(1) Background: CMV infections remain a problem after kidney transplantation, particularly if patients are refractory or resistant (r/r) to treatment with valganciclovir (VGCV) or ganciclovir (GCV). (2) Methods: In a single-center retrospective study, kidney transplant recipients (KTR) receiving letermovir (LTV) as rescue therapy for VGCV-/GCV-r/r CMV disease were analyzed regarding CMV history, immunosuppression, and outcomes. (3) Results: Of 201 KTR treated for CMV between 2017 and 2022, 8 patients received LTV following treatment failure with VGCV/GCV. All patients received CMV prophylaxis with VGCV according to the center’s protocol, and 7/8 patients had a high-risk (D+/R−) CMV constellation. In seven of eight cases, rising CMV levels occurred during prophylaxis. In seven of eight patients, a mutation in UL97 associated with a decreased response to VGCV/GCV was detected. In four of eight patients, LTV resulted in CMV clearance after 24 ± 10 weeks (16–39 weeks), two of eight patients stabilized at viral loads <2000 cop/mL (6–20 weeks), and two of eight patients developed LTV resistance (range 8–10 weeks). (4) Conclusion: LTV, which is currently evaluated for CMV prophylaxis in kidney transplantation, also shows promising results for the treatment of patients with VGCV/GCV resistance despite the risk of developing LTV resistance. Additional studies are needed to further define its role in the treatment of patients with CMV resistance.

Kidney transplant recipients (KTRs) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTRs. Between 1 February 2020 and 1 July 2022, 578 KTRs were infected with SARS-CoV-2, with 25 (4%) recurrent infections. In total, 208 KTRs (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed that being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas a steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both virological changes in the Omicron variant and vaccination reduce the risk for morbidity and mortality from COVID-19 in KTRs. Our data extend the knowledge from the general population to KTRs and provide important insights into outcomes during the Omicron era.

Background/Aim: Pancreatic ductal adenocarcinoma (PDAC) shows poor survival and early systemic dissemination. Cancer associated fibroblasts (CAFs) enhance migration and invasion of cancer cells. We aimed to investigate the role of CAFs in cell migration and their underlying paracrine effects. Materials and Methods: Using Transwell^® migration assays, PDAC cells (PANC-1) and three distinct types of fibroblasts were analyzed: CAFs, genetically transformed human foreskin-fibroblasts (BJeLR), and non-transformed human foreskin-fibroblasts (VH7). IL6 in the culture supernatant was measured to investigate paracrine communication in monocultures and direct/indirect cocultures. Results: CAFs showed a significantly higher capacity to migrate in vitro when compared to benign fibroblasts (p=0.009). They also facilitated the migration of PDAC cells in coculture (p=0.001). Neither BJeLR, nor VH7 displayed such features. This was accompanied by a significant increase in IL-6 when CAFs were cocultured with PANC-1 (p=0.009). Conclusion: CAFs are a key element of intra-tumoral migration and should be further investigated as a potential therapeutic target.

Kidney transplant recipients (KTR) show higher morbidity and mortality from COVID-19 than the general population and have an impaired response to vaccination. We analyzed COVID-19 incidence and clinical outcomes in a single-center cohort of approximately 2500 KTR. Between February 1, 2020 and July 1, 2022, 578 KTR were infected with SARS-CoV-2, with 25 (4%) recurrent infections. 208 KTR (36%) were hospitalized, and 39 (7%) died. Among vaccinated patients, infection with the Omicron variant had a mortality of 2%. Unvaccinated patients infected with the Omicron variant showed mortality (9% vs. 11%) and morbidity (hospitalization 52% vs. 54%, ICU-admission 12% vs. 18%) comparable to the pre-Omicron era. Multivariable analysis revealed, being unvaccinated (OR = 2.15, 95% CI [1.38, 3.35]), infection in the pre-Omicron era (OR = 3.06, 95% CI [1.92, 4.87]), and higher patient age (OR = 1.04, 95% CI [1.03, 1.06]) are independent risk factors for COVID-19 hospitalization, whereas steroid-free immunosuppressive regimen was found to reduce the risk of COVID-19 hospitalization (OR = 0.51, 95% CI [0.33, 0.79]). This suggests that both, virological changes in the Omicron variant and vaccination, reduce the risk for morbidity and mortality from COVID-19 in KTR. Our data extend the knowledge from the general population to KTR and provide important insights into outcome during the Omicron era.