Contributions of collagen and elastin to elastic behaviours of tendon fascicle.

Tendon exhibits the capacity to be stretched and to return to its original length without suffering structural damage in vivo, a capacity known as elastic recoil. Collagen fibres are aligned longitudinally and elastin fibres mostly run parallel to collagen fibres in tendon. However, their interactions and contributions to tendon elastic behaviours are not well understood. The present study examined functional roles of collagen and elastin in tendon elastic behaviours using a variety of mechanical tests. We prepared three types of fascicle specimens from mouse tail tendon: fascicles freshly isolated, those digested with elastase in PBS to selectively remove elastin, and those incubated in PBS without elastase. A quasi-static tensile test demonstrated that elastase-treated fascicles had higher tangent moduli and strength compared to fresh and PBS fascicles. Cyclic stretching tests showed that fresh and PBS fascicles could withstand cyclic strain at both small and large amplitudes, but elastase-treated fascicles could only behave elastically to a limited degree. Fibre-sliding analysis revealed that fresh fascicles could be elongated both through stretching of collagen fibers and through movement of the fibres. However, elastase-treated fascicles could be stretched only via fibre stretching. This evidence suggests that normal tendons can be extended through both fibre stretching and fibre sliding, whereas tendons without elastin can only extend as much as collagen fibers can withstand. Accordingly, collagen fibres mainly contribute to tendon elastic behaviours by furnishing rigidity and elasticity, whereas elastin provides tendon viscoelasticity and also enables sliding of collagen fibres during elastic behaviours. STATEMENT OF SIGNIFICANCE: The present study revealed distinct mechanical functions of collagen and elastin fibres in elastic behaviours of mouse tail tendon fascicle using a variety of mechanical tests at both microscopic and macroscopic levels. It was demonstrated that collagen mainly governs tendon fascicle rigidity and elasticity, but only possesses limited extensibility, whereas elastin contributes to viscoelasticity and collagen fibre sliding, enabling elastic recoil behaviour against relatively large deformation. By their interactions, tendon can be elongated without suffering major structural damage and withstand a large magnitude of tensile force in response to mechanical loading. Such information should be particularly useful in designing collagen-based biomaterials such as artificial tendons, in that previous studies have merely considered collagen without incorporation of elastin.

Evaluation of Fecal Pancreatic Elastase-1 as a Measure of Pancreatic Exocrine Function in Children with Pancreatitis.

Pancreatic exocrine insufficiency occurs as a clinical consequence of chronic pancreatitis leading to fat maldigestion, malabsorption and malnutrition. Fecal elastase-1 is a laboratory-based test used for the diagnosis or exclusion of pancreatic exocrine insufficiency. The aim of the study was to observe the value of fecal elastase-1 in children with pancreatitis as an indicator of pancreatic exocrine insufficiency. This was a cross-sectional descriptive study conducted from January 2017 through June 2018. Thirty children with pain abdomen as control and 36 patients with pancreatitis as cases were included. An ELISA technique which recognizes human pancreatic elastase-1 from spot stool sample was employed for the test. Fecal elastase-1 activity in spot stool samples in acute pancreatitis (AP) ranged from 198.2-500µg/g with a mean of 342.1±136.4µg/g, acute recurrent pancreatitis (ARP) ranged from 15-500µg/g with a mean of 332.8±194.5µg/g and chronic pancreatitis (CP) ranged from 15-492.8µg/g with a mean of 222.2±197.1µg/g was obtained. In controls, fecal elastase-1 ranged from 28.4-500µg/g with a mean of 398.8±114.9µg/g. Disease severity was classified as mild to moderate pancreatic insufficiency (fecal elastase-1 100 to 200µg/g stool) was found in AP (14.3%) and CP (6.7%) cases. The severe pancreatic insufficiency (fecal elastase-1<100µg/g stool) was observed in ARP (28.6%) and CP (46.7%) cases. Malnutrition was observed in severe pancreatic insufficiency cases. This study result showed that fecal elastase-1 can be used as a measure of pancreatic exocrine function in children with pancreatitis.

THE STRUCTURAL AND FUNCTIONAL STATE OF THE PANCREAS AND LIVER IN CHRONIC PANCREATITIS IN COMBINATION WITH CHRONIC VIRAL HEPATITIS C DEPENDING ON THE INDEX OF THE SURVEY ACCORDING TO THE INTERNATIONAL CAGE QUESTIONNAIRE.

