[Catatonia in youth with developmental disabilities: challenges in recognition and management]. / Katatonie bij jongeren met een ontwikkelingsstoornis: uitdagingen in herkenning en aanpak.

Catatonia in children and adolescents is not rare and, as in adults, has a favorable outcome, provided it is recognized and treated promptly. Nevertheless, in clinical practice we encounter several obstacles in terms of diagnosis and treatment in this population of patients. We describe a 14-year-old boy with an intellectually disability and autism spectrum disorder (ASD) in which clinicians did not diagnose catatonia until 1 year after the development of symptoms. Moreover, hesitations surrounding the correct treatment led to its delayed initiation. With this case report we aim to contribute to reduced reluctance and increased alertness in the treatment of catatonia in adolescents with developmental disorders.

Frailty score for elderly patients is associated with short-term clinical outcomes in patients with ST-segment elevated myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVE: Consistent with the aging population in the Western world, there is a growing number of elderly patients with ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) is the recommended reperfusion strategy in elderly patients; risk models to determine which of these patients are prone to have poor clinical outcomes are, however, essential. The purpose of this study was to assess the association between frailty and short-term mortality and PCI-related serious adverse events (SAE) in elderly patients. METHODS: All STEMI patients (aged ≥70 years) treated with primary PCI in 2013-2015 at the Leiden University Medical Centre were assessed. The Safety Management Programme (VMS) score was used to identify frail elderly patients. The primary endpoint was 30-day all-cause mortality; the secondary endpoint included 30-day clinical death, target vessel failure, major bleeding, contrast induced kidney insufficiency and stroke. RESULTS: A total of 206 patients were included (79 ± 6.4 years, 119 [58%] male). The VMS score was ≥1 in 28% of all cases. Primary and secondary endpoint rates were 5 and 23% respectively. VMS score ≥1 was an independent predictor for both 30-day mortality (odds ratio [OR] 9.6 [95% confidence interval, CI 1.6-56.9] p-value = 0.013) and 30-day SAE (OR 2.9 [95% CI 1.1-7.9] p-value = 0.038). CONCLUSIONS: VMS score for frailty is independently associated with short-term mortality and PCI-related SAE in elderly patients with STEMI treated with primary PCI. These results suggest that frailty in elderly patients is an important feature to measure and to be taken into account when developing risk models.

Low frequency of acetyl salicylic acid hypersensitivity in mastocytosis: The results of a double-blind, placebo-controlled challenge study.

BACKGROUND: Patients with mastocytosis are at increased risk of anaphylaxis. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often discouraged because of this reason. However, the actual prevalence and severity of NSAID-related hypersensitivity among patients with mastocytosis is unknown. METHODS: A double-blind, placebo-controlled acetylsalicylic acid (ASA) challenge up to a cumulative dose of 520 mg was performed among adult patients with mastocytosis. In addition, a retrospective search of the entire outpatient cohort was performed to obtain "real-life" data on NSAID hypersensitivity. RESULTS: Fifty patients underwent an ASA challenge. Seventy percent had indolent systemic mastocytosis, 18% had mastocytosis in the skin, and 12% had advanced mastocytosis. The ASA challenge was positive in 1 patient who developed urticaria. The additional retrospective chart review revealed that 8 of 191 patients had a history of NSAID-related hypersensitivity reaction(s), of whom 3 reported severe systemic reactions. All 8 patients had already experienced NSAID-related hypersensitivity reactions before mastocytosis was diagnosed. CONCLUSIONS: The frequency of ASA hypersensitivity was 2% in a prospective challenge study and 4.1% in a retrospective chart review of 191 patients with mastocytosis. NSAIDs can be administered safely to most patients with mastocytosis. Extra caution should be taken in patients with a history of hypersensitivity reactions to other drugs, or traditional risk factors for NSAID hypersensitivity.

Capnocytophaga canimorsus meningitis diagnosed by 16S rRNA PCR.

Capnocytophaga canimorsus is a common Gram-negative anaerobic bacterium from the oral flora of dogs, typically transmitted to humans by dog bites. We report a case of C. canimorsus meningitis where there was (on presentation) no apparent predisposing risk factor and in whom we used 16S rRNA PCR gene sequencing to identify the pathogen quickly and to switch to appropriate antibiotic therapy. Physicians should be aware of potential C. canimorsus meningitis if conventional cerebrospinal fluid bacterial culture is negative but Gram staining identifies bacteria, especially in patients with a recent dog bite or known immunodeficiency.

