Protocol design for randomized clinical trial to compare underwater cold snare polypectomy to conventional cold snare polypectomy for non-pedunculated colon polyps of size 5-10 mm (COLDWATER study).

BACKGROUND: Colorectal cancer is internationally the third leading cause of death from a malignant disease. The aim of screening colonoscopy in adults > 45 years of age is early diagnosis and treatment of precancerous polyps. Endoscopic polyp removal (polypectomy) can be achieved with various techniques depending on the size, morphology, and location of the polyp. According to current guidelines, small non-pedunculated polyps should be removed with a cold snare after the colorectal lumen has been insufflated with air (conventional cold snare polypectomy).In recent years, several studies have described the benefits of water aided colonoscopy, as well as the safety and efficacy of underwater cold snare polypectomy for large colon polyps. However, there are insufficient data on conventional and underwater techniques for small polyps, the most commonly diagnosed colorectal polyps. METHODS: We have designed a prospective randomized double-blind clinical trial to compare the safety and efficacy of conventional and underwater cold snare polypectomy for non-pedunculated polyps 5-10 mm in size. A total of 398 polyps will be randomized. Randomization will be carried out using the random numbers method of Microsoft Excel 2016. The primary endpoint is the muscularis mucosa resection rate. Secondary endpoints are the depth and percentage of R0 excisions, complications, and the recurrence rate at follow-up endoscopy 6-12 months after polypectomy. DISCUSSION: We hypothesize underwater polypectomy will result in a higher muscularis mucosa resection rate. The results of our study will provide useful data for the development of guidelines in polypectomy techniques for non-pedunculated polyps 5-10 mm in size. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT05273697.

Preoperative Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Perioperative Liver-Related Complications Following Liver Resection for Colorectal Cancer Metastases.

BACKGROUND AND AIMS: There are limited data on the potential role of preoperative non-invasive markers, specifically the aspartate-to-alanine aminotransferase ratio and the aspartate aminotransferase-to-platelet ratio index, in predicting perioperative liver-related complications after hepatectomy for colorectal cancer metastases. METHODS: Patients undergoing liver resection for colorectal cancer metastases in a European institution during 2003-2010 were retrospectively enrolled. Relevant data, such as neoadjuvant chemotherapy, preoperative liver function tests, and perioperative complications, were collected from medical records. The nontumorous liver parenchyma in the surgical specimens of 31 patients was re-evaluated. RESULTS: Overall, 215 patients were included. In total, 40% underwent neoadjuvant chemotherapy and 47% major resection, while 47% had perioperative complications (6% liver-related). In multivariate regression analysis, the aspartate aminotransferase-to-platelet ratio index was independently associated with liver-related complications (odds ratio: 1.149, p = 0.003) and perioperative liver failure (odds ratio: 1.155, p = 0.012). The latter was also true in the subcohort of patients with neoadjuvant chemotherapy (odds ratio: 1.157, p = 0.004) but not in those without such therapy (p = 0.062). The aspartate-to-alanine aminotransferase ratio was not related to liver-related complications (p = 0.929). The area under the receiver operating characteristics curve for the aspartate aminotransferase-to-platelet ratio index as a predictor of liver-related complications was 0.857 (p = 0.008) in patients with neoadjuvant chemotherapy. Increasing aspartate aminotransferase-to-platelet ratio index was observed with an increase in degrees of sinusoidal obstruction syndrome (p = 0.01) but not for fibrosis (p = 0.175) or steatosis (p = 0.173) in the nontumorous liver in surgical specimens. CONCLUSION: The preoperative aspartate aminotransferase-to-platelet ratio index, but not the aspartate-to-alanine aminotransferase ratio, predicts perioperative liver-related complications following hepatectomy due to colorectal cancer metastases, in particular after neoadjuvant chemotherapy. The aspartate aminotransferase-to-platelet ratio index is related to sinusoidal obstruction syndrome in the nontumorous liver.

Intramammary lipopolysaccharide infusion alters gene expression but does not induce lysis of the bovine corpus luteum.

