GIFTS: Geriatric Intensive Functional Therapy Sessions - For the older trauma patient.

BACKGROUND: Considering resources for comprehensive geriatric (GERI) care, it would be beneficial for geriatric trauma (GTP) and medical patients to be co-managed in one program focusing on ancillary therapeutics (AT): physical (PT), occupational (OT), speech (SLP), respiratory (RT) and sleep wake hygiene (SWH). This pilot describes outcomes of GTP in a hospital-wide program focused on GERI-specific AT. METHODS: GTP and GERI patients were screened by program coordinator (PC) for enrollment at one Level II trauma center from Aug 2021-Dec 2022. Enrolled patients (EP) were admitted to trauma or medicine floors and received repetitive AT with attention to SWH throughout hospitalization and compared to similar non-enrolled patients (NEP). Excluded patients had any of the following: indication of geriatric syndrome with FRAIL 5, no frailty with FRAIL 0, comfort focused plans, or arrived from skilled care. Retrospective chart review of demographics and outcomes was completed for both EP and NEP. RESULTS: 224 EP (28 trauma (TR)) were compared to 574 NEP (148 TR). EP showed shorter LOS (mean 3.8 vs 6.1, p = 0.0001), less delirium (3.1% vs 9.6%, p = 0.00222), less time to ambulate (13 h vs 39 h, p = 0.0005), and higher likelihood to discharge home (56% vs 27%, p < 0.0001) as compared to NEP. Median FRAIL was 3 for both groups. Medical enrolled (M-EP) ambulated the soonest at 11 average hours, compared to 23 hours for TR-EP, compared to 39 hours for NEP. Zero delirium events among TR-EP; 25% among TR-NEP, p = 0.00288. CONCLUSION: Despite a small trauma cohort, results support feasibility to include GTP in hospital-wide programs with GERI specific AT. Mobility and cognitive strategies may improve opportunities to avoid delirium, decrease LOS and influence more frequent disposition to home. TYPE OF STUDY: Original observational retrospective review. LEVEL OF EVIDENCE: Level IV- Therapeutic / Care Management.

Risk factors associated with student distress in medical school: Associations with faculty support and availability of wellbeing resources.

BACKGROUND: It is estimated that over half of medical students experience severe distress, a condition that correlates with low mental quality-of-life, suicidal ideation and serious thoughts of dropping out. While several risk factors for the development of severe distress have been identified, most focus on individual student characteristics. Currently, little is known about the impact medical schools have on student wellbeing. METHODS: Prospective, observational survey study from 2019-2020 from a national cohort of US medical students. Student wellbeing, school characteristics, and wellbeing resource availability was measured with a 30-question electronic survey. Medical student distress was defined as a Medical Student Wellbeing Index (MS-WBI) of ≥4. Risk factors for the development of severe distress were evaluated in a multivariate logistic regression model. The impact of the number of wellbeing resources available on student wellbeing was measured along multiple wellbeing domains. Independent reviewers categorized free text analysis of survey responses about desired wellbeing resources into themes. RESULTS: A total of 2,984 responses were included in the study, representing 45 unique medical schools. Medical school characteristics independently associated with severe distress included low faculty support (OR 4.24); the absence of mentorship resources (OR 1.63) and the absence of community building programs (OR 1.45) in a multivariate model. Increased availability of wellbeing resources was associated with lower average MS-WBI (4.58 vs. 3.19, p<0;05) and a smaller percentage of students who had taken or considered taking a leave of absence (40% vs. 16%, p<0.05). The resources most desired by students were mental health services and scheduling adjustments. CONCLUSIONS: The majority of medical school characteristic that contribute to student distress are modifiable. Improving faculty support and offering more and varied wellbeing resources may help to mitigate medical student distress. Student feedback is insightful and should be routinely incorporated by schools to guide wellbeing strategies.

The DISTANCE study: Determining the impact of social distancing on trauma epidemiology during the COVID-19 epidemic-An interrupted time-series analysis.