OBJECTIVE: The aim: To conduct a comparative analysis of parameters of the structural and functional state of the liver and pancreas in patients with chronic pancreatitis in comorbidity with treated etiologically chronic viral hepatitis C, depending on the results of testing according to the international CAGE questionnaire. PATIENTS AND METHODS: Materials and methods: 100 ambulatory patients with CP with concomitant HCV, treated etiotropically, were examined. All patients were examined ac-cording to generally accepted algorithms. To establish the role of alcohol on the formation of CP and the condition of patients with treated HCV, latent craving for alcohol was verified using the international CAGE questionnaire. The study of the density of the liver parenchyma and the liver of the patients was carried out not only according to the ultrasound data in the B-mode, but also with the simultaneous measurement of the shear wave elastography (SWE) method on the Ultima PA scanning ultrasound device with the further determination of the median of the parameters, which characterizes the stiffness in kilopascals (kPa). Determination of the presence and depth of pancreatic exocrine insufficiency (PEI) was carried out by the content of fecal elastase-1 (FE-1), which was determined by the enzyme immunoassay method. RESULTS: Results: Screening-testing of patients with CP on the background of etiotropically treated HCV using the CAGE scale made it possible to state that 65.0% of such patients had a hidden craving for alcohol, and 21.0% of this cohort were women, which needs to be taken into account in the management of such patients. It has been proven that in the group of patients with CAGE≥2.0, the level of functional and structural changes in the liver and liver was significantly more severe (according to the deepening of the PEI, a decrease in fecal α-elastase by 13.01%, according to an increase in the total index of the coprogram by 15.11% and the total US-indicator of the pancreas structure by 28.06%, and the total US-indicator of the liver structure - by 40.68% (p<0.05) and corresponded to the average degree of severity of the process in panceas according to the criteria of the Marseille-Cambridge classification, and in the group with CAGE<2.0 - only a mild degree. CONCLUSION: Conclusions: The negative effect of the factor of increased alcohol use according to CAGE was proven by increasing the density of the echostructure of the liver by 5.73% (p<0.05), and the liver by 5.16% (p<0.05). According to the results of the correlation analysis of the dependence of the structural state of the liver and PW of the studied patients on the value of the CAGE scale, which was R=0.713, p<0.05, and R=0.686, p<0.05, respectively, it was established that there is a strong direct dependence of the structural state of the liver and PW from the value of the CAGE questionnaire, which proved an independent, reliably significant role of alcohol consumption for patients with a comorbid course of CP and HCV.

Verification of the Bühlmann fPELA turbo faecal elastase assay on the Binding Site Optilite benchtop analyser.

BACKGROUND: Pancreatic elastase-1 (PE1) can be measured to assess exocrine activity of the pancreas. A semi-automated particle-enhanced, open-channel turbidimetric immunoassay has been introduced by Bühlmann (fPELA turbo, Bühlmann Laboratories AG, Schoenenbuch, Switzerland). Published evaluation data is lacking. We therefore verified performance of the assay on the Binding Site Optilite benchtop analyser and undertook a sample comparison with the DiaSorin PE1 assay on the Liaison. METHODS: Accuracy, imprecision, lower limit of quantitation (LLoQ) and linearity of the Bühlmann fPELA turbo assay on the Binding Site Optilite analyser was ascertained. Comparison with the DiaSorin Liaison PE1 assay was also undertaken. Difference between assays was evaluated using the Wilcoxon signed-rank test and method comparison was undertaken using Spearman's rank correlation (rs), Bland-Altman and Passing-Bablok regression analyses. RESULTS: The fPELA turbo assay was linear between 5 and 2500 µg/g. The LLoQ was 5 µg/g. Intra- and inter-assay imprecision was <6%. There was a good agreement (rs = 0.92) and no significant bias (5.8 µg/g, P = 0.29) present between the Bühlmann fPELA turbo and DiaSorin PE1 assays. CONCLUSION: The Bühlmann fPELA turbo assay performs well on the Binding Site Optilite analyser. Faecal elastase results are commutable between with Bühlmann fPELA turbo and DiaSorin Liaison PE1 assays.

The clinical and laboratory impact of reporting faecal elastase-1 in watery stool samples.