[Levels of target achievement for major modifiable cardiovascular risk factors in Belgium]. / Niveaux d'atteinte des valeurs cibles thérapeutiques pour des facteurs majeurs modifiables du risque cardiovasculaire en Belgique.

Cardiovascular disease (CVD) is the main cause of premature mortality in Europe. The burden of CVD could be reduced by controlling the major modifiable CVD risk factors (dyslipidaemia, arterial hypertension, hyperglycaemia, smoking, and physical inactivity) through lifestyle and dietary changes and appropriate drug therapies. The objective of this article is to assess the level of target achievement for key modifiable CVD risk factors in Belgium by referring to the data from four recent studies. The overall results show that the main CVD risk factors are poorly controlled in patients with established CVD and in patients at high CVD risk. Therapeutic targets may be incompletely reached because of the suboptimal implementation of European guidelines for CVD prevention in routine clinical practice (insufficient lifestyle and dietary adaptations; poor applications of drug therapy to control blood pressure, dyslipidaemia and hyperglycaemia) or because of the insufficient efficacy of currently available treatment options in some patients. This review provides clear and updated evidence for non-target achievement for all major risk factors, with four different study designs and inclusion criteria; it highlights the need for a more comprehensive and intensive application of recommendations of the European guidelines for CVD prevention in Belgium.

High Coxiella burnetii DNA load in serum during acute Q fever is associated with progression to a serologic profile indicative of chronic Q fever.

PCR is very effective in diagnosing acute Q fever in the early stages of infection, when bacterial DNA is present in the bloodstream but antibodies have not yet developed. The objective of this study was to further analyze the diagnostic value of semiquantitative real-time PCR (qPCR) in diagnosing acute Q fever in an outbreak situation. At the Jeroen Bosch Hospital, in 2009, qPCR testing for Coxiella burnetii DNA was performed for 2,715 patients suspected of having acute Q fever (positive, n = 385; negative, n = 2,330). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the qPCR assay were calculated for patients with negative qPCR results with a follow-up sample obtained within 14 days (n = 305) and qPCR-positive patients with at least one follow-up sample (n = 369). The correctness of the qPCR result was based on immunofluorescence assay results for samples submitted for qPCR and follow-up testing. The sensitivity of the Q fever qPCR assay was 92.2%, specificity 98.9%, PPV 99.2%, and NPV 89.8%. Patients who later developed serologic profiles indicative of chronic Q fever infection had significantly higher C. burnetii DNA loads during the acute phase than did patients who did not (P < 0.001). qPCR testing is a valuable tool for the diagnosis of acute Q fever and should be used in outbreak situations when the onset of symptoms is <15 days earlier. Special attention is needed in the follow-up monitoring of patients with high C. burnetii DNA loads during the acute phase, as this might be an indicator for the development of a serologic profile indicative of chronic infection.

Real-time PCR to distinguish livestock-associated (ST398) from non-livestock-associated (methicillin-resistant) Staphylococcus aureus.

BACKGROUND: The Netherlands is one of the most densely populated countries in the world, with extensive livestock of pigs. In 2005, the emergence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) was a fact, with a relatively high MRSA colonisation among pig farmers. These MRSA isolates mostly belonged to sequence type 398 (ST398). Compared to hospital-associated MRSA (HA-MRSA), severe infections due to LA-MRSA and transmission between individuals are still relatively rare. Therefore, LA-MRSA may warrant less stringent containment measures than HA-MRSA in hospital settings. RESULTS: The aim of this study was to develop a rapid diagnostic tool to distinguish LA-MRSA from non-LA-MRSA in aid of infection control. Here, we show that ST398 strains can be readily detected with real-time polymerase chain reaction (PCR). Analysis of a large panel of related and unrelated microorganisms confirmed that the real-time ST398 PCR (ST398-qPCR) assay does not cross-react with other microorganisms or with non-LA-S. aureus strains. ST398-qPCR analysis of MRSA isolates collected in 2010, 2011 and 2012 at the Jeroen Bosch Hospital (n = 275) showed that an average of 78 % of MRSA belonged to sequence type ST398. CONCLUSION: We conclude that the ST398 real-time PCR is a reliable assay to detect LA-S. aureus and anticipate that the use of this assay can prevent the unnecessary closing of hospital wards, which may lead to substantial savings for the health care system.

