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Wiebke Bartels, Simon Adamson, Lisa Leung, Don D Sin, Stephan F van Eeden Centre for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC, Canada Rationale: Readmissions are common following acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and are partially responsible for increased morbidity and mortality in COPD. Numerous factors have been shown to predict readmission of patients previously admitted to hospital for AECOPD; however, factors related to readmission in patients who are triaged in emergency departments (EDs) and sent directly home are poorly understood. We postulate that patients seen in the ED for AECOPD and directly sent home have a high readmission rate, and we suspect that inadequate management and follow-up contribute to this high readmission rate. Methods: We conducted a 1-year retrospective study of all patients seen in the ED for AECOPD at an inner-city tertiary care hospital; 30- and 90-day readmission rates for COPD and all-cause admissions to the ED and hospital were determined. Patients discharged directly home from the ED were compared with those admitted to hospital for management. Patient, treatment, and system variables that could potentially impact readmission were documented. Multivariate Poisson regression models were used to determine which factors predicted readmissions. Results: The readmission rates in the ED group (n=240) were significantly higher than that in the hospitalized group (n=271): 1) the 90-day ED readmissions (1.29 vs 0.51, p

Background 13Carbon urea breath testing is reliable to detect current infection with Helicobacter pylori but has been reported to be of limited value in selected patients with atrophic body gastritis or acid-lowering medication. Aim To evaluate the accuracy of 13carbon urea breath testing for H. pylori detection in 20 asymptomatic patients with histologically confirmed atrophic body gastritis in a primary care setting. Methods 13Carbon urea breath testing and serology were compared with H. pylori culture of a corpus biopsy as reference test. Results All tests were in agreement in 12 patients, being all positive in six and all negative in six. One patient was positive for serology and culture but negative for 13carbon urea breath testing, five patients had only positive serology and two patients had only positive 13carbon urea breath testing. 13Carbon urea breath testing showed an accuracy with culture of 85% and anti- H. pylori serology with culture of 75%. 13Carbon urea breath testing carried out in patients with positive serology showed an accuracy of 92%. Receiver operating characteristic curve analysis of 13carbon urea breath testing shows optimal discrimination at the prescribed cut-off value. Conclusions 13Carbon urea breath testing can be used as diagnostic H. pylori test in asymptomatic patients with atrophic body gastritis, preferably in addition to serology, to select subjects for anti- H. pylori therapy. [ABSTRACT FROM AUTHOR]

Abdulmajeed Alshabanat,1 Michael C Otterstatter,2,3 Don D Sin,4,5 Jeremy Road,5,6 Carmen Rempel,6 Jane Burns,6 Stephan F van Eeden,4,5 JM FitzGerald5–7 On behalf of the COPD Transition Team Program 1Department of Experimental Medicine, University of British Columbia, 2British Columbia Centre for Disease Control, 3School of Population and Public Health, 4Department of Medicine, Centre for Heart Lung Innovation, St Paul’s Hospital, 5Division of Respirology, Department of Medicine, 6Department of Medicine, Faculty of Medicine, Institute for Heart and Lung Health, University of British Columbia, 7Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Institute, Vancouver, BC, Canada Background: COPD accounts for the highest rate of hospital admissions among major chronic diseases. COPD hospitalizations are associated with impaired quality of life, high health care utilization, and poor prognosis and result in an economic and a social burden that is both substantial and increasing.Aim: The aim of this study is to determine the efficacy of a comprehensive case management program (CCMP) in reducing length of stay (LOS) and risk of hospital admissions and readmissions in patients with COPD.Materials and methodology: We retrospectively compared outcomes across five large hospitals in Vancouver, BC, Canada, following the implementation of a systems approach to the management of COPD patients who were identified in the hospital and followed up in the community for 90 days. We compared numbers, rates, and intervals of readmission and LOS during 2 years of active program delivery compared to 1 year prior to program implementation.Results: A total of 1,564 patients with a clinical diagnosis of COPD were identified from 2,719 hospital admissions during the 3 years of study. The disease management program reduced COPD-related hospitalizations by 30% and hospitalizations for all causes by 13.6%. Similarly, the rate of readmission for all causes showed a significant decline, with hazard ratios (HRs) of 0.55 (year 1) and 0.51 (year 2) of intervention (P