BACKGROUND: Low faecal elastase-1 (FE-1) results are suggestive of pancreatic insufficiency, but watery diarrhoea may lead to falsely low results. METHODS: FE-1 results reported on watery samples over a three-year period were reviewed. Results in watery samples were compared to those from a formed sample. The follow-up of patients in whom an FE-1 result ≤199 ug/g stool (Schebo ELISA) was reported on a watery sample was also reviewed. RESULTS: In total, 288 watery samples were identified. All results (19/19) ≥200 ug/g in watery samples were also ≥200 ug/g when measured in a formed sample from the same patient. There were 41 results ≤199 ug/g in watery samples, of which 29 (71%) were ≥200 ug/g when measured in a formed sample. Thirty-seven patients with a single FE-1 value ≤199 ug/g from a watery sample were followed up. Pancreatic Enzyme Replacement Therapy (PERT) was commenced in 15 patients. This was inappropriate in at least one patient. Reporting practice was subsequently changed to not report FE-1 values ≤199 ug/g in watery samples. This change was assessed after 12 months. Repeat samples were received from 15/56 (27%) of patients. Overall, 10/15 (67%) of samples were ≥200 ug/g on repeat. PERT was not commenced inappropriately in any of these patients. CONCLUSIONS: There is value in measuring FE-1 in watery samples, as 144/288 (50%) of watery samples analysed were ≥200 ug/g, enabling a diagnosis of exocrine pancreatic insufficiency to be excluded. Not reporting FE-1 values ≤199 ug/g in a first-time watery stool samples appears clinically safe and has potentially reduced inappropriate diagnoses and prescribing.

Chemical Composition, Antiaging Activities and Molecular Docking Studies of Essential Oils from Acca sellowiana (Feijoa).

This study aimed to investigate the chemical composition of essential oils isolated from Acca sellowiana (feijoa) leaves and stems and elaborate on their relevance as natural anti-aging, coupled with molecular-docking studies. The isolated oils were analysed using gas chromatography-mass spectrometry analysis and investigated for inhibitory effects against acetylcholinesterase, ß-secretase, collagenase, elastase and tyrosinase. Molecular-modelling study was performed using MOE-Dock program to evaluate binding interactions of major components with the above-mentioned targets. The leaf oil revealed the predominance of caryophyllene oxide (24.3 %), linalool (7.9 %), and spathulenol (6.6 %), while the stem oil was presented by caryophyllene oxide (38.1 %), α-zingiberene (10.1 %) and humulene oxide II (6.0 %). The stem oil expressed superior inhibitory activities against acetylcholinesterase (IC50 =0.15±0.01 µg/mL), ß-secretase (IC50 =3.99±0.23 µg/mL), collagenase (IC50 =408.10±20.80 µg/mL), elastase (IC50 =0.17±0.01 µg/mL) and tyrosinase (IC50 =8.45±0.40 µg/mL). The valuable binding interactions and docking scores were observed for caryophyllene oxide and α-zingiberene with acetylcholinesterase. Besides, α-zingibirene followed by linalool and τ-cadinol revealed tight fitting with collagenase and elastase. Additionally, linalool, spathulenol and τ-cadinol showed the best binding energy to tyrosinase. This study provides valuable scientific data on A. sellowiana as potential candidates for the development of natural antiaging formulations. The current study provided scientific evidence for the potential use of feijoa essential oils in antiaging formulations and as an adjuvant for the prophylaxis against Alzheimer disease.

Defining the rate of nutritional and metabolic derangements after pancreatic resection.

