Eosinophil recruitment to nasal nerves after allergen challenge in allergic rhinitis.

In allergen challenged animal models, eosinophils localize to airway nerves leading to vagally-mediated hyperreactivity. We hypothesized that in allergic rhinitis eosinophils recruited to nasal nerves resulted in neural hyperreactivity. Patients with persistent allergic rhinitis (n=12), seasonal allergic rhinitis (n=7) and controls (n=10) were studied. Inferior nasal turbinate biopsies were obtained before, 8 and 48h after allergen challenge. Eight hours after allergen challenge eosinophils localized to nerves in both rhinitis groups; this was sustained through 48h. Bradykinin challenge, with secretion collection on the contralateral side, was performed to demonstrate nasal nerve reflexes. Twenty fourhours after allergen challenge, bradykinin induced a significant increase in secretions, indicating nasal hyperreactivity. Histological studies showed that nasal nerves expressed both vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 26 (CCL-26). Hence, after allergen challenge eosinophils are recruited and retained at nerves and so may be a mechanism for neural hyperreactivity.

To assess the effects of cross-education on strength and motor function in post stroke rehabilitation: a systematic literature review and meta-analysis.

BACKGROUND: Cross-education refers to the increase in motor output of the untrained limb following unilateral training of the opposite limb. Cross education has been shown to be beneficial in clinical settings. OBJECTIVES: This systematic literature and meta-analysis aims to assess the effects of cross-education on strength and motor function in post stroke rehabilitation. DATA SOURCES: MEDLINE, CINAHL, Cochrane Library, PubMed, PEDro, Web of Science, ClinicalTrails.gov and Cochrane Central registers were searched up to 1st October 2022. STUDY SELECTION: Controlled trials using unilateral training of the less affected limb in individuals diagnosed with stroke and English language. DATA SYNTHESIS: Methodological quality was assessed using Cochrane Risk-of-Bias tools. Quality of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation. Meta-analyses were performed using RevMan 5.4.1. RESULTS: Five studies capturing 131 participants were included in the review and three studies capturing 95 participants were included in the meta-analysis. Cross education was shown to have a statistically and clinically significant effect on upper limb strength (p < 0.003; SMD 0.58; 95% CI 0.20-0.97; n = 117) and upper limb function (p = 0.04; SMD 0.40; 95% CI 0.02-0.77; n = 119). LIMITATIONS: Small number of studies, with all studies identified as having some risk of bias. Quality of evidence graded 'low' due to limitations and imprecision. CONCLUSION: Cross education may be beneficial in improving strength and motor function in the more affected upper limb post stroke. Further studies are needed as the research into the benefits of cross education in stroke rehabilitation is still limited. Systematic Review Registration Number: PROSPERO (CRD42020219058).

Rare presentation of Brunner's gland adenoma: another differentiation in patients with recurrent "idiopathic" pancreatitis.

BACKGROUND: Brunner's gland adenoma (BGA) is an unusual benign neoplasm arising from Brunner's glands in the duodenum. When symptomatic it presents either with duodenal obstruction or bleeding. However, pancreatitis secondary to ampullary obstruction from a BGA is very rare. METHODS: A 23-year-old female presented with recurrent episodes of "idiopathic" pancreatitis. She was extensively investigated and was found to have a large polypoid BGA, intermittently obstructing the ampulla. This created a ball-valve effect causing secondary intermittent obstruction of the pancreatic duct resulting in pancreatitis. The condition was cured surgically, through transduodenal excision of the BGA. We reviewed the surgical literature pertaining to these unusual and similar causes of obstructive pancreatitis, not related to gallstones. RESULTS: BGA of the duodenum is a rare cause of pancreatitis. Extensive investigations should be carried out in all cases of unexplained pancreatitis before classifying the condition as "idiopathic". Discovery of a lesion of this nature gives an opportunity to provide a permanent surgical cure. CONCLUSIONS: BGA adds an unusual etiology for pancreatitis. All patients with pancreatitis should undergo extensive investigations before being termed "idiopathic". Surgical excision of the BGA provides a definitive curative treatment for the adenoma and pancreatitis.

Sociodemographic variables as predictors of adverse outcome in SARS-CoV-2 infection: an Irish hospital experience.