Data from various studies indicate that the ovarian function in dairy cows can be compromised during intramammary infections. Therefore, in this study, we investigated if an experimentally induced mastitis has an effect on corpus luteum (CL) function in 14 lactating cows. On d 9 of the estrous cycle (d 1=ovulation), cows received a single dose of 200 µg of Escherichia coli lipopolysaccharide (LPS; dissolved in 10 mL of NaCL; n=8) or 10 mL of saline (control; n=6) into one quarter of the mammary gland. Measurements included plasma cortisol, haptoglobin, and progesterone (P4) concentrations, as well as luteal size (LTA) and relative luteal blood flow (rLBF). Sampling was performed on d 1, 4, and 8. On d 9, the main examination day, sampling was performed immediately before (0 h), every 1h (or at 3-h intervals for LTA and rLBF) until 9 h, as well as 12 and 24 h after treatment. Thereafter, measurements were taken on d 12, 15, 18, and then every 2 d until ovulation. Luteal tissue was collected for biopsy 24 h before and 6 h after treatment. Quantitative real-time PCR was applied to assess mRNA expression of steroidogenic factors (STAR, HSD3B), caspase 3, toll-like receptors (TLR2, -4), tumor necrosis factor α (TNFA), and prostaglandin-related factors (PGES, PGFS, PTGFR). Intramammary LPS infusion caused considerable inflammatory responses in the treated udder quarters. No decrease in plasma P4 concentrations was noted after LPS-challenge, and P4 levels did not differ between LPS-treated and control cows. Furthermore, LTA and rLBF values were not decreased after LPS challenge compared with the values obtained immediately before treatment. However, LPS infusion increased plasma levels of cortisol and haptoglobin compared with the control group. In the CL, mRNA abundance of TLR2 and TNFA was increased in cows after LPS-challenge (but not in control cows), whereas TLR4, steroidogenic, and prostaglandin-related factors remained similar to the mRNA abundance before treatment. In conclusion, intramammary LPS challenge induces systemic inflammatory reactions which alter the luteal mRNA abundance of TLR2 and TNFA but does not induce lysis of the CL.

Use of statins in patients with liver disease.

Statins are generally well tolerated and shown to have a good safety profile. In clinical trials a similar proportion of patients randomized to statins and placebo treated developed abnormal liver tests. However, idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction and clinical trials are underpowered to detect uncommon side effects. Although probably very rare, idiosyncratic DILI due to statins has been reported among other drugs in all major prospective and retrospective series on DILI. A summary of 40 cases of statin hepatoxicity has been published and, a series of 76 cases suspected statin induced liver injury has recently been published. In the last mentioned series, three patients died and/or underwent liver transplantation and three cases had a rechallenge with the same statin which produced a similar pattern of liver injury. Statin therapy appears to be safe in the treatment of non-alcoholic fatty liver disease, in compensated patients with chronic hepatitis B or C. Statins have also been shown to have an inhibitory effect on hepatitis C virus replication in vitro. Retrospective data as well as data from a recent randomized controlled trial suggest that statin therapy might be a useful adjunct to standard combination antiviral therapy in patients with chronic hepatitis C. Statin therapy seems to be related to a reduced risk for hepatocellular carcinoma in patients with chronic liver disease, but randomized data are lacking.

Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case-control study.

