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.

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.

Freshwater sponge hosts and their green algae symbionts: a tractable model to understand intracellular symbiosis.

In many freshwater habitats, green algae form intracellular symbioses with a variety of heterotrophic host taxa including several species of freshwater sponge. These sponges perform important ecological roles in their habitats, and the poriferan:green algae partnerships offers unique opportunities to study the evolutionary origins and ecological persistence of endosymbioses. We examined the association between Ephydatia muelleri and its chlorophyte partner to identify features of host cellular and genetic responses to the presence of intracellular algal partners. Chlorella-like green algal symbionts were isolated from field-collected adult E. muelleri tissue harboring algae. The sponge-derived algae were successfully cultured and subsequently used to reinfect aposymbiotic E. muelleri tissue. We used confocal microscopy to follow the fate of the sponge-derived algae after inoculating algae-free E. muelleri grown from gemmules to show temporal patterns of symbiont location within host tissue. We also infected aposymbiotic E. muelleri with sponge-derived algae, and performed RNASeq to study differential expression patterns in the host relative to symbiotic states. We compare and contrast our findings with work in other systems (e.g., endosymbiotic Hydra) to explore possible conserved evolutionary pathways that may lead to stable mutualistic endosymbioses. Our work demonstrates that freshwater sponges offer many tractable qualities to study features of intracellular occupancy and thus meet criteria desired for a model system.

Tracing animal genomic evolution with the chromosomal-level assembly of the freshwater sponge Ephydatia muelleri.

The genomes of non-bilaterian metazoans are key to understanding the molecular basis of early animal evolution. However, a full comprehension of how animal-specific traits, such as nervous systems, arose is hindered by the scarcity and fragmented nature of genomes from key taxa, such as Porifera. Ephydatia muelleri is a freshwater sponge found across the northern hemisphere. Here, we present its 326 Mb genome, assembled to high contiguity (N50: 9.88 Mb) with 23 chromosomes on 24 scaffolds. Our analyses reveal a metazoan-typical genome architecture, with highly shared synteny across Metazoa, and suggest that adaptation to the extreme temperatures and conditions found in freshwater often involves gene duplication. The pancontinental distribution and ready laboratory culture of E. muelleri make this a highly practical model system which, with RNAseq, DNA methylation and bacterial amplicon data spanning its development and range, allows exploration of genomic changes both within sponges and in early animal evolution.

New Sonographic Classification of Adenomyosis: Do Type and Degree of Adenomyosis Correlate to Severity of Symptoms?

STUDY OBJECTIVE: To correlate the type and degree of adenomyosis, scored through a new system based on the features of transvaginal sonography, to patients' symptoms and fertility. DESIGN: This is a multicenter, observational, prospective study. SETTING: Two endometriosis tertiary referral centers (University of Rome "Tor Vergata" and University of Siena). PATIENTS: A total of 108 patients with ultrasonographic signs of adenomyosis. INTERVENTIONS: A new ultrasonographic scoring system designed to assess the severity and the extent of uterine adenomyosis was used to stage the disease in correlation with the clinical symptoms. Menstrual uterine bleeding was assessed by a pictorial blood loss analysis chart, painful symptoms were evaluated using a visual analog scale, and infertility factors were considered. MEASUREMENTS AND MAIN RESULTS: A total of 108 patients with ultrasonographic signs of adenomyosis (mean age ± standard deviation, 37.7 ± 7.7 years) were classified according to the proposed scoring system. Women with ultrasound diagnosis of diffuse adenomyosis were older (p = .04) and had heavier menstrual bleeding (p = .04) than women with focal disease; however, no statistically significant differences were found regarding the presence and severity of dyspareunia and dysmenorrhea. Higher values of menstrual bleeding were found for severe diffuse adenomyosis, with the highest values being found in those with adenomyomas. In patients trying to conceive, the presence of ultrasound findings of focal disease was associated with a higher percentage of infertility than in those with diffuse disease, and the focal involvement of the junctional zone showed a higher percentage of at least 1 miscarriage than in those with diffuse adenomyosis. CONCLUSION: The ultrasonographic evaluation of the type and extension of adenomyosis in the myometrium seems to be important in correlation to the severity of symptoms and infertility.

Ulipristal acetate therapy increases ultrasound features of adenomyosis: a good treatment given in an erroneous diagnosis of uterine fibroids.