BACKGROUND AND AIMS: Pancreatic resection is associated with pancreatic exocrine insufficiency (PEI) leading to nutritional consequences. The Pancreatic Nutrition Clinic was established to diagnose and manage PEI through standardised nutritional assessment. In this prospective observational study, we aimed to define the rate of PEI, diabetes mellitus and nutritional abnormalities in patients who underwent pancreatic resection. METHODS: All Pancreatic Nutrition Clinic patients were included for analysis. Clinical data were prospectively obtained at initial assessment. Biochemical data included micronutrient levels, faecal elastase-1 and haemoglobin A1c. Bone mineral density and nutritional assessment were undertaken. RESULTS: Ninety-eight patients were included. Fifty-nine per cent (58/98) had undergone a pancreatoduodenectomy. Ninety-three patients had a faecal elastase-1 result, 65% (60/93) of which had a faecal elastase-1 less than 200 µg/g of faeces. Seventy-five patients (76%) of the total population required PERT, and thirty-nine (40%) were classified as malnourished using the patient-generated subjective global assessment tool. Seventy-two per cent (70/97) had a biochemical deficiency of one or more micronutrients. Thirty-eight people (39%) had diabetes mellitus. Of the seventy-eight patients with a bone mineral density scan available for analysis, 29% (23/78) had osteoporosis and 49% (38/78) osteopenia. CONCLUSIONS: Pancreatic exocrine insufficiency, micronutrient deficiency, bone disease, diabetes mellitus and malnutrition are highly prevalent in patients who have undergone pancreatic resection.

A Novel Fecal Elastase Assay for the Detection of Pancreatic Exocrine Insufficiency.

BACKGROUND: Fecal pancreatic elastase 1 (FPE1) is an established screening test for pancreatic exocrine insufficiency (PEI), a condition that is underdiagnosed and if not treated may cause significant morbidity. The aim of this study was to compare a new FPE1 machine based CLIA kit to an ELISA assay which is considered the de facto gold standard in our laboratory for FPE1 measurement. METHODS: Levels of FPE1 from the 227 stool samples were analyzed by the ScheBo ELISA kit and the CLIA Liaison XL system simultaneously with the same cutoff values for both assays. Performance of the Liaison XL system was assessed by calculating sensitivity, specificity, and accuracy. RESULTS: The comparison between the Liaison XL system performance and the ScheBo ELISA kit as reference revealed a sensitivity, specificity, and accuracy of 86.8%, 94.3%, and 92.1%, respectively, using a cutoff of 100 µg FPE1/g stool. When the cutoff is 200 µg FPE1/g stool the sensitivity, specificity, and accuracy were 86.6%, 97.1%, and 90.7%, respectively. Furthermore, linear correlation of FPE1 levels between the two assays were found to be significant by Pearson's correlation coefficient test (R = 0.85, p-values < 0.0001). CONCLUSIONS: The Liaison XL system showed good laboratory performance with our pre-determined cutoff values when compared to our previous assay. An important advantage of this system is its semi-automated mechanism that enables large scale analysis of FPE1. In addition to that, the Liaison XL system is ideal for both qualitative and quantitative analysis of FPE1 allowing for its application to the clinical setting.

In Vitro Identification and Isolation of Human Neutrophil Extracellular Traps.

Neutrophils release web like-structures known as neutrophil extracellular traps (NETs) that ensnare and kill microorganisms. These networks are constituted of a DNA scaffold with associated antimicrobial proteins, which are released to the extracellular space as an effective mechanism to fight against invading microorganisms. In parallel with this beneficial role to avoid microbial dissemination and wall off infections, accumulating evidence supports that under certain circumstances, NETs can exert deleterious effects in inflammatory, autoimmune, and thrombotic pathologies. Research on NET properties and their role in pathophysiological processes is a rapidly evolving and expanding field. Here, we describe a combination of methods to achieve a successful in vitro NET visualization, semiquantification, and isolation.

Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency: Rationale and Methodology of a Prospective, Observational, Multicenter Cohort Study.

OBJECTIVES: We describe the methodology of Post-Acute Pancreatitis Pancreatic Exocrine Insufficiency (PAPPEI), a prospective, observational, multicenter cohort study. The objectives of PAPPEI are to estimate the incidence rate of post-acute pancreatitis (AP) pancreatic exocrine insufficiency (PEI), define factors that determine the development of post-AP PEI, and evaluate the impact of post-AP PEI on nutritional status and quality of life. METHODS: Enrollment started in June 2017 in 3 expert academic centers in the United States. Data were collected during hospitalization (baseline) at 3 and 12 months after enrollment. Fecal elastase-1 was used to assess PEI. Study questionnaires are completed by patient interview and review of electronic medical records. Blood is obtained to evaluate vitamin deficiencies and nutritional markers. RESULTS: As of August 2020, 77 subjects have completed the baseline evaluation. The median age was 58 years (interquartile range, 39-67 years), 38% were male, and 90% were white. The etiology of AP was biliary in 39 subjects (51%), and 51 subjects (66%) had mild AP. Three- and 12-month follow-up data have been collected in 29 and 13 subjects, respectively. CONCLUSION: The PAPPEI study aims to expand our understanding of post-AP PEI incidence, including its impact on nutritional status and quality of life.

