Intestinal inflammation and permeability in patients recovered from SARS-CoV-2 infection.

INTRODUCTION: Different works suggest a close link between Long COVID Gastrointestinal (GI) manifestations and the post-infection disorders of gut-brain interaction (PI-DGBIs). However, the actual mechanisms underlying long-term GI sequelae are still not clear. Our study was aimed to assess both intestinal inflammation and permeability among subjects recovered from SARS-CoV-2 infection and their eventual correlation with long-term GI sequelae. METHODS: Eighty-six subjects attending the Post-COVID Service and recovered from SARS-CoV-2 infection for six months, were investigated for Long COVID manifestations. Those subjects complaining of long-term GI symptoms were further evaluated by Rome IV questionnaire to assess PI-DGBIs. Intestinal inflammation (by fecal calprotectin, FC), and permeability (by serum and fecal levels of zonulin) were evaluated in all subjects. The Hospital Anxiety and Depression Scale (HADS) and The Gastrointestinal Quality of Life Index (GIQLI) questionnaires were further provided to all participants. RESULTS: Thirty-seven subjects (43%) complained of long-term GI symptoms, while 49 subjects (57%) did not. Thirty-three subjects fulfilled Rome IV criteria for PI-DGBIs. FC values resulted higher in those subjects who did not complain GI symptoms (p=0.03), although remaining quite close to the normal range. No significant differences were shown regarding the assessment of intestinal permeability. By GIQLI, long-term gastrointestinal sequelae were inversely correlated with quality of life (p=0.009). CONCLUSION: Long COVID GI complaints unlikely recognize underlying local inflammatory mechanisms. Since the healthcare, economic, and social burden of post-COVID DGBIs, a deeper understanding of this emerging condition should be encouraged to improve management of the affected subjects.

Acute Diarrhea in a Tertiary Emergency Department: From Readmission Determinants to Antibiotic Prescription.

Acute diarrhea represents a major public health issue, and the management of adult patients admitted to the emergency department (ED) for this problem is still challenging. In a retrospective analysis on more than 20,000 patients visiting a tertiary ED for acute diarrhea and then being discharged home, we found that age > 65 years, onset of symptoms > 24 h since ED admission, refusal of hospitalization, and a history of chronic renal and liver diseases were independently associated with ED readmission for abdominal symptoms within 7 days. In the younger group, the presence of comorbidities significantly impacted on ED readmission, while fever and alteration of serum creatinine were the main determinants in the older group. Antibiotics were prescribed in about 25% of patients, although diarrhea etiology (viral or bacterial) was usually not available. According to international guidelines, fluoroquinolones were the most prescribed class, showing an inverse correlation to ED readmission. However, ß-lactams and probiotics were also commonly prescribed; the latter were independently correlated to ED readmission in the elderly group. A comprehensive, guideline-based approach, including a detailed clinical history and laboratory and comorbidity assessment, should be encouraged to support physicians in the management of different age subgroups of adults admitted to the ED for acute diarrhea.

Mild cognitive impairment and microbiota: what is known and future perspectives.

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.

Lactose malabsorption and intolerance in older adults.

PURPOSE OF REVIEW: Lactose malabsorption and intolerance are very common conditions. However, their optimal approach, including the diagnostic assessment, remains a matter of debate, especially in advanced age. In this brief review, we focused on current knowledge, concerns, and impact in clinical practice of lactose malabsorption and intolerance in elderly. RECENT FINDINGS: Older adults are at high risk of malnutrition, owing to frequent occurrence of cognitive impairment, loss of appetite, dysphagia, and poor oral health. A significant decrease in the consumption of dairy products may lead to inadequate intake of high-quality protein and minerals, with a consequent impact on muscle and bone health. Testing for lactose malabsorption may be challenging in older adults, if not useless. Instead, a detailed clinical evaluation should always be pursued to identify both lactose intolerance and all confounding factors mimicking the same clinical picture. SUMMARY: The management of lactose malabsorption and intolerance in older adults deserves a personalized approach. Because of the importance of maintaining an adequate nutritional status in this age group, efforts should be put forth to avoid excessively restrictive diets.

Platelets and Neurodegenerative Diseases: Current Knowledge and Future Perspectives.

Platelets have a fundamental role in mediating hemostasis and thrombosis. However, more recently, a new idea is making headway, highlighting the importance of platelets as significant actors in modulating immune and inflammatory responses. In particular, platelets have an important role in the development of vascular amyloid-b-peptide(ab) deposits, known to play a relevant role in Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. The involvement of platelets in the pathogenesis of AD opens up the highly attractive possibility of applying antiplatelet therapy for the treatment and/or prevention of AD, but conclusive results are scarce. Even less is known about the potential role of platelets in mild cognitive impairment (MCI). The aim to this brief review is to summarize current knowledge on this topic and to introduce the new perspectives on the possible role of platelet activation as therapeutic target both in AD and MCI.

