Publications by authors named "Witzke O"

Purpose: Urinary tract infections (UTIs) are common complications after kidney transplantation (KT), often resulting in severe outcomes like acute graft failure and sepsis. Factors such as diabetes, age, sex, and type of transplantation significantly influence disease progression. Rising antibiotic resistance complicates treatment, emphasizing the importance of Antimicrobial Stewardship (AMS), particularly during the post-transplant immunosuppression phase.

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Vaccinations are an important preventive measure against viral diseases and have saved many lives since their introduction. Nowadays, any doctor can administer a vaccination. Patients with chronic diseases should be vaccinated according to indications.

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HLA-G, an important immune-checkpoint (IC) molecule that exerts inhibitory signalling on immune effector cells, has been suggested to represent a key player in regulating the immune response to Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2). Since specific single-nucleotide polymorphisms (SNP) in the HLA-G 3'untranslated region (UTR), which arrange as haplotypes, are crucial for the regulation of HLA-G expression, we analysed the contribution of these genetic variants as host factors in SARS-CoV-2 infection during acute and post-acute phases. HLA-G gene polymorphisms in the 3'UTR were investigated by sequencing in an unvaccinated Coronavirus Disease 2019 (COVID-19) cohort during acute SARS-CoV-2 infection (N = 505) and in the post-acute phase (N = 253).

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Background: In the phase 3 SOLSTICE study (NCT02931539), maribavir was superior to investigator-assigned therapy (IAT) for confirmed cytomegalovirus viremia clearance at study week 8 in hematopoietic cell/solid organ transplant (HCT/SOT) recipients. We report additional efficacy and safety analyses from the SOT subgroup.

Methods: Eligible SOT recipients (n=211) received maribavir 400 mg twice daily (n=142) or IAT (n=69) for 8 weeks (12 weeks' follow-up).

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Vaccination against is advised for transplant recipients to reduce morbidity and mortality associated with invasive pneumococcal disease. However, data on alloantibodies after sequential vaccination (with a pneumococcal conjugate vaccine followed by a polysaccharide vaccine) are still lacking. In the current study, we determined HLA class I and II and major histocompatibility class I-related chain A (MICA) antibodies in 41 clinically stable kidney transplant recipients.

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Lemierre Syndrome is a condition that appears to have been overlooked in recent decades in clinical practice, often resulting in death or long-lasting sequelae when left undetected and untreated. Typically, it occurs following an upper respiratory tract infection, often stemming from tonsillitis, leading to thrombosis of the internal jugular vein and subsequent multiple septic emboli. Here, we present a case a 46-year-old patient with the clinical presentation of pneumogenic sepsis.

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While SARS-CoV-2 has transitioned to an endemic phase, infections caused by newly emerged variants continue to result in severe, and sometimes fatal, outcomes or lead to long-term COVID-19 symptoms. Vulnerable populations, such as PLWH, face an elevated risk of severe illness. Emerging variants of SARS-CoV-2, including numerous Omicron subvariants, are increasingly associated with breakthrough infections.

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The emergence of SARS-CoV-2 in 2019 led to a global pandemic with a significant impact on healthcare systems. Healthcare workers were particularly vulnerable due to frequent contact with COVID-19 patients. Despite vaccination, they remained at higher risk as the vaccines provided limited protection against infection with viral variants, like Delta or Omicron BA.

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Article Synopsis
  • Sarcopenia is a serious muscle disorder that can worsen health outcomes in people with HIV, prompting this study to explore its prevalence and risk factors using updated definitions.
  • The study involved 379 HIV-positive patients and assessed muscle mass using bioelectrical impedance, alongside measuring strength and mobility through specific tests.
  • Results showed a 3.4% prevalence of pre-sarcopenia and 2.1% for sarcopenia, with significant risk factors including older age, lower body mass index, and a CD4 T-cell count below 500/μl; sarcopenia also strongly correlated with frailty.
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Objectives: Farnesyltransferase inhibitors (FTI), which inhibit the prenylation of Ras GTPases, were developed as anti-cancer drugs. As additional target proteins for prenylation were identified in the past, it is likely that FTI have potential value for therapeutic purposes beyond cancer. The effect of FTI on B-cells remains unclear.

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Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in people who are immunocompromised, such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in people who are immunosuppressed have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in patients who are immunocompromised and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with noncontrolled CMV infection.

