Associations between health-related quality of life and subsequent need for specialized palliative care and hospital utilization in patients with gastrointestinal cancer-a prospective single-center cohort study.

BACKGROUND: We lack knowledge of which factors are associated with the risk of developing complex palliative care needs. The aim of this study was to investigate the associations between patient-reported health-related quality of life and subsequent referral to specialized palliative care (SPC) and hospital utilization. METHODS: This was a prospective single-center cohort study. Data on patient-reported outcomes were collected through the European Organization of Research and Treatment of Cancer Questionnaire-Core-15-Palliative Care (EORTC QLQ-C15-PAL) at the time of diagnosis. Covariates and hospital utilization outcomes were collected from medical records. Adjusted logistic and Poisson regression were applied in the analyses. Participants were newly diagnosed with incurable gastrointestinal cancer and affiliated with a palliative care case management intervention established in a gastroenterology department. RESULTS: Out of 397 patients with incurable gastrointestinal cancer, 170 were included in the study. Patients newly diagnosed with incurable gastrointestinal cancer experienced a substantial burden of symptoms. Pain was significantly associated with subsequent referral to SPC (OR 1.015; 95% CI 1.001-1.029). Patients with lower education levels (OR 0.210; 95% CI 0.056-0.778) and a Charlson Comorbidity Index score of 2 or more (OR 0.173; 95% CI 0.041-0.733) were less likely to be referred to SPC. Pain (IRR 1.011; 95% CI 1.005-1.018), constipation (IRR 1.009; 95% CI 1.004-1.015), and impaired overall quality of life (IRR 0.991; 95% CI 0.983-0.999) were significantly associated with increased risk of hospital admissions. CONCLUSION: The study indicates a need for interventions in hospital departments to identify and manage the substantial symptom burden experienced by patients, provide palliative care, and ensure timely referral to SPC.

Frequency and risk factors of atrial fibrillation after acute abdominal surgery: A prospective cohort study.

BACKGROUND AND AIM: Scarce data exist on the true incidence of postoperative atrial fibrillation (POAF) after acute abdominal surgery and associated outcomes. The current study aimed to identify the frequencies of clinically recognized POAF and associated complications, along with their risk factors. METHODS: This study was a prospective, single-center cohort study of unselected adult patients referred for acute abdominal surgery during a 3-month period. Through careful review, demographics, comorbidity, and surgical characteristics were prospectively drawn from medical charts. The primary outcome was clinically recognized POAF occurring in-hospital. Logistic regression was used to determine the risk factors of POAF and associated complications. A subgroup was enrolled in a feasibility study of peri- and postoperative continuous cardiac rhythm monitoring. RESULTS: In total, 450 patients were enrolled. Clinically recognized in-hospital POAF was observed in 22 patients (4.9%). All cases were observed in patients aged ≥60 years, corresponding to 22 of 164 patients (13.4%). Multiple risk factors were observed, such as age, prior atrial fibrillation, heart failure, hypertension, diabetes mellitus, chronic renal disease, and major (vs. minor) surgery. POAF was associated with severe in-hospital complications (POAF group 45.5% vs. non-POAF group 8.6%, p < .001) and in-hospital mortality (POAF group 13.6% vs. non-POAF group 3.0%, p = .043). In total, 295 patients were monitored by continuous cardiac rhythm monitoring for 12,148 h, yielding five patients with asymptomatic AF. CONCLUSIONS: In conclusion, this prospective study of POAF in patients undergoing acute abdominal surgery showed that one in 20 patients developed clinically recognized in-hospital POAF. Multiple risk factors of POAF were identified. POAF was associated with severe complications up to 30 days after surgery.

Qualitative evaluation of a palliative care case management intervention for patients with incurable gastrointestinal cancer (PalMaGiC) in a hospital department.

PURPOSE: Generalist palliative care in hospital departments largely lacks an overall structure to fully manage the symptom burden and support needs of patients with incurable gastrointestinal cancer. Palliative care case management interventions show promising results in reducing healthcare use and enhancing quality of life. Less is known about these interventions and their potential to improve the quality of generalist palliative care in hospital departments. The aim of this study was to explore patients' experience of a palliative care case management intervention (PalMaGiC) to acquire knowledge about its advantages and disadvantages and, if needed, adjust the intervention. METHODS: Qualitative semi-structured interviews with patients (n = 14) with incurable gastrointestinal cancers of the oesophagus, pancreas, colon, or rectum were conducted and analysed using content analysis. Participants in the study were affiliated with PalMaGiC, an intervention in a gastroenterology department based on symptom assessment, care planning, care coordination, and needs-based follow-up. RESULTS: Participants perceived the intervention as filling a gap and as a secure lifeline in the healthcare system since it provided 24-h access, a designated specialist nurse, and a patient-healthcare alliance. Using a needs-based approach, PalMaGiC changed the participants' focus from disease to quality of life. Participants requested more open dialog within complementary and alternative medicine, greater focus on promoting hope and using need assessment questionnaires differently in assessing symptoms and problems. CONCLUSION: The PalMaGiC intervention can potentially meet the needs of patients requiring palliative care in hospital departments, but further development of the content and personalised approach is needed.

