A multicenter, randomized trial of patients with infected necrotizing pancreatitis evaluated immediate drainage within 24 hours after infected necrosis was diagnosed as compared with postponed ...drainage. Immediate drainage was not superior to postponed drainage in reducing complications. Patients assigned to immediate drainage underwent a greater number of invasive procedures.
We kindly thank Larghi et al and Tiwari et al for their interest in our study.1–3 We acknowledge the limitations of our study. However, we would like to make some additional remarks.
Respiratory failure worsens the outcome of acute pancreatitis (AP) and underlying factors might be early detectable.
To evaluate the prevalence and prognostic relevance of early pleuropulmonary ...pathologies and pre-existing chronic lung diseases (CLD) in AP patients.
Multicentre retrospective cohort study. Caudal sections of the thorax derived from abdominal contrast enhanced computed tomography (CECT) performed in the early phase of AP were assessed. Independent predictors of severe AP were identified by binary logistic regression analysis. A one-year survival analysis using Kaplan-Meier curves and log rank test was performed.
358 patients were analysed, finding pleuropulmonary pathologies in 81%. CECTs were performed with a median of 2 days (IQR 1-3) after admission. Multivariable analysis identified moderate to severe or bilateral pleural effusions (PEs) (OR = 4.16, 95%CI 2.05-8.45, p<0.001) and pre-existing CLD (OR = 2.93, 95%CI 1.17-7.32, p = 0.022) as independent predictors of severe AP. Log rank test showed a significantly worse one-year survival in patients with bilateral compared to unilateral PEs in a subgroup.
Increasing awareness of the prognostic impact of large and bilateral PEs and pre-existing CLD could facilitate the identification of patients at high risk for severe AP in the early phase and thus improve their prognosis.
Anthocyanins and volatile phenylpropenes (isoeugenol and eugenol) in petunia (Petunia hybrida) flowers have the precursor 4-coumaryl coenzyme A (CoA) in common. These phenolics are produced at ...different stages during flower development. Anthocyanins are synthesized during early stages of flower development and sequestered in vacuoles during the lifespan of the flowers. The production of isoeugenol and eugenol starts when flowers open and peaks after anthesis. To elucidate additional biochemical steps toward (iso)eugenol production, we cloned and characterized a caffeoyl-coenzyme A O-methyltransferase (PhCCoAOMT1) from the petals of the fragrant petunia ‘Mitchell’. Recombinant PhCCoAOMT1 indeed catalyzed the methylation of caffeoyl-CoA to produce feruloyl CoA. Silencing of PhCCoAOMT1 resulted in a reduction of eugenol production but not of isoeugenol. Unexpectedly, the transgenic plants had purple-colored leaves and pink flowers, despite the fact that cv Mitchell lacks the functional R2R3-MYB master regulator ANTHOCYANIN2 and has normally white flowers. Our results indicate that down-regulation of PhCCoAOMT1 activated the anthocyanin pathway through the R2R3-MYBs PURPLE HAZE (PHZ) and DEEP PURPLE, with predominantly petunidin accumulating. Feeding cv Mitchell flowers with caffeic acid induced PHZ expression, suggesting that the metabolic perturbation of the phenylpropanoid pathway underlies the activation of the anthocyanin pathway. Our results demonstrate a role for PhCCoAOMT1 in phenylpropene production and reveal a link between PhCCoAOMT1 and anthocyanin production.
Chronic pancreatitis (CP) has a negative impact on quality of life (QoL). Because CP is a chronic condition, multiple assessments of QoL are required to obtain a thorough understanding of its impact ...on patients. Such studies are currently lacking. This study aims to gain insight into the course and predictors of QoL in patients with CP using prospective longitudinal data from a large cohort of patients.
Post hoc analysis of consecutive patients with definite CP registered in a prospective database between 2011 and 2019 in the Netherlands. Patient and disease characteristics, nutritional status, pain severity, medication usage, pancreatic function, and pancreatic interventions were assessed from medical records and through standard follow-up questionnaires. The physical and mental component summary scales of the Short-Form 36 were used to assess physical and mental QoL at baseline and during follow-up. The course of both physical and mental QoL and their associated factors were longitudinally assessed by using generalized linear mixed models.
Overall, 1,165 patients with definite CP were included for this analysis. During 10-year follow-up, generalized linear mixed model analyses revealed improvements in both physical (41.6-45.2, P < 0.001) and mental (45.9-46.6, P = 0.047) QoL. Younger age, current alcohol consumption, employment, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, and pain coping mechanism were positively associated with physical QoL ( P < 0.05). For mental QoL, a positive correlation was found between employment, nonalcoholic CP, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, pain coping mechanism, and surgical treatment. No association was observed between disease duration and longitudinal QoL per patient.
This nationwide study provides insight into the dynamics of physical and mental QoL in patients with CP over time. Important and potentially influenceable factors to improve QoL are nutritional status, exocrine pancreatic function, employment status, and patients' coping strategy.
In a 2010 randomized trial (the PANTER trial), a surgical step-up approach for infected necrotizing pancreatitis was found to reduce the composite endpoint of death or major complications compared ...with open necrosectomy; 35% of patients were successfully treated with simple catheter drainage only. There is concern, however, that minimally invasive treatment increases the need for reinterventions for residual peripancreatic necrotic collections and other complications during the long term. We therefore performed a long-term follow-up study.
We reevaluated all the 73 patients (of the 88 patients randomly assigned to groups) who were still alive after the index admission, at a mean 86 months (±11 months) of follow-up. We collected data on all clinical and health care resource utilization endpoints through this follow-up period. The primary endpoint was death or major complications (the same as for the PANTER trial). We also measured exocrine insufficiency, quality of life (using the Short Form-36 and EuroQol 5 dimensions forms), and Izbicki pain scores.