NPWT or HRT-dressing? Results of an expert panel and a Delphi panel analysis.

OBJECTIVE: To investigate the similarities and differences between Hydration Response Technology (HRT) and negative pressure wound therapy (NPWT) with regard to wound bed preparation, and to devise a set of recommendations for their use on the basis of the opinion of two panels. METHOD: An expert panel that analysed in vitro and clinical data as well as the similarities and differences between the two modalities was established. This culminated in a series of recommendations on which modality to use for which indication. These recommendations were presented to a Delphi panel, consisting of users of both NPWT and HRT-dressing. The panel was then asked to produce its own recommendations. RESULTS: The outcomes and recommendations of both panels were reported. NPWT is the preferred treatment modality for abdominal dehisced wounds, and to a lesser extent, for surgical wound healing by secondary intention. For all other indications, the treatment modalities are at least equal, with HRT-dressing often being the superior mode to treat wounds such as venous leg ulcers, arterial ulcers and vasculitis. CONCLUSION: In the opinion of the expert panel and the Delphi panel, both modalities share a number of clinical and non-clinical properties. However, because of the numerous advantages of HRT technology, HRT dressing has the potential to replace NPWT in a number of indications, where the patient, health-care providers and institutions may benefit. DECLARATION OF INTEREST: This study was sponsored by Sorbion GmbH & Co, Senden, Germany. Authors M. Hermans and K. Cutting are consultants to Sorbion GmbH & Co, Senden, Germany.

The mast cell: A Janus in kidney transplants.

Mast cells (MCs) are innate immune cells with a versatile set of functionalities, enabling them to orchestrate immune responses in various ways. Aside from their known role in allergy, they also partake in both allograft tolerance and rejection through interaction with regulatory T cells, effector T cells, B cells and degranulation of cytokines and other mediators. MC mediators have both pro- and anti-inflammatory actions, but overall lean towards pro-fibrotic pathways. Paradoxically, they are also seen as having potential protective effects in tissue remodeling post-injury. This manuscript elaborates on current knowledge of the functional diversity of mast cells in kidney transplants, combining theory and practice into a MC model stipulating both protective and harmful capabilities in the kidney transplant setting.

Corrigendum: The mast cell: A Janus in kidney transplants.

[This corrects the article DOI: 10.3389/fimmu.2023.1122409.].

The value of the Mortality in Emergency Department Sepsis (MEDS) score, C reactive protein and lactate in predicting 28-day mortality of sepsis in a Dutch emergency department.

BACKGROUND: The tendency of sepsis to progress rapidly and the benefit of an early start of treatment emphasise the importance of fast risk stratification in the emergency department (ED). The aim of the present work was to validate the Mortality in Emergency Department Sepsis (MEDS) score as a predictor of 28-day mortality in ED patients with sepsis in The Netherlands, and to compare its performance to C reactive protein (CRP) and lactate. METHODS: This was a historical cohort study in a secondary and tertiary care university hospital. Patients were included if they were seen by an internist in the ED, fulfilled the clinical criteria for sepsis and were admitted to the hospital. Primary outcome was all-cause in-hospital mortality within 28 days. RESULTS: In the 6-month study period, 331 patients were included, of whom 38 (11.5%) died. Mortality varied significantly per MEDS category: ≤4 points (very low risk: 3.1%), 5-7 points (low risk: 5.3%), 8-12 points (moderate risk 17.3%), 13-15 points (high risk: 40.0%), >15 points (very high risk: 77.8%). Receiver operating characteristic (ROC) analysis showed that the MEDS score predicted 28-day mortality better than CRP (area under the curve (AUC) values of 0.81 (95% CI 0.73 to 0.88) and 0.68 (95% CI 0.58 to 0.78), respectively). Lactate was not measured in enough patients (47) for a valid evaluation, but seemed to predict mortality at least fairly (AUC 0.75, 95% CI 0.60 to 0.90). CONCLUSIONS: The MEDS score is an adequate tool for predicting mortality in patients with sepsis in a Dutch internistic ED population. CRP is less useful in this context. Lactate appears to be at least a fair predictor of mortality, but needs to be investigated more systematically in a larger population.

Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far ?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.

Microfluidic quantum sensing platform for lab-on-a-chip applications.

