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Management of patients with small pancreatic neuroendocrine tumors from a biomarker and surgical perspective
No full text: Pancreatic neuroendocrine tumors (PanNETs) have an age-adjusted incidence of 1.5 per 100,000 people, with a notable rise in the incidence of small (≤ 2 cm) non-functional (NF-PanNETs) in recent decades. While surgery is traditionally the preferred treatment for localized NF-PanNETs, active surveillance is now an accepted management strategy for tumors smaller than 2 cm due to their relatively benign behavior. However, this approach has not yet been fully integrated into routine clinical practice. There is considerable histopathological heterogeneity observed in NF-PanNETs which results in significant variability in clinical presentation, behavior and treatment outcomes. Hence, tumor size alone does not provide sufficient certainty regarding a benign clinical course for decision-making. Although studies advocate for incorporating WHO grade into clinical prognostic assessments, also this marker has limitations. Several established tissue-based markers, such as ATRX and DAXX alterations, alternative lengthening of telomeres (ALT), and copy number variations can be used for PanNET subtyping and correlate with metastatic risk. Combining these markers with traditional histopathological parameters may yield a more comprehensive and accurate prognostic assessment. This review discusses advantages and limitations of current prognostication methods for small NF-PanNETs and highlights recently established prognostic markers, along with the requirements for their implementation into routine clinical practice. It also proposes practical solutions to address the challenges associated with an immediate integration of these biomarkers into routine care
Association between MASLD and increased risk of serious bacterial infections requiring hospital admission: A meta-analysis
No full textBackground: Previous studies have reported an association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of serious bacterial infections. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the association between MASLD and serious bacterial infections requiring hospital admission.Methods: We systematically searched PubMed, Scopus, Web of Science and Embase from database inception to 1 April 2024, using predefined keywords to identify studies examining the risk of serious bacterial infections among individuals with and without MASLD. MASLD was diagnosed using liver biopsy, imaging or International Classification of Diseases codes. Meta-analysis was performed using random-effects modelling.Results: We identified six cross-sectional and two prospective cohort studies with aggregate data on similar to 26.6 million individuals. MASLD was significantly associated with higher odds of serious bacterial infections (pooled random-effects odds ratio 1.93, 95% confidence interval [CI] 1.44-2.58; I-2= 93%). Meta-analysis of prospective cohort studies showed that MAFLD was associated with an increased risk of developing serious bacterial infections (pooled random-effects hazard ratio 1.80, 95% CI 1.62-2.0; I-2 = 89%). This risk further increased across the severity of MASLD, especially the severity of fibrosis (pooled random-effects hazard ratio 2.42, 95% CI 1.89-2.29; I-2 = 92%). These results remained significant after adjusting for age, sex, obesity, diabetes and other potential confounders. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias.Conclusions: This metaanalysis shows a significant association between MASLD and an increased risk of serious bacterial infections requiring hospital admission
NUTRIENT RECOVERY FROM ANAEROBIC DIGESTATE BY DIFFERENT COMBINATION OF PRESSURE DRIVEN MEMBRANES
Get PDFAnaerobic digestate, the main by-product from anaerobic digestion process, will increase in the next years arriving at 177 Mt dry matter from the current level of 31 Mt by 2050. This huge amount cannot be directly applied on the soil as the EU “Directive Nitrate” limits this option at 170 kgN/ha for year. Considering the high content of nitrogen, phosphorous and potassium compounds in agricultural digestate, innovative and green methods have been investigated by the scientific community to exploit the digestate for bio-fertilizers production. This work tested different combinations of pressure driven membrane steps (micro, ultra, nanofiltrations and reverse osmosis) to maximize the nutrients and water recovery from agricultural digestate. The microfiltration (MF) step was ineffective in fully separating nutrients and removing colloids and suspended solids. As a result, it can be skipped to prevent nutrient loss in the reverse osmosis (RO) concentrate. Nanofiltration (NF) also underperformed due to rapid membrane fouling caused by its small mesh size. Conversely, ultrafiltration (UF) successfully removed fine and colloidal particles while allowing ammonium and potassium compounds to pass through. Consequently, the nutrients recovery in the concentrate of the RO and the total water recovered in the combination including the UF step was 40–50% w/w and 32.7% w/w, respectively. Moreover, the UF concentrate was also adopted as inoculum for biogas production tests, whose performances were compared to the conventional inoculum represented by the liquid fraction of the agricultural digestate. The performances were similar, but the kinetics were higher with the UF concentrate, as an effect of the higher microorganisms and nutrient concentrations
Omsk Hemorrhagic Fever Virus: A Comprehensive Review from Epidemiology to Diagnosis and Treatment
No full text: Omsk hemorrhagic fever virus (OHFV) is the etiological agent of a poorly studied acute viral disease, causing several epidemic waves observed in the western Siberia regions of Omsk, Kurgan, Novosibirsk, and Tyumen. OHFV is a flavivirus and shares structural and morphological features with tick-borne encephalitis (TBE) complex viruses. The disease's symptoms show high variability, from flu-like symptoms, hyperesthesia, and petechial rush in the upper body to high fever and hemorrhagic manifestations, with a fatality rate of about 1%. The real number of OHFV-infected people is still unknown due to the difficulties in diagnosis and the presence of asymptomatic patients that lead to an underestimation of the total cases. Little is known about the viral infection dynamics at the molecular and cellular levels, the viral involvement in immune escape, cellular pathways alteration, or metabolic influence. It is noteworthy that no clinical trials have currently been performed for effective and specific drug treatments. In this review, we will give an overview of OHFV interactions with humans and animals, diagnostic tools, and drug treatments. We aim to highlight the importance of a frequently undiagnosed or misdiagnosed viral infection that might also even cause severe clinical manifestations such as meningitis and hemorrhage, in order to point out the need to develop new research studies, new diagnostic tools, and new treatments for OHFV
Early noninvasive ventilation in general wards for acute respiratory failure: an international, multicentre, open-label, randomised trial
No full textBackground: The impact of noninvasive ventilation (NIV) managed outside the intensive care unit in patients with early acute respiratory failure remains unclear. We aimed to determine whether adding early NIV prevents the progression to severe respiratory failure. Methods: In this multinational, randomised, open-label controlled trial, adults with mild acute respiratory failure (arterial oxygen partial pressure/fraction of inspiratory oxygen [PaO2/FiO2] ratio >= 200) were enrolled across 11 hospitals in Italy, Greece, and Kazakhstan. Patients were randomised to receive early NIV or usual care. Patients in the early NIV group received 2-h cycles of NIV applied every 8 h for up to 12 days. The primary outcome was the progression to severe acute respiratory failure, defined by severe hypoxaemia, severe respiratory distress, or hypercapnic acidaemia during hospitalisation. Results: Between May 6, 2012, and July 18, 2023, we randomised 524 patients (44.8% female; median age 73 yr, inter- quartile range [IQR] 63-83 yr). One patient withdrew consent. Progression to severe acute respiratory failure occurred in 49/265 (18.5%) patients randomised to early NIV, compared with 73/258 (28.3%) patients receiving usual care (relative risk 0.65, 95% confidence interval 0.48-0.90, P=0.0080). Median length of hospital stay was 10 (IQR 6-16) days in the early NIV group and 9 (IQR 5-16) days in the usual care group (P=0.30). Respiratory complications, 28-day mortality, and adverse events were not different between early NIV and usual care. Conclusions: In patients with mild acute respiratory failure treated in nonintensive care wards, early NIV reduced the progression to severe acute respiratory failure
To (the) brain or not to (the) brain? Distal signaling and non-neural players in brain hyperexcitability.
No full textThe brain is a highly dynamic organ whose functions depend on the intricate interplay among neurons, glial cells, endothelial cells, and immune components. Traditionally viewed as the domain of neuronal signaling, emerging evidence underscores the crucial role of the neurovascular unit, where neuronal, glial, vascular, and immune interactions collectively sustain brain health and adaptability.