Increased incidence and severity of Clostridium difficile infections (CDIs) is of major concern. However, by minimizing known risk factors, the incidence can be decreased. The aim of this investigation was to calculate the incidence and assess risk factors for CDI in our population. A 1-year prospective population-based nationwide study in Iceland of CDIs was carried out. For risk factor evaluation, each case was matched with two age- and sex-matched controls that tested negative for C. difficile toxin. A total of 128 CDIs were identified. The crude incidence was 54 cases annually per 100,000 population >18 years of age. Incidence increased exponentially with older age (319 per 100,000 population >86 years of age). Community-acquired origin was 27 %. Independent risk factors included: dicloxacillin (odds ratio [OR]: 7.55, 95 % confidence interval [CI]: 1.89-30.1), clindamycin (OR: 6.09, 95 % CI: 2.23-16.61), ceftriaxone (OR: 4.28, 95 % CI: 1.59-11.49), living in a retirement home (OR: 3.9, 95 % CI: 1.69-9.16), recent hospital stay (OR: 2.3, 95 % CI: 1.37-3.87). Proton pump inhibitors (PPIs) were used by 60/111 (54 %) versus 91/222 (41 %) (p = 0.026) and ciprofloxacin 19/111 (17 %) versus 19/222 (9 %) (p = 0.027) for cases and controls, respectively. In all, 75 % of primary CDIs treated with metronidazole recovered from one course of treatment. CDI was mostly found among elderly patients. The most commonly identified risk factors were broad-spectrum antibiotics and recent contact with health care institutions. PPI use was significantly more prevalent among CDI patients.

Review article: autoimmune pancreatitis - management of an emerging disease.

BACKGROUND: Autoimmune pancreatitis is a steroid-responsive inflammatory pancreatic disease considered to be part of an immunoglobulin G4 (IgG4)-associated systemic disease. AIM: To review the management of autoimmune pancreatitis. METHODS: We conducted a PubMed search using the following key words: autoimmune pancreatitis, IgG4-associated systemic disease, IgG4-associated cholangitis, diagnosis, natural history, treatment. RESULTS: Although there are reports of spontaneous resolution of autoimmune pancreatitis, steroids have been shown to be effective in inducing remission, reducing the frequency of relapse and that of long-term unfavourable events compared to historical controls. There are no randomised data on autoimmune pancreatitis treatment. Oral steroids are used for induction of remission. Reported response results are excellent with variable proportions of patients achieving remission in different studies. After a period of 2-4 weeks, steroids are tapered and usually withdrawn within several months, although long-term maintenance therapy for all autoimmune pancreatitis patients has also been proposed. Disease relapse occurs in more than 40% of patients and can be effectively treated with additional immunosuppression, including azathioprine. CONCLUSIONS: Steroids are effective in inducing remission and in treating relapse in patients with autoimmune pancreatitis. Randomised trials on autoimmune pancreatitis therapy are lacking. To date, questions concerning the timing, choice and duration of long-term immunosuppression remain unanswered.

Macromineral status of dairy cows with concurrent left abomasal displacement and fatty liver.

AIM: To evaluate the macromineral status of field cases of dairy cows surgically treated for left abomasal displacement (LDA), with concurrent fatty liver of different severity, and compare this for animals that died or recovered. METHODS: Sixty-eight Holstein dairy cows with LDA and 110 control cows, from 28 farms, were used in the study. Blood samples and liver biopsies were obtained during standing surgery for correction of LDA, and from control cows. The concentration of macrominerals in serum, and of total lipids (tLPD) and triglycerides (TG) in liver were determined. Liver was examined histologically, and classified for its severity of fatty liver. Cows with LDA were grouped according to severity of fatty liver. Cows in Groups 1 to 3 recovered, whereas those in Group 4 died within 4 weeks of surgery. Group 1 = mild (n=4) or moderate (n=6 cows, n=4 heifers) fatty liver, Group 2 = moderate to severe fatty liver (n=13), Group 3 = severe fatty liver (n=15 cows, n=5 heifers), Group 4 = severe fatty liver (n=17 cows, n=4 heifers). RESULTS: The concentration of macrominerals in serum was affected by the concurrence of fatty liver and LDA; Ca, K and Mg were significantly (p<0.05) lower in animals that died than those that survived. For cows with severe fatty liver, concentrations of tLD and TG were higher in the animals that died compared with those that recovered (p<0.01). Cows with LDA and severe fatty liver that died were earlier in lactation (median days in milk (DIM) 13 days) compared with the other cows with LDA (median DIM 21-26 days) (p<0.05); they were also significantly older (median 6 years old) than cows in the other groups (median 4 or 5 years old) (p<0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of macrominerals in serum were influenced by the concurrence of LDA and fatty liver. Animals with low concentrations of Ca, K and Mg had a guarded prognosis. The concentration of K should always be evaluated in cows with LDA and concurrent fatty liver when providing a prognosis. Most cows with severe fatty liver were detected in the first 4 weeks of lactation, but older animals and those that had more recently calved had a worse prognosis.

