrane was punctured with a 5-4-3 catheter, followed by wire guided balloon dilation to 8 mm. In 3 mo, the stricture was dilated to 12-mm. Outcome: All patients gained weight & their PEG tubes were removed. Complications:nil. Conclusions: PCES can be successfully managed by endoscopic dilation without significant morbidity or mortality. Special techniques like the Laryngeal Jack assistance or the combined approach can be useful in difficult cases. Reconstructive surgery can be avoided.

Introduction: There is little data on the time spent by the patient for endoscopy. Information on the time spent for various components may help identify areas for future improvement to contain the cost of endoscopy. Aim: To prospectively study the time spent by the patient in the endoscopy unit (before, during, and after the procedure) for conscious sedation endoscopy in an academic center. Methods & Results: Data was collected on a proforma prospectively by the endoscopy unit nurses on all the pts undergoing GI endoscopy for four weeks in August & September 1999. 165 endoscopies were done on 160 pts. Data collection was complete (100%) in 121 (73%) procedures and data of this 121 pts forms the basis for this report. Demography of the endoscopy unit: a) Endoscopy Unit: Procedure rooms for endocopy: 2 (3rd room for bronchoscopy, liver biopsy, paracentesis, and bone biopsy); Preparation & recovery beds for all the procedures: 5; b) Staff: One endoscopist supervised 2 fellows in training for the day; a nurse & a technician assisted the procedure in each room; 2 nurses staffed the preparation & recovery area; 2 secretaries ran the endoscopy office. c) Endoscopy equipment: EGD: 5 (3 adult, 1 Pediatric, 1 Therapeutic); colonoscopes: 4; ERCP scopes: 2; scope cleaning units: 2. Time study: See table Conclusions: Our findings suggest that efforts should be directed towards reducing preparation & recovery time & waiting prior to the procedure. Alternatives include unsedated endoscopy & reversal of sedation.