Salivary IL-6 mRNA was previously identified as a promising biomarker of oral squamous cell carcinoma (OSCC). We performed a multi-center investigation covering all geographic areas of Hungary. Saliva from 95 patients with OSCC and 80 controls, all Caucasian, were collected together with demographic and clinicopathological data. Salivary IL-6 mRNA was quantified by real-time quantitative PCR. Salivary IL-6 protein concentration was measured by enzyme-linked immune-sorbent assay. IL-6 protein expression in tumor samples was investigated by immunohistochemistry. Normalized salivary IL-6 mRNA expression values were significantly higher (p < 0.001) in patients with OSCC (mean ± SE: 3.301 ± 0.885) vs. controls (mean ± SE: 0.037 ± 0.012). Differences remained significant regardless of tumor stage and grade. AUC of the ROC curve was 0.9379 (p < 0.001; 95% confidence interval: 0.8973–0.9795; sensitivity: 0.945; specificity: 0.819). Salivary IL-6 protein levels were significantly higher (p < 0.001) in patients (mean ± SE: 70.98 ± 14.06 pg/mL), than in controls (mean ± SE: 12.45 ± 3.29). Specificity and sensitivity of IL-6 protein were less favorable than that of IL-6 mRNA. Salivary IL-6 mRNA expression was significantly associated with age and dental status. IL-6 manifestation was detected in tumor cells and tumor-infiltrating leukocytes, suggesting the presence of a paracrine loop of stimulation. Salivary IL-6 mRNA is one of the best performing and clinically relevant biomarkers of OSCC.

If not detected early, oral squamous cell carcinoma (OSCC) has very poor prognosis, emphasizing the need for reliable early diagnostics. Saliva is considered a promising surrogate biosample for OSCC detection, because it comes into contact with many cells of the tumor mass, providing a comprehensive sampling of tumor-specific biomolecules. Although several protein- and RNA-based salivary biomarkers have been proposed for the detection of OSCC, the results of the studies show large differences. Our goal was to clarify which salivary microRNAs (miRNA) show reliably high expression in the saliva of OSCC patients, to be used as cancer-specific biomarkers, and potentially as early diagnostic biomarkers. Based on a detailed literature search, we selected six miRNAs commonly overexpressed in OSCC, and analyzed their expression in saliva samples of cancer patients and controls by real-time quantitative PCR. Our results suggest that miR-345 and miR-31-5p are consistently upregulated salivary biomarkers for OSCC, and a three-miRNA panel of miR-345, miR-31-5p, and miR-424-3p can distinguish cancer and control patients with high sensitivity.

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

Aspects of oral health related quality of life (OHRQoL) attracted an increased attention recently. The aim of the study was to assess self-reported oral health related quality of life (OHRQoL) among patients requiring prosthetic rehabilitation and to determine the rate of improvement 1 month and 6–12 months after therapy. In addition, effect of age, gender, oral health indicators and denture types before treatment were assessed on OHRQoL as evaluated and reported by the patients. Hungarian version of OHIP-49 (OHIP-49-H) questionnaire was completed before oral rehabilitation (T0-phase) by 389 patients undergoing prosthetic replacement. After 1 month (T1-phase) and 6–12 months (T2-phase) recall periods 235 and 92 patients completed the questionnaire. The median interquartile range (IQR) values of the total OHIP-49-H score were calculated for T0-, T1- and T2-phases. Reliability of the questionnaire was checked by Cronbach’s statistics. Age, gender, oral health indicators and denture types of patients before and after treatment were recorded and treatment-associated changes in OHRQoL were evaluated. The study demonstrated the excellent reliability and internal consistency of OHIP-49-H by a high and narrow range of Cronbach’s alpha value (0.81-0.93). A median OHIP-49-H score of 52; IQR = 25-83 demonstrated a poor OHRQoL on first admission. Decreasing median total OHIP-49-H scores 1 month (24; IQR = 9-51; p < 0.001) and 6–12 months (20; IQR = 7-37; p = 0,055) after therapy indicated an improvement of OHRQoL. Patients’ age and CPI value assessed before treatment proved to be significant factors of OHRQoL. Here we presented representative data about self-assessed OHRQoL of patients requiring prosthetic treatment from Hungary using OHIP-49-H questionnaire. The results demonstrated that the restoration of oral health was associated with an improvement in patients’ OHRQoL. According to the demographical and T0 phase clinical status, the treatment was more effective in the respect of OHIP-49-H score improvement among females (than among males), among younger (than among more aged), and among patients with more serious CPI assessed at T0. The type of prosthetic interventions did not exert a significant effect on total OHIP-49-H score, suggesting that the improvement in OHRQoL is independent from the type of denture applied.

Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in patients with von Willebrand disease (VWD) who have a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, noncontrolled, international phase 3 trial, investigated the efficacy and safety of Wilate prophylaxis in severe patients with VWD. Male and female patients 6 years or older with VWD types 1, 2 (except 2N), or 3 who had completed a prospective, 6-month, on-demand, run-in study (WIL-29) were eligible to receive Wilate prophylaxis for 12 months. At baseline, patients (n = 33) had a median age of 18 years. Six (18%) patients had severe type 1, 5 (15%) had type 2, and 22 (67%) had type 3 VWD. The primary end point of a >50% reduction in mean total annualized bleeding rate (TABR) with Wilate prophylaxis vs prior on-demand treatment was met; mean TABR during prophylaxis was 5.2, representing an 84.4% reduction. The bleeding reduction was consistent across age, sex, and VWD types. The mean spontaneous ABR was 3.2, representing an 86.9% reduction vs on-demand treatment. During prophylaxis, 10 (30.3%) patients had 0 bleeding events and 15 (45.5%) patients had 0 spontaneous bleeding events. Of 173 BEs, 84.4% were minor and 69.9% treated. No serious adverse events related to study treatment and no thrombotic events were recorded. Overall, WIL-31 showed that Wilate prophylaxis was efficacious and well-tolerated in pediatric and adult patients with VWD of all types. The WIL-29 and WIL-31 trials were registered at www.ClinicalTrials.gov as #NCT04053699 and #NCT04052698, respectively.

Undernutrition is a prevalent condition in pediatric malignancy patients leading to unfavorable outcomes. The aim of this retrospective study was to determine the nutritional status and rate of undernutrition in 174 Hungarian pediatric patients with malignancies and the impact on 5-year survival based on anthropometric measurements. At the time of diagnosis, 5.0%, 4.6%, and 4.0% of patients were undernourished as determined by body weight (BW), weight-for-height (WFH), and body mass index (BMI) Z-score, respectively. The rate of undernutrition was 30.5% using ideal body weight percent (IBW%). Undernutrition at the time of diagnosis worsened the five-year overall survival only in solid tumor patients as defined by BMI Z-score and IBW%. Furthermore, 26.5% of patients became undernourished based on IBW% during the treatment period. Deterioration of nutritional status during treatment unfavorably influenced overall survival in both hematological and solid tumor subsets. Abnormal BW, WFH, and BMI Z-score were associated with poor prognosis in the hematologic group. The mortality risk was higher among hematologic patients with weight loss exceeding 20%. In conclusion, IBW% seems to be the most sensitive parameter to estimate undernutrition. Furthermore, BMI Z-score in both groups and severe weight loss in the hematological group may influence clinical outcome and play a role in prognosis assessment.