BACKGROUND: The large-scale social distancing efforts to reduce SARS-CoV-2 transmission have dramatically changed human behaviors associated with traumatic injuries. Trauma centers have reported decreases in trauma volume, paralleled by changes in injury mechanisms. We aimed to quantify changes in trauma epidemiology at an urban Level I trauma center in a county that instituted one of the earliest shelter-in-place orders to inform trauma care during future pandemic responses. METHODS: A single-center interrupted time-series analysis was performed to identify associations of shelter-in-place with trauma volume, injury mechanisms, and patient demographics in San Francisco, California. To control for short-term trends in trauma epidemiology, weekly level data were analyzed 6 months before shelter-in-place. To control for long-term trends, monthly level data were analyzed 5 years before shelter-in-place. RESULTS: Trauma volume decreased by 50% in the week following shelter-in-place (p < 0.01), followed by a linear increase each successive week (p < 0.01). Despite this, trauma volume for each month (March-June 2020) remained lower compared with corresponding months for all previous 5 years (2015-2019). Pediatric trauma volume showed similar trends with initial decreases (p = 0.02) followed by steady increases (p = 0.05). Reductions in trauma volumes were due entirely to changes in nonviolent injury mechanisms, while violence-related injury mechanisms remained unchanged (p < 0.01). CONCLUSION: Although the shelter-in-place order was associated with an overall decline in trauma volume, violence-related injuries persisted. Delineating and addressing underlying factors driving persistent violence-related injuries during shelter-in-place orders should be a focus of public health efforts in preparation for future pandemic responses. LEVEL OF EVIDENCE: Epidemiological study, level III.

Medical students in distress: The impact of gender, race, debt, and disability.

BACKGROUND: In 2012, over half of US medical students experienced burnout and depression. Since that time, there have been many changes to student demographics, school resources and awareness of burnout in the medical field altogether. New tools are also available to screen for student distress, a condition that correlates with low mental quality-of-life, suicidal ideation and serious thoughts of dropping out. Despite increased attention on wellbeing and improved screening methods, no large-scale studies have evaluated student distress in the modern era of medical education. The objective of this study was to determine the current prevalence of medical student distress and contributing risk factors. METHODS: Student wellbeing from a national cohort of US medical students was measured with an electronic survey in a prospective, observational survey study from 2019-2020. Medical student distress was defined as a Medical Student Wellbeing Index (MS-WBI) of ≥4. Demographic details including age, race, gender, marital status, disability, desired specialty, and debt burden were evaluated in a multivariate logistic regression model to determine possible risk factors for the development of distress. RESULTS: A total of 3,162 students responded to the survey, representing 110 unique medical schools. Of these respondents, 52.9% met criteria for distress and 22% had either taken or considered taking a leave of absence for personal wellbeing. Independent risk factors for distress included involvement in the clinical phase of medical school (OR 1.37); non-male gender (OR 1.6); debt burden >$20,000 (OR 1.37), >$100,000 (OR 1.81), and >$300,000 (OR 1.96); and disability status (OR 1.84). CONCLUSIONS: Medical student wellbeing remains poor in the modern era of medical education despite increased attention to wellbeing and increased availability of wellbeing resources. Disability status is a novel risk factor for distress identified in this study. The persistence of previously identified risk factors such as non-male gender, debt burden and clinical phase of school suggest that efforts to curb medical student distress have been inadequate to date.

CHRFAM7A reduces monocyte/macrophage migration and colony formation in vitro.

OBJECTIVE AND DESIGN: CHRFAM7A is a unique human gene that encodes a dominant negative inhibitor of the α7 nicotinic acetylcholine receptor. We have recently shown that CHRFAM7A is expressed in human leukocytes, increases cel-cell adhesion, and regulates the expression of genes associated with leukocyte migration. MATERIAL: Human THP-1, RAW264.7 and HEK293 cells. METHODS: Cell migration, cell proliferation and colony formation in soft agar to compare the biological activity of vector vs. CHRFAM7A-transduced cells. RESULTS: We show that gene delivery of CHRFAM7A into the THP-1 human monocytic cell line reduces cell migration, reduces chemotaxis to monocyte chemoattractant protein, and reduces colony formation in soft agar. CONCLUSION: Taken together, the findings demonstrate that CHRFAM7A regulates the biological activity of monocytes/macrophages to migrate and undergo anchorage-independent growth in vitro.

