Comprehensive geriatric assessment as an essential tool to register or update DNR codes in a tertiary care hospital.

PURPOSE: To investigate the prevalence of Do not Resuscitate (DNR) code registration in patients with a geriatric profile admitted to Antwerp University Hospital, a tertiary care hospital in Flanders, Belgium, and the impact of comprehensive geriatric assessment (CGA) on DNR code registration. PATIENTS AND METHODS: Retrospective analysis of a population of 543 geriatric patients (mean age 82.4 ± 5.19 years, 46.4% males) admitted to Antwerp University Hospital from 2018 to 2020 who underwent a CGA during admission. An association between DNR code registration status before and at hospital admission and age, gender, ethnicity, type of residence, clinical frailty score (CFS), cognitive and oncological status, hospital ward and stay on intensive care was studied. Admissions before and during the first wave of the pandemic were compared. RESULTS: At the time of hospital admission, a DNR code had been registered for 66.3% (360/543) of patients. Patients with a DNR code at hospital admission were older (82.7 ± 5.5 vs. 81.7 ± 4.6 years, p = 0.031), more frail (CFS 5.11 ± 1.63 vs. 4.70 ± 1.61, p = 0.006) and less likely to be admitted to intensive care. During the hospital stay, the proportion of patients with a DNR code increased to 77% before and to 85.3% after CGA (p < 0.0001). Patients were consulted about and agreed with the registered DNR code in 55.8% and 52.1% of cases, respectively. The proportion of patients with DNR codes at the time of admission or registered after CGA did not differ significantly before and after the start of the COVID-19 pandemic. CONCLUSION: After CGA, a significant increase in DNR registration was observed in hospitalized patients with a geriatric profile.

Do-Not-ResuscitateDecision-Making during the COVID-19 Pandemic in a Teaching Hospital: Lessons Learned for the Future.

Method: A cross-sectional survey study was conducted between February 2021 and April 2021 for all doctors and doctors in training, working in the Antwerp University Hospital during the COVID-19 pandemic. Results: 127 doctors participated in this study. The familiarity with the different scores used in the triage during the COVID-10 pandemic was 51% for the Clinical Frailty Scale (CFS) and 20% for the Charlson Comorbidity Index (CCI). Participants indicated that their DNR decision is based on various aspects such as clinical assessment, comorbidities, patient's wishes, age, prognosis, and functional state. Conclusion: The familiarity with the different scores used during triage assessments is low. The total clinical picture of the patient is needed to make a considered decision, and this total picture of the patient seems to be well encompassed by frailty measurement (CFS). Although many participants indicated that the different scores do not offer much added value compared to their clinical assessment, it can help guide DNR decisions, especially for doctors in training.

Bedside medication review with cognitive and depression screening by a clinical pharmacist as part of a comprehensive geriatric assessment in hospitalized older patients with polypharmacy: A pilot study.

BACKGROUND: Polypharmacy is highly prevalent in older patients with multimorbidity and is associated with increased risk of adverse drug events. This pilot study investigated the added value of a bedside medication review with cognitive and depression screening by a clinical pharmacist to identify potentially inappropriate medications (PIMs) and medication use issues in older patients with polypharmacy. METHODS AND RESULTS: In the period from September 2018 to March 2019, a clinical pharmacist took part in the comprehensive geriatric assessment of 37 older patients hospitalized at Antwerp University Hospital and conducted a medication review consisting of a record review, a bedside interview questionnaire covering medication use, evaluation of cognitive function (abbreviated MMSE), depression (GDS-4), and systematic check for possible PIMs (STOPP/START criteria). Patients were 83±4 years old and on a median of 12 home medications (range 5-20). The clinical pharmacist formulated an average of 7.7 recommendations to optimize medication use per patient, of which 89.9% were considered clinically relevant by the geriatrician. Only 2 out of 286 PIMs were discovered during routine electronic validation of medication prescriptions. Supervision of medication intake was absent in 75% of cognitively impaired patients, but advice to do so was implemented in 86.4% of cases. The multidisciplinary geriatric advice was communicated to the treating physician, who fully implemented 33.8% of the recommendations. CONCLUSIONS: Bedside medication review with cognitive and depression screening by a clinical pharmacist is useful to discover polypharmacy related problems and medication intake issues in a population of geriatric patients. Systematic screening for cognitive impairment and depression are needed to detect patients in need of support for correct medication use and therapy compliance.

