Target attainment of beta-lactam antibiotics and ciprofloxacin in critically ill patients and its association with 28-day mortality.

Objectives: This study aims to assess pharmacodynamic target attainment in critically ill patients and identify factors influencing target attainment and mortality outcomes.

Methods: We analysed data from the DOLPHIN trial. Beta-lactam and ciprofloxacin peak and trough concentration were measured within the first 36 h (T1) after initiation of treatment.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life.

Dissemination of extensively drug-resistant NDM-producing in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-β-lactamase (NDM)-producing from Ukrainian patients among European countries.

Functional Homologous Recombination (HR) Screening Shows the Majority of -Mutant Breast and Ovarian Cancer Cell Lines Are HR-Proficient.

Tumors with a pathogenic mutation are homologous recombination (HR)-deficient (HRD) and consequently sensitive to platinum-based chemotherapy and Poly-[ADP-Ribose]-Polymerase inhibitors (PARPi). We hypothesized that functional HR status better reflects real-time HR status than mutation status. Therefore, we determined the functional HR status of 53 breast cancer (BC) and 38 ovarian cancer (OC) cell lines by measuring the formation of RAD51 foci after irradiation.

Best practices, implementation and challenges of outpatient parenteral antimicrobial therapy: results of a worldwide survey among healthcare providers.

Background: Outpatient Parenteral Antimicrobial Therapy (OPAT) is considered a patient-friendly and cost-effective practice. Patients in the OPAT service can be at risk for developing adverse events. Due to extensive variations in practice, guidelines have been developed to minimize the risks.

Proof-of-concept study linking ex vivo sensitivity testing to neoadjuvant anthracycline-based chemotherapy response in breast cancer patients.

We developed a functional ex vivo anthracycline-based sensitivity test. Surgical resection material of primary breast cancer (BC) was used to determine criteria for the ex vivo sensitivity assay based on morphology, proliferation and apoptosis. Subsequently, a proof-of-concept study was performed correlating results of this assay on primary BC biopsies with in vivo response after treatment with anthracycline-containing neoadjuvant chemotherapy (NAC).

Clinical Characteristics and Outcomes of Patients With Cutibacterium acnes Endocarditis.

Importance: It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement.

Objective: To assess the clinical characteristics and outcomes of patients with C acnes endocarditis.

Less Is More: When to Repeat Antimicrobial Susceptibility Testing.

This study investigated the frequency of change of the antimicrobial susceptibility pattern when the same isolate was found in the same patient in various situations. We used laboratory data collected over a period of 8 years (January 2014 to December 2021) at the clinical microbiology laboratory of a tertiary hospital for Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Staphylococcus aureus.

Contact tracing for vancomycin-resistant Enterococcus faecium (VRE): evaluation of the Dutch policy of quintuple screening cultures.

Detection of vancomycin-resistant Enterococcus faecium (VRE) is hampered by low sensitivity of rectal swab cultures. This study aimed to define the number of screening cultures needed to increase sensitivity to detect VRE transmission, and to determine time from presumed exposure to detectable colonization. In a tertiary care setting, we retrospectively analyzed data from 9 VRE outbreaks.

DNA-PKcs inhibitors sensitize neuroendocrine tumor cells to peptide receptor radionuclide therapy and .

Peptide receptor radionuclide therapy (PRRT) increases progression-free survival and quality of life of neuroendocrine tumor (NET) patients, however complete cures are rare and dose-limiting toxicity has been reported. PRRT induces DNA damage of which DNA double strand breaks (DSBs) are the most cytotoxic. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key player in DSB repair and its inhibition therefore is a potential way to enhance PRRT efficacy without increasing the dosage.

Safe shortening of antibiotic treatment duration for complicated bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.

Introduction: A major knowledge gap in the treatment of complicated bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.

In Vivo Efficacy Testing of Peptide Receptor Radionuclide Therapy Radiosensitization Using Olaparib.

Peptide receptor radionuclide therapy (PRRT), a form of internal targeted radiation treatment using [Lu]Lu [DOTA-Tyr]octreotate, is used to treat patients with metastasized neuroendocrine tumors (NETs). Even though PRRT is now the second line of treatment for patients with metastasized NETs, the majority of patients will not be cured by the treatment. PRRT functions by inducing DNA damage upon radioactive decay and inhibition of DNA damage repair proteins could therefore be used as a strategy to potentiate PRRT.

