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Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition, there is a recent growing interest in the identification of non-invasive markers able to predict the progression from MCI to a more advanced stage of the disease. Previous evidence showed the close link between gut microbiota and neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Conversely, the actual relationship between gut microbiota and MCI is yet to be clarified. In this work, we provide an overview about the current knowledge regarding the role of gut microbiota in the context of MCI, also assessing the potential for microbiota-targeted therapies. Through the review of the most recent studies focusing on this topic, we found evidence of an increase of Bacteroidetes at phylum level and Bacteroides at genus level in MCI subjects with respect to healthy controls and patients with AD. Despite such initial evidence, the definitive identification of a typical microbiota profile associated with MCI is still far from being achieved. These preliminary results, however, are growingly encouraging research on the role of gut microbiota modulation in improving the cognitive status of pre-dementia subjects. To date, few studies evaluated the role of probiotics in MCI subjects, and they showed favorable results, although still biased by small sample size, heterogeneity of study design and short follow-up.
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Fecal calprotectin (FC) has been largely recognized as a surrogate marker of intestinal neutrophilic inflammation, very reliable in distinguishing between inflammatory bowel diseases and functional gastrointestinal (GI) disorders. Aging has been suggested to influence FC results and their diagnostic accuracy; however, no studies are specifically targeted on this focus. In a retrospective study, we evaluated the eventual age-differences of the diagnostic accuracy of FC in discriminating between organic-inflammatory GI diseases and functional GI disorders. In 573 younger and 172 older (≥65 years) subjects undergoing an FC assay, we found that the latter showed higher median FC values, 72 (25-260) µg/g vs. 47 (25-165) µg/g (p < 0.01). Younger patients were more commonly affected by IBDs, while colorectal cancer and high-risk polyps, infective colitis, and diverticular disease represented the most common findings in the older subgroup. However, the estimated optimum FC threshold in discriminating between organic-inflammatory GI diseases and functional GI disorders was quite similar between the two groups (109 µg/g for the younger subgroup and 98 µg/g for the older subgroup), maintaining a very high specificity. In conclusion, we show that FC also represents a very specific test for intestinal inflammation in older patients, at similar threshold levels to younger subjects.
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Introduction: Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Up until now, a few reports have described autoimmune hepatitis (AIH) triggered by SARS-CoV-2 infection, but no data are available about the specific liver inflammatory infiltrate and cluster of differentiation. We report a case of AIH triggered by SARS-CoV-2 infection, with a particular focus on its histological and mainly immunohistochemical features. Case description: A 60-year-old man, with a history of paucisymptomatic SARS-CoV-2 infection that occurred one month earlier, was admitted for alterations of hepatocellular necrosis and cholestasis indexes. He completed vaccination for SARS-CoV-2 a year earlier. The serologies for hepatotropic viruses were negative. The anti- smooth muscle antibodies (ASMA) and antinuclear antibodies (ANA) results were positive. Anti-liver kidney microsome (anti-LKM) antibodies and antimitochondrial (AMA) were negative. By liver biopsy, haematoxylin-eosin staining highlighted severe portal inflammation with a rich CD38+ plasma cell component, while immunohistochemical staining showed low cell CD4+ count and prevalence of CD8+ and CD3+. After biopsy, the patient started an immunosuppressant regimen, with benefit. Discussion: We can conclude that the patient developed a type 1 AIH triggered by SARS-CoV-2 infection. The presence of CD8 T-cells at immunohistochemical examination suggests different mechanisms from classic AIH. Similar cases are described after AIH triggered by SARS-CoV-2 vaccination. Conclusion: The AIH after SARS-CoV-2 infection developed by the patient showed a histological picture similar to a classic AIH for the abundant presence of plasma cells, and immunohistochemical features similar to those described after SARS-CoV-2-vaccination. LEARNING POINTS: Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Underlying mechanisms are not still clear, more likely consisting of an inflammatory and immune mediated process rather than a direct cytopathic damage.Our report describes a rare case of type 1 AIH triggered by SARS-CoV-2 infection, showing a peculiar histological pattern, different from classic AIH, conversely similar to AIH triggered by SARS-CoV-2 vaccination.The mechanisms underlying liver involvement in SARS-CoV-2 infection are still under investigation. Further studies should be encouraged to improve understanding on this focus and to support physicians in its management.