Development and validation of circulating protein signatures as diagnostic biomarkers for biliary tract cancer.

Background & Aims: Biliary tract cancer (BTC) is associated with a dismal prognosis, partly because it is typically diagnosed late, highlighting the need for diagnostic biomarkers. The purpose of this project was to identify and validate multiprotein signatures that could differentiate patients with BTC from non-cancer controls. Methods: In this study, we included treatment-naïve patients with BTC, healthy controls, and patients with benign conditions including benign biliary tract disease. Participants were divided into three non-overlapping cohorts: a case-control-based discovery cohort (BTC = 186, controls = 249); a case-control-based validation cohort (validation cohort 1: BTC = 113, controls = 241); and a cohort study-based validation cohort including participants (BTC = 8, controls = 132) referred for diagnostic work-up for suspected cancer (validation cohort 2). Immuno-Oncology (I-O)-related proteins were measured in serum and plasma using a proximity extension assay (Olink Proteomics). Lasso and Ridge regressions were used to generate protein signatures of I-O-related proteins and carbohydrate antigen 19-9 (CA19-9) in the discovery cohort. Results: Sixteen protein signatures, including 2 to 82 proteins, were generated. All signatures included CA19-9 and chemokine C-C motif ligand 20. Signatures discriminated between patients with BTC vs. controls, with AUCs ranging from 0.95 to 0.99 in the discovery cohort and 0.94 to 0.97 in validation cohort 1. In validation cohort 2, AUCs ranged from 0.84 to 0.94. Nine signatures achieved a specificity of 82% to 84% while keeping a sensitivity of 100% in validation cohort 2. All signatures performed better than CA19-9, and signatures including >15 proteins showed the best performance. Conclusion: The study demonstrated that it is possible to generate protein signatures that can successfully differentiate patients with BTC from non-cancer controls. Impact and implications: We attempted to find blood sample-based protein profiles that could differentiate patients with biliary tract cancer from those without cancer. Several profiles were found and tested in different groups of patients. The profiles were successful at identifying most patients with biliary tract cancer, pointing towards the utility of multiprotein signatures in this context.

Blood-based tumor fibrosis markers as diagnostic and prognostic biomarkers in patients with biliary tract cancer.

Biliary tract cancer (BTC) is characterized by a desmoplastic extracellular matrix (ECM). We tested the diagnostic and prognostic use of seven circulating biomarkers of ECM remodeling: pro-peptides of type III collagen (PRO-C3), VI (PRO-C6) and XI (PRO-C11), matrix metalloprotease (MMP) degraded type III collagen (C3M) and type IV collagen (C4M) fragments, granzyme B degraded type IV collagen fragments (C4G) and MMP degraded and citrullinated vimentin (VICM) a marker of macrophage activation. The study included 269 patients with all stages of BTC and 49 patients with benign biliary tract diseases. Serum samples from BTC patients were collected before surgery, or before first- or second-line chemotherapy. C3M, C4M, PRO-C3, PRO-C6, PRO-C11 and VICM levels were elevated in patients with BTC compared to patients with benign disease. Receiver operating characteristics curve analyses identified PRO-C3 (area under curve [AUC] = 0.87) as the ECM marker with the best diagnostic performance. The ECM biomarkers correlated with inflammation biomarkers (C-reactive protein [CRP], interleukin-6 [IL-6] and YKL-40) but not with CA19-9. To investigate prognostic performance, patients were split into three cohorts (first-line, second-line and surgery). Elevated ECM biomarker levels were associated with short overall survival (OS), but only pretreatment PRO-C3 and PRO-C6 were associated with OS in both the first-line and second-line settings when adjusting for CA19-9, performance status and stage in a multivariate Cox-regression analyses. Our results indicate that collagen remodeling is increased in patients with BTC and associated with survival. The collagen pro-peptides (PRO-C3 and PRO-C6) could be used as novel biomarkers in these patients.

SARS-CoV-2 RBD-Specific Antibodies Induced Early in the Pandemic by Natural Infection and Vaccination Display Cross-Variant Binding and Inhibition.