The effect of cirrhosis on trauma outcomes: A systematic review and meta-analysis.

BACKGROUND: The negative effect of cirrhosis on mortality following traumatic injury has been quantified in multiple observational studies. However, to our knowledge, the information contained in these studies has never been synthesized. The aims of this study were: (1) to determine the magnitude of the effect of liver cirrhosis on mortality, morbidity, and hospital course among trauma patients and (2) to analyze sources of study heterogeneity that may lead to differing estimates in the observed mortality rate among patients with cirrhosis. METHODS: A systematic search of EMBASE and PubMed was conducted. Data were extracted from eligible studies and analyzed using a random-effects model to compare trauma outcomes in cirrhotic and noncirrhotic patients (PROSPERO Registration CRD42018088464). Mortality was the primary outcome. Secondary outcomes included complication rate, length of hospital stay, length of intensive care unit stay, and mechanical ventilation days. RESULTS: Title and abstract review of 15,958 articles led to the identification of 31 relevant articles. Ultimately, 18 observational studies were included in this meta-analysis. The pooled effect sizes for mortality (odds ratio [OR], 4.52; 95% confidence interval [CI], 3.13-6.54) and complication rate (OR, 1.92; 95% CI, 1.30-2.85) were higher in the cirrhotic group than the noncirrhotic group. Trauma patients with cirrhosis also incurred longer hospital stays (mean difference, 3.81 days; 95% CI, 1.22-6.41) and longer ICU stays (mean difference, 2.40 days; 95% CI, 0.65-4.15). There was no difference in days spent on mechanical ventilation. CONCLUSION: Preexisting liver cirrhosis is associated with increased mortality rate, complication rate, and length of hospitalization among trauma patients, even after adjusting for confounding factors and potential sources of between-study heterogeneity. Trauma patients with cirrhosis would benefit from heightened surveillance and injury prevention interventions. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level III.

Uniquely human CHRFAM7A gene increases the hematopoietic stem cell reservoir in mice and amplifies their inflammatory response.

A subset of genes in the human genome are uniquely human and not found in other species. One example is CHRFAM7A, a dominant-negative inhibitor of the antiinflammatory α7 nicotinic acetylcholine receptor (α7nAChR/CHRNA7) that is also a neurotransmitter receptor linked to cognitive function, mental health, and neurodegenerative disease. Here we show that CHRFAM7A blocks ligand binding to both mouse and human α7nAChR, and hypothesized that CHRFAM7A-transgenic mice would allow us to study its biological significance in a tractable animal model of human inflammatory disease, namely SIRS, the systemic inflammatory response syndrome that accompanies severe injury and sepsis. We found that CHRFAM7A increased the hematopoietic stem cell (HSC) reservoir in bone marrow and biased HSC differentiation to the monocyte lineage in vitro. We also observed that while the HSC reservoir was depleted in SIRS, HSCs were spared in CHRFAM7A-transgenic mice and that these mice also had increased immune cell mobilization, myeloid cell differentiation, and a shift to inflammatory monocytes from granulocytes in their inflamed lungs. Together, the findings point to a pathophysiological inflammatory consequence to the emergence of CHRFAM7A in the human genome. To this end, it is interesting to speculate that human genes like CHRFAM7A can account for discrepancies between the effectiveness of drugs like α7nAChR agonists in animal models and human clinical trials for inflammatory and neurodegenerative disease. The findings also support the hypothesis that uniquely human genes may be contributing to underrecognized human-specific differences in resiliency/susceptibility to complications of injury, infection, and inflammation, not to mention the onset of neurodegenerative disease.

Plasma D-dimer safely reduces unnecessary CT scans obtained in the evaluation of pediatric head trauma.