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Lactose malabsorption is a very common condition due to intestinal lactase deficiency. Post weaning, a genetically programmed and irreversible reduction of lactase activity occurs in the majority of the world's population. Lactose malabsorption does not necessarily result in gastrointestinal symptoms, i.e. lactose intolerance, which occurs in approximately one third of those with lactase deficiency. In the absence of well-established guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Mainly in particular categories, such as the older adults, the approach to lactose malabsorption may deserve careful considerations. Milk and dairy products are an important supply of a wide range of nutrients that contribute to meet the nutritional needs in different life stages. Dietary composition can significantly impact the mechanisms leading to age-related loss of bone mineral density, skeletal muscle mass or function and overall risk of sarcopenia. Moreover, in the latest years, different lines of evidence have highlighted an association between dairy intake and prevention of chronic diseases as well as all-cause mortality. The aim of this opinion paper is to provide an overview of lactose malabsorption and intolerance in the older adults and their implications in clinical practice.
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Enfermedades Gastrointestinales , Intolerancia a la Lactosa , Síndromes de Malabsorción , Humanos , Anciano , Animales , Intolerancia a la Lactosa/diagnóstico , Leche , Enfermedades Gastrointestinales/complicaciones , Dieta , Síndromes de Malabsorción/complicaciones , Lactasa/genética , LactosaRESUMEN
The long-term impact of COVID-19 disease is becoming a major global concern. In this retrospective monocentric analysis, we included consecutive subjects admitted to our COVID-19 Post-Acute Care Service for a SARS-CoV-2 infection that occurred between three and twelve months before. A home medication list relative to the period before SARS-CoV-2 infection (baseline) was recorded and compared with that one relative to the time of outpatient visit (follow-up). Drugs were coded according to the Anatomical Therapeutic Chemical Classification (ATC) System. In a total of 2007 subjects, at follow-up, a significant increase with respect to baseline was reported in the total median number of chronic medications (two [0-4] vs. one [0-3]) and in specific ATC-group drugs involving the alimentary, blood, cardiovascular, genitourinary, muscle-skeletal, nervous and respiratory systems. In a multivariate analysis, COVID-19 disease severity and age > 65 years resulted in the best predictors for an increase in the number of medications, while anti-SARS-CoV-2 vaccination played a significant protective role. The long-term care of patients infected by COVID-19 may be more complex than reported so far. Multidisciplinary and integrated care pathways should be encouraged, mainly in older and frailer subjects and for patients experiencing a more severe disease. Vaccination may also represent a fundamental protection against long-term sequelae.
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In febrile patients with known systemic autoimmune disease, early discrimination between infection and disease flare often represents a clinical challenge. This study aimed at evaluating the efficacy of procalcitonin (PCT) and other common inflammatory biomarkers in discriminating disease flare from bacterial infections in the Emergency Department (ED). In a cross-sectional observational retrospective study, we identified consecutive febrile patients with a known diagnosis of systemic autoimmune disease, admitted to the ED, and subsequently hospitalized. Flare vs infective disease was defined on clinical records at hospital discharge. Dosage of common inflammatory markers was performed at ED admission. Out of 177 patients, those with infection were most commonly elderly, frail, and with reduced peripheral oxygen saturation at admission. When compared to C-reactive protein (CRP) and white blood count (WBC), PCT showed the best performance in discriminating infections vs flare. However, only at a very high threshold value of 2 ng/ml, the PCT had a satisfactory negative predictive value of 88.9%, although with a very low specificity of 13.6% and a positive predictive value of 35.8%. Our data suggest that in the ED setting, the early PCT determination has low accuracy in the differentiation of disease flare from infection in patients with known rheumatologic disease. However, the PCT could be useful in elderly and comorbid subjects, in supporting clinical assessment and in recognizing those febrile patients needing prompt antibiotic treatment.