In this study, we explored the modulation of neuronal excitability, a fundamental property underlying cognition, sensory processing, and movement, by focusing on the interplay between immune signaling and the microbiota-gut-brain axis. Neuronal excitability is finely regulated by the balance of excitatory and inhibitory signals, and disruptions in this equilibrium are often implicated in pathological conditions such as epilepsy and neurodegenerative diseases.
A central focus of our investigation was CXCL17, a chemokine widely expressed in mucosal tissues. Our findings revealed its expression not only in intestinal mucosal tissues but also in key brain regions such as the hippocampus and cerebellum. Through its receptor, GPR25, CXCL17 may influence not only immune cell recruitment, but also neuronal function and plasticity. This suggests a potential role in memory and learning, as well as involvement in pathological mechanisms, including epilepsy and multiple sclerosis. Experimental evidence supports the hypothesis that CXCL17 and its receptor GPR25 modulate inflammation, immune cell recruitment, and may influence neuronal excitability, offering new insights into disease mechanisms and potential therapeutic avenues.
We also investigated the role of gut microbiota in brain excitability via the microbiota-gut-brain axis. Our findings provide evidence that mice receiving microbiota from epileptic animals exhibit greater susceptibility to status epilepticus compared to those receiving “healthy” microbiota, following a subclinical dose of pilocarpine. The lower seizure thresholds observed in these animals support the hypothesis that the microbiota influences neuronal excitability in the brain.
Moreover, using a mouse model of temporal lobe epilepsy, we characterized dynamic shifts in microbiota composition during acute and chronic disease phases. Notably, we identified an abundance increase of Desulfovibrio, a bacterium that produces hydrogen sulfide, an agent with dual roles in neuroprotection and neurotoxicity. Conversely, Akkermansia Muciniphila, which emerged in the chronic phase, may exert neuroprotective effects by maintaining gut barrier integrity and modulating immune responses. These findings highlight the complexity of microbial interactions, where certain bacteria exacerbate neuroinflammation and lower seizure thresholds, whereas others contribute to neuroprotection and seizure resistance.
By integrating the study of chemokine signaling, neuroinflammatory pathways, and microbiota dynamics, our work underscores the intricate connections between the immune system, gut, and brain. This research opens new perspectives on targeting these interactions to develop innovative therapeutic strategies for neurological disorders such as epilepsy. Future studies should further investigate the complex relationship between immune signaling, microbiota, and neuronal excitability to uncover novel approaches for disease prevention and treatment
Integrating the concept of Aktionsart into the teaching of Russian verbal aspect
No full textThis paper evaluates a pedagogical intervention targeting verbal aspect selection in L2 Russian through explicit reflection on the role of Aktionsart. In some contexts, aspect in native use is mainly determined by this category, which, however, is hardly part of L2 Russian syllabi. In this study, 99 Italian learners of L2 Russian were divided into an experimental and a control group. The control group followed the standard syllabus, while the experimental group participated in a metalinguistic discussion on the interaction between aspect and Aktionsart. All the participants were then asked to select the appropriate aspectual value in a set of 32 sentences manipulated with respect to Aktionsart and various types of aspectual cues. To verify to what extent the pedagogical intervention shifted the respondents’ choices away from the default behaviour instantiated by the control group, associating the expression of completed events to the PF aspect, the experimental group completed the task again after a year. At the second test time, the participants were also asked to translate 12 Russian sentences into Italian and justify their choice of aspectual forms. The experimental group demonstrated greater sensitivity to the role of Aktionsart in contexts that lacked aspectual cues, even though they failed to explicitly describe its role. Altogether, the pedagogical intervention seemed to exert a beneficial effect on the learners’ ability to select the most prototypical aspectual value but not on their ability to justify their choice
