Lack of patient and primary care physician follow-up in geriatric emergency department patients with head trauma from a fall.

STUDY OBJECTIVE: Falls are the leading cause of injuries in the US for older adults. Follow-up after an ED-related fall visit is essential to initiate preventive strategies in these patients who are at very high risk for recurrent falls. It is currently unclear how frequently follow-up occurs and whether preventive strategies are implemented. Our objective is to determine the rate of follow-up by older adults who sustain a fall related head injury resulting in an ED visit, the rate and type of risk assessment and adoption of preventive strategies. METHODS: This 1-year prospective observational study was conducted at two South Florida hospitals. All older ED patients with an acute head injury due to a fall were identified. Telephone surveys were conducted 14 days after ED presentation asking about PCP follow-up and adoption of fall prevention strategies. Clinical and demographic characteristics were compared between patients with and without follow up. RESULTS: Of 4951 patients with a head injury from a fall, 1527 met inclusion criteria. 905 reported follow-up with their PCP. Of these, 72% reported receiving a fall assessment and 56% adopted a fall prevention strategy. Participants with PCP follow-up were significantly more likely to have a history of cancer or hypertension. CONCLUSION: Only 60% of ED patients with fall-related head injury follow-up with their PCP. Further, 72% received a fall assessment and only 56% adopted a fall prevention strategy. These data indicate an urgent need to promote PCP fall assessment and adoption of prevention strategies in these patients.

Sudden Decompensation of Patients Admitted to Non-ICU Settings Within 24 h of Emergency Department Admission.

BACKGROUND: Patients admitted to the hospital floor (non-intensive care (ICU) settings) from the emergency department (ED) are generally stable. Unfortunately, some will unexpectedly decompensate rapidly. This study explores these patients and their characteristics. METHODS: This retrospective, observational study examined patients admitted to non-ICU settings at a community hospital. Patients were identified by rapid response team (RRT) activation, triggered by acute decompensation. ED chief complaint, reason for activation, and vital signs were compared between patients transferred to a higher level of care versus those who were not. RESULTS: Throughout 2019, 424 episodes of acute decompensation were identified, 118 occurring within 24 h of admission. A higher rate of ICU transfers was seen in patients with initial ED chief complaints of general malaise (87.5% vs 12.5%, p = 0.023) and dyspnea (70.6% vs 29.4%, p = 0.050). Patients with sudden decompensation were more likely to need ICU transfer if the RRT reason was respiratory issues (47% vs 24%, p = 0.010) or hypertension (9.1% vs 0%, p = 0.019). Patients with syncope as a reason for decompensation were less likely to need transfer (0% vs 10.3%, p = 0.014). Patients requiring ICU transfer were significantly older (74.4 vs 71.8 years, p = 0.016). No differences in admission vital signs, APACHE score, or qSOFA score were found. CONCLUSIONS: Patients admitted to the floor with chief complaint of general malaise or dyspnea should be considered at higher risk of having a sudden decompensation requiring transfer to a higher level of care. Therefore, greater attention should be taken with disposition of these patients at the time of admission.

Comparing rates of skull fractures in female versus male geriatric patients who sustain head injuries.

BACKGROUND: Head trauma is the leading cause of serious injury in the older adult population with skull fractures as a serious reported outcome. This study aims to evaluate the role of sex in the risk of skull fracture in patients over the age of 65. METHODS: A prospective cohort study was conducted at two level-one trauma centers, serving a population of 360,000 geriatric residents. Over a year-long period, consecutive patients aged 65 years and older who presented with blunt head injury were included. Patients who did not receive head CT imaging were excluded. The primary outcome was rate of skull fracture due to the acute trauma, compared by sex. Additional factors examined included patient race/ethnicity and mechanism of injury. RESULTS: Among 5402 patients enrolled, 3010 (56%) were female and 2392 (44%) were male. 4612 (85%) of the head injuries sustained were due to falls, and 4536 (90%) of all subjects were Caucasian. Overall, 199 patients (3.7%) sustained skull fractures. Males had a significantly greater rate of skull fracture when compared to females (4.6% vs 3.0%, OR 1.5, 95% CI: 1.2-2.1, p = 0.002). This trend was also seen across race/ethnicity and mechanism of injury. CONCLUSIONS: Older males were found to have a higher rate of skull fractures compared to females after sustaining blunt head trauma, mostly due to falls.