Inflammatory Pseudotumor of the Mesentery.

Teaching point: An inflammatory pseudotumor can occur almost everywhere in the body and has nonspecific imaging findings.

Bile acids in sputum and increased airway inflammation in patients with cystic fibrosis.

BACKGROUND: Up to 80% of patients with cystic fibrosis (CF) may have increased gastroesophageal reflux and aspiration of duodenogastric contents into the lungs. We aimed to assess aspiration in patients with CF by measuring duodenogastric components in induced sputum and to investigate whether the presence of bile acids (BAs) in sputum was correlated with disease severity and markers of inflammation. METHODS: In 41 patients with CF, 15 healthy volunteers, 29 patients with asthma, and 28 patients with chronic cough, sputum was obtained after inhalation of hypertonic saline. Sputum supernatant was tested for BA and neutrophil elastase. Spirometry and BMI were assessed on the day of sputum collection. RESULTS: Two of 15 healthy patients (13%), eight of 29 patients (28%) with asthma, four of 28 patients (14%) with chronic cough, and 23 of 41 patients (56%) with CF had BA in sputum. BA concentrations were similar in patients who are positive for BA with genotype F508del homozygote, F508del heterozygote, and other CF mutations and were not related with BMI and age. Patients with CF with BA in sputum had a higher concentration of neutrophil elastase compared with patients without BA in sputum (31.25 [20.33-54.78] µg/mL vs 14.45 [7.11-27.88] µg/mL, P < .05). There was a significant correlation between BA concentrations and dynamic lung volumes (FEV(1) % predicted [r = -0.53, P < .01], FVC% [r = -0.59, P < .01]) as well as with number of days of antibiotic IV treatment (r = 0.58, P < .01). CONCLUSIONS: BAs are present in the sputum of more than one-half of patients with CF, suggesting aspiration of duodenogastric contents. Aspiration of BA was associated with increased airway inflammation. In patients with BA aspiration, the levels of BA were clearly associated with the degree of lung function impairment as well as the need for IV antibiotic treatment.

Nocturnal gastroesophageal reflux revisited by impedance-pH monitoring.

BACKGROUND/AIMS: Impedance-pH monitoring allows detailed characterization of gastroesophageal reflux and esophageal activity associated with reflux. We assessed the characteristics of nocturnal reflux and esophageal activity preceding and following reflux. METHODS: Impedance-pH tracings from 11 healthy subjects and 76 patients with gastroesophageal reflux disease off acid-suppressive therapy were analyzed. Characteristics of nocturnal supine reflux, time distribution and esophageal activity seen on impedance at 2 minute intervals preceding and following reflux were described. RESULTS: Patients had more nocturnal reflux events than healthy subjects (8 [4-12] vs 2 [1-5], P = 0.002), with lower proportion of weakly acidic reflux (57% [35-78] vs 80% [60-100], P = 0.044). Nocturnal reflux was mainly liquid (80%) and reached the proximal esophagus more often in patients (6% vs 0%, P = 0.047). Acid reflux predominated in the first 2 hours (66%) and weakly acidic reflux in the last 3 hours (70%) of the night. Most nocturnal reflux was preceded by aboral flows and cleared by short lasting volume clearance. In patients, prolonged chemical clearance was associated with less esophageal activity. CONCLUSIONS: Nocturnal weakly acidic reflux is as common as acid reflux in patients with gastroesophageal reflux disease, and predominates later in the night. Impedance-pH can predict prolonged chemical clearance after nocturnal acid reflux.