A novel de novo GFAP variant causes a juvenile-onset Alexander disease with bilateral vocal cord paralysis
Get PDFAlexander disease (AxD), an autosomal dominant leukodystrophy, is caused by mutations in the GFAP, the gene encoding glial fibrillary acidic protein (GFAP). The disease, classified by age of onset into infantile, juvenile, and adult forms, is characterized by white matter degeneration and astrocytic inclusions called Rosenthal fibers. A patient underwent clinical, radiological, and molecular analyses to confirm a suspected diagnosis of AxD. The functional effect of the variant identified was tested using computational tools and in HeLa and astrocytoma cell lines. We report a case of juvenile AxD that clinically developed acute respiratory distress due to bilateral vocal cord paralysis. Brain and spinal cord MRI revealed the typical findings of the disease, including bulbospinal atrophy and T2-weighted hyperintensities in the frontal periventricular white matter. Molecular genetic testing identified a novel de novo c.713 T > G (p.I238S) variant of GFAP. In silico analyses revealed that the variant at evolutionarily conserved residue likely affects protein function. In vitro assays confirmed its pathogenic effect, showing that p.I238S protein expression significantly associates with aggregate formation in cellular models. Extending the clinical and molecular characterization of new cases of AxD is an important achievement to better characterize the disease
“A Related yet Foreign Element”. Schleiermacher Reviews Fichte’s The Destination of Man
Get PDFThis essay focuses on a review of Johann G. Fichte’s The Destination of Man,
published by Friedrich D.E. Schleiermacher in the journal "Athenæum" in 1800. The author places the book within the context of the debates on the critical function of reviewing that took place between the Schlegel brothers and the Enlightenment writers of the Allgemeine Literatur-Zeitung. Schleiermacher’s Notiz can indeed be seen as a genuine attempt at a mise en abîme: a review of the value of reviewing. Distancing himself from Fichte’s rationalistic approach, and in line with Heinrich Jacobi’s philosophy of religion, Schleiermacher rejects the universal concept of destination in favour of a morality based
on the principle of existence (as openness and contact with the infinite). However, unlike the Schlegel brothers, he does not settle for a solipsistic and aestheticizing conception of man. Instead, he presents a theory that focuses on the progressive social formation of the original essence of the individual. The critical act of reviewing as a means of establishing formative relationships (bildende Beziehungen) with others
Failure to Rescue After Resection of Perhilar Cholangiocarcinoma in an International Multicenter Cohort
No full textBackground. Failure to rescue (FTR) is defined as the inability to prevent death after the development of a complication. FTR is a parameter in evaluating multidisciplinary postoperative complication management. The aim of this study was to evaluate FTR rates after major liver resection for perihilar cholangiocarcinoma (pCCA) and analyze factors associated with FTR. Patients and Method. Patients who underwent major liver resection for pCCA at 27 centers were included. FTR was defined as the presence of a Dindo grade III or higher complication followed by death within 90 days after surgery. Liver failure ISGLS grade B/C were scored. Multivariable logistic analysis was performed to identify predictors of FTR and reported using odds ratio and 95% confidence intervals. Results. In the 2186 included patients, major morbidity rate was 49%, 90-day mortality rate 13%, and FTR occurred in 24% of patients with a grade III or higher complication. Across centers, major complication rate varied from 19 to 87%, 90-day mortality rate from 5 to 33%, and FTR ranged from 11 to 50% across hospitals. Age [1.04 (1.02-1.05) years], ASA 3 or 4 [1.40 (1.01-1.95)], jaundice at presentation [1.79 (1.16-2.76)], right-sided resection [1.45 (1.06-1.98)], and annual hospital volume < 6 [1.44 (1.07-1.94)] were positively associated with FTR. When liver failure is included, the odds ratio for FTR is 9.58 (6.76-13.68). Conclusion. FTR occurred in 24% of patients after resection for pCCA. Liver failure was associated with a nine-fold increase of FTR and hospital volume below six was also associated with an increased risk of FTR