How much do preverbal children signal a wish to be fed? Nested case control study comparing weight faltering and healthy infants.

We aimed to 1/develop an observational tool to rate non-verbal cues infants give when being fed 2/test whether these differ between healthy children and those with weight faltering (WF) 3/describe how well these predict whether offered food is eaten. SUBJECTS: and methods: The study used videos of infants eating a standardised meal studied in a case control study nested within the Gateshead Millennium Study (GMS). Infants with weight faltering (WF) were each matched to 2 healthy controls. Half the control videos (N = 28) were used to develop the scale. Food offers were identified and the child's head, eyes, hands, and mouth position/activity rated as signalling a readiness to be fed (engaged), or not (disengaged) as well as whether food was accepted; 5 of these videos were used to assess inter-rater and test-re- test reliability. The scale was then applied to the videos of 28 WF infants (mean age 15.3 months) and 29 remaining controls (mean age 15.8 months) to identify and code all feeding events. RESULTS: test-re-test rates varied from 0.89 for events to 0.74 for head; inter-rater reliability varied from 0.78 for hands to 0.67 for mouth. From 2219 observed interactions, 48% showed at least one engaged element, and 73% at least one disengaged; 67% of interactions resulted in food eaten, with no difference between WF and control. Food was eaten after 73% interactions with any engagement, but also in 62% with disengagement. CONCLUSIONS: Infants were commonly disengaged during meals, but a majority accepted food despite this. Those with weight faltering did not differ compared to healthy controls.

Computed Tomography Imaging of Geriatric Patients with Uncertain Head Trauma.

BACKGROUND: Although clinical decision rules exist for patients with head injuries, no tool assesses patients with unknown trauma events. Patients with uncertain trauma may have unnecessary brain imaging. OBJECTIVE: This study evaluated risk factors and outcomes of geriatric patients with uncertain head injury. METHODS: This prospective cohort study included geriatric patients with definite or uncertain head injury presenting to two emergency departments (EDs). Patients were grouped as definite or uncertain head trauma based on history and physical examination. Outcomes were intracranial hemorrhage (ICH) on head computed tomography (CT), need for neurosurgical intervention, and mortality. Risk factors assessed included gender, alcohol use, tobacco use, history of dementia, anticoagulant use, antiplatelet use, and Glasgow Coma Scale (GCS) score < 15. RESULTS: We enrolled 2905 patients with definite head trauma and 950 with uncertain head trauma. Rates of acute ICH (10.7% vs. 1.5%; odds ratio [OR] 8.02; 95% confidence interval [CI] 4.67-13.76), delayed ICH (0.7% vs. 0.1%; OR 6.58; 95% CI 4.67-13.76), and neurosurgical intervention (1.2% vs. 0.3%; OR 3.74; 95% CI 1.15-12.20) were all higher in definite vs. uncertain head injuries. There were no differences in mortality. Patients with definite trauma had higher rates of ICH with male gender (OR 1.58; 95% CI 1.24-1.99), alcohol use (OR 1.62; 95% CI 1.25-2.09), antiplatelet use (OR 1.84; 95% CI 1.46-2.31), and GCS score < 15 (OR 3.24; 95% CI 2.54-4.13). Patients with uncertain trauma had no characteristics associated with increased ICH. CONCLUSIONS: Although ICH rates among patients with uncertain head trauma was eight times lower than those with definite head trauma, the risk of ICH is high enough to warrant CT imaging of all geriatric patients with uncertain head injury.

Age adjusted D-dimer cutoffs for pulmonary embolism in a geriatric population utilizing a D-dimer unit assay.