INTRODUCTION: Our hospital found itself at the epicentre of the Irish COVID-19 pandemic. We describe the organisational challenges faced in managing the surge and identified risk factors for mortality and ICU admission among hospitalised SARS-CoV-2-infected patients. METHODS: All hospitalised SARS-CoV-2 patients diagnosed between March 13 and May 1, 2020, were included. Demographic, referral, deprivation, ethnicity and clinical data were recorded. Multivariable regression, including age-adjusted hazard ratios (HR (95% CI), was used to explore risk factors associated with adverse outcomes. RESULTS: Of 257 inpatients, 174 were discharged (68%) and 39 died (15%) in hospital. Two hundred three (79%) patients presented from the community, 34 (13%) from care homes and 20 (8%) were existing inpatients. Forty-five percent of community patients were of a non-Irish White or Black, Asian or minority ethnic (BAME) population, including 34 Roma (13%) compared to 3% of care home and 5% of existing inpatients, (p < 0.001). Twenty-two patients were healthcare workers (9%). Of 31 patients (12%) requiring ICU admission, 18 were discharged (58%) and 7 died (23%). Being overweight/obese HR (95% CI) 3.09 (1.32, 7.23), p = 0.009; a care home resident 2.68 (1.24, 5.6), p = 0.012; socioeconomically deprived 1.05 (1.01, 1.09), p = 0.012; and older 1.04 (1.01, 1.06), p = 0.002 were significantly associated with death. Non-Irish White or BAME were not significantly associated with death 1.31 (0.28, 6.22), p = 0.63 but were significantly associated with ICU admission 4.38 (1.38, 14.2), p = 0.014 as was being overweight/obese 2.37 (1.37, 6.83), p = 0.01. CONCLUSION: The COVID-19 pandemic posed unprecedented organisational issues for our hospital resulting in the greatest surge in ICU capacity above baseline of any Irish hospital. Being overweight/obese, a care home resident, socioeconomically deprived and older were significantly associated with death, while ethnicity and being overweight/obese were significantly associated with ICU admission.

Safety of peripheral administration of vasopressor medications: A systematic review.

OBJECTIVE: Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of vasoconstrictive medications. Recent studies have suggested that vasopressor administration via peripheral intravenous catheters (PiVCs) may be a feasible and safe alternative. This systematic review evaluates the safety of delivering vasopressor medications via PiVCs. METHODS: We performed a systematic review to assess the frequency of complications associated with the delivery of vasopressors via PiVCs. A literature search for prospective and retrospective studies of vasopressor infusions in adults was performed. We included studies of continuous infusions of vasopressor medications (noradrenaline, adrenaline, metaraminol, phenylephrine, dopamine and vasopressin) delivered via a PiVCs that included at least 20 patients. Data on patient factors, cannulation approach, monitoring protocols, vasopressor dosing and dilutions and adverse events were collected and summarised. RESULTS: Seven studies were identified that fulfilled the inclusion criteria, including 1382 patients. No study fulfilled all of the validity criteria. Noradrenaline was the most commonly administered agent (n = 702 episodes of administration), followed by phenylephrine (n = 546), dopamine (n = 108), metaraminol (n = 74) and vasopressin and adrenaline (<5 patients). Mean duration of infusion was 22 h (95% confidence interval [CI] 8-36 h). Extravasation occurred in 3.4% (95% CI 2.5-4.7%) of patients. There were no reported episodes of tissue necrosis or limb ischaemia. All extravasation events were successfully managed conservatively or with vasodilatory medications. CONCLUSIONS: Reports of the administration of vasopressors via PiVCs, when given for a limited duration, under close observation, suggest that extravasation is uncommon and is unlikely to lead to major complications.

Chronic hepatitis C infection and sicca syndrome: a clear association with HLA DQB1*02.

BACKGROUND: Hepatitis C virus infection is a major cause of nonA, nonB hepatitis worldwide. A high prevalence of immunological abnormalities has been shown to occur in patients with chronic hepatitis C virus infection. AIM: The aim of this study was to assess the development of sicca syndrome in a cohort of patients infected with a single strain of hepatitis C virus, namely genotype 1b, and correlate this with viral persistence and human leukocyte antigen type of the patients. METHODS: Ninety-five patients infected with the single strain hepatitis C virus were used in this study, 32 of whom were polymerase chain reaction-negative and 63 polymerase chain reaction-positive. Patient details were reviewed for symptoms consistent with sicca syndrome. Human leukocyte antigen class I (A, B and C) and class II (DRB and DQB1) typing was performed on all patients. Auto-antibodies were also measured. RESULTS: DQB1*02 was highly significantly associated with viral persistence (P<0.0001). Nineteen of 21 patients with sicca syndrome were hepatitis C virus-polymerase chain reaction-positive demonstrating a strong association with viral persistence and the development of the syndrome. Human leukocyte antigen DQB1*02 was significantly associated with the development of sicca syndrome, P=0.02. CONCLUSION: The development of autoimmune disease in patients with chronic hepatitis C virus infection depends on the interaction of multiple factors. This study suggests that important factors in this process are viral persistence and human leukocyte antigen type of the patients.

Hepatic manifestations of gastrointestinal diseases. Inflammatory bowel disease, celiac disease, and Whipple's disease.

The gastrointestinal tract and the liver are closely related anatomically, physiologically, and pathologically. Some disease associations are well documented, such as PSC in association with IBD, whereas others are less well defined. A heightened clinical suspicion is required in these patients who do not present with the classical disease associations. The underlying causes of their diseases are the subject of much debate and research, and their diagnosis and management remain challenging.

Nonsteroidal anti-inflammatory drug-induced diaphragms and ulceration in the colon.