PURPOSE: Serum D-dimer has been proposed as a biomarker to aid in the diagnosis of pediatric traumatic brain injury (TBI). We investigated the accuracy of D-dimer in predicting the absence of TBI and evaluated the degree by which D-dimer could limit unnecessary computed tomography scans of the head (CTH). METHODS: Retrospective review of patients with suspected TBI from 2011 to 2013 who underwent evaluation with CTH and quantitative D-dimer. D-dimer levels were compared among patients with clinically-important TBI (ciTBI), TBI, isolated skull fracture and no injury. RESULTS: Of the 663 patients evaluated for suspected TBI, ciTBI was identified in 116 (17.5%), TBI in 77 (11.6%), skull fracture in 61 (9.2%) and no head injury in 409 (61.7%). Patients with no head injury had significantly lower D-dimer values (1531±1791pg/µL) compared to those with skull fracture, TBI and ciTBI (2504±1769, 2870±1633 and 4059±1287pg/µL, respectively, p<0.005). Using a D-dimer value <750pg/µL as a negative screen, no ciTBIs would be missed and 209 CTHs avoided (39.7% of total). CONCLUSION: Low plasma D-dimer predicts the absence of ciTBI for pediatric patient with suspected TBI. Incorporating D-dimer into current diagnostic algorithms may significantly limit the number of unnecessary CTHs performed in this population. TYPE OF STUDY: Study of diagnostic test. LEVEL OF EVIDENCE: I.

Low Infection-Related Re-Admission Rates in a Retrospective of 4725 Children with Appendicitis Using a Clinical Pathway in a Tertiary Care Pediatric Center.

BACKGROUND: Standardization of antibiotic management of appendicitis in tertiary care pediatric centers has been associated with improved outcomes. Rady Children's Hospital-San Diego implemented an appendicitis clinical pathway in 2005. We evaluated infection-related re-admission risk factors since 2010, when an electronic medical record was established, with the aim to optimize the clinical pathway. METHODS: Between January 2010 and August 2015, 4725 children with a diagnosis of appendicitis were evaluated for demographic data, pathology diagnoses, culture results, and inpatient and oral step-down antibiotic therapy regimens. From children originally admitted for appendicitis, those who were re-admitted with infection were compared with those who were not re-admitted for infection. The populations were controlled by severity of infection using a pathology-defined appendicitis severity scale: Grade 0, no appendicitis; grade 1, simple acute appendicitis with gross and microscopic evidence of inflammation, but no perforation; grade 2, gangrenous/necrotizing/micro-perforated appendicitis with subserosal or serosal exudate, but no frank or visually appreciated perforation; and grade 3, frank perforation. RESULTS: Of 4725 children (total population, TP) admitted with a diagnosis of appendicitis, only 199 (4.2%) were re-admitted, with 125 of these admissions for infection (2.65% of the TP). Age, race/ethnicity, language preference, and body mass index were not found to correlate with re-admission for infection. Length of stay significantly differed between the no infection-related re-admission population and infection-related re-admission population (3.02 vs. 4.03 d, p < 0.001). There was a trend toward higher infection-re-admission rates as the pathology grade increased (odds ratio grade 1 vs. grade 3 = 2.28, 95% confidence interval 1.03, 5.03). CONCLUSIONS: Infection-related re-admission rates for children on the clinical pathway in our institution were infrequent. The greater association of all-cause and infection-related re-admission rates with pathology grade suggest that defining appendicitis by pathology and clinical severity may provide an evidence-based scoring system to support clinical observation in the use and duration of antibiotic therapy.

Enteric glia cells are critical to limiting the intestinal inflammatory response after injury.