BACKGROUND: Age adjusted serum d-dimer (AADD) with clinical decision rules have been utilized to rule out pulmonary embolism (PE) in low-risk patients; however, its use in the geriatric population has been questioned and the use of d-dimer unit (DDU) assay is uncommon. OBJECTIVE: The present study aims to compare the test characteristics of the AADD (age × 5) measured in DDU with the standard cutoff (DDU < 250) and study hospital laboratory's d-dimer cutoff (DDU < 600) in geriatric patients presenting with suspected PE. METHODS: This retrospective study enrolled patients ≥65 years old with suspected PE and d-dimer performed between January 1, 2019 and December 31, 2019 who presented to the emergency department (ED). Charts were reviewed for CTA chest and ventilation perfusion imaging results for PE. Diagnostic parameters for each cutoff were calculated for the primary outcome. RESULTS: 510 patients were included, 20 with PE. There was no significant difference between the sensitivities of AADD (100%, 95% CI: 80-100), standard cutoff (100%, 95% CI: 80-100), and hospital cutoff (90%, 95% CI: 66.9-98.2). The hospital cutoff specificity (22.7%, 95% CI: 17.1-29.3) was significantly greater than the AADD (13.4%, 95% CI: 9.1-19.2) and standard cutoff (10.8%, 95% CI: 7.0-16.3) specificities. CONCLUSIONS: In geriatric patients presenting to the ED with suspected PE, the AADD measured in DDUs maintained sensitivity with improved specificity compared to standard cutoff. In this population, the AADD would have safely reduced imaging by 19% without missing any PEs. AADD remains a valid tool with high sensitivity and negative predictive value in ruling out PE in geriatric patients.

Time from hospital presentation to head imaging in White, Black, and Hispanic geriatric trauma patients.

BACKGROUND: Health care disparities have been shown to negatively affect non-White people sustaining traumas, leading to increased morbidity and mortality. One possible explanation could be delays in emergent medical care. This study aims to assess if a disparity between races exists amongst acutely head-injured geriatric patients, as evidenced by the time it takes from emergency department (ED) presentation to performance of head computerized tomography (CT) imaging. METHODS: A prospective cohort study was conducted from August 15, 2019 to August 14, 2020 at the two trauma centers in a south Florida county covering 1.5 million residents. Patients aged ≥ 65 years who sustained a head injury were identified daily. Patients who had a head injury >24 h prior, sustained penetrating trauma, or were transferred from another hospital were excluded. The primary outcome was time measured between ED presentation and CT head performance. Patients were grouped by race as selected from White, Black, Hispanic, and other. Comparisons were made using ANOVA analysis. RESULTS: 4878 patients were included. 90% were White. The mean times to CT head were 90.3 min for White patients, 98.1 min for Black patients, and 86.6 min for Hispanic patients. There was a significant difference comparing time to CT between the three groups (F = 2.892, p = 0.034). Comparing each group to a combined others, there were no significant differences for White vs non-White (90.3 vs 91.3, F = 0.154, p = 0.695) or Hispanic vs non-Hispanic (86.6 vs 90.5, F = 0.918, p = 0.338); however Black vs non-Black (98.1 vs 89.9, F = 4.828, p = 0.028) was significant. CONCLUSIONS: Geriatric Black patients who sustained head trauma were found to have a longer time from ED presentation to performance of head CT than their non-Black counterparts.

Pelvic Exam Laws in the United States: A Systematic Review.

Laws regulating patient care are an essential component of protecting patients and doctors alike. No studies have previously examined what laws exist regarding pelvic examinations in the United States (US). This study systematically reviews and compares regulation and legislation of pelvic examinations in the U.S. and provides a comprehensive resource to educate clinicians, patients, and lawmakers. Each of the fifty States in the U.S. was included. The primary outcome was existence of any pelvic or rectal exam laws. Data was obtained for the type of examination defined within the law, exceptions to the law, to whom the law applied to, the type of consent required, and to whom the consent applied to. Laws were identified from each of the individual state legislative websites. All sections of each law pertaining to pelvic examination were reviewed and organized by state. Descriptive statistics were performed for each of the variables, including frequencies of each amongst the fifty states. State regulation for pelvic examinations varied from no law or regulation to laws pertaining to pelvic, rectal, prostate, and breast examination performed in any context. As of November 22, 2022, there are twenty states (40%) with pelvic examination laws applying to anesthetized or unconscious patients. Thirteen additional states (26%) have proposed pelvic exam laws. Seventeen states (34%) do not have any laws regarding pelvic examinations. Regulation of pelvic examinations has become an increasingly important issue over the past few years in response to growing concerns of patient autonomy and the ethical issues raised by such sensitive examinations. While pelvic examination laws that balance protection for patient autonomy and the needs of caregivers and educators exist in much of the U.S., more work needs to continue in consultation with physicians and health care providers to ensure that all states have reasonable laws protecting the autonomy of patients while also maintaining quality of care.