Liver and pancreas: 'Castor and Pollux' regarding the relationship between hepatic steatosis and pancreas exocrine insufficiency.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is found in 30-50% of diabetes mellitus (DM). Insulin resistance is triggering factor in both DM and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to investigate frequency of PEI in NAFLD, and relationship of fecal pancreatic elastase (PE) levels with liver histology and pancreatic fat. METHODS: Ninety-seven biopsy proven NAFLD patients and 50 controls were enrolled. Pancreas exocrine functions were measured by PE. Magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) was used to quantify fat. RESULTS: NAFLD patients had significantly lower PE levels than controls (297 [204-517] vs. 500 [298-678] µg/g, p < 0.01). PEI (PE < 200 µg/g) ratio of NAFLD patients (22.7%, n = 22) was higher than PEI ratio of controls (6%, n = 3) (p = 0.011). Among diabetic (n = 35) NAFLD patients, 9 (25.7%) exhibited PEI, compared to 13 (21%) of non-diabetics. There was no significant difference in patients with and without DM in terms of PEI (p = 0.592). Among NASH (n = 68) patients 16 (23.5%) exhibited PEI, compared to (20.7%) of non-NASH (p = 0.76). Multiple analysis revealed NAFLD as a predictor of PEI independent of age, sex and DM (OR = 4.892, p = 0,021). Mean pancreas MRI-PDFF was significantly higher in diabetics (13.7% ± 3.6% vs. 8.7% ± 5.1%, p = 0.001). There was no significant pancreas MRI-PDFF difference between NASH and non-NASH (P = 0.95). Mean pancreas MRI-PDFF was significantly higher in patients with PEI (13.7% ± 3.4% vs. 8.9% ± 5.2%, P < 0.01). CONCLUSION: This is the first study demonstrating the high frequency of PEI in NAFLD independent of DM. Moreover, increasing pancreatic steatosis appears to be associated with higher frequency of PEI in NAFLD.

Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor.

Prior to the use of cystic fibrosis (CF) modulator therapy, exocrine pancreatic insufficiency in CF was thought to be irreversible. Improvement in pancreatic function on ivacaftor has been reported in open label studies in 1-5 year olds. The mechanism by which ivacaftor might improve exocrine pancreatic function is unclear. Although the effect of ivacaftor on pancreatic function may be more significant in younger children, evidence is mounting that there may still be potential for improvement in older children on long term therapy.

Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice. OBJECTIVES: The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy. METHODS: Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy. RESULTS: One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%. CONCLUSIONS: In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

Changes in pancreatic exocrine function in young at-risk children followed to islet autoimmunity and type 1 diabetes in the ENDIA study.

BACKGROUNDS: We aimed to monitor pancreatic exocrine function longitudinally in relation to the development of islet autoimmunity (IA) and type 1 diabetes (T1D) in at-risk children with a first-degree relative with T1D, who were followed prospectively in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. METHODS: Fecal elastase-1 (FE-1) concentration was measured longitudinally in 85 ENDIA children from median age 1.0 (IQR 0.7,1.3) year. Twenty-eight of 85 children (progressors) developed persistent islet autoantibodies at median age of 1.5 (IQR 1.1,2.5) years, of whom 11 went on to develop clinical diabetes. The other 57 islet autoantibody-negative children (non-progressors) followed similarly were age and gender-matched with the progressors. An adjusted linear mixed model compared FE-1 concentrations in progressors and non-progressors. RESULTS: Baseline FE-1 did not differ between progressors and non-progressors, or by HLA DR type or proband status. FE-1 decreased over time in progressors in comparison to non-progressors (Wald statistic 5.46, P = .02); in some progressors the fall in FE-1 preceded the onset of IA. CONCLUSIONS: Pancreatic exocrine function decreases in the majority of young at-risk children who progress to IA and T1D.

Which factors determine exocrine pancreatic dysfunction in diabetes mellitus?