Vagal nerve stimulation (VNS) has been shown to limit intestinal inflammation following injury; however, a direct connection between vagal terminals and resident intestinal immune cells has yet to be identified. We have previously shown that enteric glia cell (EGC) expression is increased after injury through a vagal-mediated pathway to help restore gut barrier function. We hypothesize that EGCs modulate immune cell recruitment following injury and relay vagal anti-inflammatory signals to resident immune cells in the gut. EGCs were selectively ablated from an isolated segment of distal bowel with topical application of benzalkonium chloride (BAC) in male mice. Three days following BAC application, mice were subjected to an ischemia-reperfusion injury (I/R) by superior mesenteric artery occlusion for 30 min. VNS was performed in a separate cohort of animals. EGC+ and EGC- segments were compared utilizing histology, flow cytometry, immunohistochemistry, and intestinal permeability. VNS significantly reduced immune cell recruitment after I/R injury in EGC+ segments with cell percentages similar to sham. VNS failed to limit immune cell recruitment in EGC- segments. Histologic evidence of gut injury was diminished with VNS application in EGC+ segments, whereas EGC- segments showed features of more severe injury. Intestinal permeability increased following I/R injury in both EGC+ and EGC- segments. Permeability was significantly lower after VNS application compared with injury alone in EGC+ segments only (95.1 ± 30.0 vs. 217.6 ± 21.7 µg/ml, P < 0.05). Therefore, EGC ablation uncouples the protective effects of VNS, suggesting that vagal-mediated signals are translated to effector cells through EGCs.NEW & NOTEWORTHY Intestinal inflammation is initiated by local immune cell activation and epithelial barrier breakdown, resulting in the production of proinflammatory mediators with subsequent leukocyte recruitment. Vagal nerve stimulation (VNS) has been shown to limit intestinal inflammation following injury; however, direct connection between vagal terminals and resident intestinal immune cells has yet to be identified. Here, we demonstrate that intact enteric glia cells are required to transmit the gut anti-inflammatory effects of VNS.

Exosomes, not protein or lipids, in mesenteric lymph activate inflammation: Unlocking the mystery of post-shock multiple organ failure.

BACKGROUND: Previous studies have shown that mesenteric lymph (ML) has a crucial role in driving the systemic inflammatory response after trauma/hemorrhagic shock (T/HS). The specific mediators in the ML that contribute to its biological activity remain unclear despite decades of study. Exosomes are extracellular vesicles that are shed into body fluids such as serum and urine that can mediate intercellular communication. We hypothesized that exosomes are present in the ML after trauma/shock and are responsible for the biological activity of ML. METHODS: Male rats underwent cannulation of the vessels and mesenteric lymph duct. T/HS was induced by laparotomy and 60 minutes of HS (mean arterial pressure, 35 mmHg), followed by resuscitation. The ML was collected during three distinct time periods (pre-shock, shock, and resuscitation phase) and subsequently separated into exosome and supernatant fractions. Exosomes were characterized by electron microscope, nanoparticle tracking analysis, and immunoblotting. The biological activity of exosomes and supernatant of ML were characterized using a monocyte NF-κB reporter assay and by measuring macrophage intracellular TNF-α production. RESULTS: Exosomes were identified in ML by size and expression of the exosome markers CD63 and HSP70. The number of exosomes present in the ML was 2-fold increased during shock and 4-fold decreased in resuscitation phase compared to pre-shock. However, biological activity of exosomes isolated during the resuscitation phase was markedly increased and caused an 8-fold increase in monocyte NF-κB activation compared to supernatant. Macrophage TNF-α production was also increased after exposure to exosomes harvested in the resuscitation phase. The ML supernatant fraction had no effect on TNF-α production during any phase. CONCLUSIONS: Our findings show that exosomes, and not the liquid fraction of ML, are the major component triggering inflammatory responses in monocytes and macrophages after experimental T/HS.

Isolated traumatic brain injury in patients with cirrhosis: do different treatment paradigms result in increased mortality?

BACKGROUND: Cirrhosis is associated with increased mortality in trauma, yet its effects on outcomes after traumatic brain injury (TBI) are unclear. We hypothesized that cirrhosis adversely effects mortality and increases complications after TBI. METHODS: Cirrhotic patients with isolated TBI were matched with noncirrhotic TBI patients in a 3:1 ratio based on age, sex, injury mechanism, and injury severity score at our academic, level 1 trauma center. RESULTS: Of the 8,748 patients with isolated TBI, 65 patients had concurrent cirrhosis. Cirrhotic patients had increased mortality compared with matched controls (31% vs 17%, P = .03) and were less likely to undergo emergent neurosurgical operation (12% vs 25%, P = .03). There was no difference in admission Glasgow Coma Score, type of intracranial hemorrhage, length of stay, or complications between the groups. CONCLUSIONS: Cirrhotic patients have increased mortality after TBI and were less likely to undergo operative intervention. New treatment paradigms may be needed to improve outcomes for cirrhotic patients suffering TBI.