The New Serious Incident Response Scheme and the Responsive Regulation of Abuse in Aged Care.

In response to criticisms of the reporting criteria for abuse in aged care that were aired in the Australian Law Reform Commission's Report into Elder Abuse and more recently, the Royal Commission into Aged Care Quality and Safety, a new Serious Incident Response Scheme (SIRS) came into effect in April 2021. The new SIRS expands the definition of elder abuse and removes the exemption for reporting resident on resident abuse where the perpetrator has a diagnosed cognitive impairment. The Aged Care Quality Commission has outlined a comprehensive plan for the new SIRS in line with their model of responsive regulation. This article questions the extent to which the new scheme will improve regulation of reporting and management of resident-to-resident assaults, and reduce abuse in the aged care sector if not accompanied by improvements in the staffing levels and working conditions for the aged care workforce.

A National US Survey of Pediatric Emergency Department Coronavirus Pandemic Preparedness.

OBJECTIVE: We aim to describe the current coronavirus disease 2019 (COVID-19) preparedness efforts among a diverse set of pediatric emergency departments (PEDs) within the United States. METHODS: We conducted a prospective multicenter survey of PED medical director(s) from selected children's hospitals recruited through a long established national research network. The questionnaire was developed by physicians with expertise in pediatric emergency medicine, disaster readiness, human factors, and survey development. Thirty-five children's hospitals were identified for recruitment through an established national research network. RESULTS: We report on survey responses from 25 (71%) of 35 PEDs, of which 64% were located within academic children's hospitals. All PEDs witnessed decreases in non-COVID-19 patients, 60% had COVID-19-dedicated units, and 32% changed their unit pediatric patient age to include adult patients. All PEDs implemented changes to their staffing model, with the most common change impacting their physician staffing (80%) and triaging model (76%). All PEDs conducted training for appropriate donning and doffing of personal protective equipment (PPE), and 62% reported shortages in PPE. The majority implemented changes in the airway management protocols (84%) and cardiac arrest management in COVID patients (76%). The most common training modalities were video/teleconference (84%) and simulation-based training (72%). The most common learning objectives were team dynamics (60%), and PPE and individual procedural skills (56%). CONCLUSIONS: This national survey provides insight into PED preparedness efforts, training innovations, and practice changes implemented during the start of COVID-19 pandemic. Pediatric emergency departments implemented broad strategies including modifications to staffing, workflow, and clinical practice while using video/teleconference and simulation as preferred training modalities. Further research is needed to advance the level of preparedness and support deep learning about which preparedness actions were effective for future pandemics.

Seed traits are pleiotropically regulated by the flowering time gene PERPETUAL FLOWERING 1 (PEP1) in the perennial Arabis alpina.

The life cycles of plants are characterized by two major life history transitions-germination and the initiation of flowering-the timing of which are important determinants of fitness. Unlike annuals, which make the transition from the vegetative to reproductive phase only once, perennials iterate reproduction in successive years. The floral repressor PERPETUAL FLOWERING 1 (PEP1), an ortholog of FLOWERING LOCUS C, in the alpine perennial Arabis alpina ensures the continuation of vegetative growth after flowering and thereby restricts the duration of the flowering episode. We performed greenhouse and garden experiments to compare flowering phenology, fecundity and seed traits between A. alpina accessions that have a functional PEP1 allele and flower seasonally and pep1 mutants and accessions that carry lesions in PEP1 and flower perpetually. In the garden, perpetual genotypes flower asynchronously and show higher winter mortality than seasonal ones. PEP1 also pleiotropically regulates seed dormancy and longevity in a way that is functionally divergent from FLC. Seeds from perpetual genotypes have shallow dormancy and reduced longevity regardless of whether they after-ripened in plants grown in the greenhouse or in the experimental garden. These results suggest that perpetual genotypes have higher mortality during winter but compensate by showing higher seedling establishment. Differences in seed traits between seasonal and perpetual genotypes are also coupled with differences in hormone sensitivity and expression of genes involved in hormonal pathways. Our study highlights the existence of pleiotropic regulation of seed traits by hub developmental regulators such as PEP1, suggesting that seed and flowering traits in perennial plants might be optimized in a coordinated fashion.