Study Objectives: To examine the peripheral effects of BAL on the neutrophil counts and cytokine levels in the circulation.Design and Methods: WBC counts and plasma cytokines were measured before and 4 h after fiberoptic bronchoscopy (FOB) without further interventions (n = 6), or combined with BAL in normal volunteer subjects (n = 6), and in patients with bacterial pneumonia (n = 4). The bronchus of the right middle lobe was wedged, and three 50-mL aliquots of sterile saline solution was instilled. There was no endotoxin contamination in the saline solution or the fluid obtained through the working channel of bronchoscope.Results: In volunteers, peripheral WBC counts and the number of nonsegmented and segmented neutrophils increased after the BAL procedure (p < 0.05) associated with the increase in plasma concentration (mean +/- SEM) of interleukin (IL)-6 (0.99 +/- 0.32 pg/mL before BAL and 20.38 +/- 13.42 pg/mL after BAL; p < 0.05) and granulocyte colony-stimulating factor (G-CSF; 14.1 +/- 1.7 pg/mL before BAL and 38.5 +/- 9.7 pg/mL after BAL; p < 0.05). The increase in WBC counts and neutrophil counts was positively correlated to the increase in IL-6 (p < 0.05) and the increase in G-CSF (p < 0.05). In patients with pneumonia, IL-6 and G-CSF levels were higher after BAL than in normal volunteer subjects (p < 0.05). There was no increase in plasma concentration of IL-1beta, tumor necrosis factor-alpha, or IL-8 after BAL in normal volunteer subjects or in patients with pneumonia. FOB without BAL did not increase the WBC count, neutrophil count, or plasma cytokine levels.Conclusion: The BAL procedure increases the number of WBCs, and segmented and nonsegmented neutrophils in the peripheral circulation as well as circulating IL-6 and G-CSF levels. [ABSTRACT FROM AUTHOR]

Simon L Adamson,1 Jane Burns,1,2 Pat G Camp,1,2 Don D Sin,1,3 Stephan F van Eeden1,31The Centre for Heart Lung Innovation, St Paul’s Hospital, University of British Columbia, 2Department of Physical Therapy, 3Division of Respirology, Department of Medicine, University of British Columbia, Vancouver, BC, CanadaBackground: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) increase COPD morbidity and mortality and impose a great burden on health care systems. Early readmission following a hospitalization for AECOPD remains an important clinical problem. We examined how individualized comprehensive care influences readmissions following an index hospital admission for AECOPD.Methods: We retrospectively reviewed data of patients admitted for AECOPD to two inner-city teaching hospitals to determine the impact of a comprehensive and individualized care management strategy on readmissions for AECOPD. The control group consisted of 271 patients whose index AECOPD occurred the year before the comprehensive program, and the experimental group consisted of 191 patients who received the comprehensive care. The primary outcome measure was the total number of readmissions in 30- and 90-day postindex hospitalizations. Secondary outcome measures included the length of time between the index admission and first readmission and all-cause mortality.Results: The two groups were similar in terms of age, sex, forced expiratory volume in 1 second, body mass index (BMI), pack-years, and the number and types of comorbidities. Comprehensive care significantly reduced 90-day readmission rates in females (P=0.0205, corrected for age, BMI, number of comorbidities, substance abuse, and mental illness) but not in males or in the whole group (P>0.05). The average times between index admission and first readmission were not different between the two groups. Post hoc multivariate analysis showed that substance abuse (P