The exocrine structure is significantly affected by diabetes because of endocrine structure-function disorder within the pancreas. Exocrine pancreatic dysfunction (EPD) is the general name of the malabsorption process resulting from inadequate production, release, decreased activation, and/or insufficient degradation of enzymes required for digestion from pancreatic acinar cells. It is important to diagnose patients early and correctly, since there may be both macro- and micro-nutrient deficiency in EPD. In this paper, EPD, the diabetes-EPD relationship, and the predictive, effective factors affecting the emergence of EPD are briefly explained and summarized with contemporary literature and our experienced based on clinical, lab, and radiological findings.

Pancreatic Steatosis Is Associated With Impaired Exocrine Pancreatic Function.

OBJECTIVES: The aim of this study was to investigate if pancreatic steatosis measured by proton density fat fraction (PDFF) is associated with exocrine pancreatic function defined by fecal elastase concentrations. MATERIALS AND METHODS: A total of 1458 volunteers (777 women; age range, 21-88 years) underwent magnetic resonance imaging of the pancreas, and organ fat content was quantified by using confounder corrected PDFF. Exocrine pancreatic function was categorized by fecal elastase levels using defined cutoffs: greater than 200 µg/g normal function (n = 1319) and 200 µg/g or less impaired function (n = 139). Statistical analysis to correlate pancreatic fat content with fecal elastase included linear regression, and analyses were adjusted for known confounders for pancreatic steatosis, such as age, sex, and body mass index. RESULTS: Overall mean (±standard deviation) of pancreatic fat content was 7.50% ± 3.78%. Pancreatic fat content was significantly higher in subjects with impaired pancreatic exocrine function (9.36% ± 4.95%) compared with subjects with normal function (7.30% ± 3.59%; P < 0.01). Linear regression analyses showed an inverse correlation between pancreatic fat and fecal elastase levels over the whole study population (beta, -7.19 [standard error, 1.39]; P < 0.01) as well as in the subgroup of subjects with normal function (-4.26 [1.32]; P < 0.01). Among subjects with impaired pancreatic exocrine function, a trend toward an inverse relation was detected (-1.28 [0.84]; P < 0.13). CONCLUSIONS: An inverse correlation between PDFF of the pancreas and fecal elastase suggests an association between pancreatic steatosis and impaired pancreatic exocrine function.

Zinc deficiency in patients with chronic pancreatitis.

BACKGROUND: Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis (CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency (PEI), which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting results. AIM: To investigate serum zinc levels in patients with CP of various etiologies. METHODS: Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the M-ANNHEIM classification system into the following etiological subcategories: alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal (fecal elastase 1 > 200 µg/g), mildly reduced (100-200 µg/g) and severely reduced (fecal elastase 1 < 100 µg/g). RESULTS: A total of 150 patients were included in the analysis. Zinc deficiency (< 11 µmol/L) was present in 39 (26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency (FE-1 < 200 µg/g). Older age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients < 40 years of age [OR: 3.8, 95%CI (1.08-13.4); P = 0.04]; [OR 6.26, 95%CI (1.94-20.2), P > 0.002]. Smoking and number of pack-years were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher compared to those who had never smoked. Gender, body mass index, etiology of CP, presence of diabetes mellitus, levels of glycated hemoglobin (HbA1c), bone mineral density, alcohol intake and presence of PEI were not associated with low zinc levels. CONCLUSION: Zinc deficiency is common in patients with CP and is significantly associated with age ≥ 60, smoking and the number of pack-years, but not with PEI.

Nutritional markers in patients with diabetes and pancreatic exocrine failure.

AIMS: Altered pancreatic exocrine function can be observed in patients with type 1 or type 2 diabetes. In the present study, we evaluated the potential nutritional consequences of this dysfunction. METHODS: Serum concentrations of nutritional markers, including albumin, cholesterol, triacylglycerol, vitamins A, D, and E, were assessed in a cohort of 468 patients (137 with type 1 diabetes and 331 with type 2 diabetes), after exclusion of the patients with a CRP > 10 mg/l. These patients were compared with 47 patients with diseases of the exocrine pancreas and diabetes (type 3c diabetes or pancreatogenic diabetes). Fecal elastase-1 and chymotrypsin concentrations were measured and patients with type 1 and type 2 diabetes were divided into three groups according to whether zero (group NN), one (group LN), or both (group LL) concentrations were decreased. RESULTS: Several markers differed significantly between the groups of patients, including BMI, albumin, phosphorus, and fat-soluble vitamins. Patients with pancreatogenic diabetes had markedly more profound alterations than patients with type 1 or type 2 diabetes and altered exocrine function. However, patients with type 1 or type 2 diabetes and decreased concentrations of both elastase-1 and chymotrypsin had lower albumin, phosphorus, and vitamin A than patients with normal pancreatic exocrine function. CONCLUSIONS: Modest nutritional alterations were found in patients with type 1 or type 2 diabetes and altered exocrine function. Patients with type 1 or type 2 diabetes and altered exocrine function may thus deserve to be screened for nutritional deficiencies.