Lab-on-a-chip (LOC) applications have emerged as invaluable physical and life sciences tools. The advantages stem from advanced system miniaturization, thus, requiring far less sample volume while allowing for complex functionality, increased reproducibility, and high throughput. However, LOC applications necessitate extensive sensor miniaturization to leverage these inherent advantages fully. Atom-sized quantum sensors are highly promising to bridge this gap and have enabled measurements of temperature, electric and magnetic fields on the nano- to microscale. Nevertheless, the technical complexity of both disciplines has so far impeded an uncompromising combination of LOC systems and quantum sensors. Here, we present a fully integrated microfluidic platform for solid-state spin quantum sensors, like the nitrogen-vacancy (NV) center in diamond. Our platform fulfills all technical requirements, such as fast spin manipulation, enabling full quantum sensing capabilities, biocompatibility, and easy adaptability to arbitrary channel and chip geometries. To illustrate the vast potential of quantum sensors in LOC systems, we demonstrate various NV center-based sensing modalities for chemical analysis in our microfluidic platform, ranging from paramagnetic ion detection to high-resolution microscale NV-NMR. Consequently, our work opens the door for novel chemical analysis capabilities within LOC devices with applications in electrochemistry, high-throughput reaction screening, bioanalytics, organ-on-a-chip, or single-cell studies.

Clinical and biochemical characteristics and analysis of risk factors for euglycaemic diabetic ketoacidosis in type 2 diabetic individuals treated with SGLT2 inhibitors: A review of 72 cases over a 4.5-year period.

BACKGROUND AND AIMS: To study euglycemic diabetic ketoacidosis (euDKA) outcomes associated with sodium-glucose co-transporter 2 inhibitors (SGLT2is) METHODS: Review of 72 euDKA cases in T2DM between September 2015 and January 2020 (PUBMED). RESULTS: euDKA could occur at any time during SGLT2is treatment, with nausea, abdominal pain and vomiting as main symptoms. Hyperglycemia did not correlate with pH and ß-hydroxybutyrates. Low pH and high ß-hydroxybutyrates were significantly associated with euDKA. In biguanides users, acidosis was unrelated to lactic acidosis. euDKA occurred during fasting, surgery, acute infection, insulin deprivation (endogenous or exogenous). CONCLUSIONS: These data support avoidance of euDKA risk states in SGLT2i users.

Validation and implementation of the Panbio COVID-19 Ag rapid test for the diagnosis of SARS-CoV-2 infection in symptomatic hospital healthcare workers.

BACKGROUND: RT-PCR is the current recommended laboratory method to diagnose SARS-CoV-2 in healthcare workers (HCW). As RT-PCR is not widely available and is time-consuming, it limits decision making on removal from and return to work of possibly contagious HCW. AIM: In this study we evaluated the Panbio™ COVID-19 Ag rapid test (PanbioCAgRT) in 825 hospital HCW. METHODS AND FINDING: This study consisted of two phases. In the validation phase, we tested hospital HCW with mild symptoms (three days or less) in parallel using the PanbioCAgRT and the RT-qPCR test. The PanbioCAgRT demonstrated 86.7% sensitivity, 100% specificity, 100% PPV and 98.5% NPV with regard to RT-qPCR. For HCW with PanbioCAgRT-/RT-qPCR+, the median Ct value was 30.9, whereas for the HCW with PanbioCAgRT+/RT-qPCR+ the median Ct value was 19.3 (P<0.001). In the second phase, we implemented an on-site antigen test-based strategy for symptomatic hospital HCW: HCW that tested positive with the PanbioCAgRT on-site were considered SARS-CoV-2 positive and were sent home. HCW that tested negative with the PanbioCAgRT on-site were allowed to work with PPE pending RT-qPCR test results from the laboratory. Sensitivity of the antigen test-based strategy was 72.5% and NPV was 97%. For HCW with PanbioCAgRT-/RT-qPCR+ median Ct values were 27.8. CONCLUSION: The PanbioCAgRTt validated in this study showed a high sensitivity and specificity in samples obtained from HCW with high viral loads. The antigen-based testing strategy proposed in this study seems to be effective, safe and easy to implement in a wide range of occupational healthcare settings.

The extent of clonal structure in different lymphoid organs.

