Publications by authors named "Christian van Delden"

BK polyomavirus (BKPyV) causes premature renal failure in 10% to 30% of kidney transplant recipients (KTRs). Current guidelines recommend screening for new-onset BKPyV-DNAemia/nephropathy and reducing immunosuppression to regain BKPyV-specific immune control. Because BKPyV encompasses 4 major genotype (gt)-encoded serotypes (st1,-2,-3,-4), st-specific antibodies may inform the risk and course of BKPyV-DNAemia/nephropathy.

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We recently showed that solid-phase peptide synthesis using racemic amino acids yields stereorandomized peptides comprising all possible diastereomers as homogeneous, single-mass products that can be purified by HPLC and that stereorandomization modulates activity, toxicity, and stability of membrane-disruptive cyclic and linear antimicrobial peptides (AMPs) and dendrimers. Here, we tested if stereorandomization might be compatible with target binding peptides with the example of the proline-rich AMP oncocin, which inhibits the bacterial ribosome. Stereorandomization of up to nine -terminal residues preserved ribosome binding and antibacterial effects including activities against drug-resistant bacteria and protected against serum degradation.

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Article Synopsis
  • The study explores the impact of HIV on infectious disease events in kidney transplant recipients, showing that these patients have similar survival rates to HIV-negative individuals.
  • It analyzed data from the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study, focusing on demographic and clinical characteristics since 2008.
  • The results indicated that while 70.8% of the HIV-positive patients experienced infectious disease events, HIV itself was not a significant risk factor for these events post-transplant.
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Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC.

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Background: Infectious diseases (IDs) are highly relevant after solid organ transplantation in terms of morbidity and mortality, being among the most common causes of death. Patients undergoing kidney retransplantation (re-K-Tx) have been already receiving immunosuppressive therapy over a prolonged period, potentially facilitating subsequent infections. Comparing ID events after re-K-Tx and first kidney transplantation (f-K-Tx) can delineate patterns and risks of ID events associated with prolonged immunosuppression.

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Purpose Of Review: Bacteria are the leading cause of infections in solid organ transplant (SOT) recipients, significantly impacting patient outcome. Recently detailed and comprehensive epidemiological data have been published.

Recent Finding: This literature review aims to provide an overview of bacterial infections affecting different types of SOT recipients, emphasizing underlying risk factors and pathophysiological mechanisms.

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Among 292 recipients of allogeneic hematopoietic cell transplant (2018-2022), 64 (21.9%) tested positive for anti-hepatitis E virus (HEV) immunoglobulin G. Among 208 recipients tested by plasma/serum HEV polymerase chain reaction (2012-2022), 3 (1.

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Background: A transplant infectious disease (TID) assessment is essential to select recipients for an allogeneic hematopoietic cell transplant (HCT) and tailor prophylactic and empirical treatment recommendations.

Methods: We performed a retrospective single-center study to describe our model of care based on a routine TID consultation prior to an allogeneic HCT between 2018 and 2022 in 292 adult (≥18-year-old) consecutive patients. We describe the performance of a TID consultation, arbitrarily defined as major (HCT postponement, procedure, cytomegalovirus [CMV] recipient serology reinterpretation) and minor interventions.

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Among synthetic analogues of antimicrobial peptides (AMPs) under investigation to address antimicrobial resistance, peptoids (-alkylated oligoglycines) have been reported to act both by membrane disruption and on intracellular targets. Here we gradually introduced peptoid units into the membrane-disruptive undecapeptide KKLLKLLKLLL to test a possible transition toward intracellular targeting. We found that selected hybrids containing up to five peptoid units retained the parent AMP's α-helical folding, membrane disruption, and antimicrobial effects against Gram-negative bacteria including multidrug-resistant (MDR) strains of and while showing reduced hemolysis and cell toxicities.