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.

Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity. Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool. Design, Setting, and Participants: A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017. Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months. Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events. Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group. Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety. Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.

Worth a Try? Describing the Experiences of Families during the Course of Care in the Neonatal Intensive Care Unit When the Prognosis is Poor.

OBJECTIVE: To determine how parents of infants in the neonatal intensive care unit with a poor or uncertain prognosis view their experience, and whether they view their choices as "worth it," regardless of outcome. STUDY DESIGN: Parents of eligible neonates at 2 institutions underwent audiotaped, semistructured interviews while their infants were still in the hospital and then again 6 months to 1 year after discharge or death. Interviews were transcribed and data were analyzed using thematic analysis. Two authors independently reviewed and coded each interview and discrepancies were resolved by consensus. RESULTS: Twenty-six families were interviewed in the initial group and 17 families were interviewed in the follow-up group. The most common themes identified included realism about death (24 families), appreciation for the infant's care team (23 families), and optimism and hope (22 families). Overall themes were very similar across both centers, and among parents of infants who died and those who survived. Themes of regret, futility, distrust of care team, and infant pain were brought up infrequently or not at all. CONCLUSIONS: No family believed that the care being provided to their infant was futile; rather, parents were grateful for the care provided to their infant, regardless of outcome. Even in the case of a poor prognosis or the death of an infant, families in our study viewed their infant's stay in the neonatal intensive care unit favorably.

Targeted Ocular Drug Delivery with Pharmacokinetic/Pharmacodynamic Considerations.

The development of ophthalmic drug delivery systems is a long and comprehensive process including research, nonclinical, and clinical development stages. It is critical to understand the similarity and differences between animal models and patients. There are many anatomically and physiologically important parameters for targeted drug delivery into eyes. This paper reviews the constraints to various routes of ocular drug delivery and discusses the respective pharmacokinetic considerations, to lay the foundation for formulation approaches pharmaceutical scientists can use to maximize successful drug delivery for each route. The overall goal is to give both researchers and drug developers a better understanding of ocular drug delivery and offer tools to successfully develop new medicines that will fulfil unmet medical needs and improve patients' quality of life.

A quick and simple benchtop vortex egg-disruption approach for the molecular diagnosis of Fasciola hepatica from ruminant faecal samples.

Commonly employed diagnostic methods for Fasciola spp., such as a traditional sedimentation and faecal egg count, or a commercially available coprological ELISA, have limitations in their sensitivity or ability to differentiate species. A reliable DNA isolation method coupled with real-time PCR addresses these issues by providing highly sensitive and quantitative molecular diagnosis from faecal samples. The current study evaluated a standard benchtop vortex for F. hepatica egg disruption in sheep and cattle faecal samples and determined the minimum faecal egg load required for a positive result from un-concentrated (raw) faecal samples. The minimum faecal egg load for a positive real-time PCR result from 150 mg raw faecal sample was 10 and 20 eggs per gram for sheep and cattle, respectively. No significant difference (P = 0.4467) between disruptions on a benchtop vortex for 5 or 10 min was observed when compared to 40 s of disruption at 6.0 m/s in a benchtop homogeniser.

Bimatoprost sustained-release intracameral implant reduces episcleral venous pressure in dogs.