The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern (VoCs), is needed. In this study, samples collected in Denmark early in the pandemic from paucisymptomatic subjects (n = 165) and symptomatic subjects (n = 57) infected with SARS-CoV-2 were used to assess IgG binding and inhibition in the form of angiotensin-converting enzyme 2 receptor (ACE2) competition against the wild-type and four SARS-CoV-2 VoCs (Alpha, Beta, Gamma, and Omicron). Antibodies induced early in the pandemic via natural infection were cross-reactive and inhibited ACE2 binding of the VoC, with reduced inhibition observed for the Omicron variant. When examined longitudinally, sustained cross-reactive inhibitory responses were found to exist in naturally infected paucisymptomatic subjects. After vaccination, receptor binding domain (RBD)-specific IgG binding increased by at least 3.5-fold and inhibition of ACE2 increased by at least 2-fold. When vaccination regimens were compared (two doses of Pfizer-BioNTech BNT162b2 (n = 50), or one dose of Oxford-AstraZeneca ChAdOx1 nCoV-19 followed by Pfizer-BioNTech BNT162b2 (ChAd/BNT) (n = 15)), higher levels of IgG binding and inhibition were associated with mix and match (ChAd/BNT) prime-boosting and time since vaccination. These results are particularly relevant for countries where vaccination levels are low.

Preoperative, single, high-dose glucocorticoid administration in abdominal wall reconstruction: A randomized, double-blinded clinical trial.

BACKGROUND: Although preoperative administration of high-dose glucocorticoid may lead to improved recovery after operative procedures, this regimen has not been examined in patients undergoing abdominal wall reconstruction for repair of large ventral hernias. The aim of the current trial was to examine the effects of preoperative, single high-dose glucocorticoid on recovery after abdominal wall reconstruction. METHOD: Forty patients undergoing abdominal wall reconstruction for repair of ventral incisional hernias with a horizontal fascial defect >10 cm were randomized to intravenous administration of either 125 mg methylprednisolone or placebo at the induction of anesthesia. The primary endpoint was pain in the supine position as assessed by a numeric rating scale of 0 to 10 at rest at 8 am on the first postoperative day. Secondary outcomes included postoperative pain during activity, nausea, fatigue, inflammatory response (measured by plasma levels of C-reactive protein), duration of stay, and 30-day complications or readmissions. RESULTS: There was no difference in pain at rest on the first postoperative day (methylprednisolone mean 1.7 vs placebo 2.2, P > .95), whereas patients in the methylprednisolone group reported less pain during activity (mean 3.0 vs 5.0; P = .011) and during coughing (3.4 vs 5.9; P = .010). There were no differences between the 2 groups regarding postoperative fatigue or nausea. Postoperative levels of C-reactive protein were less in the methylprednisolone group (P = .039). CONCLUSION: A single-shot, high-dose methylprednisolone before abdominal wall reconstruction for a large incisional hernia decreased early postoperative pain and attenuated the inflammatory response.

[Simple ways of reducing the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis].

The most common and potentially devastating complication of endoscopic retrograde cholangiopancreatography (ERCP) remains post-ERCP pancreatitis (PEP). Recent advances in prophylaxis have reduced but not eliminated the risk of PEP. This review aims at providing an evidence-based, clinically applicable approach to PEP-prevention through patient selection, risk assessment, optimisation of procedural techniques, and multimodality prophylaxis.

How to Avoid Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

Pancreatitis remains the most common and potentially devastating complication of endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Recent advances in prophylaxis have improved but not eliminated this problem, underscoring the importance of ongoing research toward this goal. This review aims to provide an evidence-based approach to post-ERCP pancreatitis prevention through patient selection, risk stratification, procedural technique, and multimodality prophylaxis, and discusses ongoing and future research initiatives in this important area.

Quality of life, performance status, and work capacity after post-endoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVES: This study evaluated the long-term consequences of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) on health related quality of life (HRQOL), performance status, and work capacity. MATERIALS AND METHODS: A follow-up study with prospective outcome measurements on patients with previous PEP and matched controls from a Danish cohort of 772 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). HRQOL was evaluated by the short form 36 health surveys, performance status by the Zubrod score, and work capacity by employment status. Multivariable models were applied to adjust for potential confounders. RESULTS: Twenty-nine cases and 49 controls were included. Twelve (41%), eight (28%), and nine (31%) patients had mild, moderate, and severe PEP, respectively. Mean follow-up time was 4.8 ± 1.7 years. PEP was associated with long-term reduced mental HRQOL (-13.0 role-emotional score points, 95% CI: -25.4; -0.52). An increased Zubrod score representing reduced performance status was present in 12 of the 29 cases (41.4%) and in nine of the 49 controls (18.4%), p = .002. Reduced work capacity was present in 14 of the 29 cases (48.2%) and in 12 of the 49 controls (24.4%), p = .023. CONCLUSIONS: This study indicates that PEP has a detrimental effect on long-term HRQOL, performance score, and work capacity.