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Article Synopsis
  • * The study discovered that deep incisional and organ/space infections were the most common types of SSIs, with Escherichia coli and Enterococcus spp. being the most frequently identified bacteria.
  • * Key risk factors for developing SSIs included a BMI of 25 or higher and delayed graft function, both of which were linked to increased chances of graft loss post-transplant.
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Article Synopsis
  • * A total of 193 patients were randomized into two groups: one with immune monitoring and the other receiving standard prophylaxis for set periods (180 or 90 days).
  • * Results showed that while immune monitoring significantly reduced the duration of antiviral treatment by about 26 days, it did not demonstrate a clear advantage in preventing clinically significant CMV infections when compared to the control group.
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Background: Allogeneic hematopoietic cell transplant recipients (allo-HCTRs) with positive cytomegalovirus (CMV) serology may have false-positive results due to blood product transfusion-associated passive immunity.

Methods: This single-center cohort study included allo-HCTRs with negative baseline (at malignancy diagnosis) CMV serology and indeterminate/low-positive (CMV IgG titer, ≥0.6-<50 U/mL) pretransplant CMV serology with negative pretransplant plasma CMV DNAemia.

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Background: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population.

Methods: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant.

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Bacteriophage therapy has been suggested as an alternative or complementary strategy for the treatment of multidrug resistant (MDR) bacterial infections. Here, we report the favourable clinical evolution of a 41-year-old male patient with a Kartagener syndrome complicated by a life-threatening chronic MDR Pseudomonas aeruginosa infection, who is treated successfully with iterative aerosolized phage treatments specifically directed against the patient's isolate. We follow the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples.

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Background: There are limited contemporary data on the epidemiology and outcomes of bacteremia in solid organ transplant recipients (SOTr).

Methods: Using the Swiss Transplant Cohort Study registry from 2008 to 2019, we performed a retrospective nested multicenter cohort study to describe the epidemiology of bacteremia in SOTr during the first year post-transplant.

Results: Of 4383 patients, 415 (9.

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Background: Fulminant herpetic hepatitis due to herpes simplex virus (HSV), serotype 1 or 2, is a rare but often fatal complication after solid organ transplantation (SOT). HSV hepatitis in SOT recipients can occur either due to primary infection acquired post transplantation, viral reactivation in a seropositive patient, or as donor-derived infection. Cases of fatal hepatitis have been reported in the liver as well as in other SOT recipients.

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Membrane disruptive α-helical antimicrobial peptides (AMPs) offer an opportunity to address multidrug resistance; however, most AMPs are toxic and unstable in serum. These limitations can be partly overcome by introducing D-residues, which often confers protease resistance and reduces toxicity without affecting antibacterial activity, presumably due to lowered α-helicity. Here, we investigated 31 diastereomers of the α-helical AMP KKLLKLLKLLL.

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In this single-center study of 61 allogeneic hematopoietic cell transplant (HCT) recipients receiving letermovir primary cytomegalovirus (CMV) prophylaxis for the first 100 days, we report 23% incidence of clinically significant CMV infection during the first 100 days after letermovir discontinuation, predominately in haploidentical HCT recipients, without any associations with CMV-DNAemia under letermovir.

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Importance: Vaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear.

Objectives: To assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population.

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Cytomegalovirus (CMV) infection remains a significant infectious complication after transplantation. In this article, we summarize the recent advances in the management of CMV infection in solid-organ and hematopoietic stem-cell transplant recipients. Firstly, recent trials have better delineated the indications for the preventive strategies available, namely antiviral prophylaxis and the preemptive approach.

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Background: Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries.

Methods: We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions.

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Membrane-disruptive amphiphilic antimicrobial peptides behave as intrinsically disordered proteins by being unordered in water and becoming α-helical in contact with biological membranes. We recently discovered that synthesizing the α-helical antimicrobial peptide dendrimer L- ((KL)(KL)(LL) KLL) using racemic amino acids to form stereorandomized -, an analytically pure mixture of all possible diastereoisomers of L-, preserved antibacterial activity but abolished hemolysis and cytotoxicity, pointing to an intrinsically disordered antibacterial conformation and an α-helical cytotoxic conformation. In this study, to identify non-toxic intrinsically disordered homochiral antimicrobial peptide dendrimers (AMPDs), we surveyed sixty-three -analogs of - selected by virtual screening.

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