Background: Use of age‐adjusted reference values is crucial for correct diagnosis and management of thrombotic and hemorrhagic disease in children. They vary with utilized reagents and analyzers.
...Objectives: We established reference values with the Sysmex CA‐1500 System and in parallel with the Behring BCS System using reagents from Siemens Healthcare Diagnostics Products GmbH.
Methods: After informed consent, blood samples were obtained from 218 healthy children and 52 healthy adults, grouped as 1–6 months (n = 29), 7–12 months (n = 25), 1–5 years (n = 57), 6–10 years (n = 57), 11–18 years (n = 50) and > 19 years (n = 52).
Results: Most coagulation parameters demonstrate good comparability between analyzers with the exception of PT and APTT. Single coagulation factors fibrinogen, factor (F) II, FIX, FXI and XII were significantly decreased in the youngest children; the strongest age dependency was found for coagulation inhibitors Protein C and S, both significantly decreased in infancy and young childhood. We confirmed that high levels of von Willebrand factor are found in the youngest children without increased levels of FVIII followed by decreased von Willebrand levels in the subsequent age group. In children with blood group O a less distinct increase in time was found, compared with individuals with one of the other blood groups.
Conclusions: The correlation between the CA‐1500 and the BCS system was remarkable. Differences were most pronounced between children < 12 months and older children and adults, confirming the phenomenon of developmental hemostasis. The rationale for age‐related changes in the hemostatic system remains unraveled. Our results underline the need for age‐specific reference ranges.
Abstract Background Respiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm ...(sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi. Methods NMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi. Results 593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (N tolerant = 155, 37%, N strict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (N tolerant = 145, 35%, N strict = 145, 31%), and high sEAdi area under the baseline (N tolerant = 94, 23%, N strict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH 2 O. Conclusion Advanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.
What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)?
...Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL.
Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol.
This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021.
Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses.
A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years.
The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2-5 years post-diagnosis.
The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol.
The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K., D.K., W.H.W., D.H., M.C., A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest.
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A multimodal approach is advised for neurological prognostication in comatose patients after out-of-hospital cardiac arrest (OHCA). Grey-white matter differentiation (grey-white ratio, GWR) obtained ...from a brain CT scan performed < 24 hours after return of circulation can be part of this approach. The aims of this study were to investigate the frequency and method of reporting the GWR in brain CT scan reports and their association with outcome.
This is a post-hoc descriptive analysis of the COACT trial. The primary endpoint was the reporting of GWR by the radiologist. Secondary endpoints were APACHE IV score, Cerebral Performance Categories at discharge and 90-day follow-up, Glasgow Coma Scale at discharge, GWR-stratified 1-year survival, and RAND-36 stratified by normal versus abnormal GWR. Associations were analysed using multivariable analysis.
A total of 427 OHCA patients were included in this study, 234 (55%) of whom underwent a brain CT scan within 24 hours after ROSC. Median time between arrest and initial CT scan was 12 hours. In 195 patients (83%), the GWR was described in the reports, but always expressed qualitatively. The GWR was deemed abnormal in 57 (29%) CT scans. No differences were found in secondary endpoints between the two groups.
GWR was frequently described in CT scan reports. Early abnormal GWR, as assessed qualitatively by a radiologist within 24 hours after ROSC, was a poor predictor of neurological prognosis.
Rapid diagnosis and appropriate antimicrobial therapy are of major importance to decrease morbidity and mortality in patients with blood stream infections (BSI). Blood culture, the current gold ...standard for detecting bacteria in blood, requires at least 24-48 hours and has limited sensitivity if obtained during antibiotic treatment of the patient. The aim of this prospective multicenter study was to clinically evaluate the application of a commercial universal 16S/18S rDNA PCR, SepsiTest™ (PCR-ST), directly on whole blood.
In total 236 samples from 166 patients with suspected sepsis were included in the study. PCR-ST results were compared to blood culture, the current gold standard for detecting BSI. Because blood cultures can give false-negative results, we performed an additional analysis to interpret the likelihood of bloodstream infection by using an evaluation based on clinical diagnosis, other diagnostic tests and laboratory parameters.
Clinical interpretation of results defined the detected organism to be contaminants in 22 of 43 positive blood cultures (51.2 %) and 21 of 47 positive PCR-ST results (44.7 %). Excluding these contaminants resulted in an overall sensitivity and specificity of the PCR-ST of 66.7 and 94.4 % respectively. Of the 36 clinically relevant samples, 11 BSI were detected with both techniques, 15 BSI were detected with PCR-ST only and 10 with blood culture only. Therefore, in this study, SepsiTest™ detected an additional 71 % BSI compared to blood culture alone.