Pancreatic function following post-endoscopic retrograde cholangiopancreatography pancreatitis: A controlled cohort study with long-term follow-up.

BACKGROUND: Acute pancreatitis is one of the most common causes of gastrointestinal-related hospitalization and the incidence is increasing. Endo- and exocrine pancreatic function can be compromised after acute pancreatitis. OBJECTIVE: The purpose of this study was to explore the long-term consequences of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) on pancreatic function. METHODS: A follow-up study was carried out with prospective assessment of endo- and exocrine pancreatic function among cases with previous PEP and matched controls from a Danish cohort consisting of 772 patients undergoing first-time ERCP. Pancreatic function was evaluated by faecal-elastase-1 test, blood levels of haemoglobin A1c, C-peptide, vitamin B12, vitamin D and indirectly by changes in body weight. RESULTS: Twenty-nine cases and 49 controls participated in the study. Mean follow-up time (standard deviation) was 58 (21) months. Twelve (41%), eight (28%) and nine (31%) patients had mild, moderate and severe PEP, respectively. There was no difference between cases and controls with regard to pancreatic function parameters and PEP severity was not associated with pancreatic function. Factors associated with pancreatic function impairment included body mass index, alcohol consumption, age and smoking. CONCLUSION: This study suggests that long-term pancreatic function following PEP is similar to the pancreatic function of other patients with comparable gallstone-related morbidity.

Effect of body weight on fixed dose of diclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVE: The aim of this study was to assess the influence of patient body weight on the clinical effect of 100 mg diclofenac administered as a single dose for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). MATERIALS AND METHODS: All patients subjected to endoscopic retrograde cholangiopancreatography (ERCP) from 2009 to 2014 were evaluated for inclusion. In total, 772 patients were included of whom 378 (49%) received diclofenac prophylaxis. RESULTS: In the diclofenac prophylaxis group, body weight was higher in patients with PEP (mean ± SD: 82 ± 18 kg) than in patients without PEP (74 ± 18 kg) (p = 0.029). In patients not receiving prophylaxis, body weight was not associated with the occurrence of PEP (mean ± SD: 77 ± 18 vs 75 ± 18 kg, respectively, p = 0.450). In an adjusted analysis, higher patient body weight was inversely associated with the clinical effect of 100 mg diclofenac for the prophylaxis of PEP. CONCLUSIONS: High patient body weight was associated with a reduced effect of 100 mg diclofenac for prophylaxis of PEP.

[Acute pancreatitis after ingestion of ibuprofen in a 16-year-old boy]. / Akut pankreatitis hos en 16-årig dreng efter indtag af ibuprofen.

This is a case report of a 16-year-old boy with possible drug-induced pancreatitis (DIP) caused by ibuprofen. The patient had a history of psychiatric, but no somatic, disease, and he was admitted with a clinical presentation consistent with acute pancreatitis after a bolus ingestion of 10 g of ibuprofen in a suicidal attempt. No evidence of other causality for acute pancreatitis was identified. The patient was treated with a standard pancreatitis treatment regime and was discharged against medical advice after four days. The case represents a possible causality between ibuprofen and DIP.

Diclofenac is associated with a reduced incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis: results from a Danish cohort study.

OBJECTIVE: The aim of this study was to assess the clinical effect of diclofenac administered as a single dose for the prevention of postprocedure pancreatitis in a consecutive series of patients who had undergone endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients with a native papilla Vateri subjected to ERCP during 2010 (control group, n = 218) and 2012 (diclofenac group, n = 182) were included. Patients with a history of chronic pancreatitis or recent acute pancreatitis were excluded. From January 2012, a rectal suppository containing 100 mg of diclofenac was administered immediately after endoscopy in all patients. The primary outcome of post-ERCP pancreatitis was assessed retrospectively by reviewing the patients' charts. RESULTS: The overall incidence of post-ERCP pancreatitis was 32 (14.7%) of the 218 patients in the control group and 9 (4.9%) of the 182 patients in the diclofenac group (P = 0.002). Moderate to severe pancreatitis occurred in 22 (10.1%) of the 218 patients in the control group versus 8 (4.4%) of the 182 patients in the diclofenac group (P = 0.036). CONCLUSIONS: This controlled cohort study suggests that the implementation of a single dose of 100 mg of diclofenac rectally administered significantly reduces the incidence of post-ERCP pancreatitis in an unselected material of patients with native papilla.