Comparison of general vs regional anaesthesia for BM harvesting: a retrospective study of anaesthesia-related complications.

This retrospective study was conducted to evaluate the safety and complications profile of general anaesthesia (GA) compared with that of regional anaesthesia (RA) for BM harvesting (BMH). The study included 281 donations carried out between 1992 and 1999. Of these, 204 (73%) were allogeneic donations, and GA was carried out in 69% (140 of 204) and RA in 31% (64 of 204) of cases. The other 77 donations were autologous (27%), using GA in 87% (67 of 77) and RA in 13% (10 of 77) of cases. No life-threatening complications occurred, but there were minor intra- and postoperative events during 26 (9%) and after 58 (21%) donations. Postoperative nausea and vomiting was reported in 40 (14%) cases and post-spinal headache after five out of 58 (8.6%) donations in which spinal anaesthesia was carried out. The incidence of intra- and postoperative events did not differ significantly between the GA and RA groups. However, the incidence of postoperative events was higher in the allogeneic group compared with that in the autologous group (25 vs 10%, P<0.01) and in female donors compared with male donors (29 vs 14%, P=0.002). In conclusion, both GA and RA are comparable with regard to BMH. Nevertheless, non-severe intra- and postoperative events were frequent.

Factors affecting the reproductive performance of Awassi sheep flocks in north-east of Jordan: an epidemiological study.

A prospective cohort study was conducted using 32 randomly selected Awassi sheep flocks to identify factors hypothesized to be associated with the occurrence of pregnancy, twinning and fetal loss between August 2005 and May 2006 in the region of Al-Safawi (northeast of Jordan). Vitamins A and E and selenium concentrations were determined on 448 blood samples. Using the forward selection procedure of the logistic regression module, models with statistically significant risk factors (P < 0.05) were constructed for three outcomes; pregnancy, twinning and fetal loss. Serum vitamin A concentration levels were associated with pregnancy (OR = 2.26, 2.48), twinning (OR = 6.49, 17.74) and fetal loss (OR = 0.13, 0.19). Primiparous ewes were 48% less likely to become pregnant than fourth or higher parity ewes. The likelihood of twinning increased significantly in ewes up to the third parity. Ewes that were fed 700-900 g barley, 250-300 g wheat-bran per head per day and grazed on vegetables residues were 4.15 times more likely to have twins than ewes that were fed 600 g barley and 200 g wheat-bran per head per day. Fetal loss in first and second parity ewes was about 3 times more likely than that in third or higher-parity ewes. Ewes pregnant with twins were about 14 times more likely to have fetal loss than ewes carrying single fetus. Pregnant ewes of the stationary flocks were 37% less likely to have fetal loss than ewes of the semi-nomadic flocks. These results demonstrate that stationary Awassi sheep flocks had higher pregnancy and twinning rates and less pregnancy loss. Supplementation of vitamin A, providing sufficient quantity of dry feed and increasing ram: ewe ratio for primiparous ewes of semi-nomadic flocks is essential to improve Awassi sheep reproductive performance.

Defining the lymph node burden in a Northern European population without malignancy: the potential effect of geography in determining a need for FNA?