More clinically relevant BSI were diagnosed by molecular detection, which might influence patient treatment. An improved SepsiTest™ assay suited for routine use can have additional value to blood culture in diagnosing bacteremia in septic patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It remains unclear if quality of life (QoL) improvements could be expected in young patients after malignant bone tumour surgery after 2 years. To assess the course of QoL over time during a ...long‐term follow‐up, malignant bone tumour survivors of a previous short‐term study were included. Assessments were done at least 5 years after surgery. QoL was measured with Short‐form (SF)‐36, TNO‐AZL Questionnaire for Adult's Quality of Life (TAAQOL) and Bone tumour (Bt)‐DUX. QoL throughout the follow‐up was analysed by linear mixed model analysis. From the original cohort of 44 patients; 20 patients were included for this study, 10 males; mean age at surgery 15.1 years and mean follow‐up 7.2 years. Twenty‐one patients of the initial cohort (47%) deceased. Fifteen patients (75%) underwent limb‐salvage and five (25%) ablative surgery. QoL improved significantly during follow‐up at Physical Component Summary Scale scale of the SF‐36 and TAAQOL and all subscales of the Bt‐DUX (p < .01). No significant differences were found between current evaluations and previous evaluations at 2 years after surgery (p = .41–.98). Significant advantages after limb‐salvage were seen at the PCS scale of the SF‐36 (MD 13.7, p = .05) and the cosmetic scale of the Bt‐DUX (MD 17.7, p = .04).
Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are ...clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting.
In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting.
The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs.
Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.
•Of 103,871 ICU patients, 38% are exposed to a clinically relevant potential drug-drug interaction.•The most frequent interactions involve QT-prolonging agents, digoxin or NSAIDs.•Tailoring computerized decision support systems to the ICU may improve medication safety by reducing alert fatigue.
Summary
Introduction
Neutrophilic granulocytes express cluster of differentiation 64 (CD64) antigen upon activation. CD64 can be used as a marker of bacterial infection and sepsis. The goal of this ...study was to determine whether CD64 is a useful biomarker for critically ill patients and analyze longitudinal measurements with regard to outcome and sepsis severity.
Methods
In this prospective observational study, CD64 analysis was performed daily until discharge from ICU or death. Demographics, clinical, laboratory data, and outcome defined as 28‐day survival were recorded. Patients were included when admitted to the ICU with sepsis, severe sepsis, or septic shock and within 24 h from start of antibiotic treatment.
Results
Hundred and fifty‐five consecutive patients were enrolled. At baseline, a difference in CD64 of 2.26 (1.33–4.47) vs. 1.49 (0.89–2.24) (P = 0.004) was seen between patients with a positive culture and negative culture. CD64 at day 1 was higher with patients with septic shock when compared with sepsis (P = 0.012). No difference of CD64 between survivors and nonsurvivors was seen.
Conclusion
This study demonstrated that CD64 discriminates between critically ill patients with culture positive and negative sepsis and correlates with severity of disease. However, CD64 index is not a good predictor for 28‐day mortality in the critically ill patient.
Drug-drug interactions (DDIs) may cause adverse outcomes in patients admitted to the Intensive Care Unit (ICU). Computerized decision support systems (CDSSs) may help prevent DDIs by timely showing ...relevant warning alerts, but knowledge on which DDIs are clinically relevant in the ICU setting is limited. Therefore, the purpose of this study was to identify DDIs relevant for the ICU.
We conducted a modified Delphi procedure with a Dutch multidisciplinary expert panel consisting of intensivists and hospital pharmacists to assess the clinical relevance of DDIs for the ICU. The procedure consisted of two rounds, each included a questionnaire followed by a live consensus meeting.
In total the clinical relevance of 148 DDIs was assessed, of which agreement regarding the relevance was reached for 139 DDIs (94%). Of these 139 DDIs, 53 (38%) were considered not clinically relevant for the ICU setting.
A list of clinically relevant DDIs for the ICU setting was established on a national level. The clinical value of CDSSs for medication safety could be improved by focusing on the identified clinically relevant DDIs, thereby avoiding alert fatigue.
•Almost 40% of the DDIs were perceived as not clinically relevant for the ICU setting.•In the group of frequently occurring DDIs, 63% of the DDIs were perceived as not clinically relevant.•The number of DDI alerts shown to ICU prescribers can be substantially decreased.
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