Machine Learning Logistic Regression Model for Early Decision Making in Referral of Children with Cervical Lymphadenopathy Suspected of Lymphoma

While cervical lymphadenopathy is common in children, a decision model for detecting high-grade lymphoma is lacking. Previously reported individual lymphoma-predicting factors and multivariate models were not sufficiently discriminative for clinical application. To develop a diagnostic scoring tool, we collected data from all children with cervical lymphadenopathy referred to our national pediatric oncology center within 30 months (n = 182). Thirty-nine putative lymphoma-predictive factors were investigated. The outcome groups were classical Hodgkin lymphoma (cHL), nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), non-Hodgkin lymphoma (NHL), other malignancies, and a benign group. We integrated the best univariate predicting factors into a multivariate, machine learning model. Logistic regression allocated each variable a weighing factor. The model was tested in a different patient cohort (n = 60). We report a 12-factor diagnostic model with a sensitivity of 95% (95% CI 89–98%) and a specificity of 88% (95% CI 77–94%) for detecting cHL and NHL. Our 12-factor diagnostic scoring model is highly sensitive and specific in detecting high-grade lymphomas in children with cervical lymphadenopathy. It may enable fast referral to a pediatric oncologist in patients with high-grade lymphoma and may reduce the number of referrals and unnecessary invasive procedures in children with benign lymphadenopathy.</p

Agminated Spitz naevi or metastatic spitzoid melanoma?

Dermatology-oncolog

Whole-body MRI versus an [18F]FDG-PET/CT-based reference standard for early response assessment and restaging of paediatric Hodgkin’s lymphoma: a prospective multicentre study

Child; Diffusion magnetic resonance imaging; Whole-body imagingNiño; Imágenes por resonancia magnética de difusión; Imágenes de cuerpo enteroNen; Imatge per ressonància magnètica de difusió; Imatge de cos sencerObjectives To compare WB-MRI with an [18F]FDG-PET/CT-based reference for early response assessment and restaging in children with Hodgkin’s lymphoma (HL). Methods Fifty-one children (ages 10–17) with HL were included in this prospective, multicentre study. All participants underwent WB-MRI and [18F]FDG-PET/CT at early response assessment. Thirteen of the 51 patients also underwent both WB-MRI and [18F]FDG-PET/CT at restaging. Two radiologists independently evaluated all WB-MR images in two separate readings: without and with DWI. The [18F]FDG-PET/CT examinations were evaluated by a nuclear medicine physician. An expert panel assessed all discrepancies between WB-MRI and [18F]FDG-PET/CT to derive the [18F]FDG-PET/CT-based reference standard. Inter-observer agreement for WB-MRI was calculated using kappa statistics. Concordance, PPV, NPV, sensitivity and specificity for a correct assessment of the response between WB-MRI and the reference standard were calculated for both nodal and extra-nodal disease presence and total response evaluation. Results Inter-observer agreement of WB-MRI including DWI between both readers was moderate (κ 0.46–0.60). For early response assessment, WB-MRI DWI agreed with the reference standard in 33/51 patients (65%, 95% CI 51–77%) versus 15/51 (29%, 95% CI 19–43%) for WB-MRI without DWI. For restaging, WB-MRI including DWI agreed with the reference standard in 9/13 patients (69%, 95% CI 42–87%) versus 5/13 patients (38%, 95% CI 18–64%) for WB-MRI without DWI. Conclusions The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric HL improved agreement with the [18F]FDG-PET/CT-based reference standard. However, WB-MRI remained discordant in 30% of the patients compared to standard imaging for assessing residual disease presence.This project was financially supported by the Stichting Kinderen Kankervrij (KiKa, project number 87). The data collection, analysis and interpretation of data, the writing of the paper and the decision to submit were not influenced by KiKa

Soluble receptor for advanced glycation end products as an indicator of pulmonary vascular injury after cardiac surgery

Background: Cardiac surgery is frequently complicated by an acute vascular lung injury and this may be mediated, at least in part, by the (soluble) receptor for advanced glycation end products (sRAGE).Methods: In two university hospital intensive care units, circulating sRAGE was measured together with the 68Gallium-transferrin pulmonary leak index (PLI), a measure of pulmonary vascular permeabiliy, in 60 consecutive cardiac surgery patients stratified by the amount of blood transfusion, within 3 hours of admission to the intensive care.Results: Cardiac surgery resulted in elevated plasma sRAGE levels compared to baseline (315 ± 181 vs 110 ± 55 pg/ml, P = 0.001). In 37 patients the PLI was elevated 50% above normal. The PLI correlated with sRAGE (r2 = 0.11, P = 0.018). Plasma sRAGE discriminated well between those with an elevated PLI and those with a normal PLI (area under the operator curve 0.75; P = 0.035; 95% CI 0.55-0.95), with 91% sensitivity but low specificity of 36% at a cutoff value of 200 pg/mL