Data from the USA suggest that morphological specificity is insufficient to permit an assumption of malignancy in nodal staging with endoscopic ultrasound (EUS). This may not hold true elsewhere as the background lymph node burden may vary in different geographic regions. We aimed to assess the prevalence and features of mediastinal and abdominal lymph nodes at EUS in a Northern European population without malignant disease. A total of 129 consecutive patients without malignant disease referred for radial EUS were prospectively evaluated for the prevalence and echo features of lymph nodes in the mediastinum and upper abdomen. Sixty-two percent of patients had mediastinal lymph nodes and 17% had abdominal nodes at EUS. A mean of 1.4 (standard deviation 1.3, range 0-8) nodes were found per patient. No celiac nodes were seen. The majority of detected nodes were 0.5 cm or less in short axis, had oval shape, centrally echogenic pattern, and indistinct borders. The most common node locations were the subcarinal and paraesophageal areas, and the hepatoduodenal ligament. In multivariate analysis mediastinal lymphadenopathy was related to body mass index and abdominal lymphadenopathy to acute pancreatitis. The occurence of mediastinal lymphadenopathy is markedly lower in Northern Europeans than reported for US patients. Celiac nodes are extremely rare in patients without malignancy. The majority of nodes have a width of 0.5 cm or less, have oval shape, centrally echogenic pattern, and indistinct borders. The characterization of the background lymph node burden may improve the selection of lymph nodes for fine needle aspiration.

The impact of eosinophilia and hepatic necrosis on prognosis in patients with drug-induced liver injury.

BACKGROUND: Drug-induced liver injury may be immunologically mediated or metabolically induced. Peripheral eosinophilia and liver eosinophilia in suspected drug-induced liver injury generally supports the role of drug aetiology. AIM: To assess the importance of eosinophilia and hepatic necrosis on outcome in patients with suspected drug-induced liver injury. METHODS: We performed search of MEDLINE for case reports on drug-induced liver injury associated with: amoxicillin/clavulanic acid, carbamazepine, diclofenac, disulfiram, erythromycin, flucloxacillin, halothane, isoniazid, phenytoin, sulindac and trimethoprim/sulfametoxazol. RESULTS: A total of 570 case reports were retrieved. Mortality/transplantation occurred in 112 (20%). Eosinophilia in peripheral blood was reported in 34% of cases, eosinophilia in liver biopsies in 40%, and hepatic necrosis in 41%. Bilirubin levels were lower in patients with peripheral eosinophilia [5.5 x upper limit of normal (interquartile range 2.9-10) vs. 7.7 (4-17); P = 0.02] and patients with liver eosinophilia [5 x upper limit of normal (2.7-10) vs. 10 (5.4-20); P = 0.003] as compared with those without eosinophilia. Eosinophilia in peripheral blood and eosinophilia in liver biopsies were more common in patients who recovered (37% vs. 15.6%; P = 0.0001 and 48% vs. 18.8%; P < 0.0001, respectively). Hepatic necrosis was present in 24% in the survivors vs. 84% in non-survivors (P < 0.0001). CONCLUSIONS: In drug-induced liver injury, a favourable outcome was related to the occurrence of eosinophilia, whereas hepatic necrosis was associated with a poor prognosis.

Long-term follow-up of patients with mild to moderate drug-induced liver injury.

AIM: To evaluate the long-term prognosis of patients diagnosed with drug-induced liver injury, and the nature of the liver injury. METHODS: Patients with a diagnosis of drug-induced liver injury between 1994 and 2005 were identified in a university hospital clinic. Patients surviving drug-induced liver injury-associated liver failure were excluded. RESULTS: Seventy-seven cases were identified and those who were alive (69) were invited to attend follow-up. Of those patients who had died, none had died of liver disease. Of those patients who had survived, 59 were reviewed in the clinic. Patients had a median follow-up of 48 months. Before the diagnosis of drug-induced liver injury, nine had a chronic liver disease, four with autoimmune hepatitis, two with non-alcoholic liver disease, one each with non-alcoholic fatty liver disease, primary biliary cirrhosis and primary sclerosing cholangitis. There was no evidence of progression of their liver disease during follow-up. Among 50 patients without a known liver disease prior to the drug-induced liver injury, 10 had abnormal liver tests. Diagnostic work-up revealed alternative cause of liver disease in all except three patients (6%), who had asymptomatic abnormal liver tests (but normal bilirubin in all). CONCLUSIONS: Chronic abnormalities in liver tests, not explained by an identified liver disease, are very rare in patients previously diagnosed with drug-induced liver injury. This group of patients did not seem to have a clinically significant liver injury at long-term follow-up.