Ulipristal acetate (UPA) is used for medical treatment of uterine fibroids. The aim of this study was to describe the effects on painful symptoms and the sonographic uterine modifications in patients with adenomyosis erroneously treated with UPA. This is an observational study on six women affected by adenomyosis and treated with three months of UPA (5 mg/24h). The baseline ultrasonography (US) was not performed at out center nor was the diagnosis of fibroids. The patients came to our attention after the treatment with UPA, prescribed by an external physician. During our post-treatment scan we found aspects of adenomyosis, while no fibroids were detected. Symptoms, myometrial and endometrial ultrasound features were evaluated. All patients reported an increase in pelvic pain. At US evaluation intramyometrial cystic areas were found in all six cases (100%). All patients showed an enhancement of adenomyosis features.The intra-myometrial cysts appeared enlarged and the vascularization enhanced when compared to the images of the pretreatment scan. In patients with adenomyosis treated with UPA due to an erroneous diagnosis of uterine fibroids we observed a worsening of the US features of adenomyosis and of the painful symptoms.

Using VigiBase to Identify Substandard Medicines: Detection Capacity and Key Prerequisites.

BACKGROUND: Substandard medicines, whether the result of intentional manipulation or lack of compliance with good manufacturing practice (GMP) or good distribution practice (GDP), pose a significant potential threat to patient safety. Spontaneous adverse drug reaction reporting systems can contribute to identification of quality problems that cause unwanted and/or harmful effects, and to identification of clusters of lack of efficacy. In 2011, the Uppsala Monitoring Centre (UMC) constructed a novel algorithm to identify reporting patterns suggestive of substandard medicines in spontaneous reporting, and applied it to VigiBase(®), the World Health Organization's global individual case safety report database. The algorithm identified some historical clusters related to substandard products, which were later able to be confirmed in the literature or by contact with national centres (NCs). As relevant and detailed information is often lacking in the VigiBase reports but might be available at the reporting NC, further evaluation of the algorithm was undertaken with involvement from NCs. OBJECTIVE: To evaluate the effectiveness of an algorithm that identifies clusters of potentially substandard medicines, when these are assessed directly at the NC concerned. METHODS: The algorithm identifies countries and time periods with disproportionately high reporting of product inadequacy. NCs with at least 20 clusters were eligible to participate in the study, and six NCs-those in the Republic of Korea, Malaysia, Singapore, South Africa, the UK and the USA-were selected, taking into account the geographical spread and prevalence of recent clusters. The clusters were systematically assessed at the NCs, following a standardized protocol, and then compiled centrally at the UMC. The clusters were classified as 'confirmed', 'potential' or 'unlikely' substandard products; or as 'confirmed not substandard' when confirmed by an investigation; or as 'indecisive' when the information available did not allow a sound assessment even at the NC. RESULTS: The assessment of a total of 147 clusters resulted in 8 confirmed, 12 potential and 51 unlikely substandard products, and a further 19 clusters were confirmed as not substandard. Reflecting the difficulty of evaluating suspected substandard products retrospectively when additional information from the primary reporter, as well as samples, are no longer available, 57 clusters were classified as indecisive. CONCLUSION: While application of the algorithm to VigiBase allowed identification of some substandard medicines, some key prerequisites have been identified that need to be fulfilled at the national level for the algorithm to be useful in practice. Such key factors are fast handling and transfer of incoming reports into VigiBase, detailed information on the product and its distribution channels, the possibility of contacting primary reporters for further information, availability of samples of suspected products and laboratory capacity to analyse suspected products.

Emergency use authorization for intravenous peramivir: evaluation of safety in the treatment of hospitalized patients infected with 2009 H1N1 influenza A virus.

BACKGROUND: On 23 October 2009, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for intravenous peramivir, an unapproved antiviral, to treat suspected or confirmed 2009 H1N1 influenza A virus infection. Eligible hospitalized patients were unresponsive to or unable to tolerate available antivirals or lacked dependable oral or inhaled drug delivery routes. The EUA required healthcare providers to report medication errors, selected adverse events (AEs), serious AEs, and deaths to the FDA. METHODS: An FDA safety team analyzed reports submitted to the Adverse Event Reporting System (AERS) and sought follow-up in selected cases. RESULTS: The FDA received AERS reports for 344 patients (including 28 children and 3 pregnant women). Many patients were critically ill on mechanical ventilation (41%) and renal replacement therapies (19%); 38% had received oseltamivir. The most frequently reported serious AEs by MedDRA preferred term were death (15%), H1N1 influenza (8%), respiratory failure (8%), acute renal failure (7%), and acute respiratory distress syndrome (7%). Six medication errors were reported. Most deaths occurred among patients who were obese, immunosuppressed, aged >65 years, or received oseltamivir. Rash was the only treatment-emergent AE attributable to peramivir. Influenza severity, comorbidities, and concomitant medications confounded additional peramivir AE assessments. Missing clinical and laboratory data precluded evaluation of some reports. CONCLUSIONS: Many peramivir recipients under the EUA were critically ill and at risk for influenza-related complications. The safety data were insufficient to assess whether peramivir affected outcome or caused adverse reactions other than rash. Clinical trials in hospitalized patients with serious influenza infections should provide additional information.