Background & Aims
Idiopathic chronic pancreatitis (ICP) is a complex inflammatory disorder associated with multiple genetic and environmental factors. In individuals without cystic fibrosis (CF), variants of CFTR that inhibit bicarbonate conductance but maintain chloride conductance might selectively impair secretion of pancreatic juice, leading to trypsin activation and pancreatitis. We investigated whether sequence variants in the gene encoding the pancreatic secretory trypsin inhibitor, SPINK1, further increase the risk of pancreatitis in these patients.
Methods
We screened patients with ICP (sporadic or familial) and controls for variants in SPINK1 associated with chronic pancreatitis (CP) risk (in exon 3) and in all 27 exons of CFTR. The final study group included 53 patients with sporadic ICP, 27 probands with familial ICP, and 150 unrelated controls, plus 503 controls for limited genotyping. CFTR wild-type (wt) and p.R75Q were cloned and expressed in HEK293 cells and relative conductances of HCO3− and Cl− were measured.
Results
SPINK1 variants were identified in 36% of subjects and 3% controls (odds ratio [OR]=16.5). One variant of CFTR that has not been associated with CF, p.R75Q, was found in 16% of subjects and 5.4% controls (OR=3.4). Co-inheritance of CFTR p.R75Q and SPINK1 variants occurred in 8.75% of patients and 0.15% controls (OR=62.5). Patch-clamp recordings of cells that expressed CFTR p.R75Q demonstrated normal chloride currents but significantly reduced bicarbonate currents (P=0.0001).
Conclusions
The CFTR variant p.R75Q causes a selective defect in bicarbonate conductance and increases risk for pancreatitis. Co-inheritance of CF-associated, and some not associated, CFTR variants with SPINK1 variants significantly increase risk of ICP.
BackgroundBoth C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD.MethodsFifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system.ResultsSerum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels.ConclusionSerum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.
Aim
The aim of this study was to evaluate nutritional status and sarcopenia in patients with inflammatory bowel disease (IBD) in clinical remission.
Methods
A total of 344 patients with IBD in clinical remission were included in this cross-sectional study. Patients with clinical activity (Harvey-Bradshaw index >5 for Crohn’s disease and partial Mayo scores ≥5 for ulcerative colitis) were excluded. Sociodemographic, clinical, and anthropometric data were recorded. BMI was categorized according to WHO criteria. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire. Body composition included fat-free mass (FFM) analyzed with Tanita-330 ST. Muscle strength was measured with a Takei digital hand grip dynamometer using a standard protocol. Physical performance was measured as 4-m gait speed. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People 2 criteria.
Results
Overall, 5.5% of patients were underweight, 9.9% were malnourished, and 39.5% were at risk of malnutrition. Sarcopenia and probable sarcopenia were diagnosed in 41.3% of patients. Total number of flares requiring hospitalization (100%) was the most important predictor of sarcopenia, followed by total number of flares (80.1%), FFMI (46.5%), age (44.6%), BMI (31.8%), MNA score (27.7%), serum creatinine (23.6%), anti-tumor necrosis factor alpha use (23.3%), and gender (17.8%).
Conclusion
In conclusion, our findings revealed a considerable proportion of IBD patients in clinical remission to be malnourished or at risk of malnutrition along with a high rate of sarcopenia. This emphasizes the need for concomitant screening for nutritional status and body composition analysis in patients with IBD for provision of appropriate nutritional support, even during the remission period, and prevention of sarcopenia-related surgical and poor clinical outcomes.
It seems likely that mast cell activity may play an important role in the initiation and progression of acute pancreatitis. Ketotifen treatment may reduce the severity of AP in rats. The protective action of ketotifen in cerulein-induced acute pancreatitis is most probably owing to mast cell stabilization and stimulation of NO synthesis.
SDs are common in cirrhotics and STSQS could be an appropriate and practical method for diagnosis of SDS in these patients. We can use it in cirrhotic patients at outpatient clinics.
Sequential therapy using "rabeprazole and amoxicillin 7 days followed by rabeprazole, metronidazole and levofloxacin for 7 days" is a new regimen with acceptable eradication rates in naïve patients in Turkey. Further modifications in the dose or duration of this new sequential therapy might increase its effectiveness as both first and second line treatment.
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