Abstract Background Bone marrow (BM)-derived progenitor cells have been shown to have the potential to differentiate into a diversity of cell types involved in tissue repair. The characteristics of these progenitor cells in pneumonia lung is unknown. We have previously shown that Streptococcus pneumoniae induces a strong stimulus for the release of leukocytes from the BM and these leukocytes preferentially sequester in the lung capillaries. Here we report the behavior of BM-derived lineage negative progenitor cells (Lin- PCs) during pneumococcal pneumonia using quantum dots (QDs), nanocrystal fluorescent probes as a cell-tracking technique. Methods Whole BM cells or purified Lin- PCs, harvested from C57/BL6 mice, were labeled with QDs and intravenously transfused into pneumonia mice infected by intratracheal instillation of Streptococcus pneumoniae. Saline was instilled for control. The recipients were sacrificed 2 and 24 hours following infusion and QD-positive cells retained in the circulation, BM and lungs were quantified. Results Pneumonia prolonged the clearance of Lin- PCs from the circulation compared with control (21.7 ± 2.7% vs. 7.7 ± 0.9%, at 2 hours, P < 0.01), caused preferential sequestration of Lin- PCs in the lung microvessels (43.3 ± 8.6% vs. 11.2 ± 3.9%, at 2 hours, P < 0.05), and homing of these cells to both the lung (15.1 ± 3.6% vs. 2.4 ± 1.2%, at 24 hours, P < 0.05) and BM as compared to control (18.5 ± 0.8% vs. 9.5 ± 0.4%, at 24 hours, P < 0.01). Very few Lin- PCs migrated into air spaces. Conclusion In this study, we demonstrated that BM-derived progenitor cells are preferentially sequestered and retained in pneumonic mouse lungs. These cells potentially contribute to the repair of damaged lung tissue.

Abstract Background Studies from our laboratory have shown that human alveolar macrophages (AM) and bronchial epithelial cells (HBEC) exposed to ambient particles (PM10) in vitro increase their production of inflammatory mediators and that supernatants from PM10-exposed cells shorten the transit time of monocytes through the bone marrow and promote their release into the circulation. Methods The present study concerns co-culture of AM and HBEC exposed to PM10 (EHC-93) and the production of mediators involved in monocyte kinetics measured at both the mRNA and protein levels. The experiments were also designed to determine the role of the adhesive interaction between these cells via the intercellular adhesion molecule (ICAM)-1 in the production of these mediators. Results AM/HBEC co-cultures exposed to 100 μg/ml of PM10 for 2 or 24 h increased their levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, macrophage inflammatory protein (MIP)-1β, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6 and ICAM-1 mRNA, compared to exposed AM or HBEC mono-cultures, or control non-exposed co-cultures. The levels of GM-CSF, M-CSF, MIP-1β and IL-6 increased in co-cultured supernatants collected after 24 h exposure compared to control cells (p < 0.05). There was synergy between AM and HBEC in the production of GM-CSF, MIP-1β and IL-6. But neither pretreatment of HBEC with blocking antibodies against ICAM-1 nor cross-linking of ICAM-1 on HBEC blocked the PM10-induced increase in co-culture mRNA expression. Conclusion We conclude that an ICAM-1 independent interaction between AM and HBEC, lung cells that process inhaled particles, increases the production and release of mediators that enhance bone marrow turnover of monocytes and their recruitment into tissues. We speculate that this interaction amplifies PM10-induced lung inflammation and contributes to both the pulmonary and systemic morbidity associated with exposure to air pollution.

