This document provides an updated overview of the molecular mechanisms underlying pulmonary fibrosis associated with Systemic Sclerosis (SSc). It summarizes current knowledge on how immune activation, vascular injury, and impaired tissue repair contribute to interstitial lung disease (ILD), which is the most serious and life-threatening complication of SSc. SSc is a rare autoimmune disorder involving vascular dysfunction and progressive fibrosis of the skin and internal organs. In the lungs, the interaction between immune and vascular abnormalities and excessive extracellular matrix deposition leads to irreversible structural damage. These processes occur through complex, multifactorial mechanisms that are only partially understood. The review examines recent evidence on the cellular mediators, signaling pathways, and epigenetic alterations involved in ILD-SSc pathogenesis. It also discusses the potential roles of genetic predisposition, environmental factors, and autoantibody profiles in disease heterogeneity. Finally, it highlights emerging therapeutic strategies that target these molecular mechanisms. This work aims to integrate these advances to provide a clearer understanding of the biological basis of SSc-associated pulmonary fibrosis and support the development of novel diagnostic and therapeutic approaches that may improve patient outcomes.

The availability of highly sensitive molecular tests for the detection of Clostridioides difficile in feces leads to overtreatment of patients who are probably only colonized. In this prospective study, the usefulness of fecal calprotectin (fCP) is evaluated in a cohort of patients with detection of toxigenic C. difficile in feces. Patients were classified by an infectious diseases consultant blinded to fCP results into three groups—group I, presumed Clostridioides difficile infection (CDI); group II, doubtful but treated CDI; and group III, presumed C. difficile colonization or self-limited CDI not needing treatment. One hundred and thirty-four patients were included. The median fCP concentrations were 410 (138–815) μg/g in group I, 188 (57–524) μg/g in group II, and 51 (26–97) μg/g in group III (26 cases); p < 0.05 for all comparisons. In forty-five out of 134 cases (33.5%), the fCP concentrations were below 100 µg/g. In conclusion, fCP is low in most patients who do not need treatment against C. difficile, and should be investigated as a potentially useful test in the management of patients with detected toxigenic C. difficile.

Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. To study whether low-dose rituximab is also effective for bullous pemphigoid. Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments. This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12 weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence. Four hundred seventy-six patients were considered to have CDI (320 in patients <80 years and 156 in ≥80 years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P = .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P < .001. No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80 years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group.

Background: Bloodstream infections are associated with substantial morbidity and mortality. Rapid diagnostic tests (RDTs) have been shown to improve clinical outcomes when combined with antimicrobial stewardship (AMS) programmes. The lack of systematic reporting of rapid antimicrobial susceptibility testing (AST) can cause delays in communication to prescribers and in targeted antimicrobial treatment. Objectives: To evaluate the impact of a structured intervention in integrating systematic RAST and AMR detection within an existing AMS programme. The main outcomes were time to report (from Gram to AST report) (TTR), time from Gram to AMS recommendation (TAMS) and time to change antimicrobial prescription (TCAP) following this recommendation. Methods: We performed a contemporaneous comparative study evaluating episodes of bacteraemia managed with rapid AST (RAST) and/or antimicrobial resistance mechanisms (AMR) detection integrated into AMS workflows versus episodes managed without RAST/AMR during the same implementation period. Results: Episodes managed with RAST/AMR had significantly shorter TTR, TAMS and TCAP compared with episodes without RAST/AMR (median absolute reduction in hours of 31, 37 and 24, respectively). There was no significant reduction in duration of antimicrobial therapy, hospital length of stay (LOS) or mortality in the RAST/AMR group. Compliance with AMS recommendations was high (90%). Conclusions: As reported previously, RAST or AMR detection in combination with AMS was an effective strategy for targeting antimicrobial therapy. This intervention demonstrates that structured implementation of RAST/AMR detection, when embedded within the AMS workflow, can substantially shorten time to targeted therapy even in settings with pre-existing AMS infrastructure.