There is no specific therapy for polyoma BK virus nephropathy (BKVN) in kidney transplant recipients, a condition associated with poor outcomes. Everolimus showed promising antiviral effects, but data from prospective studies are limited. Therefore, we converted ten consecutive kidney transplant recipients with biopsy-proven BKVN from standard exposure Calcineurin inhibitors and Mycophenolate to Everolimus and reduced exposure Calcineurin inhibitors. Ten patients not administered Everolimus, on reduced exposure Calcineurin inhibitor and halved MPA doses served as controls. All kidney transplant recipients continued steroid therapy. Each patient underwent kidney graft biopsy, BKV replication by PCR, and de novo DSA determination. During a 3-year follow-up no graft loss occurred in kidney transplant recipients on Everolimus but it was observed in 5/10 controls (P = 0.032). eGFR improved on Everolimus and worsened in controls (between group difference + 25.6 ml/min/1.73 m², 95% CI 10.5–40.7, P = 0.002). BKV replication declined in the Everolimus group alone (from 6.4 ± 0.8 to 3.6 ± 1.6 Log 10 genomic copies, P = 0.0001), and we found a significant inverse relationship between eGFR and BKV genomic copy changes (P = 0.022). Average Calcineurin inhibitors trough levels did not differ between the two study groups during follow-up. By multivariable Cox regression analysis, Everolimus treatment resulted the only significant predictor of survival free of a combined endpoint of graft loss and 57% eGFR reduction (P = 0.02). Kidney transplant recipients on Everolimus had a higher survival free of adverse graft outcome (log-rank test, P = 0.009). In conclusion an Everolimus-based immunosuppressive protocol with minimization of Calcineurin inhibitors and antimetabolite discontinuation effectively treated BKVN in kidney transplant recipients.

Human papillomavirus (HPV) is a major cause of cervical cancer, a significant health concern worldwide. Despite advances in screening methods, including the Pap test and the HPV DNA test, limitations remain in accurately predicting which HPV infections will progress to cervical intraepithelial neoplasia (CIN) and, eventually, invasive cancer. This study evaluates the usefulness in real life of assessing HPV viral load and the presence of multiple HPV genotypes in enhancing the diagnostic accuracy of triage in cervical cancer screening. A retrospective analysis was performed on 55 formalin-fixed paraffin-embedded cervical samples collected from women who underwent colposcopy with a biopsy or conization at San Martino Hospital, Genova, Italy, between January and June 2021. Histological diagnoses were compared with molecular analyses (HPV genotyping, viral load quantification and co-infection) using a multiplex real-time PCR platform. Of the samples analyzed, 56.4% were HPV DNA positive, while 40% tested negative. The molecular analysis identified more HPV-negative cases than the histological analysis (p < 0.05). Higher viral loads and HPV co-infections were more frequent in high-grade CIN lesions. These markers may help identify patients at an elevated risk for persistent infections and cancer progression. These findings support the potential of integrating HPV viral load and genotype co-infection assessments into routine cervical cancer screening protocols to improve early detection and reduce overtreatment and unnecessary interventions.

First-generation somatostatin receptor ligands (fg-SRLs), such as octreotide (OCT), represent the first-line medical therapy in acromegaly. Fg-SRLs show a preferential binding affinity for somatostatin receptor subtype-2 (SST₂), while the second-generation ligand, pasireotide (PAS), has high affinity for multiple SSTs (SST₅ > SST₂ > SST₃ > SST₁). Whether PAS acts via SST₂ in somatotroph tumors, or through other SSTs (e.g., SST₅), is a matter of debate. In this light, the combined treatment OCT+PAS could result in additive/synergistic effects. We evaluated the efficacy of OCT and PAS (alone and in combination) on growth hormone (GH) secretion in primary cultures from human somatotroph tumors, as well as on cell proliferation, intracellular signaling and receptor trafficking in the rat GH4C1 cell line. The results confirmed the superimposable efficacy of OCT and PAS in reducing GH secretion (primary cultures), cell proliferation, cAMP accumulation and intracellular [Ca²⁺] increase (GH4C1 cells), without any additive effect observed for OCT+PAS. In GH4C1 cells, co-incubation with a SST₂-selective antagonist reversed the inhibitory effect of OCT and PAS on cell proliferation and cAMP accumulation, while both compounds resulted in a robust internalization of SST₂ (but not SST₅). In conclusion, OCT and PAS seem to act mainly through SST₂ in somatotroph tumor cells in vitro, without inducing any additive/synergistic effect when tested in combination.

Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology; however, the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-β-Gal in kidney biopsies obtained in a cohort [n = 22] of incident patients who were followed up for 3 years as standard of care. SA-β-Gal staining was approximately fourfold higher in the tubular compartment of patients with CKD vs. controls [26.0 ± 9 vs. 7.4 ± 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-β-Gal, but not proteinuria, at the time of biopsy correlated with eGFR loss at the follow up; moreover, SA-β-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In conclusion, our study shows that SA-β-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD and suggests that tubular SA-β-Gal is associated with accelerated loss of renal function.

Autops Case Rep, vol.12, e2021394, 2022