['More research is needed' is a meaningless conclusion].

This sentence often concludes medical research articles. We argue that 'more research is needed' is an empty phrase. There is always room for synthesis of previously existing and currently added knowledge, allowing for a conclusion on what we now know.

Trends of diagnostic adverse events in hospital deaths: longitudinal analyses of four retrospective record review studies.

Objectives: To investigate longitudinal trends in the incidence, preventability, and causes of DAEs (diagnostic adverse events) between 2008 and 2019 and compare DAEs to other AE (adverse event) types.

Methods: This study investigated longitudinal trends of DAEs using combined data from four large Dutch AE record review studies. The original four AE studies included 100-150 randomly selected records of deceased patients from around 20 hospitals in each study, resulting in a total of 10,943 patient records.

Improving emergency department flow by introducing a simple time out moment (The TRAFFIC LIGHT study).

Background And Importance: Long waiting times in the emergency department (ED) is an increasing problem in the recent years and is expected to become an even bigger problem in the future Objective: We aimed to test the hypothesis whether increasing awareness of the time lapse with the treating physician, 2 hours after patient arrival, can reduce long patient turnaround time (TAT).

Method: In this prospective single-center cohort study we compared and analyzed patient TAT in the ED before and after implementation of a so called 'traffic light' moment 2 hours after patient arrival. At this 'traffic light' moment a team member contacted the treating physician to increased awareness over the time lapse.

The Impact of First-Time SARS-CoV-2 Infection on Human Anelloviruses.

Members of the family dominate the blood virome, emerging early in life. The anellome, representing the variety of anelloviruses within an individual, stabilizes by adulthood. Despite their supposedly commensal nature, elevated anellovirus concentrations under immunosuppressive treatment indicate an equilibrium controlled by immunity.

[Glycemia reduction in type 2 diabetes patients with low cardiovascular risk].

In persons with type 2 diabetes without established cardiovascular complications data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to glycemic outcomes as well as microvascular and cardiovascular disease outcomes. The GRADE trial compared the ability of four glucose-lowering remedies to achieve and maintain a defined glycated hemoglobin target and to protect the participant from microvascular and macrovascular complications. In this article, we comment on the relevance of this trial with specific attention for the notion that GLP-1 receptor agonists seem to have a primary preventive effect.

25-Hydroxyvitamin D concentrations do not affect the humoral or cellular immune response following SARS-CoV-2 mRNA vaccinations.

Background: To improve effectiveness of vaccination against SARS-CoV-2, it is important to identify factors that influence the immune response induced by vaccination. Evidence for the role of vitamin D in immune response against SARS-CoV-2 is contradictory. It is therefore of interest whether 25-hydroxyvitamin D (25[OH]D) concentrations affect the humoral and/or cellular response following SARS-CoV-2 vaccination.

Why not to pick your nose: Association between nose picking and SARS-CoV-2 incidence, a cohort study in hospital health care workers.

Background: Hospital health care workers (HCW) are at increased risk of contracting SARS-CoV-2. We investigated whether certain behavioral and physical features, e.g.

Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection.

Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology.

Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC.

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees.

Background: Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses.

Antigenic cartography using sera from sequence-confirmed SARS-CoV-2 variants of concern infections reveals antigenic divergence of Omicron.

Large-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similarly to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates.

Decreased Passive Immunity to Respiratory Viruses through Human Milk during the COVID-19 Pandemic.

Infants may develop severe viral respiratory tract infections because their immune system is still developing in the first months after birth. Human milk provides passive humoral immunity during the first months of life. During the COVID-19 pandemic, circulation of common respiratory viruses was virtually absent due to the preventative measures resulting in reduced maternal exposure.

Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trial.

Background: Early antibiotic discontinuation has been advocated in haematology patients with fever of unknown origin during chemotherapy-induced neutropenia, but its safety is unknown. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment.

Methods: This non-inferiority, open-label, multicentre, randomised trial was done in six hospitals in the Netherlands.

Risk of SARS-CoV-2 transmission upon return to work in RNA-positive healthcare workers.

Background: Healthcare workers (HCWs) are at risk for coronavirus disease 2019 (COVID-19), and for spreading severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) amongst colleagues and patients.

Aim: To study the presence of SARS-CoV-2 RNA and possible onward transmission by HCWs upon return to work after COVID-19, and association with disease severity and development of antibodies over time.

Methods: Unvaccinated HCWs with positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) were recruited prospectively.

A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern.

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose.

Cross-reactive antibodies after SARS-CoV-2 infection and vaccination.

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity.

Time since SARS-CoV-2 infection and humoral immune response following BNT162b2 mRNA vaccination.

Background: To optimise the use of available SARS-CoV-2 vaccines, some advocate delaying second vaccination for individuals infected within six months. We studied whether post-vaccination immune response is equally potent in individuals infected over six months prior to vaccination.

Methods: We tested serum IgG binding to SARS-CoV-2 spike protein and neutralising capacity in 110 healthcare workers, before and after both BNT162b2 messenger RNA (mRNA) vaccinations.

Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination.

Emerging SARS-CoV-2 variants of concern (VOCs) pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three VOCs (B.1.

Serologic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Infection Among Hospital Health Care Workers.

Importance: It is unclear when, where, and by whom health care workers (HCWs) working in hospitals are infected with SARS-CoV-2.

Objective: To determine how often and in what manner nosocomial SARS-CoV-2 infection occurs in HCW groups with varying exposure to patients with COVID-19.

Design, Setting, And Participants: This cohort study comprised 4 weekly measurements of SARS-CoV-2-specific antibodies and collection of questionnaires from March 23 to June 25, 2020, combined with phylogenetic and epidemiologic transmission analyses at 2 university hospitals in the Netherlands.

Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination.

Emerging SARS-CoV-2 variants pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three variants of concern (B.1.

[Research into diagnostic reasoning: significant, but also relevant?].

Research into diagnostic reasoning often focuses on diagnostic errors, while ignoring the also important concepts of overdiagnosis and cost of the diagnostic process. A popular theoretic model guiding studies on the subject is the dual process model in which cognitive errors play an important role. This paradigm is also used in the study of Mamede and colleagues, who studied the effect of disease specific knowledge on the occurrence of diagnostic errors due to availability bias in internal medicine residents.

Understanding substrate binding and the role of gatekeeping residues in PigC access tunnels.

Semi-rational redesign of the substrate binding pocket and access tunnels of prodigiosin ligase PigC enhanced the catalytic efficiency in the synthesis of pyrrolic anti-cancer agents more than 45 times. A molecular understanding was gained on residues V333 and T334 relevant to substrate binding and translocation of small pyrroles through PigC access tunnels.