Modulating the Biologic Activity of Mesenteric Lymph after Traumatic Shock Decreases Systemic Inflammation and End Organ Injury.

INTRODUCTION: Trauma/hemorrhagic shock (T/HS) causes the release of pro-inflammatory mediators into the mesenteric lymph (ML), triggering a systemic inflammatory response and acute lung injury (ALI). Direct and pharmacologic vagal nerve stimulation prevents gut barrier failure and alters the biologic activity of ML after injury. We hypothesize that treatment with a pharmacologic vagal agonist after T/HS would attenuate the biologic activity of ML and prevent ALI. METHODS: ML was collected from male Sprague-Dawley rats after T/HS, trauma-sham shock (T/SS) or T/HS with administration of the pharmacologic vagal agonist CPSI-121. ML samples from each experimental group were injected into naïve mice to assess biologic activity. Blood samples were analyzed for changes in STAT3 phosphorylation (pSTAT3). Lung injury was characterized by histology, permeability and immune cell recruitment. RESULTS: T/HS lymph injected in naïve mice caused a systemic inflammatory response characterized by hypotension and increased circulating monocyte pSTAT3 activity. Injection of T/HS lymph also resulted in ALI, confirmed by histology, lung permeability and increased recruitment of pulmonary macrophages and neutrophils to lung parenchyma. CPSI-121 attenuated T/HS lymph-induced systemic inflammatory response and ALI with stable hemodynamics and similar monocyte pSTAT3 levels, lung histology, lung permeability and lung immune cell recruitment compared to animals injected with lymph from T/SS. CONCLUSION: Treatment with CPSI-121 after T/HS attenuated the biologic activity of the ML and decreased ALI. Given the superior clinical feasibility of utilizing a pharmacologic approach to vagal nerve stimulation, CPSI-121 is a potential treatment strategy to limit end organ dysfunction after injury.

Ketorolac does not reduce effectiveness of pleurodesis in pediatric patients with spontaneous pneumothorax.

PURPOSE: Antiinflammatory medications are thought to reduce the effectiveness of pleurodesis performed for the treatment of spontaneous pneumothorax. We reviewed our experience with children undergoing video-assisted thorascopic surgery (VATS) with pleurodesis for pneumothorax to determine if ketorolac administration influences patient outcomes. METHODS: A retrospective review of patients who underwent VATS pleurodesis for spontaneous pneumothorax from 2009 to 2013 at a pediatric hospital was performed. Length of stay, radiographic pneumothorax resolution prior to discharge, and ipsilateral recurrence rates were compared in patients who did and did not receive perioperative ketorolac. RESULTS: Over a 50-month period, 51 patients underwent VATS with mechanical pleurodesis for spontaneous pneumothorax. The average age was 15.5years, and 76% were male. Ketorolac was administered to 26/51 patients. There were no differences in average length of stay (11.3 vs 10.9days, p=0.36), incidence of residual pneumothorax at discharge (22/41 vs 19/41, p=0.48), or ipsilateral recurrence (5/10 vs 5/10, p=1). CONCLUSIONS: Despite the intrinsic antiinflammatory properties of ketorolac, our data suggests that its use for patients undergoing pleurodesis for spontaneous pneumothorax does not detrimentally influence the outcomes of surgery. Therefore, we conclude that ketorolac can be used for pain control in this population. Large-scale studies are warranted to validate these findings.

Vagus Nerve Mediates the Neural Stem Cell Response to Intestinal Injury.

