This diagnostic prospective study compared the feasibility and diagnostic accuracy of Pocket-size Ultrasound Devices (PUDs) against standard ultrasound (US) in detecting liver steatosis using the ...controlled attenuation parameter (CAP) and liver biopsy as reference standards.
Consecutive patients with chronic liver diseases were assessed for the presence of steatosis using PUD and US. A CAP cut-off value >275 dB/m was applied to establish ≥S1. A 26-patient subgroup underwent liver biopsy. PUD reproducibility was evaluated using Cohen's k statistic. Diagnostic accuracy of PUD and US was given as Sensibility (Sn), Specificity (Sp), Positive and Negative Predictive Values (PPV, NPV), positive and negative Likelihood Ratio (LR+, LR-).
81 consecutive patients (69% males) with multiple etiologies were enroled. PUD inter-observer agreement was good (k 0.77, 95%CI 0.62–0.93). PUD and US identified ≥S1 according to CAP values respectively with Sn 0.87, Sp 0.61, PPV 0.49, NPV 0.91, LR+ 2.04, LR- 0.07, AUROC 0.74 and Sn 0.96, Sp 0.54, PPV 0.47, NPV 0.97, LR+ 2.10, LR- 0.07, AUROC 0.75.
PUD shows good reproducibility and diagnostic accuracy in ruling liver steatosis out, representing a useful point-of-care tool to avail of hepatologists interested in excluding NAFLD, but with basic US skills.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Declining mobility is a major concern, as well as a major source of health care costs, among the elderly population. Lack of mobility is a primary cause of entry into managed care facilities, and a ...contributing factor to the frequency of damaging falls. Exercise-based therapies have shown great promise in sustaining mobility in elderly patients, as well as in rodent models. However, the genetic basis of the changing physiological responses to exercise during aging is not well understood. Here, we describe the first exercise-training paradigm in an invertebrate genetic model system. Flies are exercised by a mechanized platform, known as the Power Tower, that rapidly, repeatedly, induces their innate instinct for negative geotaxis. When young flies are subjected to a carefully controlled, ramped paradigm of exercise-training, they display significant reduction in age-related decline in mobility and cardiac performance. Fly lines with improved mitochondrial efficiency display some of the phenotypes observed in wild-type exercised flies. The exercise response in flies is influenced by the amount of protein and lipid, but not carbohydrate, in the diet. The development of an exercise-training model in Drosophila melanogaster opens the way to direct testing of single-gene based genetic therapies for improved mobility in aged animals, as well as unbiased genetic screens for loci involved in the changing response to exercise during aging.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and ...efficacy of switching from originator IFX to CT‐P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX‐double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single‐switched from originator IFX to CT‐P13 was performed, before and after an inverse probability of treatment weighting (IPTW)‐based propensity score analysis. Fifty‐two double‐switched patients with IBD were enrolled. The 24‐ and 52‐week proportions of patients continuing on IFX therapy following the second switch (CTP13 → SB2) were 98% (95% confidence interval CI 94%–100%) and 90% (95% CI 81%–99%), respectively. Four patients experienced a total of five AEs, all graded 1–3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24‐week and follow‐up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double‐switch group with a single‐switch group of 66 patients with IBD; all these results were confirmed by IPTW‐adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT‐P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
AIM：To evaluate the role of sequential therapy and Lactobacillus reuteri （L. reuteri ） supplementation, in the eradication treatment of Helicobacter pylori （H. pylori ）. METHODS：H. pylori infection ...was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor （PPI）, H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies：（1） 7-d triple therapy （PPI plus clarithromycin and amoxicillin or metronidazole） plus L. reuteri supplementation dur- ing antibiotic treatment; （2） 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; （3） sequential regimen （5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole） plus L. reuteri supplementation during antibiotic treatment; and （4） sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS：Ninety adult dyspeptic patients were en- rolled, and 83 （30 male, 53 female; mean age 57 ± 13 years） completed the study. Nineteen patients were administered a 7-d triple treatment：11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen：32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen （88% vs 63%, P = 0.01）. No difference was found between two types of PPI. No difference in erad- ication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION：The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.
Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis UC. Transmural activity, as defined by Milan Ultrasound Criteria MUC > 6.2, reliably detects ...endoscopic activity in patients with UC. The present study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy.
Consecutive adult UC patients were recruited in two IBD Referral Centres and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. Receiver operating characteristic ROC analysis was used to compare MUC baseline values and Mayo Endoscopic Scores MES in predicting colectomy risk.
Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (hazard ratio HR: 3.15, 95% confidence interval CI: 1.18-8.37, p = 0.02) and MUC HR: 1.48, 95% CI: 1.19-1.76, p < 0.001 were associated with colectomy risk, but only MUC was independently associated with this event on multivariable analysis HR: 1.46, 95% CI: 1.06-2.02, p = 0.02. MUC was the only independent variable associated with colectomy risk in patients with clinically active disease (odds ratio OR: 1.53 1.03-2.27, p = 0.03). MUC demonstrated higher accuracy than MES (area under ROC curve AUROC 0.83, 95% CI: 0.75-0.92 vs 0.71, 95% CI: 0.62-0.80) and better performance for predicting colectomy p = 0.02. The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7.
A superior predictive value was found for transmural vs endoscopic severity for colectomy risk in UC patients.
Background
Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC).
Aims
Considering the number of anti-TNF non-responders, this ...study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks.
Methods
From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events.
