The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug ...absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including
,
,
,
, and
, were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the
(rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in
(rs6811453),
(rs10008281),
(rs11401),
(rs7905939),
(rs2297595 and rs1801265),
(rs2020863), and
(rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription.
Despite the worldwide recommendations for influenza immunisation, vaccination coverage for patients exposed to the highest risk of severe complications is still far from the optimal target. The need ...to take advantage of alternative methods to provide vaccination is essential. This study presents a hospital-based strategy which offers influenza vaccination to inpatients at discharge. This study was conducted during the 2022-2023 influenza season at the University Hospital of Palermo. A questionnaire was administered to identify the determinants for the acceptance of influenza vaccination in the frail population. Overall, 248 hospitalised patients were enrolled, of which 56.1% were female and 52.0% were over 65 years of age. The proportion of patients vaccinated against influenza during hospitalisation was 62.5%, an increase of 16% in influenza vaccination uptake among frail people in comparison with the previous influenza season (46.8% vaccinated during the 2021-22 influenza season). Factors significantly associated with vaccination acceptance were the following: to have received influenza vaccine advice from hospital healthcare workers (OR = 3.57,
= 0.001), to have been previously vaccinated for influenza (OR = 3.16
= 0.005), and to have had a low level of education (OR = 3.56,
= 0.014). This study showed that offering influenza vaccination to hospitalised patients could be an effective strategy to increase vaccination coverage in the most vulnerable population, and these findings could be useful for planning and improving future influenza vaccination campaigns.
In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn’s disease (CD) by using intestinal ultrasound (IUS), a ...noninvasive imaging procedure.
STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat.
Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21–0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn’s disease terminal ileum subscore) at week 48 (negative predictive value = 73%).
In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. ClinicalTrials.gov number: NCT03107793
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Objectives: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of ...thiopurines in a current IBD setting.
Materials and methods: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.
Results: Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients 68.1%; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p = .01 and p = .03, respectively), and occurrence of nausea with Crohn's disease (p = .04).
Conclusions: Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.
Abstract
Background
The addition of an immunosuppressant (IM) after loss of response to anti-TNFα monotherapy is an emerging strategy of therapeutic optimization in patients with inflammatory bowel ...disease (IBD). However, few clinical data have been reported to date. We aimed to evaluate the efficacy and safety of this selective combination therapy in patients with IBD.
Methods
All consecutive patients with loss of response to anti-TNFα monotherapy despite an intensive dose optimization who added an IM from October 2014 to October 2016 were entered into a prospective database.
Results
Among 630 patients treated with anti-TNFα agents during the study period, 46 (7.3%) added an IM. A total of 31 patients (67.4%) were treated with an intravenous anti-TNFα (infliximab, as originator or biosimilar), while 15 (32.6%) were treated with a subcutaneous anti-TNFα agent (10 adalimumab and 5 golimumab). The mean duration of follow-up was 12.8 ± 7.3 months. Twenty-one patients (45.7%) remained on combination therapy at the end of follow-up: 15 (32.6%) maintained a steroid-free remission, and 6 (13.0%) achieved a clinical response. In patients who experienced treatment success, the median value of C-reactive protein decreased from baseline to the end of follow-up (13.2 vs 3.0, P = 0.01; normal values <5 mg/L). Adverse events leading to treatment discontinuation were reported in 8 out of 46 patients (17.4%).
Conclusions
In the largest cohort on this argument reported to date, the addition of an IM was an effective and safe optimization strategy after loss of response to anti-TNFα monotherapy. Low doses of IM were sufficient to achieve a clinical response.
10.1093/ibd/izx010_video1
izx010.video1
5721597581001
Liver transplantation is an efficacious treatment option for those with liver cirrhosis. However, the prognostic role of sarcopenia in these patients is unknown. Given this background, we conducted a ...systematic review and meta-analysis of the impact of sarcopenia on mortality in patients listed, evaluated and undergoing liver transplantation.
Several databases were searched from the inception to December 2022 for observational studies regarding sarcopenia in liver transplant and mortality. We calculated the risk of mortality in sarcopenia vs. no sarcopenia using the most adjusted estimate available and summarizing the data as risk ratios (RRs) with their 95% confidence intervals (CIs). A random-effect model was considered for all analyses.
Among 1135 studies initially considered, 33 articles were included for a total of 12,137 patients (mean age: 55.3 years; 39.4% females). Over a median of 2.6 years and after adjusting for a median of 3 covariates, sarcopenia increased the risk of mortality approximately 2-fold (RR: 2.01; 95% CI: 1.70-2.36). After accounting for publication bias, the re-calculated RR was 1.75 (95% CI: 1.49-2.06). The quality of the studies was generally low, as determined by the Newcastle Ottawa Scale.
Sarcopenia was significantly linked with an increased risk of mortality in patients listed, evaluated, and undergoing a liver transplantation, indicating the need of interventional studies in this special population with the main aim to reverse this potential reversible condition and decrease mortality risk.
Background
Only limited studies analyzed a possible relationship between frailty and infections. Our aim was to investigate the possible association between higher multidimensional prognostic index ...(MPI) values, a tool for evaluating multidimensional frailty, and the prevalence of infectious diseases, including antibiotics’ cost and the prevalence of MDR (multidrug resistance) pathogens.
Methods
Older patients, affected by COVID-19, were enrolled in the hospital of Palermo over four months.
Results
112 participants (mean age 77.6, 55.4% males) were included. After adjusting for potential confounders, frailer participants had a higher odds of any positivity to pathogens (prevalence: 61.5%, odds ratio = 15.56,
p
< 0.0001) compared to a prevalence of 8.6% in more robust, including MDR, and a higher costs in antibiotics.
Conclusions
Higher MPI values, indicating frailer subjects, were associated with a higher prevalence of infections, particularly of MDR pathogens, and a consequent increase in antibiotics’ cost.
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