| 1. |
- Ponziani, Francesca Romana, et al.
(författare)
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Characterization of the gut-liver-muscle axis in cirrhotic patients with sarcopenia
- 2021
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Ingår i: Liver international (Print). - : Wiley. - 1478-3223 .- 1478-3231. ; 41:6, s. 1320-1334
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aim: Sarcopenia is frequent in cirrhosis and is associated with unfavourable outcomes. The role of the gut-liver-muscle axis in this setting has been poorly investigated. The aim of this study was to identify gut microbiota, metabolic and inflammatory signatures associated with sarcopenia in cirrhotic patients.Methods: Fifty cirrhotic patients assessed for the presence of sarcopenia by the quantification of muscle mass and strength were compared with age- and sex-matched controls. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, was performed.Results: The gut microbiota of sarcopenic cirrhotic patients was poor in bacteria associated with physical function (Methanobrevibacter, Prevotella and Akkermansia), and was enriched in Eggerthella, a gut microbial marker of frailty. The abundance of potentially pathogenic bacteria, such as Klebsiella, was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levels of pro-inflammatory mediators and of fibroblast growth factor 21 (FGF21) in cirrhotic patients. Gut microbiota metabolic pathways involved in amino acid, protein and branched-chain amino acid metabolism were up-regulated, in addition to ethanol, trimethylamine and dimethylamine production. Correlation networks and clusters of variables associated with sarcopenia were identified, including one centred on Klebsiella/ethanol/FGF21/Eggerthella/Prevotella.Conclusions: Alterations in the gut-liver-muscle axis are associated with sarcopenia in patients with cirrhosis. Detrimental but also compensatory functions are involved in this complex network.
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| 2. |
- Ponziani, Francesca Romana, et al.
(författare)
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Gut Dysbiosis and Fecal Calprotectin Predict Response to Immune Checkpoint Inhibitors in Patients With Hepatocellular Carcinoma
- 2022
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Ingår i: Hepatology Communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 6:6, s. 1492-1501
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota is a well-known prognostic factor and a modulator of treatment sensitivity in patients with cancers treated with immune checkpoint inhibitors. However, data on hepatocellular carcinoma (HCC) are lacking. This study aimed to evaluate the prognostic role of the gut microbiota and changes produced by immunotherapy on the intestinal environment in patients with cirrhosis and HCC. Eleven patients treated with Tremelimumab and/or Durvalumab were included in the analysis. All study participants underwent gut microbiota profiling, quantification of fecal calprotectin, serum levels of zonulin-1, lipopolysaccharide binding protein (LBP), and programmed death-ligand 1 (PD-L1) at baseline and at each treatment cycle until the third cycle, then every three cycles until treatment discontinuation or last visit. The 6 patients who achieved disease control (DC) showed lower pretreatment fecal calprotectin (median, 12.5; interquartile range [IQR], 5-29 vs. median, 116; IQR, 59-129 µg/g; P = 0.047) and PD-L1 serum levels (median, 0.08; IQR, 0.07-0.09 vs. median, 1.04; IQR, 0.17-1.95 ng/mL; P = 0.02) than nonresponders. The relative abundance of Akkermansia (log2 fold change [FC], 2.72; adjusted P [Padj] = 0.012) was increased, whereas that of Enterobacteriaceae (log2 FC, −2.34; Padj = 0.04) was reduced in the DC group. During treatment, fecal calprotectin showed a temporal evolution opposite to the Akkermansia to Enterobacteriaceae ratio and gut microbiota alpha diversity, but similar to zonulin-1 and LBP. Bifidobacterium had a stable behavior in patients with a long follow-up, while Akkermansia was more variable. Akkermansia and Bifidobacterium showed similar temporal patterns and causative relationships with Prevotella, Veillonella, Ruminococcus, Roseburia, Lachnospira, Faecalibacterium, and Clostridium. Conclusion: A favorable composition of the gut microbiota and low intestinal inflammation are associated with achieving DC. The intestinal environment changes dynamically during therapy.
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| 3. |
- Fountoulakis, Konstantinos N., et al.
(författare)
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Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia : an international multicenter study
- 2022
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Ingår i: CNS Spectrums. - : CAMBRIDGE UNIV PRESS. - 1092-8529 .- 2165-6509. ; 27:6, s. 716-723
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. Methods Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 +/- 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. Results There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. Discussion Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
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| 4. |
- Fountoulakis, Konstantinos N., et al.
(författare)
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Staging of Schizophrenia With the Use of PANSS : An International Multi-Center Study
- 2019
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 22:11, s. 681-697
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionA specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method.MethodsTwenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed.ResultsExploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients.DiscussionThis study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.
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| 5. |
- Serafini, Gianluca, et al.
(författare)
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Abnormalities in kynurenine pathway metabolism in treatment-resistant depression and suicidality : a systematic review
- 2017
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Ingår i: CNS and Neurological Disorders - Drug Targets. - : Bentham Science Publishers Ltd.. - 1871-5273. ; 16:4, s. 440-453
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Forskningsöversikt (refereegranskat)abstract
- Treatment resistant depression (TRD) and suicidal behavior are among the most important public health problems and are commonly associated with significant disability and psychosocial impairment. Although there have been recent advances in identifying neurobiological correlates of these complex conditions, their pathophysiology still remains unclear. Although the recent advances concerning the neurobiological determinants underlying these complex conditions, their pathophysiology still remains unclear. Compared to non-suicidal subjects, higher mean concentrations of inflammatory mediators have been found in both the periphery and brain of individuals at risk for suicide. Several lines of evidence suggest that neuroinflammation is accompanied by a dysregulation of the kynurenine pathway (KP) in both TRD and suicidal individuals, resulting in an imbalance of neuroactive metabolites. In particular, neuroinflammation may trigger an increased production of the N-Methyl-D-aspartate (NMDA) receptor agonist quinolinic acid and a concomitant reduction of neuroprotective metabolites, potentially causing downstream effects in glutamatergic systems resulting in depressive symptoms and suicidal behavior. This systematic review of the current literature is mainly aimed at summarizing the most important evidence pertaining to KP metabolism abnormalities in TRD and suicidal behavior. Targeting the KP enzymes may provide innovative approaches in the management of both TRD and suicidality.
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| 6. |
- Serafini, Gianluca, et al.
(författare)
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The Role of Neuropeptides in Suicidal Behavior: A Systematic Review
- 2013
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Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2013
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Forskningsöversikt (refereegranskat)abstract
- There is a growing evidence that neuropeptides may be involved in the pathophysiology of suicidal behavior. A critical review of the literature was conducted to investigate the association between neuropeptides and suicidal behavior. Only articles from peer-reviewed journals were selected for the inclusion in the present review. Twenty-six articles were assessed for eligibility but only 22 studies were included. Most studies have documented an association between suicidality and some neuropeptides such as corticotropin-releasing factor (CRF), VGF, cholecystokinin, substance P, and neuropeptide Y (NPY), which have been demonstrated to act as key neuromodulators of emotional processing. Significant differences in neuropeptides levels have been found in those who have attempted or completed suicide compared with healthy controls or those dying from other causes. Despite cross-sectional associations between neuropeptides levels and suicidal behavior, causality may not be inferred. The implications of the mentioned studies were discussed in this review paper.
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