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Enfermedades Autoinmunes , Polipéptido alfa Relacionado con Calcitonina , Humanos , Anciano , Calcitonina , Péptido Relacionado con Gen de Calcitonina , Estudios Transversales , Estudios Retrospectivos , Brote de los Síntomas , Precursores de Proteínas , Fiebre/etiología , Biomarcadores , Proteína C-Reactiva/análisis , Servicio de Urgencia en Hospital , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnósticoRESUMEN
Background and Objectives: Heart failure (HF) represents a major health burden. Although several treatment regimens are available, their effectiveness is often unsatisfactory. Growing evidence suggests a pivotal role of the gut in HF. Our study evaluated the prognostic role of intestinal inflammation and permeability in older patients with acute HF (AHF), and their correlation with the common parameters traditionally used in the diagnostic-therapeutic management of HF. Materials and Methods: In a single-center observational, prospective, longitudinal study, we enrolled 59 patients admitted to the Emergency Department (ED) and then hospitalized with a diagnosis of AHF, from April 2022 to April 2023. Serum routine laboratory parameters and transthoracic echocardiogram were assayed within the first 48 h of ED admission. Fecal calprotectin (FC) and both serum and fecal levels of zonulin were measured, respectively, as markers of intestinal inflammation and intestinal permeability. The combined clinical outcome included rehospitalizations for AHF and/or death within 90 days. Results: Patients with increased FC values (>50 µg/g) showed significantly worse clinical outcomes (p < 0.001) and higher median levels of NT-proBNP (p < 0.05). No significant correlation was found between the values of fecal and serum zonulin and the clinical outcome. Median values of TAPSE were lower in those patients with higher values of fecal calprotectin (p < 0.05). After multivariate analysis, NT-proBNP and FC values > 50 µg/g resulted as independent predictors of a worse clinical outcome. Conclusions: Our preliminary finding supports the hypothesis of a close relationship between the gut and heart, recognizing in a specific marker of intestinal inflammation such as FC, an independent predictive prognostic role in patients admitted for AHF. Further studies are needed to confirm these results, as well as investigate the reliability of new strategies targeted at modulation of the intestinal inflammatory response, and which are able to significantly impact the course of diseases, mainly in older and frail patients.
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Insuficiencia Cardíaca , Humanos , Anciano , Biomarcadores , Estudios Prospectivos , Estudios Longitudinales , Reproducibilidad de los Resultados , Permeabilidad , Complejo de Antígeno L1 de Leucocito , InflamaciónRESUMEN
Clostridioides difficile infection (CDI) represents a significant cause of morbidity and mortality, mainly in older and frail subjects. Early identification of outcome predictors, starting from emergency department (ED) admission, could help to improve their management. In a retrospective single-center study on patients accessing the ED for diarrhea and hospitalized with a diagnosis of CDI infection, the patients' clinical history, presenting symptoms, vital signs, and laboratory exams at ED admission were recorded. Quick sequential organ failure assessments (qSOFA) were conducted and Charlson's comorbidity indices (CCI) were calculated. The primary outcomes were represented by all-cause in-hospital death and the occurrence of major cumulative complications. Univariate and multivariate Cox regression analyses were performed to establish predictive risk factors for poor outcomes. Out of 450 patients, aged > 81 years, dyspnea at ED admission, creatinine > 2.5 mg/dL, white blood cell count > 13.31 × 109/L, and albumin < 30 µmol/L were independently associated with in-hospital death and major complications (except for low albumin). Both in-hospital death and major complications were not associated with multimorbidity. In patients with CDI, the risk of in-hospital death and major complications could be effectively predicted upon ED admission. Patients in their 8th decade have an increased risk independent of comorbidities.
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Selective internal radiation therapy represents an endovascular treatment option for patients with primary liver malignancies, in different clinical stages. Potential applications of this treatment are in early-stage hepatocellular carcinoma, as a curative option, or in combination with systemic treatments in intermediate and advanced-stages. This review, based on existing literature and ongoing trials, will focus on the future of this treatment in patients with hepatocellular carcinoma, in combination with systemic treatments, or with the use of new devices and technological developments; it will also describe new potential future indications and structural and organizational perspectives.
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Braquiterapia , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Radioisótopos de Itrio/uso terapéuticoRESUMEN
Aging has been identified as one of the most relevant risk factors for poor outcomes in COVID-19 infection. Since now, different mechanisms responsible for worse outcomes in the elderly have been proposed, which include the remodeling of immune system, the higher prevalence of malnutrition and sarcopenia, the increased burden of multimorbidity, and, to a lesser extent, the direct effects of age on the respiratory system and hormonal profile. It seems that the interplay between all these causes, rather than the individual pathophysiological mechanism, explains the increased severity of the disease with age.