The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI), and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI.Methods: Immediately before initiation of CVVH, prefilter blood was drawn. After 10, 60, 180, and 720 minutes of CVVH, samples were collected from pre- and postfilter (in- and outlet) blood and ultrafiltrate. CVVH with the following anticoagulation regimens was studied: no anticoagulation in case of a high bleeding tendency (n = 13), unfractionated heparin (n = 8), or trisodium citrate (n = 21). NGAL levels were determined with enzyme-linked immunosorbent assay (ELISA).Results: Concentrations of NGAL at inlet and outlet were similar, and concentrations did not change over time in any of the anticoagulation groups; thus no net removal or production of NGAL occurred. Concentrations of NGAL at inlet correlated with disease severity at initiation of CVVH and at the end of a CVVH run. Concentrations of NGAL in the ultrafiltrate were lower with citrate-based CVVH (P = 0.03) and decreased over time, irrespective of anticoagulation administered (P < 0.001). The sieving coefficient and clearance of NGAL were low and decreased over time (P < 0.001).Conclusions: The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, because clearance by the filter was low. Furthermore, no evidence exists for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied

Recombinant human activated protein C in the treatment of acute respiratory distress syndrome

Rationale: Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS), by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC) may inhibit this process and thereby improve patient outcome. Methods: A prospective randomized, saline-controlled, single-blinded clinical trial was performed in the intensive care units of two university hospitals, and patients with ARDS were included within 24 h after meeting inclusion criteria. Intervention: A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38). Outcomes: The primary outcome parameter was the pulmonary leak index (PLI) of 67Gallium-transferrin as a measure of alveolocapillary permeability and secondary outcomes were disease severity scores and ventilator-free days, among others. Results: Baseline characteristics were similar; in 87% of patients the PLI was above normal and in 90% mechanical or noninvasive ventilation was instituted at a median lung injury score of 2.5. There was no evidence that Rh-APC treatment affected the PLI or attenuated lung injury and sequential organ failure assessment scores. Mean ventilator-free days amounted to 14 (rh-APC) and 12 days (saline, P = 0.35). 28-day mortality was 6% in rh-APC- and 18% in saline-treated patients (P = 0.12). There was no difference in bleeding events. The study was prematurely discontinued because rh-APC was withdrawn from the market. Conclusion: There is no evidence that treatment with intravenous rh-APC during 4 days for infectious or inflammatory ARDS ameliorates increased alveolocapillary permeability or the clinical course of ARDS patients. We cannot exclude underpowering. Trial Registration: Nederlands Trial Registe

Reproductive ability in survivors of childhood, adolescent, and young adult Hodgkin lymphoma:a review

Background: Owing to a growing number of young and adolescent Hodgkin lymphoma (HL) survivors, awareness of (long-term) adverse effects of anticancer treatment increases. The risk of impaired reproductive ability is of great concern given its impact on quality of life. There is currently no review available on fertility after childhood HL treatment. Objective and Rationale: The aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors. Search Methods: PubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged &lt;25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually. Outcomes: After screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6-34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55-59%; median 57%; two studies. elevated FSH 17-100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33-100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0-100%; median 51.5%; 26 studies. low inhibin B 19-50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0-57%, median 17%; 21 studies and low testosterone 0-43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMH&lt;p10 9%; one study and Males: azoospermia 0-50%; median 10%; six studies). Reports on chance to achieve pregnancy during survivorship are reassuring, although studies had their limitations and the results are difficult to evaluate. In the end, a diminished ovarian reserve does not exclude the chance of a live birth, and males with aberrant markers may still be able to conceive. Wider Implications: This review substantiates the negative effect of HL treatment on gonadal function and therefore young HL survivors should be counseled regarding their future reproductive life, and fertility preservation should be considered. The current level of evidence is insufficient and additional trials on the effects of HL and (current) treatment regimens on reproductive function are needed. In this review, we make a recommendation on reproductive markers that could be assessed and the timing of (repeated) measurements.</p

Whole-body MRI versus an [F-18]FDG-PET/CT-based reference standard for early response assessment and restaging of paediatric Hodgkin's lymphoma:a prospective multicentre study

Objectives To compare WB-MRI with an [F-18]FDG-PET/CT-based reference for early response assessment and restaging in children with Hodgkin's lymphoma (HL). Methods Fifty-one children (ages 10-17) with HL were included in this prospective, multicentre study. All participants underwent WB-MRI and [F-18]FDG-PET/CT at early response assessment. Thirteen of the 51 patients also underwent both WB-MRI and [F-18]FDG-PET/CT at restaging. Two radiologists independently evaluated all WB-MR images in two separate readings: without and with DWI. The [F-18]FDG-PET/CT examinations were evaluated by a nuclear medicine physician. An expert panel assessed all discrepancies between WB-MRI and [F-18]FDG-PET/CT to derive the [F-18]FDG-PET/CT-based reference standard. Inter-observer agreement for WB-MRI was calculated using kappa statistics. Concordance, PPV, NPV, sensitivity and specificity for a correct assessment of the response between WB-MRI and the reference standard were calculated for both nodal and extra-nodal disease presence and total response evaluation. Results Inter-observer agreement of WB-MRI including DWI between both readers was moderate (kappa 0.46-0.60). For early response assessment, WB-MRI DWI agreed with the reference standard in 33/51 patients (65%, 95% CI 51-77%) versus 15/51 (29%, 95% CI 19-43%) for WB-MRI without DWI. For restaging, WB-MRI including DWI agreed with the reference standard in 9/13 patients (69%, 95% CI 42-87%) versus 5/13 patients (38%, 95% CI 18-64%) for WB-MRI without DWI. Conclusions The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric HL improved agreement with the [F-18]FDG-PET/CT-based reference standard. However, WB-MRI remained discordant in 30% of the patients compared to standard imaging for assessing residual disease presence