OBJECTIVE: To determine the effect of a bimatoprost sustained-release intracameral implant (Bimatoprost SR) on episcleral venous pressure (EVP) in normal dogs. METHODS: Normotensive beagle dogs were randomized to receive Bimatoprost SR 30 µg (n = 7) or sham injection (needle insertion only, n = 7) in one eye on day 1. EVP was measured with an episcleral venomanometer through day 65. Episcleral aqueous outflow vessels were identified using fluorescence imaging following intracameral injection of indocyanine green in one additional animal. A separate cohort of dogs that had been trained for conscious intraocular pressure (IOP) measurements received Bimatoprost SR 30 µg (n = 8) in one eye; IOP was evaluated through day 66. RESULTS: Baseline mean EVP was 10.0 mmHg in the Bimatoprost SR group and 10.4 mmHg in the sham group. Eyes treated with Bimatoprost SR exhibited a transient increase in mean EVP that peaked at day 8, followed by a decrease to levels below baseline. From day 29 to day 65, the change in mean EVP from baseline ranged from -2.4 to -3.9 mmHg (P < 0.05 vs. sham). Baseline mean IOP in eyes treated with Bimatoprost SR was 14.9 mmHg, and a steady IOP reduction was maintained through day 66. Bimatoprost SR-treated eyes exhibited a selective, sustained dilation of aqueous outflow vessels that was not observed in sham-treated eyes. CONCLUSIONS: In normal dogs, Bimatoprost SR was associated with a transient increase in EVP followed by a sustained decrease. Changes in EVP were accompanied by a sustained dilation of aqueous outflow vessels.

Advances in Imaging Specific Mediators of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown, but it is thought to involve a hypersensitive immune response to environmental antigens, including the microbiota. Diagnosis and monitoring of IBD is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) of inflammatory mediators, and how these developments may be applied to the microbiota.

Iatrogenic emergency medicine procedure complications and associated trouble-shooting strategies.

PURPOSE: The purpose of this paper is to provide a consolidated reference for the acute management of selected iatrogenic procedural injuries occurring in the emergency department (ED). DESIGN/METHODOLOGY/APPROACH: A literature search was performed utilizing PubMed, Scopus, Web of Science and Google Scholar for studies through March of 2017 investigating search terms "iatrogenic procedure complications," "error management" and "procedure complications," in addition to the search terms reflecting case reports involving the eight below listed procedure complications. FINDINGS: This may be particularly helpful to academic faculty who supervise physicians in training who present a higher risk to cause such injuries. ORIGINALITY/VALUE: Emergent procedures performed in the ED present a higher risk for iatrogenic injury than in more controlled settings. Many physicians are taught error-avoidance rather than how to handle errors when learning procedures. There is currently very limited literature on the error management of iatrogenic procedure complications in the ED.

Acute colitis chronically alters immune infiltration mechanisms and sensory neuro-immune interactions.

OBJECTIVE: Little is understood regarding how disease progression alters immune and sensory nerve function in colitis. We investigated how acute colitis chronically alters immune recruitment and the impact this has on re-activated colitis. To understand the impact of disease progress on sensory systems we investigated the mechanisms underlying altered colonic neuro-immune interactions after acute colitis. DESIGN: Inflammation was compared in mouse models of health, acute tri-nitrobenzene sulphonic acid (TNBS) colitis, Remission and Reactivated colitis. Cytokine concentrations were compared by ELISA in-situ and in explanted colon tissue. Colonic infiltration by CD11b/F4-80 macrophage, CD4 THELPER (TH) and CD8 TCYTOTOXIC (TC) and α4ß7 expression on mesenteric lymph node (MLN) TH and TC was determined by flow cytometry. Cytokine and effector receptor mRNA expression was determined on colo-rectal afferent neurons and the mechanisms underlying cytokinergic effects on high-threshold colo-rectal afferent function were investigated using electrophysiology. RESULTS: Colonic damage, MPO activity, macrophage infiltration, IL-1ß and IL-6 concentrations were lower in Reactivated compared to Acute colitis. TH infiltration and α4ß7 expression on TH MLN was increased in Remission but not Acute colitis. IFN-γ concentrations, TH infiltration and α4ß7 expression on TH and TC MLN increased in Reactivated compared to Acute colitis. Reactivated explants secreted more IL-1ß and IL-6 than Acute explants. IL-6 and TNF-α inhibited colo-rectal afferent mechanosensitivity in Remission mice via a BKCa dependent mechanism. CONCLUSIONS: Acute colitis persistently alters immune responses and afferent nerve signalling pathways to successive episodes of colitis. These findings highlight the complexity of viscero-sensory neuro-immune interactions in painful remitting and relapsing diseases.