The toxic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the small bowel have been reported extensively. A growing number of reports of toxic effects of NSAIDs on the colon have appeared recently. The clinical presentation, endoscopic appearances and histological findings of so-called NSAID colopathy are quite varied, as illustrated by a series of four patients described in this report. Presenting symptoms and signs in this series include iron-deficiency anaemia and crampy abdominal pain, but alteration of bowel habit, weight loss, and even nausea and vomiting have also been described. One patient in this series has large-bowel diaphragms, considered by some to be pathognomonic of NSAID effects. Each of the four patients had right-sided colonic lesions only, possibly supporting a direct toxic effect of NSAIDs. Management usually involves simply stopping the offending NSAID. A review of the literature on this under-recognized entity is presented.

"Decentering" reflects psychological flexibility in people with chronic pain and correlates with their quality of functioning.

OBJECTIVE: Acceptance and mindfulness-based treatments for chronic pain attempts to alter the impact of pain-related thoughts and feelings on behavior without necessarily changing the thoughts and feelings themselves. A process called "decentering" appears relevant to these treatments because it includes the capacity to observe thoughts and feelings from a detached perspective, as transient events in the mind, that do not necessarily reflect reality or the self. This study examines relations of decentering with other processes related to "psychological flexibility" and the daily functioning of people with chronic pain. METHOD: Consecutive adults seeking treatment for chronic pain (N = 150) provided data for the study by completing a set of measures, including a measure of decentering, the Experiences Questionnaire (EQ). RESULTS: The EQ demonstrated adequate internal consistency reliability, and correlation results supported its validity. Decentering significantly correlated with anxiety, depression, and psychosocial disability. In multiple regression analyses it added a significant increment to explained variance in the prediction of depression and psychosocial disability. Across all measures of functioning, pain acceptance and decentering combined accounted for an average of 23.6% of variance while pain accounted for 2.5%. CONCLUSIONS: People with chronic pain may benefit from the capacity to contact their thoughts and feelings from a perspective as a "separate observer," to see them as transient, and to experience them as cognitively "defused."

Activated eosinophils in association with enteric nerves in inflammatory bowel disease.

Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related to disease activity. We hypothesized that interactions between eosinophils and nerves contribute to neural dysfunction in IBD. Tissue from patients with intractable IBD, endoscopic biopsies from patients with steroid responsive IBD, both when active and quiescent, and control tissue were studied. Immunohistochemical studies showed that eosinophils localize to nerves in the mucosal layer of patients with Crohn's disease (CD) (p<0.001) and ulcerative colitis (UC), (p<0.01). Eosinophils localized to substance P and choline acetyltransferase (ChAT) immunostained nerves. Real time PCR of laser capture micro-dissected enteric ganglia demonstrated Intercellular Adhesion Molecule 1 (ICAM-1) mRNA was increased 7-fold in UC (n = 4), (p = 0.03), and 10-fold in CD (n = 3), (p = 0.05). Compared with controls, eotaxin-3 (CCL-26) mRNA was increased 9-fold in UC (p = 0.04) and 15-fold in CD (p = 0.06). Eosinophil numbers correlated with disease activity, while deposition of major basic protein (MBP) and eosinophil Transforming Growth Factor ß-1 (TGFß-1) expression were seen in therapeutically responsive disease. These data indicate a significant localization of eosinophils to nerves in IBD, mediated through neurally expressed ICAM-1 and eotaxin-3. This cell/neural interaction may influence the function of nerves and contribute to symptoms in IBD.

The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease.

BACKGROUND & AIMS: The pregnane X receptor (PXR) regulates an array of genes involved in the response to xenobiotics. Evidence from several studies suggests that xenobiotic metabolism may play a role in inflammatory bowel disease (IBD) and that low levels of PXR may be associated with disease expression. The aim of this study was to investigate the association of functional polymorphisms of the PXR encoding gene (NR1I2) with disease in IBD populations. METHODS: This was a case-control study examining 8 NR1I2 single nucleotide polymorphisms (SNPs) previously associated with altered activity of PXR-regulated genes in an Irish cohort including 422 patients with IBD and 350 ethnically matched controls. RESULTS: We showed significant associations of NR1I2 with IBD, Crohn's disease (CD), and ulcerative colitis (UC) groups compared with a control population for SNPs -23585 (IBD: P = .000008; odds ratio [OR], 1.62; 95% confidence interval [CI], 1.31-2.00) and -24381 (IBD: P = .0002; OR, 1.50; 95% CI, 1.21-1.84). SNPs 7635 (P = .0008) and 8055 (P = .007) were found to be associated with IBD and CD but not UC. Risk of IBD is strongly correlated to genotype at these sites, especially for the -25385CC genotype (P = .00001; OR, 2.92; 95% CI, 1.87-4.66). We also show specific correlations of IBD phenotype with genotypes and haplotypes in the patient group. CONCLUSIONS: These results show that genetic variation in the PXR encoding gene, which has been associated with altered activity of PXR, is strongly associated with susceptibility to IBD, CD, and UC.