Potassium depletion affects AQP2 expression and the cellular composition of the kidney collecting duct. This, in turn, contributes to the development of a secondary form of nephrogenic diabetes insipidus and hypokalemic nephropathy. Here we show that after 14 days of potassium depletion, the cellular fraction of A-type intercalated cells increases while the fraction of principal cells decreases along the outer medullary collecting duct in rats. The intercalated cells acquired a novel distribution pattern forming rows of cells attached to each other. These morphological changes occur progressively and reverse after 7 days of recovery on normal rat chow diet. The cellular remodeling mainly occurred in the inner stripe of outer medulla similar to the previously seen effect of lithium on the collecting duct cellular profile. The cellular remodeling is associated with the appearance of cells double labelled with both specific markers of principal and type-A intercalated cells. The appearance of this cell type was associated with the downregulation of the Notch signaling via the Hes1 pathways. These results show that the epithelium of the collecting duct has a high degree of plasticity and that Notch signaling likely plays a key role during hypokalemia.

Glycogen storage disease XI, also known as Fanconi-Bickel syndrome (FBS), is a rare autosomal recessive disorder caused by mutations in theSLC2A2gene that encodes the glucose-facilitated transporter type 2 (GLUT2). Patients develop a life-threatening renal proximal tubule dysfunction for which no treatment is available apart from electrolyte replacement. To investigate the renal pathogenesis of FBS,SLC2A2expression was ablated in mouse kidney and HK-2 proximal tubule cells.GLUT2^Pax8Cre+mice developed time-dependent glycogen accumulation in proximal tubule cells and recapitulated the renal Fanconi phenotype seen in patients. In vitro suppression of GLUT2 impaired lysosomal autophagy as shown by transcriptomic and biochemical analysis. However, this effect was reversed by exposure to a low glucose concentration, suggesting that GLUT2 facilitates the homeostasis of key cellular pathways in proximal tubule cells by preventing glucose toxicity. To investigate whether targeting proximal tubule glucose influx can limit glycogen accumulation and correct symptoms in vivo, we treated mice with the selective SGLT2 inhibitor dapagliflozin. Dapagliflozin reduced glycogen accumulation and improved metabolic acidosis and phosphaturia in the animals by normalizing the expression of Napi2a and NHE3 transporters. In addition, in a patient with FBS, dapagliflozin was safe, improved serum potassium and phosphate concentrations, and reduced glycogen content in urinary shed cells. Overall, this study provides proof of concept for dapagliflozin as a potentially suitable therapy for FBS.

Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial pathogens, antimicrobial resistance, and polymicrobial infections across three pandemic phases—pre-COVID (2018–2019), COVID (2020–2022), and post-COVID (2022–2024)—in hospitalized and ambulatory patients. Methods: We retrospectively analyzed 1827 respiratory bacterial isolates (hospitalized patients, n = 1032; ambulatory patients, n = 795) collected at a tertiary care center in Northern Italy. Data were stratified by care setting, anatomical site, and pandemic phase. Species identification and susceptibility testing followed EUCAST guidelines. Statistical analysis included chi-square and Fisher’s exact tests. Results: In hospitalized patients, a significant increase in Pseudomonas aeruginosa (from 45.5% pre-COVID to 58.6% post-COVID, p < 0.0001) and Acinetobacter baumannii (from 1.2% to 11.1% during COVID, p < 0.0001) was observed, with 100% extensively drug-resistant (XDR) rates for A. baumannii during the pandemic. Conversely, Staphylococcus aureus significantly declined from 23.6% pre-COVID to 13.7% post-COVID (p = 0.0012). In ambulatory patients, polymicrobial infections peaked at 41.2% during COVID, frequently involving co-isolation of Candida spp. Notably, resistance to benzylpenicillin in Streptococcus pneumoniae reached 80% (4/5 isolates) in hospitalized patients during COVID, and carbapenem-resistant P. aeruginosa (CRPA) significantly increased post-pandemic in ambulatory patients (0% pre-COVID vs. 23.5% post-COVID, p = 0.0014). Conclusions: The pandemic markedly shifted respiratory pathogen dynamics and resistance profiles, with distinct trends observed in hospital and community settings. Persistent resistance phenotypes and frequent polymicrobial infections, particularly involving Candida spp. in outpatients, underscore the need for targeted surveillance and antimicrobial stewardship strategies.