Objective: To determine whether children born with a cleft palate ± lip (CP ± L) and additional congenital differences (ACDs - including 'Congenital malformations and deformations' as coded in ICD-10), are less likely to meet the three national speech outcome standards at age five compared to children with CP ± L and no ACDs., Design: An observational study, utilizing national data from the UK Cleft Registry and Audit NEtwork (CRANE) Database linked to national administrative data of hospital admissions., Setting: National Health Service, England., Patients: 2191 children (993 female, 1198 male) with CP ± L, born 2006-2012 in England, with complete speech data and consent to data linkage., Outcome Measure: Perceptual speech analysis utilised the Cleft Audit Protocol for Speech - Augmented (CAPS-A) rating and United Kingdom National Speech Outcome Standards (Speech Standard 1 (SS1), Speech Standard 2a (SS2a) and Speech Standard 3 (SS3))., Results: Of 2191 children, 759 (35%) had at least one ACD. Presence of one ACD did not significantly impact speech outcomes but two or more ACDs reduced the odds of achieving all three speech standards: SS1 aOR 0.602 (CI 0.45-0.82, P  = .002), SS2a aOR 0.563 (CI 0.41-0.77, P  = .001), SS3 aOR 0.606 (0.43-0.84, P  = .003). When exploring ACDs by ICD-10 groupings, congenital malformations of the 'Eye, ear, face and neck', 'Circulatory system', 'Digestive system', 'Musculoskeletal system' and 'Other congenital malformations' reduced a child's odds of achieving the speech standards., Conclusions: ACDs, in the absence of a known syndrome, have a significant impact on speech outcome at age five. Incorporating these factors into risk-adjustment models for service level outcome reporting is recommended., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Timing of Primary Surgery (TOPS) trial was published August 2023 in the New England Journal of Medicine and is a milestone achievement for a study focused on cleft palate. Due to the complexity of outcome reporting in cleft and the rarity of such comparative trials, TOPS presents a useful opportunity to critically review the design, analysis and reporting strategies utilised. This perspective article focused on the inclusion of participants, the choice of the primary outcome measure and the analysis of ordinal data within the trial. Considerations for future comparative studies in cleft care are discussed., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cleft care services in the UK have been nationally funded since centralisation 25 years ago and during this time have been able to demonstrate improved clinical outcomes. Integrated care systems have been introduced into legislature as part of the Health Care Act of 2022 and will be responsible for the paradigm shift of allocating funds on a regional basis for cleft care services in England from 2024. The proposed population-based funding formulas present an opportunity to improve current inequities in cleft care, including access to speech therapy and adult services. However, the regional footprint of integrated care systems does not align with that of the centralised cleft service system and represents a threat to the standardised patient-centred care that has taken two decades to build. Awareness needs to be raised so that cleft care providers can proactively adapt to this mandatory change to service funding to ensure that clinical standards are maintained and continue to improve., (© 2024. The Author(s), under exclusive licence to the British Dental Association.)

Up to 30% of colorectal cancers (CRCs) develop from sessile serrated lesions (SSLs). Within the serrated neoplasia pathway, at least two principally distinct oncogenetic routes exist generating microsatellite-stable and microsatellite-instable CRCs, respectively. Aberrant DNA methylation (DNAm) is found early in the serrated pathway and might play a role in both oncogenetic routes. We studied a cohort of 23 SSLs with a small focus (<10 mm) of dysplasia or cancer, 10 of which were MLH1 deficient and 13 MLH1 proficient. By comparing, for each SSL, the methylation status of (1) the region of dysplasia or cancer (SSL-D), (2) the nondysplastic SSL (SSL), and (3) adjacent normal mucosa, differentially methylated probes (DMPs) and regions (DMRs) were assessed both genome-wide as well as in a tumor-suppressor gene-focused approach. By comparing DNAm of MLH1-deficient SSL-Ds with their corresponding SSLs, we identified five DMRs, including those annotating for PRDM2 and, not unexpectedly, MLH1. PRDM2 gene promotor methylation was associated with MLH1 expression status, as it was largely hypermethylated in MLH1-deficient SSL-Ds and hypomethylated in MLH1-proficient SSL-Ds. Significantly increased DNAm levels of PRDM2 and MLH1, in particular at 'critical' MLH1 probe sites, were to some extent already visible in SSLs as compared to normal mucosa (p = 0.02, p = 0.01, p < 0.0001, respectively). No DMRs, nor DMPs, were identified for SSLs destined to evolve into MLH1-proficient SSL-Ds. Our data indicate that, within both arms of the serrated CRC pathway, the majority of the epigenetic alterations are introduced early during SSL formation. Promoter hypermethylation of PRDM2 and MLH1 on the other hand specifically initiates in SSLs destined to transform into MLH1-deficient CRCs suggesting that the fate of SSLs may not necessarily result from a stochastic process but possibly is already imprinted and predisposed., (© 2024 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)