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Unlabelled: A crucial step in lowering the risk of invasive pneumococcal illness in high-risk populations, such as individuals with plaque psoriasis, is pneumococcal vaccination. The serologic response to the sequential vaccination with Prevenar 13 (PCV13) and Pneumovax 23 (PPSV23) in psoriasis patients under immunosuppressive therapy is still poorly characterized despite national recommendations suggesting vaccination for immunocompromised patients. In this prospective study, we investigated the serological response in 57 patients under active systemic treatment for moderate to severe plaque psoriasis who underwent sequential vaccination with PCV13 followed by PPSV23.

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Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing.

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Cells of the immune defence, especially leukocytes, often have to perform their function in tissue areas that are characterized by oxygen deficiency, so-called hypoxia. Physiological hypoxia significantly affects leukocyte function and controls the innate and adaptive immune response mainly through transcriptional gene regulation via the hypoxia-inducible factors (HIFs). Multiple pathogens including components of bacteria, such as lipopolysaccharides (LPS) trigger the activation of leukocytes.

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Article Synopsis
  • - The ongoing SARS-CoV-2 pandemic, along with new variants and long-COVID, poses significant challenges, especially in developing countries where healthcare access is limited.
  • - Previous research has shown that functional inhibitors of acid sphingomyelinase can effectively combat various viral infections, including some early SARS-CoV-2 variants.
  • - A study found that the antidepressants fluoxetine and sertraline can inhibit several SARS-CoV-2 variants in vitro, suggesting they should be considered for large-scale clinical trials as potential COVID-19 treatments.
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TIMP-2 and IGFBP7 have been identified and validated for the early detection of renal injury in critically ill patients, but data on recovery of allograft function after kidney transplantation (KTx) are scarce. In a prospective observational multicenter cohort study of renal transplant recipients, urinary [TIMP-2] × [IGFBP7] was evaluated daily from day 1 to 7 after KTx. Different stages of early graft function were defined: immediate graft function (IGF) (decrease ≥ 10% in serum creatinine (s-crea) within 24 h post KTx); slow graft function (SGF) (decrease in s-crea < 10% within 24 h post KTx); and delayed graft function (DGF) (any dialysis needed within the first week after KTx).

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  • A case was reported of a 39-year-old male living with HIV who developed hypercalcemia and acute kidney damage due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium infection.
  • The patient experienced significant weight loss, muscle weakness, and had laboratory findings confirming high serum calcium levels and kidney damage despite being on antiretroviral therapy and other medications.
  • Treatment involving diuretics, bisphosphonates, and calcitonin successfully normalized calcium levels and improved kidney function, highlighting the rare but critical nature of hypercalcemia linked to IRIS in HIV patients.
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Background: Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied.

Methods: In this open-label, 6 months, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basiliximab induction, mycophenolate and steroids and either standard prolonged-release tacrolimus (trough levels: 7-9 ng/ml; Standard Care arm), or an initial 7-day fixed 5 mg/day dose of prolonged-release tacrolimus followed by lower tacrolimus predose levels (trough levels: 5-7 ng/ml; Slow & Low arm). The primary end point was the combined incidence rate of biopsy-proven acute rejections (BPAR; including borderline), graft failure, or death at 6 months with a non-inferiority margin of 12.

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Background: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce.

Methods: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation.

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Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-).

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Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients.

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Article Synopsis
  • The study investigates the effects of experimental endotoxemia, a model for systemic inflammation, on sickness behavior and depression-like symptoms in healthy males.
  • A randomized, double-blind, placebo-controlled design was used where participants received either endotoxin or placebo, with various physiological and psychological measurements taken.
  • Results showed that while endotoxin caused immediate inflammatory and sickness responses, these symptoms did not persist beyond the acute phase, although changes in C-reactive protein and cortisol levels were observed.
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Article Synopsis
  • Breakthrough infections of COVID-19, especially with variants like Omicron-BA.5, are becoming more common in vaccinated people, and the immune response to these variants is not well understood.
  • Researchers analyzed the immune responses of hospitalized COVID-19 patients during the Delta and Omicron waves using methods like ELISA and neutralization assays to measure antibodies and cellular immunity.
  • The study found reduced neutralizing antibodies against Omicron variants, with Delta and Omicron-BA.1 infections enhancing immune responses in double-vaccinated patients, but no improvement was observed for those infected with Omicron-BA.5.
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