From index admission to long-term follow-up, 19 patients (44%) died or had major complications in the step-up group compared with 33 patients (73%) in the open-necrosectomy group (P = .005). Significantly lower proportions of patients in the step-up group had incisional hernias (23% vs 53%; P = .004), pancreatic exocrine insufficiency (29% vs 56%; P = .03), or endocrine insufficiency (40% vs 64%; P = .05). There were no significant differences between groups in proportions of patients requiring additional drainage procedures (11% vs 13%; P = .99) or pancreatic surgery (11% vs 5%; P = .43), or in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain scores, or medical costs. Quality of life increased during follow-up without a significant difference between groups.
In an analysis of long-term outcomes of trial participants, we found the step-up approach for necrotizing pancreatitis to be superior to open necrosectomy, without increased risk of reinterventions.
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Floral scent is important to plant reproduction because it attracts pollinators to the sexual organs. Therefore, volatile emission is usually tuned to the foraging activity of the pollinators. In ...Petunia hybrida, volatile benzenoids determine the floral aroma. Although the pathways for benzenoid biosynthesis have been characterized, the enzymes involved are less well understood. How production and emission are regulated is unknown. By targeted transcriptome analyses, we identified ODORANT1 (ODO1), a member of the R2R3-type MYB family, as a candidate for the regulation of volatile benzenoids in Petunia hybrida cv W115 (Mitchell) flowers. These flowers are only fragrant in the evening and at night. Transcript levels of ODO1 increased before the onset of volatile emission and decreased when volatile emission declined. Downregulation of ODO1 in transgenic P. hybrida Mitchell plants strongly reduced volatile benzenoid levels through decreased synthesis of precursors from the shikimate pathway. The transcript levels of several genes in this pathway were reduced by suppression of ODO1 expression. Moreover, ODO1 could activate the promoter of the 5-enol-pyruvylshikimate-3-phosphate synthase gene. Flower pigmentation, which is furnished from the same shikimate precursors, was not influenced because color and scent biosynthesis occur at different developmental stages. Our studies identify ODO1 as a key regulator of floral scent biosynthesis.
Summary
Background
Autoimmune hepatitis requires long‐term therapy, and systemic corticosteroids are the backbone of therapeutic management. Prolonged use of corticosteroids may lead to adverse ...events but data from long‐term studies are mainly derived from studies in rheumatic diseases.
Aim
To assess cataract, diabetes and fractures in relation to corticosteroid doses in the long‐term maintenance treatment of patients with autoimmune hepatitis.
Methods
We retrospectively collected data on 476 patients (77% women) with an established diagnosis of autoimmune hepatitis. Binary logistic regression with a generalised estimating equation was used to analyse the association between current corticosteroid use and the incidence of cataract, diabetes and fractures with onset after autoimmune hepatitis diagnosis. We corrected for sex, age, cirrhosis at diagnosis and predniso(lo)ne use in the prior 3 years to account for possible ongoing effects.
Results
A total of 6634 years, with a median of 13 (range 1‐40) per patient were recorded. The median age at diagnosis was 44 years (range 2‐88). Adverse events were documented in 120 (25%) patients. Low‐dose predniso(lo)ne (0.1‐5.0 mg/d) increased the odds of fractures whereas higher doses (>5.0 mg/d) increased the odds of cataracts and diabetes. Budesonide increased the odds of cataract and fractures; this effect was independent of predniso(lo)ne use in the prior 1, 2 or 3 years.
Conclusions
Even low doses of corticosteroids frequently lead to substantial adverse events refuting the assumption that adverse events are prevented by administering low doses.
ObjectiveRoutine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary ...pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings.DesignA multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013–2017) applying the same study design.ResultsOverall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17–23) after hospital presentation and at a median of 29 hours (IQR 23–41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92).ConclusionIn patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group.Trial registration numberISRCTN15545919.
This study systematically explores the prevalence of pancreatic exocrine insufficiency (PEI) after acute pancreatitis in different subgroups of etiology (biliary/alcoholic/other), disease severity ...and follow-up time (<12, 12–36 and > 36 months after index admission).
PubMed and EMBASE databases were searched, 32 studies were included in this study level meta-analysis.
In a total of 1495 patients with acute pancreatitis, tested at a mean of 36 months after index admission, the pooled prevalence of PEI was 27.1% (95%-confidence interval CI: 20.3%–35.1%). Patients from seven studies (n = 194) underwent direct tests with pooled prevalence of 41.7% 18.5%–69.2%. Patients from 26 studies (n = 1305) underwent indirect tests with pooled prevalence of 24.4% 18.3%–31.8%. In subgroup analyses on patients that underwent fecal elastase-1 tests, PEI occurred more often in alcoholic pancreatitis (22.7% 16.6%–30.1%) than in biliary pancreatitis (10.2% 6.2%–16.4%) or other etiology (13.4% 7.7%–22.4%; P = 0.02). Pooled prevalence of PEI after mild and severe pancreatitis was 19.4% 8.6%–38.2% and 33.4% 22.6%–46.3% respectively in studies using fecal elaste-1 tests (P = 0.049). Similar results were seen in patients without (18.9% 9.3%–34.6%) and with necrotizing pancreatitis (32.0% 18.2%–49.8%; P = 0.053). Over time, the prevalence of PEI decreased in patients who underwent the fecal elastase-1 test and increased in patients who underwent the fecal fat analysis.
After acute pancreatitis, a quarter of all patients develop PEI during follow-up. Alcoholic etiology and severe and necrotizing pancreatitis are associated with higher risk of PEI. The prevalence of PEI may change as time of follow-up increases.
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