Transient Exocrine Pancreatic Insufficiency in Children: An Existing Entity?

OBJECTIVES: Pancreatic insufficiency in children is usually associated with diseases such as cystic fibrosis, Shwachman-Diamond syndrome, or chronic pancreatitis. Fecal elastase-1 is a reliable laboratory test for the diagnosis of exocrine pancreatic insufficiency (EPI). Transient pancreatic insufficiency has been rarely described and data on this entity are lacking in the medical literature. In this retrospective study we report 17 cases of transient pancreatic insufficiency presented mainly with failure to thrive and/or diarrhea. METHODS: We followed 43 children (age range 1 month-18 years) with low fecal elastase-1 in our institution between the years 2009 and 2017. We followed growth and laboratory results (particularly, complete blood count, albumin, transaminases, celiac serology, sweat test, and fat-soluble vitamins). Elastase levels <200 mg/g were considered as pancreatic insufficiency. RESULTS: Twenty-six were excluded due to missing data, a comorbidity or being syndromatic. Enrolled children (17) were all otherwise healthy.The median age at diagnosis was 3 years (range 0.2-15 years), 11 girls and 6 boys. Their main presenting symptoms were failure to thrive and/or diarrhea. Median fecal elastase-1 levels were 71 mg/g (range 18-160). Median time for normalization was 6 months (range 1-48 months). Abdominal sonography, celiac serology, and sweat test were normal for all patients. Most patients were treated with pancreatic enzymes until resolution. CONCLUSIONS: Transient EPI without clear etiology should be in the differential diagnosis of EPI after ruling out known etiologies. The resolving course pattern may be attributed to an unidentified infectious agent. Further studies to assess the etiology are mandated.

Incomplete functional and morphological recovery after acute and acute recurrent pancreatitis in children.

BACKGROUND AND AIM: There is lack of data on functional and morphological recovery after an attack of acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in children. This study aims to evaluate the functional impairment and morphological changes in the pancreas after recovery. METHODS: All consecutive patients presenting with AP (n = 61) or ARP (n = 35), as per standard diagnostic criteria, were enrolled. After 2 months of pancreatitis, fecal elastase-1 (FE-1) (µg/g) and 2-h oral glucose tolerance test to calculate oral disposition index (DIo ) (mmol/L) (ß-cell function) were performed. Morphological changes were assessed by endoscopic ultrasound and transabdominal ultrasound. Patients with chronic pancreatitis (CP) (n = 27) and healthy children (HC) (n = 26) were included as controls for functional parameters. RESULTS: At a median follow up of 12 (4-44) and 11 (2-108) months, 66.7% and 75.9% (P = 0.57) of AP and ARP demonstrated exocrine insufficiency (FE-1 < 200), respectively. Mean (SD) FE-1 was 183.64 ± 150.94 (AP), 135.70 ± 103.80 (ARP), 46.56 ± 30.20 (CP), and 240.00 ± 181.83 (HC) (P < 0.001; anova) (AP vs CP, ARP vs CP, and CP vs HC; P < 0.001). Prediabetes due to insulin resistance was seen in 16.6% and 22.6% (P = 0.56) of AP and ARP. Median (interquartile range) DIo (mmol/L) was comparable between AP (4.20 [2.36, 8.3]) and HC (5.20 [2.89, 8.68]), but was low in ARP (2.97 [1.80, 5.12]), which was comparable with CP (1.91 [1.20, 2.83]). Endoscopic ultrasound demonstrated morphological changes in 25% and 37% (P = 0.34) of AP and ARP, respectively. CONCLUSION: There was high frequency of biochemical evidence of exocrine insufficiency. ß-Cell function (DIo ) was preserved among AP but was poor in ARP. Nearly one-third showed morphological changes in imaging.