The impact of traffic air pollution on bronchiolitis obliterans syndrome and mortality after lung transplantation.

BACKGROUND: Approximately half of all patients who underwent a lung transplantation suffer from bronchiolitis obliterans syndrome (BOS), the clinical correlate of chronic rejection, within 5 years after transplantation. This prevalence is much higher than for other solid organ transplantations, possibly due to the lung's direct contact with the environment. The authors assessed the association between proximity of the home to major roads and BOS and mortality in a cohort of patients after lung transplantation. METHODS: The authors calculated hazard ratios for BOS and mortality in relation to proximity of the home to major roads, adjusting for relevant covariables, in 288 patients after lung transplantation at the Leuven University Hospital between 1997 and 2009 and with follow-up until August 2009. Inflammatory parameters in plasma and bronchoalveolar lavage were assessed in 207 patients. RESULTS: During follow-up, 117 (41%) patients developed BOS and 61 (21%) died. Patients who lived within 171 m of a major road (lowest tertile) were 2.06 (95% CI 1.39 to 3.05) times more likely to develop BOS and 2.20 (1.25 to 3.86) times more likely to die than patients living farther away. The adjusted hazard ratios of BOS and mortality were 0.57 and 0.72 for each 10-fold increase in distance from major roads. Proximity to a major road was inversely associated with plasma C-reactive protein levels, neutrophil percentage and interleukin-6 concentration in bronchoalveolar lavage. CONCLUSION: Traffic-related air pollution appears to constitute a serious risk of BOS and mortality after lung transplantation.

Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique.

BACKGROUND: Oesophageal intraluminal impedance is currently used for assessment of reflux in gastro-oesophageal reflux disease (GORD). Oesophageal mucosa integrity may have a key role in heartburn perception in non-erosive reflux disease (NERD). Severe erosive oesophagitis is associated with low impedance baseline. We hypothesised that impedance baseline measurements could be used to evaluate changes in oesophageal mucosa integrity in man. METHODS: We measured oesophageal impedance baseline before, during and after acid perfusion in rabbits and healthy subjects. Transepithelial resistance (TER) was determined and dilated intercellular spaces (DIS) were assessed in isolated rabbit oesophageal mucosa. Impedance baseline was measured retrospectively at different levels of the oesophagus in impedance-pH recordings from asymptomatic volunteers and patients with GORD. RESULTS: In healthy subjects and rabbits, impedance baseline dropped dramatically during perfusion of control solution (pH 7.2) but after perfusion, impedance recovered. In rabbits, after perfusion with saline pH 1.5 and 1.0 impedance values remained a 39.1 ± 7.0% and 63.9 ± 6.5% (p < 0.05) lower respectively. There was a positive correlation between in vivo basal impedance and in vitro TER values (r = 0.72, p = 0.0021). Tissue showed no erosions but both acidic solutions induced DIS. In healthy subjects, after perfusion with saline pH 2.0 and 1.0 the impedance baseline remained lower a 21.9 ± 6.5% and 52.7 ± 5.0%, (p < 0.0001) respectively. Patients with GORD have a lower impedance baseline than healthy volunteers at the distal oesophagus. CONCLUSIONS: Impedance baseline measurements might be used to evaluate the status of the oesophageal mucosa and to study the role of the impaired mucosal integrity in acid-induced heartburn in healthy volunteers and in patients with GORD.