Synovial fluid (SF) plays a critical role in joint lubrication, load distribution, and maintaining homeostasis within the synovial cavity. Its rheological properties, primarily influenced by hyaluronic acid (HA) and other macromolecules, are essential for normal joint function. However, alterations in the physicochemical characteristics of SF can occur due to septic conditions, including septic arthritis (SA) and periprosthetic joint infections (PJIs), which significantly impact joint health. Bacterial colonization in infected joints often leads to the formation of biofilms, microbial aggregates encased in an extracellular matrix, which confer resistance to antibiotics and host immune responses. Biofilm formation in SF-altered environments is a major challenge in treating joint infections, particularly in patients with prosthetic implants. Viscosupplementation, primarily through intra-articular hyaluronic acid (HA) injections, has been widely used to restore SF viscosity and function in degenerative joint diseases. More recently, polyacrylamide (PAA)-based gels have emerged as an alternative viscosupplementation strategy. However, concerns have been raised regarding the potential impact of viscosupplements on biofilm formation and bacterial adhesion in septic joints, as changes in SF viscosity and composition may influence bacterial colonization and persistence. This review aims to assess the interaction between viscosupplementation and biofilm formation in septic joint pathologies, examining the effects of HA and PAA on SF rheology and bacterial adhesion. Understanding these interactions is crucial for optimizing therapeutic strategies and mitigating the risk of biofilm-associated infections in patients undergoing viscosupplementation.

Objectives: To evaluate the in vitro antimicrobial activity of TiAB, a compound based on silver-bound titanium dioxide, against clinical isolates from dermatological infections. Methods: We tested 155 strains clinically isolated from ulcers and skin infections, including MRSA, ESBL-producing Enterobacterales, and P. aeruginosa. MIC and MBC values were determined using broth microdilution according to CLSI guidelines. Time-kill assays were performed at 0.5×, 1×, and 2× MIC. Median values were used to describe susceptibility profiles. Results: TiAB exhibited strong bactericidal activity against Gram-negative bacteria, including ESBL-positive E. coli and K. pneumoniae, with complete killing at 2× MIC (4–8%) within 4–8 h. Gram-positive pathogens exhibited higher MICs (≥8%) and limited response within 24 h; however, extending exposure to 48 h resulted in enhanced activity. Conclusions: TiAB exhibited in vitro bactericidal activity with median MIC values ranging from 1% to 2% (w/v) against Gram-negative clinical isolates such as E. coli and P. aeruginosa, and 2% to 4% against Gram-positive strains including MRSA. Time-kill assays confirmed ≥3 log₁₀ CFU/mL reductions for Gram-negative bacteria at 2× MIC within 24 h. These results suggest TiAB’s potential as a topical antimicrobial agent, though further in vivo studies are needed to validate its safety and efficacy.

The prevalence of heart failure (HF) and of chronic kidney disease (CKD) is continuously rising. Both diseases require significant management efforts, and more importantly, HF is often associated with CKD, aggravating the clinical scenario and leading to “cardiorenal syndrome” (CRS). Although clinical studies suggest a bidirectional interaction between HF and CKD, the pathophysiological understanding of CRS remains incomplete. Several mechanisms are involved in CRS, including changes in systemic and renal hemodynamics, endothelial dysfunction, inflammation, and activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. However, the precise mechanisms are still unclear, partly because of the incomplete characterization of experimental models recapitulating CRS. In this review, we analyze recent studies using different animal models of CRS, such as primary HF, primary CKD, and the “double-hit” models that have been proposed to investigate the pathophysiology of this condition. In HF models, data on renal pathology showed renal fibrosis, inflammation, and decreased glomerular filtration rate (GFR), whereas kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were used as markers of early kidney damage. In CKD models, data on heart pathology indicated changes in hemodynamics, increased systolic blood pressure, and the presence of fibrosis. These models provide new insights into the pathophysiological development of CRS, particularly the “double-hit” models, which may offer more information about the cross talk between the heart and kidneys. This review emphasizes the complexity of CRS and highlights the need for further research to clarify the underlying interactions and mechanisms.