To gain insight into the clonal organization of lymphoid organs, we studied the distribution in situ of donor-derived cells in near-physiological chimeras. We introduced RT7b fetal liver cells into nonirradiated congenic RT7a neonatal rats. The chimerism 6-20 wk after injection ranged from 0.3 to 20%. The numbers of cell clones simultaneously contributing to cell generation in a particular histological feature were deduced from the variance in donor cell distribution. In bone marrow and thymus, donor-derived lymphoid cells were found scattered among host cells, indicating a high mobility of cells. In bone marrow, donor cells were evenly distributed over the entire marrow, even at low chimerism. This indicates that leukopoiesis is maintained by the proliferation of many clones. In the thymus, the various lobules showed different quantities of donor-derived lymphoid cells. Mathematical analysis of these differences indicated that 17-18 cell division cycles occur in the cortex. In spleen, the distribution of donor-derived cells over the germinal centers indicated that 5 d after antigenic stimulation, germinal centers develop oligoclonally. The main conclusions of this work are that (a) bone marrow and thymus are highly polyclonal; (b) 17-18 divisions occur between prothymocyte and mature T cell; and (c) lymphoid cells disperse rapidly while proliferating and differentiating.

Sustained receptor activation and hyperproliferation in response to granulocyte colony-stimulating factor (G-CSF) in mice with a severe congenital neutropenia/acute myeloid leukemia-derived mutation in the G-CSF receptor gene.

In approximately 20% of cases of severe congenital neutropenia (SCN), mutations are found in the gene encoding the granulocyte colony-stimulating factor receptor (G-CSF-R). These mutations introduce premature stop codons, which result in truncation of 82-98 COOH-terminal amino acids of the receptor. SCN patients who develop secondary myelodysplastic syndrome and acute myeloid leukemia almost invariably acquired a GCSFR mutation, suggesting that this genetic alteration represents a key step in leukemogenesis. Here we show that an equivalent mutation targeted in mice (gcsfr-Delta715) results in the selective expansion of the G-CSF- responsive progenitor (G-CFC) compartment in the bone marrow. In addition, in vivo treatment of gcsfr-Delta715 mice with G-CSF results in increased production of neutrophils leading to a sustained neutrophilia. This hyperproliferative response to G-CSF is accompanied by prolonged activation of signal transducer and activator of transcription (STAT) complexes and extended cell surface expression of mutant receptors due to defective internalization. In view of the continuous G-CSF treatment of SCN patients, these data provide insight into why progenitor cells expressing truncated receptors clonally expand in vivo, and why these cells may be targets for additional genetic events leading to leukemia.

Do high ferritin levels confer lower cardiovascular risk in men with Type 2 diabetes?

AIMS: High ferritin levels are associated with insulin resistance and liver steatosis, both thought of as emerging cardiovascular risk factors. The association between ferritin and cardiovascular disease is poorly documented in cardiometabolic states with higher cardiovascular risk, such as diabetes and metabolic syndrome. We therefore characterized a cohort of males with Type 2 diabetes mellitus (T2DM) according to ferritin levels and prevalent macroangiopathy. METHODS: The presence of overall macroangiopathy, peripheral and/or coronary artery disease was documented in 424 consecutive T2DM males, who were divided according to ferritin quartiles (Q) as follows: QI-III, normal ferritin (NF; n=318), mean+/-1 sd ferritin 133+/-72 ng/ml; and QIV patients, high ferritin (HF; n=106), ferritin 480+/-228 ng/ml. RESULTS: Age, age at diabetes diagnosis, smoking, ethanol intake, body mass index, waist circumference, blood pressure and presence of metabolic syndrome did not differ between groups. However, the prevalence of macroangiopathy was unexpectedly much lower in patients with high ferritin, as follows: 25% vs. 43% for overall macroangiopathy; 7% vs. 16% for peripheral artery disease; and 16% vs. 31% for coronary artery disease (P=0.0009, P=0.0140 and P=0.0035, respectively, vs. NF patients). Insulin resistance index and prevalence of liver steatosis were higher in HF compared with NF patients as follows: 2.17% vs. 1.89% and 78% vs. 64% (P=0.0345 and P=0.0059, respectively). Liver enzymes (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase) were significantly higher in HF, by 33%, 42% and 72%, respectively (all P<0.0002), suggesting a higher prevalence of steatohepatitis. Glycated haemoglobin, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, urate, high-sensitivity C-reactive protein and albuminuria were not different between groups. CONCLUSIONS: Our results demonstrate that T2DM males with high ferritin levels exhibit a markedly decreased prevalence of macroangiopathy, despite more severe insulin resistance and higher markers of steatohepatitis. High ferritin levels and/or steatosis may thus paradoxically confer a lowered cardiovascular risk in diabetic males.