Heterogeneity of chronic lung allograft dysfunction: insights from protein expression in broncho alveolar lavage.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) remains a major risk factor for death after lung transplantation. Previous data suggested that within CLAD at least 2 phenotypes are present: a neutrophilic type (nCLAD or neutrophilic reversible allograft dysfunction [NRAD]), reversible with azithromycin therapy, vs a low neutrophilic type, non-responsive to azithromycin (fibrotic bronchiolitis obliterans syndrome [fBOS]). We aimed to further characterize this dichotomy by measuring multiple proteins in the bronchoalveolar lavage (BAL) fluid of 28 lung recipients. METHODS: Patients were retrospectively subdivided by the absence or presence of CLAD and subsequently by their response to azithromycin, resulting in 3 groups: 10 stable, 9 responsive (nCLAD/NRAD), and 9 non-responsive (fBOS). Enzyme-linked immunosorbent assay was used to measure 32 different proteins. RESULTS: Protein variations were predominantly present in the nCLAD/NRAD group, whereas no differences were observed in the fBOS group compared with control. MCP-1 (p < 0.01), RANTES (p < 0.05), IL-1ß (p < 0.01), IL-8 (p < 0.01), TIMP-1 (p < 0.01), MMP-8 (p < 0.01), MMP-9 (p < 0.01), HGF (p < 0.001), MPO (p < 0.01), and bile acid (p < 0.05) concentrations were upregulated in nCLAD/NRAD compared with fBOS, whereas PDGF-AA (p < 0.05) was downregulated. CONCLUSIONS: These data provide further evidence that within CLAD there is a heterogeneity of phenotypes with different mechanisms involved. Further investigation is warranted to unravel the pathophysiology of both phenotypes.

A porcine model of acute lung injury by instillation of gastric fluid.

BACKGROUND: About 15% of donor lungs are declined because of aspiration contributing to current organ shortage. The aim was to develop a porcine lung injury model by gastric juice (GJ) instillation to study different pretransplant treatment strategies. MATERIALS AND METHODS: Pigs (n = 6/group) were anesthetized and monitored. At T0 bronchoalveolar lavage (BAL) was performed followed by instillation of 4 mL/kg GJ or saline solution (SAL). Hemodynamics, aerodynamics and oxygenation were recorded for two hours. Serum samples were collected. At T120 a second BAL was performed. CT scans of explanted, inflated lungs were taken, tissue samples were collected and wet/dry weight ratio (W/D) was calculated. Pepsin and bile acids were measured in BAL. IL-8, CRP and MMP-9 were measured in serum and in BAL. RESULT: Oxygenation and lung compliance was lower in [GJ] versus [SAL] (P < 0.01 and P < 0.001, respectively). More consolidation areas were noticed on CT in GJ versus SAL (P < 0.01). Hemorrhage, edema and neutrophil inflammation were seen on histology in [GJ] (P < 0.01, P < 0.001, P < 0.001, respectively). BAL neutrophils, pepsin, bile acids, and IL-8 (P < 0.05) increased in [GJ]. W/D was higher in [GJ] versus SAL (P < 0.001). CONCLUSION: Instillation of GJ in pig lungs caused acute lung injury with impaired oxygenation and increased inflammation in BAL, on histology, and on imaging. This model holds promise to assess the efficacy of a broad range of treatment strategies including ex vivo lung perfusion (EVLP).

Effects of lesogaberan on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease.

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxations (TLESRs) are a major mechanism behind reflux. This study assessed the effects of lesogaberan (AZD3355), a novel gamma-aminobutyric acid type B receptor agonist, on reflux and lower esophageal sphincter (LES) function when used as add-on treatment in patients with reflux symptoms despite proton pump inhibitor (PPI) treatment. METHODS: In this randomized, double-blind, placebo-controlled, crossover study, patients received lesogaberan (65 mg) or placebo twice on day 1 (morning/evening) and once on day 2 (morning), in addition to existing PPI treatment. Patients consumed a standardized meal 45-60 minutes after morning doses. Ambulatory impedance-pH monitoring was conducted for 24 hours after the first dose on day 1. Stationary manometry and impedance-pH monitoring was conducted for 4 hours after the third dose on day 2. RESULTS: Of 27 randomized patients, 21 were included in the per-protocol efficacy analysis. During the 24 hours after treatment start, lesogaberan reduced the mean number of reflux events by approximately 35% compared with placebo. During the 3 postprandial hours on day 2, lesogaberan reduced the geometric mean number of TLESRs by 25% and increased geometric mean LES pressure by 28% compared with placebo. The most common adverse events were headache (placebo: 11/27 patients; lesogaberan: 8/25 patients) and paresthesia (transient; placebo: 3/27 patients; lesogaberan: 5/25 patients). CONCLUSIONS: In patients with reflux symptoms despite PPI treatment, lesogaberan decreased the number of TLESRs and reflux episodes, and increased LES pressure compared with placebo. These findings support further evaluation of lesogaberan as an add-on treatment in patients partially responding to PPIs.