Multidrug-resistant organisms in patients from Ukraine in the Netherlands, March to August 2022.

Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lineages and that 60% contain New Delhi metallo-β-lactamase (NDM) genes.

Ex Vivo Functional Assay for Evaluating Treatment Response in Tumor Tissue of Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient.

Native valve, prosthetic valve, and cardiac device-related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies.

Infective endocarditis (IE) is a life-threatening microbial infection of native and prosthetic heart valves, endocardial surface, and/or indwelling cardiac device. Prevalence of IE is increasing and mortality has not significantly improved despite technological advances. This review provides an updated overview using recent literature on the clinical presentation, diagnosis, imaging, causative pathogens, treatment, and outcomes in native valve, prosthetic valve, and cardiac device-related IE.

Left ventricular assist device-related infections and the risk of cerebrovascular accidents: a EUROMACS study.

Objectives: In patients supported by a durable left ventricular assist device (LVAD), infections are a frequently reported adverse event with increased morbidity and mortality. The purpose of this study was to investigate the possible association between infections and thromboembolic events, most notable cerebrovascular accidents (CVAs), in LVAD patients.

Methods: An analysis of the multicentre European Registry for Patients Assisted with Mechanical Circulatory Support was performed.

Preclinical Assessment of the Combination of PSMA-Targeting Radionuclide Therapy with PARP Inhibitors for Prostate Cancer Treatment.

Prostate specific membrane antigen targeted radionuclide therapy (PSMA-TRT) is a promising novel treatment for prostate cancer (PCa) patients. However, PSMA-TRT cannot be used for curative intent yet, thus additional research on how to improve the therapeutic efficacy is warranted. A potential way of achieving this, is combining TRT with poly ADP-ribosylation inhibitors (PARPi), which has shown promising results for TRT of neuroendocrine tumor cells.

The impact of the multidisciplinary Endocarditis Team on the management of infective endocarditis.

Background: In their latest guidelines for infective endocarditis (IE) (2015), the European Society of Cardiology (ESC) introduced the implementation of the Endocarditis Team (ET) to facilitate the management of IE. This study presents our experiences and the diagnostic and therapeutic impact of the ET on the management of IE.

Methods: From 2016-2020, data of all patients with suspected IE referred to the ET were prospectively collected.

Single-Center Experience With Protocolized Treatment of Left Ventricular Assist Device Infections.

Purpose: Because of the current lack of evidence-based antimicrobial treatment guidelines, Left Ventricular Assist Device (LVAD) infections are often treated according to local insights. Here, we propose a flowchart for protocolized treatment, in order to improve outcome.

Methods: The flowchart was composed based on literature, consensus and expert opinion statements.

Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests.

Germline BRCA1/2 mutation status is predictive for response to Poly-[ADP-Ribose]-Polymerase (PARP) inhibitors in breast cancer (BC) patients. However, non-germline BRCA1/2 mutated and homologous recombination repair deficient (HRD) tumors are likely also PARP-inhibitor sensitive. Clinical validity and utility of various HRD biomarkers are under investigation.

Pseudomonas aeruginosa left ventricular assist device (LVAD) driveline infection acquired from the bathroom at home.

We describe a patient with a left ventricular assist device (LVAD) infection by Pseudomonas aeruginosa acquired at home. The Pseudomonas from the driveline was similar to several surface cultures of the patient's home shower. This case illustrates the potential and importance of infection prevention measures at home.

In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T.

Purpose: Targeting the prostate-specific membrane antigen (PSMA) using lutetium-177-labeled PSMA-specific tracers has become a very promising novel therapy option for prostate cancer (PCa). The efficacy of this therapy might be further improved by replacing the β-emitting lutetium-177 with the α-emitting actinium-225. Actinium-225 is thought to have a higher therapeutic efficacy due to the high linear energy transfer (LET) of the emitted α-particles, which can increase the amount and complexity of the therapy induced DNA double strand breaks (DSBs).