Diagnostic Accuracy of Fecal Calprotectin in Discriminating Organic-Inflammatory Gastrointestinal Diseases and Functional Gastrointestinal Disorders in Older Patients.

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.

Interleukin-1 Blockers in Recurrent and Acute Pericarditis: State of the Art and Future Directions.

Diseases of the pericardium encompass a spectrum of conditions, including acute and recurrent pericarditis, where inflammation plays a pivotal role in the pathogenesis and clinical manifestations. Anti-inflammatory therapy indeed forms the cornerstone of treating these conditions: NSAIDs, colchicine, and corticosteroids (as a second-line treatment) are recommended by current guidelines. However, these medications come with several contraindications and are not devoid of adverse effects. In recent years, there has been an increased focus on the role of the inflammasome and potential therapeutic targets. Recurrent pericarditis also shares numerous characteristics with other autoinflammatory diseases, in which interleukin-1 antagonists have already been employed with good efficacy and safety. The objective of this review is to summarize the available studies on the use of anti-IL-1 drugs both in acute and recurrent pericarditis.

Peculiarity of Autoimmune Hepatitis Triggered by SARS-CoV-2 Infection.

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.

Lactose malabsorption and intolerance: What is the correct management in older adults?

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.

Increase in Chronic Medications and Polypharmacy-The Multifaceted Burden of COVID-19 Disease on Public Health Care.

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.

Fecal microbiota transplantation for recurrent Clostridioides difficile infection in frail and very old patients.

BACKGROUND: Older age is a well-known risk factor for recurrent and severe Clostridioides difficile infection (CDI). Fecal microbiota transplantation (FMT) is widely recognized as an effective and safe therapeutic option for the treatment of recurrent CDI (rCDI). However, the efficacy and safety of FMT for rCDI in very old patients are uncertain. This study evaluated the efficacy and safety of FMT in a group of very old subjects with rCDI, and the reliability of overall comorbidity and frailty assessment for identifying patients at higher risk of worse clinical outcomes. METHODS: This is a retrospective single-center study including patients ≥85 years undergoing FMT for rCDI between 2014 and 2022. Primary outcomes included efficacy of FMT, defined as cure of CDI at 8 week-follow-up, and safety evaluation. At baseline, comorbidity was measured with the Charlson Comorbidity Index (CCI). Frailty was measured with the Clinical Frailty Scale (CFS). RESULTS: Overall, 43 patients with a median age of 88 years underwent FMT by colonoscopy in the study period. The rate of first FMT success was 77%. Five of the 10 patients who failed the first FMT infusion were cured after repeat FMT, with an overall efficacy of 88%. In patients with successful treatment, the CFS was significantly lower compared to those who failed the FMT or underwent repeat FMT (p < 0.01 for both). Mild adverse events occurred in 11 patients (25%). One death, not related to FMT or rCDI, occurred within 7 days from the first procedure. CONCLUSIONS: FMT is effective and safe in very old patients. Frailty and high comorbidity do not limit use of FMT in these patients. Frailty assessment has potential to better identify patients at higher risk of worse outcomes or for repeat treatment with FMT.

A case study of impacts of an extreme weather system on the Mediterranean Sea circulation features: Medicane Apollo (2021).

The attention of the scientific community, policymakers, and public opinion on the Medicanes has recently grown because of their increase in intensity and harmful potential. Although Medicanes may be influenced by pre-existing upper-ocean conditions, uncertainties remain about how such weather extremes influence ocean circulation. This work examines a condition that has been never described before in the Mediterranean, which involves the interplay between an atmospheric cyclone (Medicane Apollo-October 2021) and a cyclonic gyre located in the western Ionian Sea. During the event, the temperature in the core of the cold gyre dropped dramatically, due to a local maximum in the wind-stress curl, Ekman pumping, and relative vorticity. Cooling and vertical mixing of the surface layer combined with upwelling in the subsurface layer caused a shoaling of the Mixed Layer Depth, halocline, and nutricline. The resulting biogeochemical impacts included an increase in oxygen solubility, chlorophyll concentration, productivity at the surface, and decreases in the subsurface layer. The presence of a cold gyre along Apollo's trajectory leads to a different ocean response from that observed with previous Medicanes, endorsing the efficiency of a multi-platform observation system integrated into an operational model for future mitigation of weather-related damages.

Procalcitonin for the early discrimination of fever etiology in patients with systemic autoimmune diseases attending the emergency department.

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.

Role of Intestinal Inflammation and Permeability in Patients with Acute Heart Failure.

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.

Early Prognostic Stratification of Clostridioides difficile Infection in the Emergency Department: The Role of Age and Comorbidities.

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.