Relevance of GERD in lung transplant patients.

Lung transplantation has become a valuable treatment for end-stage pulmonary disorders in an attempt to improve quality of life and extend survival. Development of chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is responsible for the vast majority of deaths after lung transplantation. Up to 50% of lung transplant patients develop BOS within the first 5 years after transplantation. A high prevalence of gastroesophageal reflux and aspiration of gastric components has been described after lung transplantation. Reflux and aspiration have been implicated in the development of BOS and antireflux surgery has been proposed; however, the causal relationship with BOS and the impact of reflux in lung transplantation survival needs to be further elucidated.

Gastric juice from patients "on" acid suppressive therapy can still provoke a significant inflammatory reaction by human bronchial epithelial cells.

BACKGROUND: Patients with reflux-related respiratory symptoms are frequently treated with proton pump inhibitors (PPI). It is unclear whether aspiration of gastric juice (GJ) from patients "on" PPI can provoke a similar bronchial inflammatory reaction than that observed in patients "off" medication. The goal of this study was to evaluate the effect of GJ from patients with and without PPI treatment on production of IL-8 by human primary bronchial epithelial cells (PBEC). STUDY: PBEC were exposed during 24 hours to GJ (1/1000) from patients "on" (n=10) and "off" (n=13) PPI and to nonacidic gastric components (pepsin and bile acids). IL-8 concentration in supernatant was measured with enzyme-linked immunosorbent assay. Endotoxin level in GJ samples was analyzed with a LAL assay. RESULTS: Exposure of PBEC to GJ from patients "on" PPI provoked a higher production of IL-8 than GJ from patients "off" PPI [279 pg/mL (36 to 498) vs. 11 pg/mL (9 to 27)]. A correlation was found between pH of GJ and IL-8 production (r=0.659, P=0.0006). No correlation was found between IL-8 production and concentration of bile acids or pepsin. Filtration (0.20 [mu]m) of GJ from patients "on" PPI reduced IL-8 production. A positive correlation was found between IL-8 production and endotoxin levels of GJ samples (1/1000) (r=0.654, P=0.0007). CONCLUSIONS: Exposure of bronchial epithelial cells to GJ from patients "on" PPI is able to induce high IL-8 production. These results suggest that aspiration of GJ in patients treated with PPI might still be able to provoke a significant bronchial inflammatory reaction.

Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus.

BACKGROUND: Oesophageal mucosa dilated intercellular spaces (DIS) may be important for symptom perception in non-erosive reflux disease (NERD). Patients with NERD might have DIS even in the proximal oesophagus. We aimed to assess the effect of oesophageal perfusions with acid and weakly acidic solutions on 'exposed' and 'non-exposed' oesophageal mucosa and its relationship to symptoms in healthy subjects. METHODS: 14 healthy volunteers underwent upper gastrointestinal endoscopy with biopsies at 3 and 13 cm proximal to the oesophagogastric junction (OGJ). In following sessions, subjects received 30 min perfusions with neutral, weakly acidic, acidic and acidic-bile acid solutions at 5 cm above the EGJ (separated 4 weeks). Biopsies were taken 20 min after perfusions. Electron microscopy was used to measure DIS. Subjects scored heartburn during perfusions using a visual analogue scale. RESULTS: (1) Oesophageal perfusion with acid solutions, with or without bile acids, provoked DIS in the 'exposed' oesophageal mucosa; (2) oesophageal perfusion with weakly acidic solutions provoked identical changes to those observed after perfusion with acid solutions; (3) distal oesophageal perfusions not only provoked changes in the 'exposed' but also in the more proximal 'non-exposed' mucosa; and (4) in spite of the presence of perfusion-induced DIS, most healthy subjects did not perceive heartburn during the experiments. CONCLUSIONS: The human oesophageal mucosa is very sensitive to continuous exposure with acidic and weakly acidic solutions. In spite of the presence of intraluminal acid and DIS, healthy subjects did not experience heartburn, suggesting that NERD patients should have other critical factors underlying their symptoms.