Results
We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (
p
= 0.023) and W24 (
p
= 0.004), and with a higher partial Mayo score at W8 (
p
= 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation.
Conclusions
In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
AbstractIntroduction and aimThe American Association for the Study of the Liver (AASLD) recommends contrast computerized tomography (CT-scan) and magnetic resonance (MRI) to diagnose hepatocellular ...carcinoma (HCC) arising in cirrhotic patients under semiannual surveillance with abdominal ultrasound (US). A US guided fine needle biopsy (FNB) serves the same purpose in radiologically undiagnosed tumors and incidentally detected nodules in cirrhotics outside surveillance. In this population, we evaluated the performance of radiological diagnosis of HCC according to 2010 AASLD recommendations. Materials and methodsAll cirrhotic patients with a liver nodule incidentally detected by US were prospectively investigated with a sequential application of CT-scan/MRI examination and a FNB. ResultsBetween 2011 and 2015, 94 patients (mean age 67 years) had a liver nodule (total 120) detected by US in the context of histologically confirmed cirrhosis. Mean nodules diameter was 40 (10–160) mm, 87 (73%) <5 cm. At histology, 84 (70%) nodules were HCC, 8 (7%) intrahepatic cholangiocarcinoma, 6 (5%) metastases, 2 (2%) neuroendocrine tumors and 20 (16%) benign lesions. Hyperenhancement in arterial phase followed by wash-out in venous phases on at least one radiological technique was demonstrated in 62 nodules (61 HCC, 1 high grade dysplastic nodule), with a specificity of 97% (IC95%: 85–100%), sensitivity 73% (IC95%: 62–81%) and diagnostic accuracy 80%, being 64% for ≥5 cm HCC. Sensitivity of AFP >200 ng/mL was 12% (IC95%: 6–23%). ConclusionA single contrast imaging technique showing a typical contrast pattern confidently identifies HCC also in cirrhotic patients with an incidental liver nodule, thereby reducing the need for FNB examinations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Overt hepatic encephalopathy (HE) affects patients' quantity and quality of life and places a burden on families. There is evidence that overt HE might be prevented pharmacologically, but prophylaxis ...would be justified and cost effective only for patients at risk. We aimed to identify patients with cirrhosis at risk for overt HE.
We collected data from October 2009 through December 2012 for 216 consecutive patients with cirrhosis (based on liver biopsy, 96 patients with minimal HE), admitted to the Gastroenterology Unit at the University of Rome. Patients were followed up and evaluated for an average of 14.7 ± 11.6 months; development of overt HE was recorded. We analyzed end-stage liver disease scores, shunt placement, previous overt or minimal HE, psychometric hepatic encephalopathy score (PHES), and levels of albumin, bilirubin, creatinine, and sodium to develop a prediction model. We validated the model in 112 patients with cirrhosis seen at the University of Padua and followed up for 12 ± 9.5 months.
During the follow-up period, 68 patients (32%) developed at least 1 episode of overt HE. Based on multivariate analysis, the development of overt HE was associated with previous HE, minimal HE (based on PHES), and level of albumin less than 3.5 g/dL (area under curve AUC, 0.74). A model that excluded minimal HE but included albumin level and previous HE also identified patients who would develop overt HE (AUC, 0.71); this difference in AUC values was not statistically significant (P = .104). Both models were validated in the independent group of patients (3 variables: AUC, 0.74; 95% confidence interval, 0.66-0.83; and 2 variables: AUC, 0.71; 95% confidence interval, 0.63-0.78).
We developed and validated a model to identify patients with cirrhosis at risk for overt HE based on previous HE, albumin levels, and PHES. If PHES was not available, previous HE and albumin levels still can identify patients at risk. Psychometric evaluation is essential for patients with no history of HE. These findings should aid in planning studies of pharmacologic prevention of overt HE.
Background & Aims In patients with cirrhosis, cognitive dysfunction most often results from covert hepatic encephalopathy (HE). These patients are not tested routinely for cognitive dysfunction ...despite single-center evidence that it could be associated with poor socioeconomic status (SES). We investigated the association between SES and cognition in a multicenter study of cirrhosis. Methods In a cross-sectional study, 236 cirrhotic patients from 3 centers (84 subjects from Virginia, 102 from Ohio, and 50 from Rome, Italy; age 57.7 ± 8.6 y; 14% with prior overt HE) were given recommended cognitive tests and a validated SES questionnaire that included questions about employment, personal and family income, and overall financial security. Comparisons were made among centers and between subjects who were employed or not. Regression analysis was performed using employment and personal income as outcomes. Results Only 37% of subjects had been employed in the past year. Subjects had substantial financial insecurity—their yearly personal income ranged from $16,000 to $24,999, and their family income ranged from $25,000 to $49,999. They would be able to maintain a residence for only 3 to 6 months if their income stopped, and their current liquid assets were $500 to $4999 (<$500 if debt was subtracted). Cognition and SES were worst in Ohio and best in Virginia. Cognition correlated with personal and family income, within and between centers. On regression analysis, cognitive performance (digit symbol, lures, and line tracing) was associated with personal yearly income, after controlling for demographics, country, employment, and overt HE. Unemployed subjects had a higher rate of overt HE, worse cognition, and lower personal income than employed subjects. On regression analysis, performance on digit symbol, line tracing, inhibitory control test lures, and serial dotting tests remained associated with employment, similar to income. Conclusions In an international multicenter study of patients with cirrhosis, socioeconomic condition, based on employment and personal income, was associated strongly with cognitive performance, independent of age, education, and country.
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