Intestinal paracellular permeability is not affected in chronic congestive heart failure.

BACKGROUND: In chronic heart failure (CHF) it has been proposed that a dysfunction of the gastrointestinal barrier could lead to translocation of endotoxin into the systemic circulation. A secondary inflammatory reaction, observed as increased levels of cytokines, could negatively affect cardiac function. The aims of this paper were therefore to determine whether patients with CHF have a disturbed mucosal barrier and whether it was possible to detect endotoxin in venous blood. METHODS: Nineteen stable patients with CHF (New York Heart Association II-III, EF40% and earlier hospitalisation for heart failure) were investigated. Twenty healthy subjects (HS group) and 25 patients, who were admitted for bone marrow transplantation (BMT group), served as controls. Gastrointestinal permeability was assessed by a (51)Cr-EDTA absorption test. RESULTS: Eleven patients with and eight without peripheral oedema were included. Median age was 76.5 years. Intestinal permeability was 1.82+/-1.96% in the CHF patients and 1.54+/-.59% and 1.9+/-.9% in HS and BMT groups, respectively (p=0.4 and p=0.7, CHF vs HS and BMT, respectively). No difference was found between patients with and without oedema and endotoxins were below the detection limit in all patients. DISCUSSION: This study does not support the hypothesis that patients with CHF have a dysfunctional gastrointestinal barrier, at least as assessed by the (51)Cr-EDTA resorbtion test.

Selenium, vitamin E and vitamin A status in dairy sheep reared under different feeding systems in Greece.

The main purpose of the study was to investigate whether the feeding system applied has any effect on the status of blood selenium (Se) and vitamins A and E in dairy sheep. In total 200 dairy sheep from 10 flocks were used in the study (20 animals per flock). Group A consisted of 100 sheep (five flocks) reared under the intensive feeding system and group B of 100 sheep (five flocks) reared under the semi-intensive feeding system. The 100 sheep of each group consisted of 25 lambs aged 3-6 months, 25 ewes 1-3 years, 25 ewes more than 3 years and 25 non-lactating ewes in late gestation. Another purpose was to evaluate the potential effect of the age and the reproductive stage of the animals on these parameters. To determine the effect of age, 150 of these animals were divided into three subgroups: 50 lambs, 50 non-pregnant lactating ewes aged 1-3 years and 50 non-pregnant lactating ewes aged more than 3 years. For the evaluation of the effect of the reproductive stage the 50 non-lactating ewes in late gestation and the 100 non-pregnant lactating ewes were used. Blood samplings were performed once, between December and January for non-lactating ewes in late gestation and March to May for lambs and lactating ewes. Whole blood Se and vitamin E and A serum concentrations were determined. The main conclusion is that the feeding system significantly affects Se and serum vitamin A concentration, as they were higher in the intensive one. It was secondly concluded that age affects the serum concentrations of vitamin A.

Seasonal variation of Oestrus ovis-specific antibodies in sheep and goats mixed flocks in Greece.

The aim of this survey was to investigate the year-round epidemiological patterns of Oestrus ovis ELISA sero-prevalence in sheep and goats kept together under the same husbandry system in an endemic area of Greece. Twenty-five adult female sheep and 25 adult female goats, coming from a large mixed flock, were randomly selected, eartaged and monthly blood sampled during 1 year period (November 1998-October 1999). Serological prevalence in sheep was 100% all around the year. Mean intensities of specific O. ovis antibodies follow a seasonal evolution with higher mean titers between March and July than in winter. In contrast, the serological prevalences in goats were low specially in winter months (from October to January). No significant difference were noticed in goats antibody levels during the year period. The possible reasons of this difference of O. ovis sero-prevalence between sheep and goats are discussed.