Nocturnal weakly acidic reflux promotes aspiration of bile acids in lung transplant recipients.

BACKGROUND: Gastroesophageal reflux (GER) and aspiration of bile acids have been implicated as non-alloimmune risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of our study was to investigate the association between GER and gastric aspiration of bile acids and to establish which reflux characteristics may promote aspiration of bile acids into the lungs and may feature as a potential diagnostic tool in identifying lung transplantation (LTx) patients at risk for aspiration. METHODS: Twenty-four stable LTx recipients were studied 1 year after transplantation. All patients underwent 24-hour ambulatory impedance-pH recording for the detection of acid (pH <4) and weakly acidic (pH 4 to 7) reflux. On the same day, bronchoalveolar lavage fluid (BALF) was collected and then analyzed for the presence of bile acids (Bioquant enzymatic assay). RESULTS: Increased GER was detected in 13 patients, of whom 9 had increased acid reflux and 4 had exclusively increased weakly acidic reflux. Sixteen patients had detectable bile acids in the BALF (0.6 [0.4 to 1.5] micromol/liter). The 24-hour esophageal volume exposure was significantly increased in patients with bile acids compared to patients without bile acids in the BALF. Acid exposure and the number of reflux events (total, acid and weakly acidic) were unrelated to the presence of bile acids in the BALF. However, both nocturnal volume exposure and the number of nocturnal weakly acidic reflux events were significantly higher in patients with bile acids in the BALF. CONCLUSIONS: Weakly acidic reflux events, especially during the night, are associated with the aspiration of bile acids in LTx recipients and may therefore feature as a potential risk factor for the development of BOS.

Airway colonization and gastric aspiration after lung transplantation: do birds of a feather flock together?

BACKGROUND: Both gastroesophageal reflux and airway colonization with Pseudomonas aeruginosa (P aeruginosa) are common in lung transplantation (LTx) recipients. There is mounting evidence that, due to their interaction with the epithelium, both may be involved in chronic allograft dysfunction/bronchiolitis obliterans syndrome (BOS) after LTx. We investigated whether gastric aspiration and airway colonization with P aeruginosa after LTx are associated. METHODS: In this retrospective, cross-sectional, case-control study, 24 stable double (SS) LTx recipients were included. Markers of gastroesophageal reflux (pepsin, bile acids) and airway inflammation (neutrophilia and interleukin-8 (IL-8)) were evaluated in bronchoalveolar lavage (BAL) samples of post-operatively colonized (n = 12) and non-colonized matched-control LTx recipients (n = 12). RESULTS: BAL bile acid levels, but not pepsin levels, as well as neutrophilia and IL-8 protein levels were significantly elevated in colonized compared with non-colonized patients. Furthermore, bile acid levels, but not pepsin levels, correlated positively with BAL neutrophilia and IL-8 protein levels. CONCLUSIONS: Bile acid aspiration and airway colonization by P aeruginosa after LTx seem to be associated. This relationship between reflux and airway colonization and their role in the development of chronic allograft dysfunction/BOS after LTx should be further elucidated; nevertheless, induction of IL-8-mediated neutrophilic airway inflammation may be a putative mechanism.