BACKGROUND: Intestinal ischemia and reperfusion injury results in damage to elements critical to maintaining intestinal barrier function, including neurons and glia cells, which are part of the enteric nervous system (ENS). To limit inflammation, the ENS must be restored or replaced, yet the process by which this occurs is poorly understood. Multipotent progenitor cells called enteric nervous stem cells (ENSC) can differentiate into neurons or glia when stimulated. The ability of this cell population to respond to intestinal injury is unknown. In this study, we hypothesized that resolution of intestinal barrier injury would be associated with vagus nerve-mediated expansion of ENSCs. STUDY DESIGN: Ischemia and reperfusion injury was reproduced in male mice by occluding the superior mesenteric artery for 30 minutes. Abdominal vagotomy was performed in a separate cohort to study the effects of the vagus nerve. Terminal ileum was harvested at various time points after reperfusion and analyzed with histology, flow cytometry, and immunohistochemistry. RESULTS: Enteric nervous stem cell expansion occurs at 2, 4, and 8 hours after injury compared with sham (4.6% vs 2.1%; p < 0.001) and correlated with increased glial fibrillary acidic protein on immunohistochemistry. Vagotomy prevented both ENSC expansion and increased glial fibrillary acidic protein staining after injury. Intestinal permeability was restored to baseline by 48 hours after injury, but remained elevated in the vagotomy group compared with sham and injury alone at 48 hours (3.25 mg/mL vs 0.57 mg/mL and 0.26 mg/mL, respectively; p < 0.05). CONCLUSIONS: Vagal-mediated expansion of ENSCs occurs after ischemia and reperfusion injury and results in improved kinetics of injury resolution.

Neuroenteric axis modulates the balance of regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock.

CD103(+) dendritic cells (DCs) continuously migrate from the intestine to the mesenteric lymph nodes (MLNs) and maintain tolerance by driving the development of regulatory T cells (Treg) in the gut. The relative expression of Treg and T-helper 17 (Th17) cells determines the balance between tolerance and immunity in the gut. We hypothesized that trauma/hemorrhagic shock (T/HS) would decrease the CD103(+) DC population in the mesenteric lymph and alter the Treg-to-Th17 ratio in the MLN. We further hypothesized that vagus nerve stimulation (VNS) would promote tolerance to inflammation by increasing the Treg-to-Th17 ratio in the MLN after injury. Male rats were assigned to sham shock (SS), trauma/sham shock (T/SS), or T/HS. T/HS was induced by laparotomy and 60 min of HS (blood pressure 35 mmHg) followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. MLN samples were collected 24 h after resuscitation. The CD103(+) DC population and Treg-to-Th17 cell ratio in the MLN were decreased after T/HS compared with SS and T/SS, suggesting a shift to an inflammatory response. VNS prevented the T/HS-induced decrease in the CD103(+) DC population and increased the Treg-to-Th17 ratio compared with T/HS alone. VNS alters the gut inflammatory response to injury by modulating the Treg-Th17 cell balance in the MLN. VNS promotes tolerance to inflammation in the gut, further supporting its ability to modulate the inflammatory set point and alter the response to injury.

Laparoscopic versus open reduction of intussusception in children: experience over a decade.

BACKGROUND: Intussusception is a common cause of bowel obstruction in children, which sometimes necessitates operative reduction and or resection. We report our series of patients with intussusception who were treated laparoscopically (LAP group) compared with exploratory laparotomy (OPEN group). SUBJECTS AND METHODS: After institutional review board approval, a retrospective review was performed evaluating outcomes for patients requiring surgical reduction of intussusception over a 10-year period. Analysis was based on intent to treat, and technique of exploration was surgeon's choice. Data were analyzed with the Wilcoxon rank sum test and chi-squared test where appropriate. P≤.05 was considered significant. RESULTS: During the time period studied, there were 92 patients treated surgically for intussusception: 65 LAP and 27 OPEN. Conversion to the open procedure was required for 21 patients in the LAP group, and of those, 6 required bowel resection. Seven of the patients who were started in the OPEN group ultimately required bowel resection. Operative time, length of hospital stay, time to full feeds, and total days of narcotics were all significantly shorter for the LAP group compared with the OPEN group (P=.003, P=.001, P=.001, and P=.004, respectively). A pathologic lead point was found in 14% of LAP and 15% of OPEN cases. In a subset analysis, 33% of patients who were converted from the LAP group to the open procedure had a pathologic lead point. Complication rates between the LAP and OPEN groups were comparable. CONCLUSIONS: Laparoscopy appears to be a safe and effective technique for reducing intussusception in children. The laparoscopic cases had shorter operative time, shorter time to full feeds, lower requirement for intravenous narcotics, and earlier discharges.